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1
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Zhang D, Wang Y, Jiang S, Li W. Simple methods for estimating the maximum 24-hour urinary potassium excretion in kidney failure without replacement therapy patients. Ren Fail 2025; 47:2445157. [PMID: 39780434 PMCID: PMC11721948 DOI: 10.1080/0886022x.2024.2445157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 12/11/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Adjusting dietary potassium intake based on 24-hour urinary potassium excretion is the primary method of preventing hyperkalemia. Currently, there is no accurate and convenient method for calculating maximum 24-hour urinary potassium excretion in kidney failure without replacement therapy patients. We developed and validated two new models to assess the upper limit of dietary potassium consumption in this high-risk cohort, using the maximum 24-hour urinary potassium excretion as a proxy. METHODS The data of 145 kidney failure without replacement therapy patients with hyperkalemia was gathered. The prediction models were developed using multilayer perceptron and stepwise multiple linear regression utilizing a stochastic sample of 102 (70%) patients. Within the rest 43 (30%), the performance of various models was independently verified. RESULTS The two new models had low bias (-0.02 and -0.57 mmol/24h vs 66.74 and 79.91 mmol/24h, mean absolute error = 5.57 and 5.22 vs 68.95 and 81.37), high accuracy (percentage of calculated values within_±30% of measured values = 83.45% and 84.14% vs 0.00% and 0.00%), high correlation with measured values (Spearman correlation coefficient = 0.72 and 0.72 vs 0.46 and 0.45, intraclass correlation coefficient = 0.67 and 0.70 vs 0.03 and 0.03) and high agreement with 24-hour urine potassium measurements (95% limits of agreement of Bland-Altman plot = 13.70 and 13.20 mmol/24h vs 113.8 and 191.3 mmol/24h). CONCLUSION These new models show high clinical application value for the calculation of maximum 24-hour urinary potassium excretion in kidney failure without replacement therapy patients with hyperkalemia.
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Affiliation(s)
- Danyang Zhang
- Department of Nephrology, China-Japan Friendship Hospital, Beijing, China
| | - Yukun Wang
- Department of Biomedical Engineering, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Shimin Jiang
- Department of Nephrology, China-Japan Friendship Hospital, Beijing, China
| | - Wenge Li
- Department of Nephrology, China-Japan Friendship Hospital, Beijing, China
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Theodorakopoulou M, Ortiz A, Fernandez-Fernandez B, Kanbay M, Minutolo R, Sarafidis PA. Guidelines for the management of hypertension in CKD patients: where do we stand in 2024? Clin Kidney J 2024; 17:36-50. [PMID: 39583143 PMCID: PMC11581767 DOI: 10.1093/ckj/sfae278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Indexed: 11/26/2024] Open
Abstract
Until recently, major bodies producing guidelines for the management of hypertension in patients with chronic kidney disease (CKD) disagreed in some key issues. In June 2023, the European Society of Hypertension (ESH) published the new 2023 ESH Guidelines for the management of arterial hypertension a document that was endorsed by the European Renal Association. Several novel recommendations relevant to the management of hypertension in patients with CKD appeared in these guidelines, which have been updated to reflect the latest evidence-based practices in managing hypertension in CKD patients. Most of these are in general agreement with the previous 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines-some reflect different emphasis on some topics (i.e. detailed algorithms on antihypertensive agent use) while others reflect evolution of important evidence in recent years. The aim of the present review is to summarize and comment on key points and main areas of focus in patients with CKD, as well as to compare and highlight the main differences with the 2021 KDIGO Guidelines for the management of blood pressure in CKD.
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Affiliation(s)
- Marieta Theodorakopoulou
- First Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Alberto Ortiz
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, Madrid, Spain
| | | | - Mehmet Kanbay
- Department of Nephrology, Koc University School of Medicine, Istanbul, Turkey
| | - Roberto Minutolo
- Nephrology Unit, Department of Advanced Medical and Surgical Science, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Pantelis A Sarafidis
- First Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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3
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Halimi JM, Sarafidis P, Azizi M, Bilo G, Burkard T, Bursztyn M, Camafort M, Chapman N, Cottone S, de Backer T, Deinum J, Delmotte P, Dorobantu M, Doumas M, Dusing R, Duly-Bouhanick B, Fauvel JP, Fesler P, Gaciong Z, Gkaliagkousi E, Gordin D, Grassi G, Grassos C, Guerrot D, Huart J, Izzo R, Jaén Águila F, Járai Z, Kahan T, Kantola I, Kociánová E, Limbourg F, Lopez-Sublet M, Mallamaci F, Manolis A, Marketou M, Mayer G, Mazza A, MacIntyre I, Mourad JJ, Muiesan ML, Nasr E, Nilsson P, Oliveras A, Ormezzano O, Paixão-Dias V, Papadakis I, Papadopoulos D, Perl S, Polónia J, Pontremoli R, Pucci G, Robles NR, Rubin S, Ruilope LM, Rump LC, Saeed S, Sanidas E, Sarzani R, Schmieder R, Silhol F, Sokolovic S, Solbu M, Soucek M, Stergiou G, Sudano I, Tabbalat R, Tengiz I, Triantafyllidi H, Tsioufis K, Václavík J, van der Giet M, der Niepen PV, Veglio F, Venzin R, Viigimaa M, Weber T, Widimsky J, Wuerzner G, Zelveian P, Zebekakis P, Lueders S, Persu A, Kreutz R, Vogt L. Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney. Blood Press 2024; 33:2368800. [PMID: 38910347 DOI: 10.1080/08037051.2024.2368800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 06/05/2024] [Indexed: 06/25/2024]
Abstract
Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.
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Affiliation(s)
- Jean-Michel Halimi
- Service de Néphrologie-Hypertension, Dialyses, Transplantation rénale, Hôpital Bretonneau, Tours, France
| | | | - Michel Azizi
- Université Paris Cité Department of Cardiology, Paris, France
- APHP, Service d'Hypertension Artérielle, Hôpital Européen Georges Pompidou, Paris, France
| | - Grzegorz Bilo
- Grzegorz Bilo, Department of Cardiology, Istituto Auxologico Italiano, IRCCS, Milan, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Thilo Burkard
- Medical Outpatient Department and Hypertension Clinic, University Hospital Basel, Basel, Switzerland
| | - Michael Bursztyn
- Hypertension Clinic, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem
- Faculty of Medicine, School of Medicine, Hadassah-Hebrew University, Jerusalem, Israel
| | - Miguel Camafort
- Hypertension Unit, Department of Internal Medicine, Hospital Clinic, University of Barcelona, Spain
| | - Neil Chapman
- Peart-Rose Clinic, Hammersmith Hospital, Imperial College Healthcare Trust, London, UK
| | - Santina Cottone
- PROMISE Department, Nephrology and Dialisys Unit with Hypertension ESH Excellence Centre, University Hospital P.Giaccone, Palermo, Italy
- University of Palermo Department of Nephrology, Palermo, Italy
| | - Tine de Backer
- Department of Cardiovascular Diseases, Internal Medicine, University Hospital Ghent, Ghent, Belgium
| | - Jaap Deinum
- Department of Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Philippe Delmotte
- Hypertension Unit (European Society of Hypertension Excellence Centre), Department of Cardiology, HELORA University Hospitals, Mons, Belgium
| | - Maria Dorobantu
- Emergency Clinical Hospital of Bucharest Department of Emergency Medicineap: Department of Cardiology, Bucharest, Romania
| | - Michalis Doumas
- 2nd Prop Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
| | - Rainer Dusing
- Hypertoniezentrum Bonn, Schwerpunktpraxis Kardiologie, Angiologie, Prävention, Rehabilitation, Bonn, Germany
| | | | - Jean-Pierre Fauvel
- Department of Nephrology and Hypertension, Hôpital Ed Herriot, Lyon, France
| | - Pierre Fesler
- Department of Internal Medicine, Montpellier University Hospital, Montpellier, France
- PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, Montpellier, France
| | - Zbigniew Gaciong
- Department of Internal Medicine, Hypertension and Vascular Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Eugenia Gkaliagkousi
- 3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Greece
| | - Daniel Gordin
- Department of Nephrology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Guido Grassi
- Clinica Medica, University Milano Bicocca, Milan, Italy
| | | | - Dominique Guerrot
- Service de Néphrologie, CIC-CRB 1404, INSERM EnVi U1096, CHU Rouen, France
| | - Justine Huart
- Division of Nephrology, University of Liège Hospital (ULg CHU), University of Liège, and Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA), Cardiovascular Sciences, University of Liège, Liège, Belgium
| | - Raffaele Izzo
- Department of Advanced Medical Sciences, Federico II University of Naples, Italy
| | - Fernando Jaén Águila
- Vascular Risk Unit, Internal Medicine, Virgen de las Nieves University Hospital, Granada, Spain
| | - Zoltán Járai
- South-Buda Center Hospital, St. Imre University Teaching Hospital, Budapest, Hungary
| | - Thomas Kahan
- Department of Clinical Sciences, Division of Cardiovascular Medicine, Karolinska Institute, Stockholm, Sweden
- Department of Cardiology, Danderyd University Hospital Corp, Stockholm, Sweden
| | - Ilkka Kantola
- Division of Medicine, Turku University Hospital, Turku University, Turku, Finland
| | - Eva Kociánová
- First Department of Internal Medicine - Cardiology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
| | - FlorianP Limbourg
- Dept. of Nephrology and Hypertension, Hypertension Center, Hannover Medical School, Hannover, Germany
| | - Marilucy Lopez-Sublet
- AP-HP, Unité d'hypertension artérielle, service de médecine interne, Hôpital Avicenne, Bobigny, France
- INSERM UMR 942 MASCOT, Paris 13-Université Paris Nord, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Bobigny, France
| | - Francesca Mallamaci
- Grande Ospedale Metropolitano, UOC di Nefrologia abilitata al trapianto renale, CNR Epidemiologia Clinica e Fisiopatologia delle Malattie Renali e dell'Ipertensione Arteriosa, Reggio Calabria, Italy
| | | | - Maria Marketou
- Hypertension Outpatient Clinic, Cardiology Department, Heraklion University General Hospital, Heraklion, Greece
| | - Gert Mayer
- Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck Anichstrasse, Innsbruck, Austria
| | - Alberto Mazza
- Internal Medicine Unit, Department of Medicine, ESH Excellence Center Unit, Italy
| | - IainM MacIntyre
- Cardiovascular Risk Clinic, Western General Hospital, Edinburgh, UK
| | - Jean-Jacques Mourad
- Service de Médecine Interne, Hôpital Franco-Britannique, Levallois-Perret, France
| | - Maria Lorenza Muiesan
- Centro Studi Diagnosi e Cura dell'Ipertensione Arteriosa e del Rischio Cardiovascolare (IARC), University of Brescia and ASST Spedali Civili, Italy
| | - Edgar Nasr
- St George University Medical Center Achrafieh-Beirut, Lebanon
| | - Peter Nilsson
- Department of Clinical Sciences, Lund University, Skane University Hospital, Malmö, Sweden
| | - Anna Oliveras
- Hypertension and Vascular Risk Unit, Department of Nephrology, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu Fabra, Barcelona, Spain
| | - Olivier Ormezzano
- UF Hypertension et Athérothrombose, Centre Européen d'Excellence en Hypertension Artérielle, Service de Cardiologie, CHU Michallon, Grenoble, France
| | - Vitor Paixão-Dias
- Internal Medicine Department, Hospital Centre of Vila Nova de Gaia/Espinho, Portugal
| | - Ioannis Papadakis
- Hypertension Unit, Dept. of Internal Medicine, University Hospital of Heraklion, Heraklion, Greece
| | | | - Sabine Perl
- Department of Cardiology, Medical University of Graz, Graz, Austria
| | - Jorge Polónia
- Department of Medicine CINTESIS RISE, Faculty of Medicine of Porto, Portugal
| | - Roberto Pontremoli
- Università degli Studi e IRCCS Ospedale Policlinico San Martino di Genova, Italy
| | - Giacomo Pucci
- Department of Medicine and Surgery, University of Perugia, Unit of Internal Medicine - Santa Maria Terni Hospital, Terni, Italy
| | | | - Sébastien Rubin
- Service de Néphrologie-transplantation-dialyse-aphérèses, CHU Bordeaux, France
| | | | - Lars Christian Rump
- Department of Internal Medicine/Nephrology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Sahrai Saeed
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Elias Sanidas
- Department of Cardiology, LAIKO General Hospital, Athens, Greece
| | - Riccardo Sarzani
- Università Politecnica delle Marche and IRCCS-INRCA Department of Clinical and Molecular Sciences, Ancona, Italy
| | - Roland Schmieder
- Department of Nephrology, Hypertension University Hospital Erlangen, Friedrich Alexander University Erlangen/Nürnberg, Germany
| | - François Silhol
- Service de Médecine Vasculaire et Hypertension Artérielle, Centre de compétence régional des maladies artérielles rares, Centre d'excellence Européen en Hypertension Artérielle 264, rue Saint Pierre, CHU Timone, Marseille, France
| | | | - Marit Solbu
- University Hospital of North Norway Department of Nephrology cb: Department of Internal Medicine and Cardiology, Tromsø, Norway
| | - Miroslav Soucek
- 2nd Department of Internal Medicine, St. Anne's University Hospital, Brno, Czech Republic
- Fakulty of Medicine, Masaryk University Brno, Czech Republic
| | - George Stergiou
- School of Medicine, Third Department of Medicine, Sotiria Hospital, Hypertension Center STRIDE-7, National and Kapodistrian University of Athens, Athens, Greece
| | - Isabella Sudano
- University Hospital Zurich University Heart Center, Cardiology and University of Zurich, Zurich, Switzerland
| | - Ramzi Tabbalat
- Department of Cardiology, Abdali Hospital, Amman, Jordan
| | - Istemihan Tengiz
- Division of Cardiology, Izmir Medicana International Hospital, Yenisehir, Turkey
| | - Helen Triantafyllidi
- 2nd Department of Cardiology, Medical School, University of Athens, ATTIKON Hospital, Athens, Greece
| | - Konstontinos Tsioufis
- 1st Department of Cardiology, National and Kapodistrian University of Athens, Hippocratio Hospital, Greece
| | - Jan Václavík
- Department of Internal Medicine and Cardiology, University Hospital Ostrava, Czech Republic
- Faculty of Medicine, University of Ostrava, Czech Republic
| | - Markus van der Giet
- Medinische Klinik für Nephrologie und internistische Intensivtherapie, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Patricia Van der Niepen
- Departement of Nephrology & Hypertension, Universitair Ziekenhuis Brussel Department of Nephrology and Hypertension, VUB, Belgium
| | - Franco Veglio
- Department of Medical Sciences, University of Turin, Italy
| | - RetoM Venzin
- Department of Nephrology, Cantonal Hospital Graubuenden, Chur, Switzerland
| | - Margus Viigimaa
- Centre of Cardiology, North Estonia Medical Centre, Tallinn University of Technology, Tallinn, Estonia
| | - Thomas Weber
- Cardiology Department, Klinikum Wels-Grieskirchen, Wels, Austria
| | - Jiri Widimsky
- IIIrd Internal Department, Centre for Hypertension, General Faculty Hospital, Charles University, Prague, Czech Republic
| | - Gregoire Wuerzner
- Service de néphrologie et d'hypertension, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Parounak Zelveian
- Center of Preventive Cardiology, Armenia Parounak Zelveian, Hospital N2 CJSC, Yerevan, Armenia
| | - Pantelis Zebekakis
- Hypertension Unit of the First Department of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | | | - Alexandre Persu
- Department of Cardiovascular Diseases, Division of Cardiology, Cliniques Universitaires Saint-Luc and Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Reinhold Kreutz
- Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Liffert Vogt
- Department of Internal Medicine, Section of Nephrology, Amsterdam University Medical Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, the Netherlands
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Desai NR, Kammerer J, Budden J, Olopoenia A, Tysseling A, Gordon A. The Association of Heart Failure and Edema Events between Patients Initiating Sodium Zirconium Cyclosilicate or Patiromer. KIDNEY360 2024; 5:1835-1843. [PMID: 39303023 DOI: 10.34067/kid.0000000586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 09/17/2024] [Indexed: 09/22/2024]
Abstract
Key Points
One previous study using claims data reported signals for higher hospitalizations for heart failures and severe edema in patients prescribed a potassium binder using sodium exchange.In this study, sodium zirconium cyclosilicate use was associated with increased risk of prespecified encounters of hospitalizations for heart failure and major edema encounters.Our findings highlight the need to weigh the benefits and risks of sodium zirconium cyclosilicate and patiromer in routine clinical practice.
Background
Sodium zirconium cyclosilicate (SZC) and patiromer (PAT) are potassium binders that differ by exchange ion, sodium, and calcium, respectively. There are limited data on whether using sodium exchange could affect the risks of hospitalizations for heart failure (HHF) or severe edema in patients with hyperkalemia. The goal of this study was to assess the occurrence rates of prespecified major encounters potentially related to electrolyte-/fluid-related imbalances (including HHF, edema) among new users of PAT or SZC.
Methods
Using Cerner Real World Data, we conducted a retrospective cohort study among adults (≥18 years) who were newly initiated on SZC or PAT between June 1, 2018, and December 31, 2021. Based on baseline demographic and clinical characteristics, one PAT initiator was propensity score matched with two SZC initiators. Primary outcomes were any HHF, primary HHF, major edema encounter, or death. Cox proportional hazard regression models were used to estimate the association between SZC or PAT use and each outcome in the overall population and subgroups with/without prior heart failure (HF).
Results
The final cohort included 9929 PAT initiators matched to 19, 849 SZC initiators. The mean age was 66 years; about 50% had a history of CKD stages 3–5 and 34% a history of HF. Incidence rates were significantly higher in the SZC cohort when compared with the PAT cohort for all outcomes. Risks of HHF (any/primary) (adjusted hazard ratios [HRs], 1.373; 95% confidence interval [CI], 1.337 to 1.410), major edema encounter (HR, 1.330; 95% CI, 1.298 to 1.363), and death (HR, 1.287; 95% CI, 1.255 to 1.320) were also significantly higher in the SZC cohort compared with the PAT cohort (P < 0.05). These findings were consistent among subgroups with/without prior HF.
Conclusions
SZC use (versus PAT) was associated with an increased risk of prespecified encounters that were potentially sodium-/fluid-related, including among patients with/without preexisting HF.
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Affiliation(s)
- Nihar R Desai
- Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, New Haven, Connecticut
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Logan Ellis H, Al-Agil M, Kelly PA, Teo J, Sharpe C, Whyte MB. The burden of hyperkalaemia on hospital healthcare resources. Clin Exp Med 2024; 24:190. [PMID: 39136879 PMCID: PMC11322248 DOI: 10.1007/s10238-024-01452-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 07/26/2024] [Indexed: 08/16/2024]
Abstract
Hyperkalaemia is associated with prolonged hospital admission and worse mortality. Hyperkalaemia may also necessitate clinical consults, therapies for hyperkalaemia and high-dependency bed utilisation. We evaluated the 'hidden' human and organisational resource utilisation for hyperkalaemia in hospitalised patients. This was a single-centre, observational cohort study (Jan 2017-Dec 2020) at a tertiary-care hospital. The CogStack system (data processing and analytics platform) was used to search unstructured and structured data from individual patient records. Association between potassium and death was modelled using cubic spline regression, adjusted for age, sex, and comorbidities. Cox proportional hazards estimated the hazard of death compared with normokalaemia (3.5-5.0 mmol/l). 129,172 patients had potassium measurements in the emergency department. Incidence of hyperkalaemia was 85.7 per 1000. There were 49,011 emergency admissions. Potassium > 6.5 mmol/L had 3.9-fold worse in-hospital mortality than normokalaemia. Chronic kidney disease was present in 21% with potassium 5-5.5 mmol/L and 54% with potassium > 6.5 mmol/L. For diabetes, it was 20% and 32%, respectively. Of those with potassium > 6.5 mmol/L, 29% had nephrology review, and 13% critical care review; in this group 22% transferred to renal wards and 8% to the critical care unit. Dialysis was used in 39% of those with peak potassium > 6.5 mmol/L. Admission hyperkalaemia and hypokalaemia were independently associated with reduced likelihood of hospital discharge. Hyperkalaemia is associated with greater in-hospital mortality and reduced likelihood of hospital discharge. It necessitated significant utilisation of nephrology and critical care consultations and greater likelihood of patient transfer to renal and critical care.
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Affiliation(s)
- Hugh Logan Ellis
- Department of Medicine, King's College Hospital NHS Foundation Trust, London, UK
| | - Mohammad Al-Agil
- Department of Basic and Clinical Neuroscience, School of Neuroscience, King's College London, London, UK
| | - Philip A Kelly
- Department of Medicine, King's College Hospital NHS Foundation Trust, London, UK
| | - James Teo
- Department of Basic and Clinical Neuroscience, School of Neuroscience, King's College London, London, UK
| | - Claire Sharpe
- Renal Sciences, Department of Inflammation Biology, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Martin B Whyte
- Department of Medicine, King's College Hospital NHS Foundation Trust, London, UK.
- Department of Medicine, King's College Hospital NHS Foundation Trust, London, UK.
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6
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Mugo BM, Kiio J, Munyaka A. Effect of blanching time-temperature on potassium and vitamin retention/loss in kale and spinach. Food Sci Nutr 2024; 12:5403-5411. [PMID: 39139923 PMCID: PMC11317740 DOI: 10.1002/fsn3.4186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 03/30/2024] [Accepted: 04/11/2024] [Indexed: 08/15/2024] Open
Abstract
Hyperkalemia is common among patients with end stage kidney disease. Management involves diet modification. Hot water blanching is recommended to leach potassium in vegetables which results in losses of water-soluble and heat labile vitamins. Evidence on the effect of blanching in reducing potassium level of locally consumed vegetables in Kenya is limited. This study sought to establish effect of hot water blanching time-temperature on level of potassium, vitamin B1, B3 and C in kales (Brassica oleracea var. acephala) and spinach (Spinach oleracea) on potassium and vitamins B1, B3 and C retention/loss. The study adopted a full factorial experimental design. Vitamins were determined using high performance liquid chromatography. Potassium was quantified using atomic absorption spectrophotometry. To compare nutrient content between samples, independent t-test and Analysis of Variance were used at 95% confidence level. Nutrient content of fresh kales and spinach were potassium (102 mg/100 g and 615 mg/100 g), vitamin B1 (124 μg/100 g and 51 μg/100 g), vitamin B3 (1165 μg/100 g and 812 μg/100 g) and vitamin C (102 mg/100 g and 116 mg/100 g) respectively. In kales, blanching for 20 min at 1000°C resulted to retention of 86.9%, 55.6%, 27.6% and 12.9% of vitamin B1, B3, C and potassium respectively. In spinach, blanching for 20 min at 1000°C resulted in retention of 79.9%, 88.6%, 12.2% and 40.6% retention of vitamin B1, B3, C and potassium respectively. Vitamin C and Potassium were the most sensitive to heat and leaching. Time had a greater effect than temperature in this study. This study recommends blanching of kale at 15.2 min at 800°C, spinach at 17.7 min at 840°C. Further research on optimal blanching time-temperature for potassium and vitamin retention/loss is recommended.
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Affiliation(s)
- Beatrice Muthoni Mugo
- Department of Foods Nutrition and Dietetics, School of Health SciencesKenyatta UniversityNairobiKenya
| | - Juliana Kiio
- Department of Foods Nutrition and Dietetics, School of Health SciencesKenyatta UniversityNairobiKenya
| | - Ann Munyaka
- Department of Foods Nutrition and Dietetics, School of Health SciencesKenyatta UniversityNairobiKenya
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Fishbane S, Carrero JJ, Kumar S, Kanda E, Hedman K, Ofori-Asenso R, Kashihara N, Kosiborod MN, Lainscak M, Pollock C, Stenvinkel P, Wheeler DC, Pecoits-Filho R. Hyperkalemia Burden and Treatment Pathways in Patients with CKD: Findings From the DISCOVER CKD Retrospective Cohort. KIDNEY360 2024; 5:974-986. [PMID: 39052473 PMCID: PMC11296538 DOI: 10.34067/kid.0000000000000468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 04/29/2024] [Indexed: 07/27/2024]
Abstract
Key Points Hyperkalemia (HK) is associated with increased comorbidity burden in patients with CKD. Reducing serum potassium levels after HK episodes helps continuation of renin-angiotensin-aldosterone system inhibitor treatment. In Japan, HK treatment pathways are more heterogeneous and potassium binders are more commonly prescribed compared with the United Kingdom. Background This analysis used retrospective data from the DISCOVER CKD observational study (NCT04034992 ) to describe the burden of and treatment pathways for hyperkalemia (HK) in patients with CKD. Methods Data were extracted from the following databases: UK Clinical Practice Research Datalink (2008–2019) and Japan Medical Data Vision (2008–2017). Patients with CKD (two eGFR measures <75 ml/min per 1.73 m2 recorded ≥90 days apart) and HK (at least two serum potassium [sK+] measures >5.0 mmol/L) were compared with patients without HK (sK+ <5.0 mmol/L); HK index event was the second sK+ measurement. Outcomes included baseline characteristics and treatment pathways for key medications (renin-angiotensin-aldosterone system inhibitors [RAASi], diuretics and potassium [K+] binders). Results In the UK Clinical Practice Research Datalink, 37,713 patients with HK and 142,703 patients without HK were included for analysis (HK prevalence 20.9%). In the Japan Medical Data Vision, 5924 patients with HK and 74,272 patients without HK were included for analysis (HK prevalence 7.4%). In both databases, median eGFR was lower and comorbidities such as hypertension, heart failure, type 2 diabetes, and AKI were more prevalent among patients with versus without HK, and most patients were taking RAASi at the time of HK index. Treatment pathways were more heterogeneous in Japan; <0.2% of patients with CKD and HK in the United Kingdom initiated K+ binders within 3 months of HK index versus 18.7% in Japan. The proportions of patients with CKD and HK who stopped treatment with diuretics, K+ binders, and RAASi during follow-up were 48.7%, 76.5%, and 50.6%, respectively, in the United Kingdom, and 22.9%, 53.6%, and 29.2%, respectively, in Japan. Conclusions HK was associated with increased comorbidity burden in patients with CKD. Variations in treatment pathways between the United Kingdom and Japan reflect the previous lack of a standardized approach to HK management in CKD.
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Affiliation(s)
- Steven Fishbane
- Division of Nephrology, Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York
| | - Juan-Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Supriya Kumar
- Real World Data Science, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Maryland
| | | | - Katarina Hedman
- Late Cardiovascular, Renal, Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden
| | | | | | - Mikhail N. Kosiborod
- Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri
| | - Mitja Lainscak
- Division of Cardiology, Faculty of Medicine, General Hospital Murska Sobota, University of Ljubljana, Ljubljana, Slovenia
| | - Carol Pollock
- Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Peter Stenvinkel
- Department of Renal Medicine M99, Karolinska University Hospital, Stockholm, Sweden
| | - David C. Wheeler
- Department of Renal Medicine, University College London, London, United Kingdom
| | - Roberto Pecoits-Filho
- School of Medicine, Pontifical Catholic University of Parana, Curitiba, Brazil
- Arbor Research Collaborative for Health, Ann Arbor, Michigan
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8
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Palmer BF, Clegg DJ. Hyperkalemia treatment standard. Nephrol Dial Transplant 2024; 39:1097-1104. [PMID: 38425037 DOI: 10.1093/ndt/gfae056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Indexed: 03/02/2024] Open
Abstract
Hyperkalemia is a common electrolyte disturbance in both inpatient and outpatient clinical practice. The severity and associated risk depends on the underlying cause and rate of potassium (K+) increase. Acute hyperkalemia requires immediate attention due to potentially life-threatening manifestations resulting from the rapid increase in plasma K+ concentration. Treatment is initially focused on stabilizing the cardiac membrane, followed by maneuvers to shift K+ into the cells, and ultimately initiating strategies to decrease total body K+ content. Chronic hyperkalemia develops over a more extended period of time and manifestations tend to be less severe. Nevertheless, the disorder is not benign since chronic hyperkalemia is associated with increased morbidity and mortality. The approach to patients with chronic hyperkalemia begins with a review of medications potentially responsible for the disorder, ensuring effective diuretic therapy and correcting metabolic acidosis if present. The practice of restricting foods high in K+ to manage hyperkalemia is being reassessed since the evidence supporting the effectiveness of this strategy is lacking. Rather, dietary restriction should be more nuanced, focusing on reducing the intake of nonplant sources of K+. Down-titration and/or discontinuation of renin-angiotensin-aldosterone inhibitors should be discouraged since these drugs improve outcomes in patients with heart failure and proteinuric kidney disease. In addition to other conservative measures, K+ binding drugs and sodium-glucose cotransporter 2 inhibitors can assist in maintaining the use of these drugs.
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Affiliation(s)
- Biff F Palmer
- Professor of Internal Medicine, Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Deborah J Clegg
- Professor of Internal Medicine, Vice President for Research, Texas Tech Health Sciences Center, El Paso, TX, USA
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9
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Rowan CG, Agiro A, Chan KA, Colman E, White K, Desai P, Dwyer JP. Hyperkalemia Recurrence Following Medical Nutrition Therapy in Patients with Stage 3-4 Chronic Kidney Disease: The REVOLUTIONIZE I Real-World Study. Adv Ther 2024; 41:2381-2398. [PMID: 38687454 PMCID: PMC11133091 DOI: 10.1007/s12325-024-02835-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 03/06/2024] [Indexed: 05/02/2024]
Abstract
INTRODUCTION The REVOLUTIONIZE I study aimed to characterize the relationships between medical nutrition therapy (MNT) and hyperkalemia recurrence in patients with stage 3-4 chronic kidney disease (CKD) and hyperkalemia who received MNT in real-world clinical practice. METHODS This observational cohort study used de-identified electronic health record data from patients aged ≥ 18 years with stage 3-4 CKD who received MNT between January 2019 and October 2022 and had hyperkalemia (serum potassium > 5.0 mmol/L) within 30 days before MNT. Patients were followed for 6 months or until the first censoring event (death, prescription of outpatient potassium binder, or study end). The primary outcome was the percentage of patients with ≥ 1 hyperkalemia recurrence during follow-up. Secondary outcomes included the number of hyperkalemia recurrences per patient, time to each recurrence, and hyperkalemia-related healthcare resource utilization. Exploratory outcomes included all-cause healthcare resource utilization and mortality. RESULTS The final cohort comprised 2048 patients; 1503 (73.4%) patients remained uncensored after 6 months. During the 6-month follow-up period, 56.0% of patients had ≥ 1 hyperkalemia recurrence and 37.4% had ≥ 1 recurrence within the first month. Patients with ≥ 1 hyperkalemia recurrence during follow-up had a mean ± standard deviation (SD) of 2.6 ± 2.2 recurrences. The mean ± SD time to first hyperkalemia recurrence was 45 ± 46 days; the time between recurrences decreased with subsequent episodes. Hyperkalemia-related hospitalizations and emergency department visits were recorded for 13.7% and 1.5% of patients, respectively. Sensitivity analyses showed that results were consistent across patient subgroups, including those with comorbid heart failure and patients receiving renin-angiotensin-aldosterone system inhibitor therapy at baseline. CONCLUSION Most patients with stage 3-4 CKD had hyperkalemia recurrence, and MNT alone was inadequate to prevent recurrence. These patients may require additional long-term treatment, such as novel potassium binders, to maintain normokalemia and prevent hyperkalemia recurrence following MNT. Infographic available for this article. INFOGRAPHIC.
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Affiliation(s)
- Christopher G Rowan
- Pharmacoepidemiology, COHRDATA, INC, 4030 Calle Marlena, San Clemente, CA, 92672, USA.
| | - Abiy Agiro
- US Evidence, US Medical Affairs, AstraZeneca, Wilmington, DE, USA
| | | | - Ellen Colman
- US Renal, US Medical Affairs, AstraZeneca, Wilmington, DE, USA
| | | | - Pooja Desai
- US Renal, US Medical Affairs, AstraZeneca, Wilmington, DE, USA
| | - Jamie P Dwyer
- Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
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10
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Lefevre F, Mousseaux C, Bobot M. [What's new in hyperkalemia management?]. Rev Med Interne 2024; 45:350-353. [PMID: 38220492 DOI: 10.1016/j.revmed.2024.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 12/19/2023] [Accepted: 01/01/2024] [Indexed: 01/16/2024]
Abstract
Hyperkalemia is common in everyday clinical practice, and is a major risk factor for mortality. It mainly affects patients with chronic renal failure (CKD), diabetes or receiving treatment with inhibitors of the renin-angiotensin-aldosterone system (iRAAS). Therapeutic management aims not only to avoid the complications of hyperkalemia, but also to avoid discontinuation of cardio- and nephroprotective treatments such as iRAAS. The use of polystyrene sulfonate, widely prescribed, is often limited by patient acceptability. Recent data have cast doubt on its safety, particularly in terms of digestive tolerance. Two new potassium exchange molecules have appeared on the market: patiromer and zirconium sulfonate. Their value in clinical practice, and their acceptability in the event of prolonged prescription, remain to be demonstrated. The combination of a thiazide diuretic or an inhibitor of the sodium-glucose cotransporter type 2 (iSGLT2) with iRAAS therapy in CKD, may also improve control of kalemia. At present, there are no recommendations for the positioning of the various hypokalemic treatments. The choice of these treatments must be adapted to the patient's pathologies and consider the other expected effects of these molecules.
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Affiliation(s)
- F Lefevre
- Centre de néphrologie et transplantation rénale, hôpital de la Conception, AP-HM, 147, boulevard Baille, 13005 Marseille, France
| | - C Mousseaux
- Sorbonne université, CORAKID, Inserm UMR_S1155, hôpital Tenon, Paris, France; Soins intensifs néphrologiques-Rein Aigu, hôpital Tenon, AP-HP, Paris, France
| | - M Bobot
- Centre de néphrologie et transplantation rénale, hôpital de la Conception, AP-HM, 147, boulevard Baille, 13005 Marseille, France; Aix-Marseille université, C2VN, Inserm 1263, INRAE 1260, CERIMED, Marseille, France.
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11
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Sarafidis P, Schmieder R, Burnier M, Persu A, Januszewicz A, Halimi JM, Arici M, Ortiz A, Wanner C, Mancia G, Kreutz R. A European Renal Association (ERA) synopsis for nephrology practice of the 2023 European Society of Hypertension (ESH) Guidelines for the Management of Arterial Hypertension. Nephrol Dial Transplant 2024; 39:929-943. [PMID: 38365947 PMCID: PMC11139525 DOI: 10.1093/ndt/gfae041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Indexed: 02/18/2024] Open
Abstract
In June 2023, the European Society of Hypertension (ESH) presented and published the new 2023 ESH Guidelines for the Management of Arterial Hypertension, a document that was endorsed by the European Renal Association (ERA). Following the evolution of evidence in recent years, several novel recommendations relevant to the management of hypertension in patients with chronic kidney disease (CKD) appeared in these Guidelines. These include recommendations for target office blood pressure (BP) <130/80 mmHg in most and against target office BP <120/70 mmHg in all patients with CKD; recommendations for use of spironolactone or chlorthalidone for patients with resistant hypertension with estimated glomerular filtration rate (eGFR) higher or lower than 30 mL/min/1.73 m2, respectively; use of a sodium-glucose cotransporter 2 inhibitor for patients with CKD and estimated eGFR ≥20 mL/min/1.73 m2; use of finerenone for patients with CKD, type 2 diabetes mellitus, albuminuria, eGFR ≥25 mL/min/1.73 m2 and serum potassium <5.0 mmol/L; and revascularization in patients with atherosclerotic renovascular disease and secondary hypertension or high-risk phenotypes if stenosis ≥70% is present. The present report is a synopsis of sections of the ESH Guidelines that are relevant to the daily clinical practice of nephrologists, prepared by experts from ESH and ERA. The sections summarized are those referring to the role of CKD in hypertension staging and cardiovascular risk stratification, the evaluation of hypertension-mediated kidney damage and the overall management of hypertension in patients with CKD.
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Affiliation(s)
- Pantelis Sarafidis
- 1st Department of Nephrology, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Roland Schmieder
- Department of Nephrology and Hypertension, University Hospital Erlangen, Germany
| | - Michel Burnier
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Alexandre Persu
- Division of Cardiology, Cliniques Universitaires Saint-Luc and Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Andrzej Januszewicz
- Department of Hypertension, National Institute of Cardiology, Warsaw, Poland
| | - Jean-Michel Halimi
- Service de Néphrologie-Hypertension, Dialyses, Transplantation rénale, CHRU Tours, Tours, France and INSERM SPHERE U1246, Université Tours, Université de Nantes, Tours, France
| | - Mustafa Arici
- Department of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Alberto Ortiz
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, Madrid, Spain
| | | | | | - Reinhold Kreutz
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Klinische Pharmakologie und Toxikologie, Berlin, Germany
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12
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Drapkina OM, Kontsevaya AV, Kalinina AM, Avdeev SN, Agaltsov MV, Alekseeva LI, Almazova II, Andreenko EY, Antipushina DN, Balanova YA, Berns SA, Budnevsky AV, Gainitdinova VV, Garanin AA, Gorbunov VM, Gorshkov AY, Grigorenko EA, Jonova BY, Drozdova LY, Druk IV, Eliashevich SO, Eliseev MS, Zharylkasynova GZ, Zabrovskaya SA, Imaeva AE, Kamilova UK, Kaprin AD, Kobalava ZD, Korsunsky DV, Kulikova OV, Kurekhyan AS, Kutishenko NP, Lavrenova EA, Lopatina MV, Lukina YV, Lukyanov MM, Lyusina EO, Mamedov MN, Mardanov BU, Mareev YV, Martsevich SY, Mitkovskaya NP, Myasnikov RP, Nebieridze DV, Orlov SA, Pereverzeva KG, Popovkina OE, Potievskaya VI, Skripnikova IA, Smirnova MI, Sooronbaev TM, Toroptsova NV, Khailova ZV, Khoronenko VE, Chashchin MG, Chernik TA, Shalnova SA, Shapovalova MM, Shepel RN, Sheptulina AF, Shishkova VN, Yuldashova RU, Yavelov IS, Yakushin SS. Comorbidity of patients with noncommunicable diseases in general practice. Eurasian guidelines. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2024; 23:3696. [DOI: 10.15829/1728-8800-2024-3996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024] Open
Abstract
Создание руководства поддержано Советом по терапевтическим наукам отделения клинической медицины Российской академии наук.
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13
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Hedlund Møller S, Haagensen Kofod D, Schou M, Torp-Pedersen C, Gislason G, Carlson N, Lindhardt M. Mineralocorticoid receptor antagonist treatment in patients with renal insufficiency and the associated risk of hyperkalemia and death. J Hypertens 2024; 42:564-571. [PMID: 38108246 PMCID: PMC10842657 DOI: 10.1097/hjh.0000000000003639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 11/26/2023] [Accepted: 11/26/2023] [Indexed: 12/19/2023]
Abstract
OBJECTIVES Mineralocorticoid receptor antagonist (MRA) treatment is kidney protective but not recommended to patients with advanced renal failure due to the risk of hyperkalemia and death. This study aimed to examine the impact of MRA treatment in patients with chronic kidney disease on risk of hyperkalemia and subsequent mortality. METHODS Rates of hyperkalemia were compared across strata of estimated glomerular filtration rate (eGFR) and MRA treatment based on cox regression using a nested case-control framework with 1 : 4 matching of patients with hyperkalemia (K + ≥6.0 mmol/l) with controls from the Danish general population on age, sex, diabetes, and hypertension. Risk of subsequent 30-day mortality was assessed in a cohort study with comparisons across strata of eGFR and MRA treatment based on multiple Cox regression. RESULTS Thirty-two thousand four hundred twenty-six cases with hyperkalemia were matched with 127 038 controls. MRA treatment was associated with an increased rate of hyperkalemia with hazard ratios [95% confidence interval (95% CI)] of 8.28 (7.78-8.81), 5.12 (4.67-5.62), 3.58 (3.23-3.97), and 1.89 (1.60-2.23) in patients with eGFR at least 60, 45-59, 30-44, and less than 30 ml/min/1.73 m 2 , respectively (Reference: No MRA).However, MRA-exposed patients had a lower 30-day mortality risk following hyperkalemia with absolute risks (95% CI) of 29.3% (27.8-31.1), 20.3% (18.7-22.4), 19.5% (17.9-21.7), and 19.7% (17.4-22.5) compared to 39.8% (38.8-40.8), 32.0% (30.7-33.1), 28.8% (27.5-31.2), and 22.5% (21.4-23.4) in patients without MRA exposure in patients with GFR at least 60, 45-59, 30-44, and less than 30 ml/min/1.7 3m 2 , respectively. CONCLUSION MRA treatment was associated with an increased rate of hyperkalemia but decreased risk of subsequent 30-day mortality across all stages of renal impairment.
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Affiliation(s)
- Sara Hedlund Møller
- Department of internal medicine, Copenhagen University Hospital Holbaek, Holbaek
| | | | - Morten Schou
- Department of cardiology, Herlev Hospital, University Copenhagen
- Department of cardiology, Copenhagen University Hospital Gentofte
| | | | - Gunnar Gislason
- Department of cardiology, Copenhagen University Hospital Gentofte
- Department of Research, The Danish Heart Foundation, Copenhagen, Denmark
| | - Nicholas Carlson
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet
| | - Morten Lindhardt
- Department of internal medicine, Copenhagen University Hospital Holbaek, Holbaek
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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14
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De Nicola L, Ferraro PM, Montagnani A, Pontremoli R, Dentali F, Sesti G. Recommendations for the management of hyperkalemia in patients receiving renin-angiotensin-aldosterone system inhibitors. Intern Emerg Med 2024; 19:295-306. [PMID: 37775712 PMCID: PMC10954964 DOI: 10.1007/s11739-023-03427-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 09/04/2023] [Indexed: 10/01/2023]
Abstract
Hyperkalemia is common in clinical practice and can be caused by medications used to treat cardiovascular diseases, particularly renin-angiotensin-aldosterone system inhibitors (RAASis). This narrative review discusses the epidemiology, etiology, and consequences of hyperkalemia, and recommends strategies for the prevention and management of hyperkalemia, mainly focusing on guideline recommendations, while recognizing the gaps or differences between the guidelines. Available evidence emphasizes the importance of healthcare professionals (HCPs) taking a proactive approach to hyperkalemia management by prioritizing patient identification and acknowledging that hyperkalemia is often a long-term condition requiring ongoing treatment. Given the risk of hyperkalemia during RAASi treatment, it is advisable to monitor serum potassium levels prior to initiating these treatments, and then regularly throughout treatment. If RAASi therapy is indicated in patients with cardiorenal disease, HCPs should first treat chronic hyperkalemia before reducing the dose or discontinuing RAASis, as reduction or interruption of RAASi treatment can increase the risk of adverse cardiovascular and renal outcomes or death. Moreover, management of hyperkalemia should involve the use of newer potassium binders, such as sodium zirconium cyclosilicate or patiromer, as these agents can effectively enable optimal RAASi treatment. Finally, patients should receive education regarding hyperkalemia, the risks of discontinuing their current treatments, and need to avoid excessive dietary potassium intake.
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Affiliation(s)
- Luca De Nicola
- Nephrology Unit, Advanced Medical and Surgical Sciences Department, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Pietro Manuel Ferraro
- U.O.S. Terapia Conservativa della Malattia Renale Cronica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
- Section of Nephrology, Department of Medicine, Università degli Studi di Verona, Verona, Italy.
| | - Andrea Montagnani
- Department of Internal Medicine, Hospital Misericordia, Grosseto, Italy
| | - Roberto Pontremoli
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Francesco Dentali
- Department of Medicine and Surgery, Insubria University, Varese, Italy
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy
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15
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Senni M, Sciatti E, Bussalino E, D'Elia E, Ravera M, Paoletti E. Practical patient care appraisals with use of new potassium binders in heart failure and chronic kidney diseases. J Cardiovasc Med (Hagerstown) 2023; 24:781-789. [PMID: 37695628 DOI: 10.2459/jcm.0000000000001555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
Abstract
Hyperkalaemia is a life-threatening condition leading to significant morbidity and mortality. It is common in heart failure and in chronic kidney disease (CKD) patients due to the diseases themselves, which often coexist, the high co-presence of diabetes, the fluctuations in renal function, and the use of some drugs [i.e. renin-angiotensin-aldosterone system (RAAS) inhibitors]. Hyperkalaemia limits their administration or uptitration, thus impacting on mortality. New K + binders, namely patiromer and sodium zirconium cyclosilicate (ZS-9), are an intriguing option to manage hyperkalaemia in heart failure and/or CKD patients, both to reduce its fatal effects and to let clinicians uptitrate RAAS inhibition. Even if their real impact on strong outcomes is still to be determined, we hereby provide a practical approach to favour their use in routine clinical practice in order to gain the correct confidence and provide an additive tool to heart failure and CKD patients' wellbeing. New trials are welcome to fill the gap in knowledge.
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Affiliation(s)
- Michele Senni
- Unità di Cardiologia, Dipartimento Cardiovascolare, ASST Papa Giovanni XXIII, Bergamo
- Università Milano-Bicocca, Milan
| | - Edoardo Sciatti
- Unità di Cardiologia, Dipartimento Cardiovascolare, ASST Papa Giovanni XXIII, Bergamo
| | - Elisabetta Bussalino
- Clinica Nefrologica, Dialisi e Trapianto, Policlinico San Martino, Genova, Italy
| | - Emilia D'Elia
- Unità di Cardiologia, Dipartimento Cardiovascolare, ASST Papa Giovanni XXIII, Bergamo
| | - Maura Ravera
- Clinica Nefrologica, Dialisi e Trapianto, Policlinico San Martino, Genova, Italy
| | - Ernesto Paoletti
- Clinica Nefrologica, Dialisi e Trapianto, Policlinico San Martino, Genova, Italy
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16
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Sarafidis P, Iatridi F, Ferro C, Alexandrou ME, Fernandez-Fernandez B, Kanbay M, Mallamaci F, Nistor I, Rossignol P, Wanner C, Cozzolino M, Ortiz A. Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA). Clin Kidney J 2023; 16:1885-1907. [PMID: 37915899 PMCID: PMC10616462 DOI: 10.1093/ckj/sfad139] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Indexed: 11/03/2023] Open
Abstract
Chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D) represents a major public health issue; it develops in about 30%-40% of patients with diabetes mellitus and is the most common cause of CKD worldwide. Patients with CKD and T2D are at high risk of both developing kidney failure and of cardiovascular events. Renin-angiotensin system (RAS) blockers were considered the cornerstone of treatment of albuminuric CKD in T2D for more than 20 years. However, the residual risk of progression to more advanced CKD stages under RAS blockade remains high, while in major studies with these agents in patients with CKD and T2D no significant reductions in cardiovascular events and mortality were evident. Steroidal mineralocorticoid receptor antagonists (MRAs) are known to reduce albuminuria in individuals on RAS monotherapy, but their wide clinical use has been curtailed by the significant risk of hyperkalemia and absence of trials with hard renal outcomes. In recent years, non-steroidal MRAs have received increasing interest due to their better pharmacologic profile. Finerenone, the first compound of this class, was shown to effectively reduce the progression of kidney disease and of cardiovascular outcomes in participants with T2D in phase 3 trials. This clinical practice document prepared from a task force of the European Renal Best Practice board summarizes current knowledge on the role of MRAs in the treatment of CKD in T2D aiming to support clinicians in decision-making and everyday management of patients with this condition.
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Affiliation(s)
- Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Fotini Iatridi
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Charles Ferro
- Department of Nephrology, University Hospitals Birmingham and Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK
| | - Maria-Eleni Alexandrou
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Mehmet Kanbay
- Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey
| | - Francesca Mallamaci
- CNR-IFC, Clinical Epidemiology and Pathophysiology of Hypertension and Renal Diseases, Ospedali Riuniti, Reggio Calabria, Italy
| | - Ionut Nistor
- Nephrology Department, University of Medicine and Pharmacy “Grigore T.Popa”, Iași, Romania
| | - Patrick Rossignol
- Université de Lorraine, INSERM CIC-P 1433, CHRU de Nancy, INSERM U1116, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France
- Department of Medical Specialties and Nephrology-Hemodialysis, Princess Grace Hospital, Monaco, and Centre d'Hémodialyse Privé de Monaco, Monaco
| | - Christoph Wanner
- Division of Nephrology, University Hospital Würzburg, Würzburg, Germany
| | - Mario Cozzolino
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
| | - Alberto Ortiz
- Department of Nephrology and Hypertension, IIS-Fundación Jiménez Díaz UAM, Madrid, Spain
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17
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Palmer BF, Clegg DJ. Pathophysiology and clinical management of hyperkalemia in chronic kidney disease. Minerva Med 2023; 114:719-735. [PMID: 36912858 DOI: 10.23736/s0026-4806.23.08465-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2023]
Abstract
Adaptive increases in kidney and gastrointestinal excretion of K+ help to prevent hyperkalemia in patients with chronic kidney disease (CKD) as long as the glomerular filtration rate (GFR) remains >15-20 mL/min. K+ balance is maintained by increased secretion per functioning nephron, which is mediated by elevated plasma K+ concentration, aldosterone, increased flow rate, and enhanced Na+-K+-ATPase activity. Fecal losses of potassium also increase in CKD. These mechanisms are effective in preventing hyperkalemia if urine output is in excess of 600 mL/day and the GFR exceeds 15 mL/min. Development of hyperkalemia with only mild to moderate reductions in GFR should prompt a search for intrinsic disease of the collecting duct, disturbances in mineralocorticoid activity, and/or decreased delivery of sodium to the distal nephron. The initial approach to treatment is to review the patient's medication profile and whenever possible discontinue drugs that impair kidney K+ excretion. Patients should be educated on sources of K+ in the diet and should be strongly encouraged to avoid the use of K+ containing salt substitutes as well as herbal remedies since herbs may be a hidden source of dietary K+. Effective diuretic therapy and correction of metabolic acidosis are effective strategies to minimize the potential for hyperkalemia. Discontinuation or use of submaximal doses of renin-angiotensin blockers should be discouraged given the cardiovascular protective effect these drugs provide. Potassium binding drugs can be useful to enable use of these drugs and potentially allow liberalization of the diet in CKD patients.
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Affiliation(s)
- Biff F Palmer
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA -
| | - Deborah J Clegg
- Department of Internal Medicine, Texas Tech Health Sciences Center, El Paso, TX, USA
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18
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Sampani E, Theodorakopoulou M, Iatridi F, Sarafidis P. Hyperkalemia in chronic kidney disease: a focus on potassium lowering pharmacotherapy. Expert Opin Pharmacother 2023; 24:1775-1789. [PMID: 37545002 DOI: 10.1080/14656566.2023.2245756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 08/01/2023] [Accepted: 08/04/2023] [Indexed: 08/08/2023]
Abstract
INTRODUCTION Hyperkalemia is one of the most common electrolyte disorders in chronic kidney disease (CKD) and is associated with serious adverse outcomes. Hyperkalemia risk is even greater when CKD patients also have additional predisposing conditions such as diabetes or heart failure. Renin-angiotensin-aldosterone-system blockers are first-line treatments for cardio- and nephroprotection, but their use is often limited due to K+ elevation, resulting in high rates of discontinuation. AREAS COVERED This article provides an overview of factors interfering with K+ homeostasis and discusses recent data on newer therapeutic agents used for the treatment of hyperkalemia. A detailed literature search was performed in two major databases (PubMed/MEDLINE and Scopus) up to April 2023. EXPERT OPINION Major clinical trials have tested new and promising kidney protective therapies such as sodium/glucose-cotransporter-2 inhibitors and mineralocorticoid-receptor-antagonists, with promising results. Until recently, the only treatment option for hyperkalemia was the cation-exchanging resin sodium-polystyrene-sulfonate. However, despite its common use, the efficacy and safety data of this drug in the long-term management of hyperkalemia are scarce. During the last decade, two novel orally administered K+-exchanging compounds (patiromer and sodium-zirconium-cyclosilicate) have been approved for the treatment of adults with hyperkalemia, as they both effectively reduce elevated serum K+ and maintain chronically K+ balance within the normal range with an excellent tolerability and no serious adverse events.
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Affiliation(s)
- Erasmia Sampani
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Marieta Theodorakopoulou
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Fotini Iatridi
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Al-Qusairi L, Ferdaus MZ, Pham TD, Li D, Grimm PR, Zapf AM, Abood DC, Tahaei E, Delpire E, Wall SM, Welling PA. Dietary anions control potassium excretion: it is more than a poorly absorbable anion effect. Am J Physiol Renal Physiol 2023; 325:F377-F393. [PMID: 37498547 PMCID: PMC10639028 DOI: 10.1152/ajprenal.00193.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 07/20/2023] [Accepted: 07/22/2023] [Indexed: 07/28/2023] Open
Abstract
The urinary potassium (K+) excretion machinery is upregulated with increasing dietary K+, but the role of accompanying dietary anions remains inadequately characterized. Poorly absorbable anions, including [Formula: see text], are thought to increase K+ secretion through a transepithelial voltage effect. Here, we tested if they also influence the K+ secretion machinery. Wild-type mice, aldosterone synthase (AS) knockout (KO) mice, or pendrin KO mice were randomized to control, high-KCl, or high-KHCO3 diets. The K+ secretory capacity was assessed in balance experiments. Protein abundance, modification, and localization of K+-secretory transporters were evaluated by Western blot analysis and confocal microscopy. Feeding the high-KHCO3 diet increased urinary K+ excretion and the transtubular K+ gradient significantly more than the high-KCl diet, coincident with more pronounced upregulation of epithelial Na+ channels (ENaC) and renal outer medullary K+ (ROMK) channels and apical localization in the distal nephron. Experiments in AS KO mice revealed that the enhanced effects of [Formula: see text] were aldosterone independent. The high-KHCO3 diet also uniquely increased the large-conductance Ca2+-activated K+ (BK) channel β4-subunit, stabilizing BKα on the apical membrane, the Cl-/[Formula: see text] exchanger, pendrin, and the apical KCl cotransporter (KCC3a), all of which are expressed specifically in pendrin-positive intercalated cells. Experiments in pendrin KO mice revealed that pendrin was required to increase K+ excretion with the high-KHCO3 diet. In summary, [Formula: see text] stimulates K+ excretion beyond a poorly absorbable anion effect, upregulating ENaC and ROMK in principal cells and BK, pendrin, and KCC3a in pendrin-positive intercalated cells. The adaptive mechanism prevents hyperkalemia and alkalosis with the consumption of alkaline ash-rich diets but may drive K+ wasting and hypokalemia in alkalosis.NEW & NOTEWORTHY Dietary anions profoundly impact K+ homeostasis. Here, we found that a K+-rich diet, containing [Formula: see text] as the counteranion, enhances the electrogenic K+ excretory machinery, epithelial Na+ channels, and renal outer medullary K+ channels, much more than a high-KCl diet. It also uniquely induces KCC3a and pendrin, in B-intercalated cells, providing an electroneutral KHCO3 secretion pathway. These findings reveal new K+ balance mechanisms that drive adaption to alkaline and K+-rich foods, which should guide new treatment strategies for K+ disorders.
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Affiliation(s)
- Lama Al-Qusairi
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Department of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
| | - Mohammed Z Ferdaus
- Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
| | - Truyen D Pham
- Department of Medicine Nephrology, Emory University School of Medicine, Atlanta, Georgia, United States
| | - Dimin Li
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Department of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
| | - P Richard Grimm
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Department of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
| | - Ava M Zapf
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Department of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
| | - Delaney C Abood
- Department of Medicine Nephrology, Emory University School of Medicine, Atlanta, Georgia, United States
| | - Ebrahim Tahaei
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Department of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
| | - Eric Delpire
- Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
| | - Susan M Wall
- Department of Medicine Nephrology, Emory University School of Medicine, Atlanta, Georgia, United States
| | - Paul A Welling
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Department of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
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20
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Granal M, Fouque D, Ducher M, Fauvel JP. Factors associated with kalemia in renal disease. Nephrol Dial Transplant 2023; 38:2067-2076. [PMID: 36662047 DOI: 10.1093/ndt/gfad015] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND International recommendations promote a strict potassium diet in order to avoid hyperkalemia in chronic kidney disease (CKD) patients. However, the efficiency of such a dietary recommendation has never been demonstrated. The objectives of this study were to define the relationship between kalemia, dietary potassium intake estimated by kaliuresis and renal function, and to define the factors associated with kalemia in patients using artificial intelligence. METHODS To this extent, data from patients followed in a nephrology unit, included in the UniverSel study and whose kalemia (measured on the day of urine collection; n = 367) were analyzed. RESULTS The patients included had a wide range of estimated glomerular filtration rate (eGFR), but few had stage 5 CKD. Kalemia was negatively and linearly correlated to eGFR (P < .001) but was not correlated to kaliuresis (P = .55). Kaliuresis was not correlated to eGFR (P = .08). Factors associated with kalemia were analyzed using a Bayesian network. The five variables most associated with kalemia were, in descending order, eGFR, original nephropathy, age, diabetes and plasma bicarbonate level. CONCLUSION The results of this study do not support a strict dietary potassium control to regulate kalemia in stage 1-4 CKD patients.
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Affiliation(s)
- Maelys Granal
- UMR 5558 CNRS Lyon, Université Lyon 1, Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Néphrologie, Lyon, France
| | - Denis Fouque
- CARMEN, Université Lyon 1, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre-Bénite, France
| | - Micher Ducher
- UMR 5558 CNRS Lyon, Université Lyon 1, Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Néphrologie, Lyon, France
| | - Jean-Pierre Fauvel
- UMR 5558 CNRS Lyon, Université Lyon 1, Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Néphrologie, Lyon, France
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21
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Costa D, Patella G, Provenzano M, Ielapi N, Faga T, Zicarelli M, Arturi F, Coppolino G, Bolignano D, De Sarro G, Bracale UM, De Nicola L, Chiodini P, Serra R, Andreucci M. Hyperkalemia in CKD: an overview of available therapeutic strategies. Front Med (Lausanne) 2023; 10:1178140. [PMID: 37583425 PMCID: PMC10424443 DOI: 10.3389/fmed.2023.1178140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 07/10/2023] [Indexed: 08/17/2023] Open
Abstract
Hyperkalemia (HK) is a life-threatening condition that often occurs in patients with chronic kidney disease (CKD). High serum potassium (sKsK) is responsible for a higher risk of end-stage renal disease, arrhythmias and mortality. This risk increases in patients that discontinue cardio-nephroprotective renin-angiotensin-aldosterone system inhibitor (RAASi) therapy after developing HK. Hence, the management of HK deserves the attention of the clinician in order to optimize the therapeutic strategies of chronic treatment of HK in the CKD patient. The adoption in clinical practice of the new hypokalaemic agents patiromer and sodium zirconium cyclosilicate (SZC) for the prevention and chronic treatment of HK could allow patients, suffering from heart failure and chronic renal failure, to continue to benefit from RAASi therapy. We have updated a narrative review of the clear variables, correct definition, epidemiology, pathogenesis, etiology and classifications for HK among non-dialysis CKD (ND CKD) patients. Furthermore, by describing the prognostic impact on mortality and on the progression of renal damage, we want to outline the strategies currently available for the control of potassium (K+) plasma levels.
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Affiliation(s)
- Davide Costa
- Department of Law, Economics and Sociology, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Gemma Patella
- Renal Unit, Department of Health Sciences, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
| | - Michele Provenzano
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Nicola Ielapi
- Department of Public Health and Infectious Disease, Sapienza University of Rome, Rome, Italy
| | - Teresa Faga
- Renal Unit, Department of Health Sciences, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
| | - Mariateresa Zicarelli
- Renal Unit, Department of Health Sciences, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
| | - Franco Arturi
- Unit of Internal Medicine, Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Giuseppe Coppolino
- Renal Unit, Department of Health Sciences, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
| | - Davide Bolignano
- Renal Unit, Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | | | | | - Luca De Nicola
- Renal Unit, University of Campania “LuigiVanvitelli”, Naples, Italy
| | - Paolo Chiodini
- Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Raffaele Serra
- Unit of Vascular Surgery, Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Michele Andreucci
- Renal Unit, Department of Health Sciences, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
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22
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Chang HH, Chiang JH, Tsai CC, Chiu PF. Predicting hyperkalemia in patients with advanced chronic kidney disease using the XGBoost model. BMC Nephrol 2023; 24:169. [PMID: 37308844 DOI: 10.1186/s12882-023-03227-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 06/01/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND Hyperkalemia is a common complication of chronic kidney disease (CKD). Hyperkalemia is associated with mortality, CKD progression, hospitalization, and high healthcare costs in patients with CKD. We developed a machine learning model to predict hyperkalemia in patients with advanced CKD at an outpatient clinic. METHODS This retrospective study included 1,965 advanced CKD patients between January 1, 2010, and December 31, 2020 in Taiwan. We randomly divided all patients into the training (75%) and testing (25%) datasets. The primary outcome was to predict hyperkalemia (K+ > 5.5 mEq/L) in the next clinic vist. Two nephrologists were enrolled in a human-machine competition. The area under the receiver operating characteristic curves (AUCs), sensitivity, specificity, and accuracy were used to evaluate the performance of XGBoost and conventional logistic regression models with that of these physicians. RESULTS In a human-machine competition of hyperkalemia prediction, the AUC, PPV, and accuracy of the XGBoost model were 0.867 (95% confidence interval: 0.840-0.894), 0.700, and 0.933, which was significantly better than that of our clinicians. There were four variables that were chosen as high-ranking variables in XGBoost and logistic regression models, including hemoglobin, the serum potassium level in the previous visit, angiotensin receptor blocker use, and calcium polystyrene sulfonate use. CONCLUSIONS The XGBoost model provided better predictive performance for hyperkalemia than physicians at the outpatient clinic.
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Affiliation(s)
- Hsin-Hsiung Chang
- Division of Nephrology, Department of Internal Medicine, Antai Medical Care Corporation Antai Tian-Sheng Memorial Hospital, Pingtung County, Taiwan
- Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan
| | - Jung-Hsien Chiang
- Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan.
| | - Chun-Chieh Tsai
- Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Ping-Fang Chiu
- Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
- Department of Post Baccalaureate, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
- Department of Hospitality Management, MingDao University, Changhua, Taiwan.
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23
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Huang N, Liu Y, Ai Z, Zhou Q, Mao H, Yang X, Xu Y, Yu X, Chen W. Mediation of serum albumin in the association of serum potassium with mortality in Chinese dialysis patients: a prospective cohort study. Chin Med J (Engl) 2023; 136:213-220. [PMID: 36805593 PMCID: PMC10106125 DOI: 10.1097/cm9.0000000000002588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Indexed: 02/23/2023] Open
Abstract
BACKGROUND The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum potassium and mortality in dialysis patients of a Chinese nationwide multicenter cohort, taking albumin as a consideration. METHODS This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities. RESULTS A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.7 ± 14.8 years, 55.3%(5546/10,027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30 ± 0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shape was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found ( P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation. CONCLUSIONS Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.
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Affiliation(s)
- Naya Huang
- Department of Nephrology, The First Affiliated Hospital, Key Laboratory of Nephrology, Ministry of Health of China, Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
| | - Yuanying Liu
- Department of Nephrology, The First Affiliated Hospital, Key Laboratory of Nephrology, Ministry of Health of China, Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
| | - Zhen Ai
- Department of Nephrology, The First Affiliated Hospital, Key Laboratory of Nephrology, Ministry of Health of China, Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
| | - Qian Zhou
- Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
| | - Haiping Mao
- Department of Nephrology, The First Affiliated Hospital, Key Laboratory of Nephrology, Ministry of Health of China, Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
| | - Xiao Yang
- Department of Nephrology, The First Affiliated Hospital, Key Laboratory of Nephrology, Ministry of Health of China, Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
| | - Yuanwen Xu
- Department of Nephrology, The First Affiliated Hospital, Key Laboratory of Nephrology, Ministry of Health of China, Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
| | - Xueqing Yu
- Department of Nephrology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
| | - Wei Chen
- Department of Nephrology, The First Affiliated Hospital, Key Laboratory of Nephrology, Ministry of Health of China, Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
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24
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Gadekar GJ, Bhandare PA, Bandawane DD. Amelioration of 5-Fluorouracil Induced Nephrotoxicity by Acacia catechu through Overcoming Oxidative Damage and Inflammation in Wistar Rats. Cardiovasc Hematol Disord Drug Targets 2023; 23:189-201. [PMID: 37946347 DOI: 10.2174/011871529x274030231102065433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 10/03/2023] [Accepted: 10/13/2023] [Indexed: 11/12/2023]
Abstract
AIM The research intended to explore the possible nephroprotective potential of the ethyl acetate fraction derived from Acacia catechu leaves against nephrotoxicity brought about by 5-fluorouracil (5-FU) in Wistar rats. BACKGROUND While possessing strong anticancer properties, 5-FU is hindered in its therapeutic application due to significant organ toxicity linked to elevated oxidative stress and inflammation. OBJECTIVE The study is undertaken to conduct an analysis of the ethyl acetate fraction of A. catechu leaves both in terms of quality and quantity, examining its impact on different biochemical and histopathological parameters within the context of 5-FU-induced renal damage in rats and elucidation of the mechanism behind the observed outcomes. METHODOLOGY Intraperitoneal injection of 5-FU at a dosage of 20 mg/kg/day over 5 days was given to induce nephrotoxicity in rats. The evaluation of nephrotoxicity involved quantifying serum creatinine, urea, uric acid, and electrolyte concentrations. Furthermore, superoxide dismutase, catalase antioxidant enzymes, and TNF-α concentration in serum were also measured. RESULTS 5-FU injection led to the initiation of oxidative stress within the kidneys, leading to modifications in renal biomarkers (including serum creatinine, urea, uric acid, and Na+, K+ levels), and a reduction in antioxidant enzymes namely superoxide dismutase and catalase. Notably, the presence of the inflammatory cytokine TNF-α was significantly elevated due to 5-FU. Microscopic examination of renal tissue revealed tubular degeneration and congestion. However, treatment involving the ethyl acetate fraction derived from A. catechu leaves effectively and dose-dependently reversed the changes observed in renal biomarkers, renal antioxidant enzymes, inflammatory mediators, and histopathological features, bringing them closer to normal conditions. The observed recuperative impact was mainly attributed to the antioxidant and antiinflammatory properties of the fraction. CONCLUSION The ethyl acetate fraction of A. catechu leaves exhibited a mitigating influence on the renal impairment caused by 5-FU, showcasing its potential as a nephroprotective agent capable of preventing and ameliorating 5-FU-induced nephrotoxicity.
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Affiliation(s)
- Gayatri Jaising Gadekar
- Department of Pharmacology, P. E. Society's Modern College of Pharmacy, Nigdi, Pune- 44, India
| | | | - Deepti Dinesh Bandawane
- Department of Pharmacology, P. E. Society's Modern College of Pharmacy, Nigdi, Pune- 44, India
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25
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Rafique Z, Hoang B, Mesbah H, Pappal R, Peacock FW, Juarez-Vela R, Szarpak L, Kuo DC. Hyperkalemia and Electrocardiogram Manifestations in End-Stage Renal Disease. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:16140. [PMID: 36498212 PMCID: PMC9736513 DOI: 10.3390/ijerph192316140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 11/29/2022] [Accepted: 12/01/2022] [Indexed: 06/17/2023]
Abstract
Hyperkalemia is one of the more common acute life-threatening metabolic emergencies. The aim of our study is to determine the correlation and accuracy of abnormal ECG parameters as a function of serum potassium concentration in the end-stage renal disease (ESRD) population. We performed a retrospective chart review of emergency department patients presenting with ESRD and receiving emergent hemodialysis treatment. A total of 96 patients, each with five independent ED visits, provided 480 sets of ECGs and electrolytes. Of these, four ECGs were excluded for inability to interpret, leaving a total of 476 patient encounters that met all inclusion criteria. Linear regression analysis on the limited data set for serum potassium versus T/R in V2, V3, and V4, PR, and QRS found weak correlations (r2 = 0.02 to 0.12) with statistical significance <0.05 level for T/R in V2, V3, and V4. In summary, we found that a QRS duration of 120 ms or greater is most predictive of hyperkalemia in the ESRD population. On the other hand, T/R ratio, PR interval and QRS duration have poor correlations with serum potassium and are not predictive of hyperkalemia in patients with ESRD.
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Affiliation(s)
- Zubaid Rafique
- Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Bryan Hoang
- McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77004, USA
| | - Heba Mesbah
- Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Ryan Pappal
- Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
| | - Frank W. Peacock
- Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Raul Juarez-Vela
- Group in Research in Care (GRUPAC), Department of Nursing, University of La Rioja, 93-103 Logrono, Spain
| | - Lukasz Szarpak
- Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Dick C. Kuo
- Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA
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26
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Sharif S, Tang J. Potassium Derangements: A Pathophysiological Review, Diagnostic Approach, and Clinical Management. Physiology (Bethesda) 2022. [DOI: 10.5772/intechopen.103016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Potassium is an essential cation critical in fluid and electrolyte balance, acid–base regulation, and neuromuscular functions. The normal serum potassium is kept within a narrow range of 3.5–5.2 meq/L while the intracellular concentration is approximately 140–150 meq/L. The total body potassium is about 45–55 mmol/kg; thus, a 70 kg male has an estimated ~136 g and 60 kg female has ~117 g of potassium. In total, 98% of the total body potassium is intracellular. Skeletal muscle contains ~80% of body potassium stores. The ratio of intracellular to extracellular potassium concentration (Ki/Ke) maintained by Na+/K+ ATPase determines the resting membrane potential. Disturbances of potassium homeostasis lead to hypo- and hyperkalemia, which if severe, can be life-threatening. Prompt diagnosis and management of these problems are important.
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Chronic Hyperkaliemia in Chronic Kidney Disease: An Old Concern with New Answers. Int J Mol Sci 2022; 23:ijms23126378. [PMID: 35742822 PMCID: PMC9223624 DOI: 10.3390/ijms23126378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 06/05/2022] [Accepted: 06/06/2022] [Indexed: 12/04/2022] Open
Abstract
Increasing potassium intake ameliorates blood pressure (BP) and cardiovascular (CV) prognoses in the general population; therefore the World Health Organization recommends a high-potassium diet (90–120 mEq/day). Hyperkalaemia is a rare condition in healthy individuals due to the ability of the kidneys to effectively excrete dietary potassium load in urine, while an increase in serum K+ is prevalent in patients with chronic kidney disease (CKD). Hyperkalaemia prevalence increases in more advanced CKD stages, and is associated with a poor prognosis. This scenario generates controversy on the correct nutritional approach to hyperkalaemia in CKD patients, considering the unproven link between potassium intake and serum K+ levels. Another concern is that drug-induced hyperkalaemia leads to the down-titration or withdrawal of renin-angiotensin system inhibitors (RASI) and mineralocorticoids receptors antagonists (MRA) in patients with CKD, depriving these patients of central therapeutic interventions aimed at delaying CKD progression and decreasing CV mortality. The new K+-binder drugs (Patiromer and Sodium-Zirconium Cyclosilicate) have proven to be adequate and safe therapeutic options to control serum K+ in CKD patients, enabling RASI and MRA therapy, and possibly, a more liberal intake of fruit and vegetables.
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Effects of renin-angiotensin system inhibitors on the incidence of unplanned dialysis. Hypertens Res 2022; 45:1018-1027. [PMID: 35256773 DOI: 10.1038/s41440-022-00877-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 11/19/2021] [Accepted: 12/20/2021] [Indexed: 01/20/2023]
Abstract
Unplanned dialysis initiation is associated with poor outcomes. It is controversial whether patients with advanced chronic kidney disease (CKD) should receive renin-angiotensin system (RAS) inhibitor therapy. The aim of this study was to evaluate the effect of RAS inhibitor therapy in patients with advanced CKD on the incidence of unplanned dialysis initiation. This single-center, retrospective study included patients who started maintenance dialysis at our hospital between April 2014 and March 2021. Patients who initiated dialysis within 6 months of nephrology referral or after kidney transplant were excluded. Among 334 patients (aged 70.0 [59.0-79.0] years; 28.4% women), 186 (55.7%) and 148 (44.3%) had planned and unplanned dialysis initiation, respectively. Multivariate logistic regression analysis revealed that the use of RAS inhibitors was significantly associated with a lower incidence of unplanned dialysis initiation (odds ratio [OR], 0.36; P < 0.01). Female sex (OR, 0.41; P < 0.05), use of potassium binders (OR, 0.28; P < 0.001), earlier referral to nephrology (OR, 0.39; P < 0.01), and earlier discussion of renal replacement therapy (OR, 0.33; P < 0.001) were also significantly associated with a lower incidence, whereas older age (OR, 1.28; P < 0.05), higher Charlson Comorbidity Index (OR, 1.24; P < 0.05), and faster decline in kidney function (OR, 1.29; P < 0.01) were associated with a higher risk of unplanned dialysis initiation. RAS inhibitor therapy in patients with advanced CKD is associated with a lower risk of unplanned dialysis initiation.
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Ren H, Leon SJ, Whitlock R, Rigatto C, Komenda P, Bohm C, Collister D, Tangri N. Prescription patterns of Sodium and Calcium Polystyrene Sulfonate in patients with Hyperkalemia and Chronic Kidney Disease receiving RAAS inhibitors. Clin Kidney J 2022; 15:1713-1719. [PMID: 36003673 PMCID: PMC9394712 DOI: 10.1093/ckj/sfac077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Indexed: 11/19/2022] Open
Abstract
Background Sodium and calcium polystyrene sulfonate (SPS/CPS) cation-exchange resins have had long-standing clinical use for hyperkalemia in patients with chronic kidney disease (CKD). However, uncertainty exists regarding the real-world usage of SPS/CPS for acute and chronic management of hyperkalemia. We evaluated the prescription patterns of SPS/CPS and their impact on renin–angiotensin–aldosterone system inhibitor (RAASi) treatment in patients with CKD Stages G3–G5 after an episode of de novo hyperkalemia. Methods We conducted a retrospective cohort study using population-level administrative databases in Manitoba, Canada, which included adults with CKD and a RAASi prescription who had an episode of de novo hyperkalemia (≥5.5 mmol/L) between January 2007 and December 2017. Results A total of 10 009 individuals were included in our study cohort. Among the study population, 4% received an SPS/CPS prescription within 30 days of their hyperkalemia episode. Of those, 22% received a 1-day supply of SPS/CPS and 7% received a prescription for more than 30 days. There were 8145 patients using RAASi at baseline who survived 90 days after their first hyperkalemia episode. Of those, 1447 (18%) discontinued their RAAS inhibitor and 339 (5%) received a prescription of SPS/CPS. Also, the proportion of patients who discontinued their RAASi was similar among those who did and did not receive a prescription of SPS/CPS. Conclusion In patients with CKD receiving RAASi therapy, there is a low frequency of SPS/CPS prescription after an episode of hyperkalemia. RAASi discontinuation or downtitration is the most used pharmacologic approach for the management of hyperkalemia, a strategy that deprives patients of the cardiac and renal protective benefits of RAASi. New options for the management of hyperkalemia in this population are needed.
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Affiliation(s)
- Hongru Ren
- Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba. Winnipeg, Manitoba, Canada
| | - Silvia J Leon
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, Manitoba, Canada
| | - Reid Whitlock
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, Manitoba, Canada
| | - Claudio Rigatto
- Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba. Winnipeg, Manitoba, Canada
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, Manitoba, Canada
| | - Paul Komenda
- Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba. Winnipeg, Manitoba, Canada
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, Manitoba, Canada
| | - Clara Bohm
- Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba. Winnipeg, Manitoba, Canada
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, Manitoba, Canada
| | - David Collister
- Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba. Winnipeg, Manitoba, Canada
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, Manitoba, Canada
| | - Navdeep Tangri
- Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba. Winnipeg, Manitoba, Canada
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, Manitoba, Canada
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Hiremath S, Fergusson D, Knoll G, Ramsay T, Kong J, Ruzicka M. Diet or additional supplement to increase potassium intake: protocol for an adaptive clinical trial. Trials 2022; 23:147. [PMID: 35164833 PMCID: PMC8845348 DOI: 10.1186/s13063-022-06071-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 01/31/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
High blood pressure is the leading cause of cardiovascular disease worldwide. The prevalence of high blood pressure is steadily rising as the population grows amongst older adults with the ageing population. Therapeutical treatments are widely available to decrease blood pressures, in addition to many lifestyle options, such as dietary changes and exercise. There is a marked preference amongst patients, as reiterated by Hypertension Canada, for more research into non-therapeutic methods for controlling blood pressure or to reduce the burden of taking many pills to control high blood pressure. Indeed, effective options do exist, especially with diet, specifically decreasing sodium and increasing potassium intake. Current public health outreach primarily focusses on sodium intake, even though potassium intake remains low in the Western world. Excellent data exist in published research that increasing potassium intake, either via dietary modification or supplements, reduces blood pressure and reduces risk of cardiovascular outcomes such as stroke. However, the advice most often provided by medical professionals is to ‘eat more fruits and vegetables’ which has little impact on patient outcomes.
Methods
We propose to do a clinical trial in two stages with an adaptive trial design. In the first stage, participants with high blood pressure and proven low potassium intake (measured on the basis of a 24-h urine collection) will get individually tailored dietary advice, reinforced by weekly supportive phone/email support. At 4 weeks, if there has not been a measured increase in potassium intake, participants will be prescribed an additional potassium supplement. Testing will be conducted again at 8 weeks, to confirm the efficacy of the potassium supplement. Final measurements will be planned at 52 weeks to observe and measure the persistence of the effect of diet or additional supplement. Concurrent measurements of sodium intake, blood pressure, participant satisfaction, and safety measures will also be done.
Discussion
The results of the study will help determine the most effective method of increasing potassium intake, thus reducing blood pressure and need for blood pressure-lowering medicines, and at the same time potentially increasing participant satisfaction. The current guidelines recommend changes in diet, not a potassium supplement, to increase potassium intake; hence, the two-stage design will only add supplements if the most rigorous dietary advice does not work.
Trial registration
This study has been registered on ClinicalTrials.govNCT03809884. Registered on January 18, 2019
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Riccio E, Capuano I, Buonanno P, Andreucci M, Provenzano M, Amicone M, Rizzo M, Pisani A. RAAS Inhibitor Prescription and Hyperkalemia Event in Patients With Chronic Kidney Disease: A Single-Center Retrospective Study. Front Cardiovasc Med 2022; 9:824095. [PMID: 35224054 PMCID: PMC8874323 DOI: 10.3389/fcvm.2022.824095] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 01/10/2022] [Indexed: 11/13/2022] Open
Abstract
Hyperkalemia is common in patients treated with renin-angiotensin-aldosterone system inhibitors (RAASis), and it represents the main cause of the large gap reported between guideline recommendations and real-world practice in chronic kidney disease (CKD). We conducted a CKD-population-based restrospective study to determine the prevalence of patients with CKD treated with RAASis, incidence of hyperkalemia in patients with CKD treated with RAASis, and proportion of patients with RAASi medication change after experiencing incident hyperkalemia. Among 809 patients with CKD analyzed, 556 (68.7%) were treated with RAASis, and RAASi prescription was greater in stages 2-4 of CKD. Hyperkalemia occurred in 9.2% of RAASi-treated patients, and the adjusted rate of hyperkalemia among patients with stage 4-5 CKD was 3-fold higher compared with patients with eGFR > 60 ml/min/1.73 m2. RAASi treatment was discontinued in 55.3% of the patients after hyperkalemia event (74.2% discontinued therapy, 3.2% received a reduced dose, and 22.6% reduced the number of RAASi drugs). This study shows that the incidence of hyperkalemia is frequently observed in patients with CKD patients with RAASis, and that rates increase with deteriorating levels of kidney function from stages 1 to 3. RAASi medication change following an episode of hyperkalemia occurred in almost half of the patients after experiencing hyperkalemia.
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Affiliation(s)
- Eleonora Riccio
- Institute for Biomedical Research and Innovation, National Research Council of Italy, Palermo, Italy
| | - Ivana Capuano
- Department of Public Health, Chair of Nephrology, University Federico II of Naples, Campania, Italy
| | - Pasquale Buonanno
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy
| | - Michele Andreucci
- Department of Medical and Surgical Sciences-Renal Unit, “Magna Graecia” University, Catanzaro, Italy
| | - Michele Provenzano
- Department of Medical and Surgical Sciences-Renal Unit, “Magna Graecia” University, Catanzaro, Italy
| | - Maria Amicone
- Department of Public Health, Chair of Nephrology, University Federico II of Naples, Campania, Italy
| | - Manuela Rizzo
- Department of Public Health, Chair of Nephrology, University Federico II of Naples, Campania, Italy
| | - Antonio Pisani
- Department of Public Health, Chair of Nephrology, University Federico II of Naples, Campania, Italy
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Smyrli M, Sarafidis PA, Loutradis C, Korogiannou M, Boletis IN, Marinaki S. Prevalence and factors associated with hyperkalaemia in stable kidney transplant recipients. Clin Kidney J 2022; 15:43-50. [PMID: 35035935 PMCID: PMC8757423 DOI: 10.1093/ckj/sfab129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Indexed: 12/19/2022] Open
Abstract
Background Hyperkalaemia is a frequent and potentially life-threatening condition in patients with chronic kidney disease (CKD). Even after successful kidney transplantation (KTx), KTx recipients have mild to severe CKD. Moreover, they share comorbid conditions and frequently use medications that predispose to hyperkalaemia. This study aimed to examine the prevalence and factors associated with hyperkalaemia in this population. Methods Over a pre-specified period of 6 months (1 September 2019 to 31 March 2020), we recorded in cross-sectional fashion information on serum potassium (K+) and relevant demographics, comorbidities, medications, laboratory and transplant-associated variables in clinically stable KTx recipients attending the Transplant Outpatient Clinic of our Department. Ηyperkalaemia was classified as follows: serum K+ level >5.0 mEq/L; and further as >5.0 mEq/L with concomitant use of sodium (Na+) polystyrene sulphonate; serum K+ ≥5.2 mEq/L; serum K+ ≥5.5 mEq/L. Univariate and multiple logistic regression analyses were used to identify factors associated with serum K+ >5.0 mEq/L. Results The study population consisted of 582 stable KTx recipients, 369 (63.4%) males, aged 52.4 ± 13.5 years, with estimated glomerular filtration rate (eGFR) of 55.8 ± 20.1 mL/min/1.73 m2 transplanted for >1 year. The prevalence of hyperkalaemia defined as K+ >5.0 mEq/L; >5.0 mEq/L and use of Na+ polystyrene sulphonate; K+ ≥5.2; or K+ ≥5.5 mEq/L, was: 22.7, 22.7, 14.4 and 4.1% (132, 132, 84 and 24 patients), respectively. In multivariate analysis, male gender [odds ratio (OR) = 2.020, 95% confidence interval (CI) 1.264–3.227] and use of renin–angiotensin–aldosterone system (RAAS) blockers (OR = 1.628, 95% CI 1.045–2.536) were independently associated with hyperkalaemia, while higher eGFR (OR = 0.967, 95% CI 0.955–0.979) and use of non-K+-sparing diuretics (OR = 0.140, 95% CI 0.046–0.430) were associated with lower odds of the disorder. Conclusions The prevalence of mild hyperkalaemia in stable KTx recipients is relatively high but that of moderate or severe hyperkalaemia is low. Among a wide range of factors studied, only male gender and RAAS blockade were associated with increased odds of hyperkalaemia, while higher eGFR and diuretics were associated with decreased odds of hyperkalaemia.
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Affiliation(s)
- Maria Smyrli
- Department of Nephrology, General Hospital of Euaggelismos, Athens, Greece
| | - Pantelis A Sarafidis
- Department of Nephrology, Hippokration Hospital, Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Charalampos Loutradis
- Department of Nephrology, Hippokration Hospital, Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Maria Korogiannou
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, National and Kapodistrian University, Medical School of Athens, Athens, Greece
| | - Ioannis N Boletis
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, National and Kapodistrian University, Medical School of Athens, Athens, Greece
| | - Smaragdi Marinaki
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, National and Kapodistrian University, Medical School of Athens, Athens, Greece
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Agiro A, Duling I, Eudicone J, Davis J, Brahmbhatt YG, Cooper K. The prevalence of predialysis hyperkalemia and associated characteristics among hemodialysis patients: The RE-UTILIZE study. Hemodial Int 2022; 26:397-407. [PMID: 35037388 PMCID: PMC9543597 DOI: 10.1111/hdi.13006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 12/27/2021] [Accepted: 12/28/2021] [Indexed: 11/30/2022]
Abstract
Introduction Hyperkalemia (HK), defined as serum potassium (K+) >5.0 mEq/L, is an independent predictor of mortality in patients on maintenance hemodialysis (HD). This study investigated the annual prevalence of HK and examined patient characteristics potentially associated with a higher annual HK prevalence. Methods This retrospective observational cohort study used Dialysis Outcomes and Practice Patterns Study (DOPPS) survey data from US patients undergoing in‐center HD thrice weekly from 2018 to 2019. The primary endpoint was the proportion of patients with any predialysis HK (K+ >5.0 mEq/L) within 1 year from the index date (date of DOPPS enrollment), using the first hyperkalemic K+ value. Secondary endpoints were the proportion of patients with moderate‐to‐severe (K+ >5.5 mEq/L) or severe (K+ >6.0 mEq/L) HK. Findings Overall, 9347 patients on HD were included in this analysis (58% male and 49% aged >66 years). Any predialysis HK (K+ >5.0 mEq/L) occurred in 74% of patients within 1 year of the index date, 52% within 3 months, and 38% within 1 month. The annual prevalence of moderate‐to‐severe and severe HK was 43% and 17%, respectively. Recurrent HK (at least two K+ >5.0 mEq/L within 1 year) occurred in 60% of patients, and 2.8% of patients were prescribed an oral K+ binder. Multivariable logistic regression analysis showed younger age, female sex, Hispanic ethnicity, and renin–angiotensin–aldosterone system inhibitor use were significantly associated with a higher annual prevalence of any predialysis HK, while Black race, obesity, recent initiation of HD, and dialysate K+ bath concentration ≥3 mEq/L were associated with a lower prevalence of HK. Discussion The annual prevalence of predialysis HK and recurrence were high among US patients on HD, whereas oral K+ binder use was low. Further studies are needed to understand the impact of dialysate K+ bath concentrations on predialysis HK among patients on HD.
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Calabrese V, Cernaro V, Battaglia V, Gembillo G, Longhitano E, Siligato R, Sposito G, Ferlazzo G, Santoro D. Correlation between Hyperkalemia and the Duration of Several Hospitalizations in Patients with Chronic Kidney Disease. J Clin Med 2022; 11:244. [PMID: 35011985 PMCID: PMC8746076 DOI: 10.3390/jcm11010244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 12/30/2021] [Accepted: 12/31/2021] [Indexed: 11/16/2022] Open
Abstract
(1) Background: This observational study aimed to verify the association between serum potassium levels and hospitalization days in patients with chronic kidney disease in a follow up of nine months. (2) Methods: Patients with chronic kidney disease were divided into group A (180 patients, potassium ≤ 5.1 mEq/L) and B (90 patients, potassium > 5.1 mEq/L). Student's t-test, Mann-Whitney test, Pearson's Chi-Square test, Pearson/Spearman's correlation test and linear regression test were performed in the entire sample and in stage-G4/5 subsample. (3) Results: Groups A and B differed for estimated glomerular filtration rate (eGFR) (34.89 (IQR, 16.24-57.98) vs. 19.8 (IQR, 10.50-32.50) mL/min/1.73 m2; p < 0.0001), hemoglobin (11.64 ± 2.20 vs. 10.97 ± 2.19 g/dL, p = 0.048), sum of hospitalization days (8 (IQR, 6-10) vs. 11 (IQR, 7-15) days; p < 0.0001) and use of angiotensin II receptor blockers (40.2% vs. 53.3%; p = 0.010). Considering patients with eGFR 6-30 mL/min/1.73 m2, differences in the sum of hospitalization days were confirmed. Multivariable regression analysis showed that hyperkalemia is an independent risk factor of increased hospital length. In stage G4-G5, regression analysis showed that hyperkalemia is the only independent risk factor (β = 2.93, 95% confidence interval, 0.077-5.794, p = 0.044). (4) Conclusions: We observed significantly greater odds of increased length of hospital stay among patients with higher potassium, mostly in stages G4-G5 chronic kidney disease.
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Affiliation(s)
- Vincenzo Calabrese
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.C.); (V.C.); (V.B.); (G.G.); (E.L.); (R.S.)
| | - Valeria Cernaro
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.C.); (V.C.); (V.B.); (G.G.); (E.L.); (R.S.)
| | - Valeria Battaglia
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.C.); (V.C.); (V.B.); (G.G.); (E.L.); (R.S.)
| | - Guido Gembillo
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.C.); (V.C.); (V.B.); (G.G.); (E.L.); (R.S.)
| | - Elisa Longhitano
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.C.); (V.C.); (V.B.); (G.G.); (E.L.); (R.S.)
| | - Rossella Siligato
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.C.); (V.C.); (V.B.); (G.G.); (E.L.); (R.S.)
| | - Giovanna Sposito
- Unit of Clinical Pathology, Department of Human Pathology of Adults and Developmental Age, University of Messina, 98125 Messina, Italy; (G.S.); (G.F.)
| | - Guido Ferlazzo
- Unit of Clinical Pathology, Department of Human Pathology of Adults and Developmental Age, University of Messina, 98125 Messina, Italy; (G.S.); (G.F.)
| | - Domenico Santoro
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.C.); (V.C.); (V.B.); (G.G.); (E.L.); (R.S.)
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Ni Z, Jin H, Lu R, Zuo L, Yu W, Ren Y, Yang Q, Xiao J, Zhang Q, Zhang L, Zhang X, Chen Q, Chen C, Shao G, Luo Q, Yao L, Qin S, Peng H, Zhao Q. Hyperkalaemia prevalence, recurrence and treatment in patients on haemodialysis in China: protocol for a prospective multicentre cohort study (PRECEDE-K). BMJ Open 2021; 11:e055770. [PMID: 34937724 PMCID: PMC8705221 DOI: 10.1136/bmjopen-2021-055770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
INTRODUCTION Hyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes and is common in patients with kidney failure. However, there is no evidence on the occurrence, recurrence and treatment of HK in patients on haemodialysis (HD) in China. METHODS AND ANALYSIS The HK Prevalence, Recurrence, and Treatment in Haemodialysis Study is a prospective, multicentre, observational, cohort study being conducted across 15-18 sites in China. Approximately 600 patients with end-stage kidney disease on HD are anticipated to be enrolled and will be followed up for 24 weeks. Patients will be in the long interdialytic interval (LIDI) at enrolment and will receive follow-up care every 4 weeks in LIDI for pre-dialysis and post-dialysis (at enrolment only) serum potassium measurements. To obtain pre-dialysis serum potassium levels in the short interdialytic interval (SIDI), a follow-up visit will be performed in the SIDI during the first week. Information on concomitant medications, blood gas analysis and biochemistry measurements will be obtained at enrolment and at each follow-up visit. The primary endpoint will be the proportion of patients experiencing HK (defined as serum potassium level >5.0 mmol/L) at the study enrolment or during the 24-week follow-up. The key secondary endpoint will be the proportion of patients experiencing HK recurrence (defined as any HK event after the first HK event) within 1-6 months (if applicable) during the 24-week follow-up, including enrolment assessment. ETHICS AND DISSEMINATION This study has been approved by Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee (2020-040). Other participating subcentres must also obtain ethics committee approval prior to the start of the study. The Good Clinical Practice regulations shall be strictly followed during the test implementation. Amendments to the protocol will be reviewed by the ethics committees. Written informed consent will be obtained from all participants before collection of any patient data and patient information. The findings of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Registry (NCT04799067).
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Affiliation(s)
- Zhaohui Ni
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haijiao Jin
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Renhua Lu
- Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Zuo
- Department of Nephrology, Peking University People's Hospital, Beijing, China
| | - Weimin Yu
- Department of Nephrology, Shanxi Bethune Hospital, Taiyuan, China
| | - Yuqing Ren
- Department of Nephrology, Yangquan Coal Industry (Group) General Hospital, Yangquan, China
| | - Qiongqiong Yang
- Department of Nephrology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Jie Xiao
- Department of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Qinghong Zhang
- Department of Nephrology, Taihe Hospital, Shiyan, Hubei, China
| | - Lihong Zhang
- Department of Nephrology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Xinzhou Zhang
- Department of Nephrology, Shenzhen People's Hospital, Shenzhen, Guangdong, China
| | - Qinkai Chen
- Department of Nephrology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Chaosheng Chen
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Guojian Shao
- Department of Nephrology, Wenzhou Central Hospital, Wenzhou, Zhejiang, China
| | - Qun Luo
- Department of Nephrology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China
| | - Li Yao
- Department of Nephrology, The first hospital of China Medical University, Shenyang, China
| | - Shuguang Qin
- Department of Nephrology, Guangzhou First People's Hospital, Guangzhou, Guangdong, China
| | - Hui Peng
- Department of Nephrology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Qing Zhao
- Medical Affaires, AstraZeneca Investment China Co, Shanghai, China
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Bem D, Sugrue D, Wilding B, Zile I, Butler K, Booth D, Tafesse E, McEwan P. The effect of hyperkalemia and long inter-dialytic interval on morbidity and mortality in patients receiving hemodialysis: a systematic review. Ren Fail 2021; 43:241-254. [PMID: 33478329 PMCID: PMC7833048 DOI: 10.1080/0886022x.2020.1871012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 11/18/2020] [Accepted: 12/26/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Patients with chronic kidney disease, especially those receiving hemodialysis (HD), are at risk of hyperkalemia (HK). This systematic review aimed to evaluate the prevalence of HK in patients with renal disease receiving HD and collate evidence on the effect of HK and differing HD patterns (i.e., long vs. short inter-dialytic intervals [LIDI and SIDI, respectively] in a thrice weekly schedule) on mortality. METHODS Comprehensive searches were conducted across six databases and selected conference proceedings by two independent reviewers up to September 2020. A hundred and two studies reporting frequency of HK, mortality, or cardiovascular (CV) outcomes in adult patients with acute, chronic or end-stage renal disease in receipt of HD were included. Narrative synthesis of results was undertaken with key findings presented in tables and figures. RESULTS Median prevalence of HK in patients with renal disease receiving HD was 21.6% and increased in patients receiving concomitant medications - mainly renin-angiotensin-aldosterone system inhibitors and potassium-sparing diuretics. Associations between elevated potassium levels and increased risk of both all-cause and CV mortality in the HD population were consistent across the included studies. In addition, there was a rise in all-cause and CV mortality on the day following LIDI compared with the day after the two SIDIs in patients on HD. CONCLUSIONS Evidence identified in this systematic review indicates a relationship between HK and LIDI with mortality in patients with renal disease receiving HD, emphasizing the need for effective monitoring and management to control potassium levels both in emergency and chronic HD settings.
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Affiliation(s)
- Danai Bem
- Health Economics and Outcomes Research Ltd, Birmingham, UK
| | - Daniel Sugrue
- Health Economics and Outcomes Research Ltd, Cardiff, UK
| | - Ben Wilding
- Health Economics and Outcomes Research Ltd, Cardiff, UK
| | - Ina Zile
- Health Economics and Outcomes Research Ltd, Cardiff, UK
| | - Karin Butler
- Health Economics and Outcomes Research Ltd, Cardiff, UK
| | - David Booth
- Health Economics and Outcomes Research Ltd, Cardiff, UK
| | | | - Phil McEwan
- Health Economics and Outcomes Research Ltd, Cardiff, UK
- Swansea University, Swansea, UK
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Panuccio V, Leonardis D, Tripepi R, Versace MC, Torino C, Tripepi G, D'Arrigo G, Mallamaci F, Zoccali C. Epidemiology of hyperkalemia in CKD patients under nephrological care: a longitudinal study. Intern Emerg Med 2021; 16:1803-1811. [PMID: 33575905 DOI: 10.1007/s11739-021-02653-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 01/22/2021] [Indexed: 12/17/2022]
Abstract
Hyperkalemia is a potential life-threatening condition among chronic kidney disease (CKD) patients. Available estimates of the burden of this alteration in CKD are mainly derived from large administrative databases. Since K measurements in patients in these databases are often dictated by clinical reasons, longitudinal studies including pre-planned measurements of potassium independently of clinical complication/symptoms may produce more reliable estimates of the frequency and the risk factors underlying hyperkalemia in CKD patients. We estimated the prevalence and the incidence of hyperkalemia in a longitudinal study in 752 stages 2-5 CKD patients lasting 3 years and including up to seven pre-planned assessment of key biochemical measurements including K. At baseline, 203 out of 752 patients (27%) had serum K > 5.0 mM/L and 33% had acidosis (HCO3 ≤ 22 mmol/L). Among those without hyperkalemia at baseline (n = 549), 284 patients developed this alteration across the 3-year follow-up. The point prevalence of hyperkalemia rose from 27% (baseline) to 30% (last visit) (P = 0.001). In a multivariate model, hyperkalemia at baseline [odds ratio (OR):7.29, 95% CI 5.65-9.41, P < 0.001], venous bicarbonate levels [OR (1 mmol/l): 0.92, 0.89-0.96, P < 0.001], eGFR [OR (1 ml/min/1.73m2): 0.98, 0.97-0.99, P < 0.001], use of ACE inhibitors (OR: 1.68, 1.28-2.19, P < 0.001) and angiotensin II antagonists (OR: 1.30, 1.01-1.68, P = 0.045) were related to hyperkalemia over time. Of note, venous bicarbonate levels emerged as an independent risk factor of hyperkalemia over time also in a separate analysis of patients with and without hyperkalemia at baseline. In a cohort of CKD patients including pre-planned measurements of K, 27% of patients had hyperkalemia. Metabolic acidosis and the use of drugs interfering with renin-angiotensin system were the strongest modifiable risk factors for this potentially life-threatening alteration in CKD in longitudinal analyses in the whole study cohort and in patients developing de novo hyperkalemia over time.
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Affiliation(s)
- Vincenzo Panuccio
- Nephrology, Dialysis and Transplantation Unit, Grande Ospedale Metropolitano BMM di Reggio Calabria, Reggio Calabria, Italy
| | - Daniela Leonardis
- Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC of Reggio Calabria, Reggio Calabria, Italy
| | - Rocco Tripepi
- Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC of Reggio Calabria, Reggio Calabria, Italy
| | - Maria Carmela Versace
- Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC of Reggio Calabria, Reggio Calabria, Italy
| | - Claudia Torino
- Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC of Reggio Calabria, Reggio Calabria, Italy
| | - Giovanni Tripepi
- Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC of Reggio Calabria, Reggio Calabria, Italy
| | - Graziella D'Arrigo
- Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC of Reggio Calabria, Reggio Calabria, Italy
| | - Francesca Mallamaci
- Nephrology, Dialysis and Transplantation Unit, Grande Ospedale Metropolitano BMM di Reggio Calabria, Reggio Calabria, Italy
- Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC of Reggio Calabria, Reggio Calabria, Italy
| | - Carmine Zoccali
- Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC of Reggio Calabria, Reggio Calabria, Italy.
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Valdivielso JM, Balafa O, Ekart R, Ferro CJ, Mallamaci F, Mark PB, Rossignol P, Sarafidis P, Del Vecchio L, Ortiz A. Hyperkalemia in Chronic Kidney Disease in the New Era of Kidney Protection Therapies. Drugs 2021; 81:1467-1489. [PMID: 34313978 DOI: 10.1007/s40265-021-01555-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/09/2021] [Indexed: 12/20/2022]
Abstract
Despite recent therapeutic advances, chronic kidney disease (CKD) is one of the fastest growing global causes of death. This illustrates limitations of current therapeutic approaches and, potentially, unidentified knowledge gaps. For decades, renin-angiotensin-aldosterone system (RAAS) blockers have been the mainstay of therapy for CKD. However, they favor the development of hyperkalemia, which is already common in CKD patients due to the CKD-associated decrease in urinary potassium (K+) excretion and metabolic acidosis. Hyperkalemia may itself be life-threatening as it may trigger potentially lethal arrhythmia, and additionally may limit the prescription of RAAS blockers and lead to low-K+ diets associated to low dietary fiber intake. Indeed, hyperkalemia is associated with adverse kidney, cardiovascular, and survival outcomes. Recently, novel kidney protective therapies, ranging from sodium/glucose cotransporter 2 (SGLT2) inhibitors to new mineralocorticoid receptor antagonists have shown efficacy in clinical trials. Herein, we review K+ pathophysiology and the clinical impact and management of hyperkalemia considering these developments and the availability of the novel K+ binders patiromer and sodium zirconium cyclosilicate, recent results from clinical trials targeting metabolic acidosis (sodium bicarbonate, veverimer), and an increasing understanding of the role of the gut microbiota in health and disease.
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Affiliation(s)
- José M Valdivielso
- Vascular and Renal Translational Research Group, UDETMA, REDinREN del ISCIII, IRBLleida, Lleida, Spain.
| | - Olga Balafa
- Department of Nephrology, University Hospital of Ioannina, Ioannina, Greece
| | - Robert Ekart
- Clinic for Internal Medicine, Department of Dialysis, University Medical Center Maribor, Maribor, Slovenia
| | - Charles J Ferro
- Department of Renal Medicine, University Hospitals Birmingham, Edgbaston, Birmingham, UK
| | - Francesca Mallamaci
- CNR-IFC, Clinical Epidemiology and Pathophysiology of Hypertension and Renal Diseases, Ospedali Riuniti, 89124, Reggio Calabria, Italy
| | - Patrick B Mark
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Patrick Rossignol
- Inserm 1433 CIC-P CHRU de Nancy, Inserm U1116 and FCRIN INI-CRCT, Université de Lorraine, Nancy, France
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloníki, Greece
| | - Lucia Del Vecchio
- Department of Nephrology and Dialysis, Sant'Anna Hospital, ASST Lariana, Como, Italy
| | - Alberto Ortiz
- School of Medicine, IIS-Fundacion Jimenez Diaz, University Autonoma of Madrid, FRIAT and REDINREN, Madrid, Spain
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Li W, Zeng L, Han D, Zhang S, Lei B, Zheng M, Deng Y, You L. Development of a preoperative index-based nomogram for the prediction of hypokalemia in patients with pituitary adenoma: a retrospective cohort study. PeerJ 2021; 9:e11650. [PMID: 34322317 PMCID: PMC8297473 DOI: 10.7717/peerj.11650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 05/31/2021] [Indexed: 11/29/2022] Open
Abstract
Objective To develop and validate a preoperative index-based nomogram for the prediction of hypokalemia in patients with pituitary adenoma (PA). Methods This retrospective cohort study included 205 patients with PAs between January 2013 and April 2020 in the Sun Yat-sen Memorial Hospital, Guangzhou, China. The patients were randomly classified into either a training set (N = 143 patients) and a validation set (N = 62 patients) at a ratio of 7:3. Variables, which were identified by using the LASSO regression model were included for the construction of a nomogram, and a logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) in the training set. The area under the curve (AUC) was used to evaluate the performance of the nomogram for predicting hypokalemia. Multivariate logistic regression analysis with a restricted cubic spline analysis was conducted to identify a potential nonlinear association between the preoperative index and hypokalemia. Results The incidence of hypokalemia was 38.05%. Seven preoperative indices were identified for the construction of the nomogram: age, type of PA, weight, activated partial thromboplastin time, urea, eosinophil percentage, and plateletocrit. The AUCs of the nomogram for predicting hypokalemia were 0.856 (95% CI [0.796–0.915]) and 0.652 (95% CI [0.514–0.790]) in the training and validation sets, respectively. Restricted cubic splines demonstrated that there was no nonlinear association between hypokalemia and the selected variables. Conclusion In this study, we constructed a preoperative indices-based nomogram that can assess the risk of hypokalemia after the surgical treatment of pituitary adenomas. This nomogram may also help to identify high risk patients who require close monitoring of serum potassium.
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Affiliation(s)
- Wenpeng Li
- Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lexiang Zeng
- Pediatric Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Deping Han
- Neurosurgery, JieXi People's Hospital, JieXi, China
| | - Shanyi Zhang
- Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bingxi Lei
- Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Meiguang Zheng
- Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yuefei Deng
- Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lili You
- Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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Yu H, Zhou A, Liu J, Tang Y, Yuan Q, Man Y, Xiang L. Management of systemic risk factors ahead of dental implant therapy: A beard well lathered is half shaved. J Leukoc Biol 2021; 110:591-604. [PMID: 34231923 DOI: 10.1002/jlb.6mr0621-760rr] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 06/18/2021] [Accepted: 06/22/2021] [Indexed: 02/05/2023] Open
Abstract
As the most successful therapy for missing teeth, dental implant has become increasingly prevalent around the world. A lot of papers have reported diverse local risk factors affecting the success and survival rate of dental implants, either for a short or a long period. However, there are also many types of systemic disorders or relatively administrated medicine that may jeopardize the security and success of dental implant treatment. Additionally, the coronavirus disease 2019 pandemic also poses a challenge to dental implant clinicians. Some of these risk factors are clinically common but to some extent unfamiliar to dentists, thus optimal measurements are often lacking when they occur in dental clinics. In this review, we analyze potential systemic risk factors that may affect the success rate of dental implants. Some of them may affect bone mineral density or enhance the likelihood of local infection, thus impeding osseointegration. Others may even systemically increase the risk of the surgery and threaten patients' life. In order to help novices receive high-risk patients who need to get dental implant treatment in a more reasonable way, we accordingly review recent research results and clinical experiments to discuss promising precautions, such as stopping drugs that impact bone mineral density or the operation, and addressing any perturbations on vital signs.
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Affiliation(s)
- Hui Yu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Anqi Zhou
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jiayi Liu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yufei Tang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Quan Yuan
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yi Man
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Lin Xiang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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41
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Murphy D, Ster IC, Kaski JC, Anderson L, Banerjee D. The LIFT trial: study protocol for a double-blind, randomised, placebo-controlled trial of K +-binder Lokelma for maximisation of RAAS inhibition in CKD patients with heart failure. BMC Nephrol 2021; 22:254. [PMID: 34229607 PMCID: PMC8258742 DOI: 10.1186/s12882-021-02439-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 06/10/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND CKD is common in heart failure (HF) and associated with morbidity and mortality, yet life-prolonging medications such as renin-angiotensin-aldosterone inhibitors (RAASi) are underused due to risk of hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is a potassium-binding medication that has been shown to reduce incidence of hyperkalaemia in CKD, non-CKD, and HF populations, which we propose will support maximisation of RAASi therapy. METHODS We propose a 1:1 randomised, double-blind, placebo-controlled trial in which participants will receive either SZC or placebo. We will up-titrate participants' RAASi therapy while monitoring their serum potassium levels and adjusting their SZC dose if necessary. Participants with CKD and HF will be recruited from CKD and HF clinics at St George's Hospital. The total study period will be 18 months; 130 participants will be enrolled for approximately two months each following screening. Our primary outcome will be the proportion of participants who achieve maximum RAASi dose while maintaining normokalaemia. Secondary outcomes include participants reaching maximum RAASi dose without severe hyperkalaemia; time from randomisation to hyperkalaemia; time from randomisation to severe hyperkalaemia; number of RAASi dose escalations per participant; final doses of RAASi therapy; changes in quality of life score, eGFR, ACR, serum sodium, troponin T; number and duration of hospital admissions; and within-participant change in serum potassium compared to baseline. DISCUSSION This trial will be the first to examine the use of SZC for the maximisation of RAASi dosing in patients with advanced CKD and HF. We will assess the impact of achieving target RAASi dosing on hospital admission rates and duration of stay, with the hope that optimum RAASi treatment will translate into reduced morbidity and improved QoL. If clinical benefit is demonstrated, we hope that the joint multidisciplinary CKD-HF approach will be expanded. TRIAL REGISTRATION EudraCT number 2020-002946-18. Registered on 08 June 2020. Online record pending.
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Affiliation(s)
- Daniel Murphy
- St George's University Hospitals NHS Foundation Trust, London, UK
- St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
| | - Irina Chis Ster
- St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
| | - Juan-Carlos Kaski
- St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
| | - Lisa Anderson
- St George's University Hospitals NHS Foundation Trust, London, UK
- St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
| | - Debasish Banerjee
- St George's University Hospitals NHS Foundation Trust, London, UK.
- St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
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Folkerts K, Kelly AMB, Petruski-Ivleva N, Fried L, Blankenburg M, Gay A, Velentgas P, Kovesdy CP. Cardiovascular and Renal Outcomes in Patients with Type-2 Diabetes and Chronic Kidney Disease Identified in a United States Administrative Claims Database: A Population Cohort Study. Nephron Clin Pract 2021; 145:342-352. [PMID: 33789294 DOI: 10.1159/000513782] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 12/11/2020] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION CKD, a common complication of type-2 diabetes (T2D), causes considerable disease burden. Patients with T2D and CKD are considered high-risk for complications; however, studies describing patients with T2D and incident CKD identified from real-world data using the diagnostic gold-standard criteria - estimated glomerular filtration rate and urine albumin-to-creatinine ratio (UACR) - are scarce. METHODS In this population-based cohort study, we sought to estimate the rates of cardiovascular and renal outcomes among patients with T2D and CKD by comorbidity subgroups and CKD severity. Patients were sampled between 2008 and 2017 from de-identified US administrative claims enriched with laboratory data. Analyses were stratified by prevalent heart failure (HF), anemia, and resistant hypertension and the KDIGO categories at index. RESULTS We identified 106,369 patients with T2D and incident CKD. The rate of all-cause hospitalization was 189 [95% CI: 187, 191] per 1,000 person-years with cardiovascular-related hospitalizations being more frequent than kidney-related outcomes. The rate of acute kidney failure was 77.3 [95% CI: 76.2, 78.5] per 1,000 person-years. Patients with HF experienced a 4-times higher rate for cardiovascular events compared to those without. Rates of hospitalization increased from 5- to 6-fold with increasing KDIGO severity. CONCLUSIONS Multimorbidity and advance stages of CKD increase the risk of cardiovascular and renal complications among patients with T2D diabetes. Earlier CKD diagnosis as well as interventions and coordinated care addressing other comorbid conditions present at diagnosis may reduce the overall disease burden in this population.
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Affiliation(s)
- Kerstin Folkerts
- Digital & Commercial Innovation, Pharmaceuticals HEOR CV, Bayer AG, Wuppertal, Germany
| | | | | | - Linda Fried
- VA Pittsburgh Healthcare System, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Michael Blankenburg
- Medical Affairs & Pharmacovigilance, Pharmaceuticals, Studies & Pipeline TA Cardiovascular, Bayer AG, Berlin, Germany
| | - Alain Gay
- Medical Affairs & Pharmacovigilance, Pharmaceuticals, Studies & Pipeline TA Cardiovascular, Bayer AG, Berlin, Germany
| | | | - Csaba P Kovesdy
- Division of Nephrology, Department of Medicine, University of Tennessee, Memphis, Tennessee, USA
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Current Management of Hyperkalemia in Non-Dialysis CKD: Longitudinal Study of Patients Receiving Stable Nephrology Care. Nutrients 2021; 13:nu13030942. [PMID: 33804015 PMCID: PMC8000881 DOI: 10.3390/nu13030942] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 03/08/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023] Open
Abstract
Background: No study has explored the limitations of current long-term management of hyperkalemia (HK) in outpatient CKD clinics. Methods: We evaluated the association between current therapeutic options and control of serum K (sK) during 12-month follow up in ND-CKD patients stratified in four groups by HK (sK ≥ 5.0 mEq/L) at baseline and month 12: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). Results: We studied 562 patients (age 66.2 ± 14.5 y; 61% males; eGFR 39.8 ± 21.8 mL/min/1.73 m2, RAASI 76.2%). HK was “absent” in 50.7%, “resolving” in 15.6%, “new onset” in 16.6%, and “persistent” in 17.1%. Twenty-four hour urinary measurements testified adherence to nutritional recommendations in the four groups at either visit. We detected increased prescription from baseline to month 12 of bicarbonate supplements (from 5.0 to 14.1%, p < 0.0001), K-binders (from 2.0 to 7.7%, p < 0.0001), and non-K sparing diuretics (from 34.3 to 41.5%, p < 0.001); these changes were consistent across groups. Similar results were obtained when using higher sK level (≥5.5 mEq/L) to stratify patients. Mixed-effects regression analysis showed that higher sK over time was associated with eGFR < 60, diabetes, lower serum bicarbonate, lower use of non-K sparing diuretics, bicarbonate supplementation, and K-binder use. Treatment-by-time interaction showed that sK decreased in HK patients given bicarbonate (p = 0.003) and K-binders (p = 0.005). Conclusions: This observational study discloses that one-third of ND-CKD patients under nephrology care remain with or develop HK during a 12-month period despite low K intake and increased use of sK-lowering drugs.
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Hundemer GL, Talarico R, Tangri N, Leon SJ, Bota SE, Rhodes E, Knoll GA, Sood MM. Ambulatory Treatments for RAAS Inhibitor-Related Hyperkalemia and the 1-Year Risk of Recurrence. Clin J Am Soc Nephrol 2021; 16:365-373. [PMID: 33608262 PMCID: PMC8011018 DOI: 10.2215/cjn.12990820] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 01/04/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVE The optimal ambulatory management of renin-angiotensin-aldosterone system inhibitor (RAASi)-related hyperkalemia to reduce the risk of recurrence is unknown. We examined the risk of hyperkalemia recurrence on the basis of outpatient pharmacologic changes following an episode of RAASi-related hyperkalemia. DESIGN We performed a population-based, retrospective cohort study of older adults (n=49,571; mean age 79 years) who developed hyperkalemia (potassium ≥5.3 mEq/L) while on a RAASi and were grouped as follows: no intervention, RAASi discontinuation, RAASi dose decrease, new diuretic, diuretic dose increase, or sodium polystyrene sulfonate within 30 days. The primary outcome was hyperkalemia recurrence, with secondary outcomes of cardiovascular events and all-cause mortality within 1 year. RESULTS Among patients who received a pharmacologic intervention (23% of the cohort), RAASi discontinuation was the most commonly prescribed strategy (74%), followed by RAASi decrease (15%), diuretic increase (7%), new diuretic (3%), and sodium polystyrene sulfonate (1%). A total of 16,977 (34%) recurrent hyperkalemia events occurred within 1 year. Compared with no intervention (35%, referent), the cumulative incidence of recurrent hyperkalemia was lower with RAASi discontinuation (29%; hazard ratio, 0.82; 95% confidence interval, 0.78 to 0.85), whereas there was no difference with RAASi dose decrease (36%; hazard ratio, 0.94; 95% confidence interval, 0.86 to 1.02), new diuretic (32%; hazard ratio, 0.95; 95% confidence interval, 0.78 to 1.17), or diuretic increase (38%; hazard ratio, 0.99; 95% confidence interval, 0.87 to 1.12) and a higher incidence with sodium polystyrene sulfonate (55%; hazard ratio, 1.30; 95% confidence interval, 1.04 to 1.63). RAASi discontinuation was not associated with a higher risk of 1-year cardiovascular events (hazard ratio, 0.96; 95% confidence interval, 0.91 to 1.02) or all-cause mortality (hazard ratio, 1.05; 95% confidence interval, 0.96 to 1.15) compared with no intervention. CONCLUSIONS Among older adults with RAASi-related hyperkalemia, RAASi discontinuation is associated with the lowest risk of recurrent hyperkalemia, with no apparent increase in short-term risks for cardiovascular events or all-cause mortality.
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Affiliation(s)
- Gregory L. Hundemer
- Division of Nephrology, Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - Robert Talarico
- Institute for Clinical Evaluative Sciences, Ottawa, Ontario, Canada
| | - Navdeep Tangri
- Department of Internal Medicine, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Silvia J. Leon
- Department of Internal Medicine, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Sarah E. Bota
- Institute for Clinical Evaluative Sciences, Ottawa, Ontario, Canada
| | - Emily Rhodes
- Institute for Clinical Evaluative Sciences, Ottawa, Ontario, Canada
| | - Greg A. Knoll
- Division of Nephrology, Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - Manish M. Sood
- Division of Nephrology, Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada,Institute for Clinical Evaluative Sciences, Ottawa, Ontario, Canada
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Loutradis C, Price A, Ferro CJ, Sarafidis P. Renin-angiotensin system blockade in patients with chronic kidney disease: benefits, problems in everyday clinical use, and open questions for advanced renal dysfunction. J Hum Hypertens 2021; 35:499-509. [PMID: 33654237 DOI: 10.1038/s41371-021-00504-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 01/23/2021] [Accepted: 02/03/2021] [Indexed: 01/13/2023]
Abstract
Management of hypertension and albuminuria are considered among the primary goals of treatment to slow the progression of chronic kidney disease (CKD). Renin-angiotensin system (RAS) blockers, i.e., angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are the main drugs to achieve these goals. Seminal studies have showed that RAS blockers present significant renoprotective effects in CKD patients with very high albuminuria. In post hoc analyses of such trials, these renoprotective effects appeared more robust in patients with more advanced CKD. However, randomized trials specifically addressing whether RAS blockers should be initiated or maintained in patients with advanced CKD are scarce and do not include subjects with normoalbuminuria, thus, many clinicians are unconvinced for the beneficial effects of RAS blockade in these patients. Further, the fear of hyperkalemia or acute renal decline is another factor due to which RAS blockers are usually underprescribed and are easily discontinued in patients with more advanced CKD; i.e., those in Stages 4 and 5. This review summarizes evidence from the literature regarding the use of RAS blockers in patients with advanced CKD.
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Affiliation(s)
- Charalampos Loutradis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Anna Price
- Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Charles J Ferro
- Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Increased colonic K + excretion through inhibition of the H,K-ATPase type 2 helps reduce plasma K + level in a murine model of nephronic reduction. Sci Rep 2021; 11:1833. [PMID: 33469051 PMCID: PMC7815745 DOI: 10.1038/s41598-021-81388-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 12/21/2020] [Indexed: 11/09/2022] Open
Abstract
Hyperkalemia is frequently observed in patients at the end-stage of chronic kidney disease (CKD), and has possible harmful consequences on cardiac function. Many strategies are currently used to manage hyperkalemia, one consisting of increasing fecal K+ excretion through the administration of cation-exchange resins. In this study, we explored another more specific method of increasing intestinal K+ secretion by inhibiting the H,K-ATPase type 2 (HKA2), which is the main colonic K+ reabsorptive pathway. We hypothetised that the absence of this pump could impede the increase of plasma K+ levels following nephronic reduction (N5/6) by favoring fecal K+ secretion. In N5/6 WT and HKA2KO mice under normal K+ intake, the plasma K+ level remained within the normal range, however, a load of K+ induced strong hyperkalemia in N5/6 WT mice (9.1 ± 0.5 mM), which was significantly less pronounced in N5/6 HKA2KO mice (7.9 ± 0.4 mM, p < 0.01). This was correlated to a higher capacity of HKA2KO mice to excrete K+ in their feces. The absence of HKA2 also increased fecal Na+ excretion by inhibiting its colonic ENaC-dependent absorption. We also showed that angiotensin-converting-enzyme inhibitor like enalapril, used to treat hypertension during CKD, induced a less severe hyperkalemia in N5/6 HKA2KO than in N5/6 WT mice. This study therefore provides the proof of concept that the targeted inhibition of HKA2 could be a specific therapeutic maneuver to reduce plasma K+ levels in CKD patients.
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Desai NR, Alvarez PJ, Golestaneh L, Woods SD, Coca SG, Rowan CG. Healthcare utilization and expenditures associated with hyperkalemia management: a retrospective study of Medicare Advantage patients. J Med Econ 2021; 24:1025-1036. [PMID: 34357841 DOI: 10.1080/13696998.2021.1965389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
AIMS This study aimed to estimate the association of patiromer exposure vs. no potassium (K+) binder (NoKb) exposure with healthcare utilization and expenditures among a cohort of Medicare Advantage patients with hyperkalemia (HK). METHODS Using Optum's Clinformatics Data Mart (study period 2016-2019), the authors assessed propensity score-matched patients (1:1) with a serum K+ concentration ≥5.0 mmol/L and an HK diagnosis that were exposed to patiromer or NoKb on baseline characteristics. The following outcomes were compared: (1) inpatient/emergency department (ED) encounters, (2) inpatient costs greater than or equal to mean Medicare Advantage inpatient cost (i.e. $14,900), and (3) the relative healthcare spending rate. Logistic regression and zero-inflated negative binomial regression were used to analyze the outcomes. RESULTS The study cohort included 1,539 patiromer and NoKb matched pairs. Baseline characteristics were (patiromer/NoKb): age 74/75 years; female 42/40%; serum K+ 5.6/5.6 mmol/L; eGFR rate 36/36 mL/min/1.73 m2; low-income subsidy 42/41%, chronic kidney disease 96/96%; end-stage renal disease 12/12%; and congestive heart failure 37/36%. A total of 253 matched pairs (506 patients) remained uncensored and were analyzed at 6 months. Inpatient/ED encounters were observed for 25% (patiromer) and 37% (NoKb) (odds ratio [OR] 0.58, 95% confidence interval [CI]: 0.38-0.89). The relative odds of having inpatient costs ≥$14,900 were ∼50% less for patients exposed to patiromer vs. NoKb (OR [95% CI]: 0.47 [0.25-0.89]). The relative total healthcare spending rate (including inpatient, outpatient, ED, and pharmacy costs) was 19% less for patients exposed to patiromer vs. NoKb (spending rate ratio [95% CI]: 0.81 [0.67-0.98]). CONCLUSION AND LIMITATIONS Among Medicare Advantage patients with HK, patiromer exposure (vs. NoKb) was associated with statistically significant reductions in the proportion with inpatient/ED encounters, inpatient costs ≥$14,900, and lower total healthcare spending. Further research, with larger sample size, is warranted to fully validate these findings.
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Affiliation(s)
- Nihar R Desai
- Center for Outcomes Research and Evaluation, Yale University, New Haven, CT, USA
| | | | - Ladan Golestaneh
- Renal Division, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | | | - Steven G Coca
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Ramos CI, González-Ortiz A, Espinosa-Cuevas A, Avesani CM, Carrero JJ, Cuppari L. Does dietary potassium intake associate with hyperkalemia in patients with chronic kidney disease? Nephrol Dial Transplant 2020; 36:2049-2057. [DOI: 10.1093/ndt/gfaa232] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Indexed: 12/13/2022] Open
Abstract
Abstract
Background
Dietary potassium restriction is a strategy to control hyperkalemia in chronic kidney disease (CKD). However, hyperkalemia may result from a combination of clinical conditions. This study aimed to investigate whether dietary potassium or the intake of certain food groups associate with serum potassium in the face of other risk factors.
Methods
We performed a cross-sectional analysis including a nondialysis-dependent CKD (NDD-CKD) cohort and a hemodialysis (HD) cohort. Dietary potassium intake was assessed by 3-day food records. Underreporters with energy intake lower than resting energy expenditure were excluded. Hyperkalemia was defined as serum potassium >5.0 mEq/L.
Results
The NDD-CKD cohort included 95 patients {median age 67 [interquartile range (IQR) 55–73] years, 32% with diabetes mellitus (DM), median estimated glomerular filtration rate 23 [IQR 18–29] mL/min/1.73 m2} and the HD cohort included 117 patients [median age 39 (IQR 18–67) years, 50% with DM]. In NDD-CKD, patients with hyperkalemia (36.8%) exhibited lower serum bicarbonate and a tendency for higher serum creatinine, a higher proportion of DM and the use of renin–angiotensin–aldosterone system blockers, but lower use of sodium bicarbonate supplements. No association was found between serum and dietary potassium (r = 0.01; P = 0.98) or selected food groups. Conditions associated with hyperkalemia in multivariable analysis were DM {odds ratio [OR] 3.55 [95% confidence interval (CI) 1.07–11.72]} and metabolic acidosis [OR 4.35 (95% CI 1.37–13.78)]. In HD, patients with hyperkalemia (50.5%) exhibited higher serum creatinine and blood urea nitrogen and lower malnutrition inflammation score and a tendency for higher dialysis vintage and body mass index. No association was found between serum and potassium intake (r = −0.06, P = 0.46) or food groups. DM [OR 4.22 (95% CI 1.31–13.6)] and serum creatinine [OR 1.50 (95% CI 1.24–1.81)] were predictors of hyperkalemia in multivariable analyses.
Conclusions
Dietary potassium was not associated with serum potassium or hyperkalemia in either NDD-CKD or HD patients. Before restricting dietary potassium, the patient’s intake of potassium should be carefully evaluated and other potential clinical factors related to serum potassium balance should be considered in the management of hyperkalemia in CKD.
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Affiliation(s)
- Christiane I Ramos
- Division of Nephrology, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Ailema González-Ortiz
- Nefrología y Metabolismo Mineral, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institute Ringgold Standard Institution, Stockholm, Sweden
| | - Angeles Espinosa-Cuevas
- Nefrología y Metabolismo Mineral, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Carla M Avesani
- Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institute Ringgold Standard Institution, Stockholm, Sweden
- Department of Applied Nutrition, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Juan Jesus Carrero
- Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institute Ringgold Standard Institution, Stockholm, Sweden
| | - Lilian Cuppari
- Division of Nephrology, Universidade Federal de São Paulo, São Paulo, Brazil
- Nutrition programe, Universidade Federal de Sao Paulo, São Paulo, Brazil
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Jiménez-Marrero S, Cainzos-Achirica M, Monterde D, Garcia-Eroles L, Enjuanes C, Yun S, Garay A, Moliner P, Alcoberro L, Corbella X, Comin-Colet J. Real-World Epidemiology of Potassium Derangements Among Chronic Cardiovascular, Metabolic and Renal Conditions: A Population-Based Analysis. Clin Epidemiol 2020; 12:941-952. [PMID: 32982459 PMCID: PMC7494006 DOI: 10.2147/clep.s253745] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 07/14/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The aims of the present analysis are to estimate the prevalence of five key chronic cardiovascular, metabolic and renal conditions at the population level, the prevalence of renin-angiotensin-aldosterone system inhibitor (RAASI) medication use and the magnitude of potassium (K+) derangements among RAASI users. METHODS AND RESULTS We used data from more than 375,000 individuals, 55 years of age or older, included in the population-based healthcare database of the Catalan Institute of Health between 2015 and 2017. The conditions of interest were chronic heart failure (CHF), chronic kidney disease (CKD), diabetes mellitus, ischemic heart disease and hypertension. RAASI medications included angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists (MRAs) and renin inhibitors. Hyperkalemia was defined as K+ levels >5.0 mEq/L and hypokalemia as K+ <3.5 mEq/L. The prevalence of chronic cardiovascular, metabolic and renal conditions was high, and particularly that of hypertension (prevalence ranging from 48.2% to 48.9%). The use of at least one RAASI medication was almost ubiquitous in these patients (75.2-77.3%). Among RAASI users, the frequency of K+ derangements, mainly of hyperkalemia, was very noticeable (12% overall), particularly in patients with CKD or CHF, elderly individuals and users of MRAs. Hypokalemia was less frequent (1%). CONCLUSION The high prevalence of K+ derangements, and particularly hyperkalemia, among RAASI users highlights the real-world relevance of K+ derangements, and the importance of close monitoring and management of K+ levels in routine clinical practice. This is likely to benefit a large number of patients, particularly those at higher risk.
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Affiliation(s)
- Santiago Jiménez-Marrero
- Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Miguel Cainzos-Achirica
- Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
- Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA
- School of Medicine and Health Sciences, International University of Catalonia, Barcelona, Spain
| | - David Monterde
- Healthcare Information and Knowledge Unit, Catalan Health Service, Barcelona, Spain
| | - Luis Garcia-Eroles
- Healthcare Information and Knowledge Unit, Catalan Health Service, Barcelona, Spain
| | - Cristina Enjuanes
- Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Sergi Yun
- Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
- Department of Internal Medicine, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
| | - Alberto Garay
- Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Pedro Moliner
- Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Lidia Alcoberro
- Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Xavier Corbella
- Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
- Department of Internal Medicine, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Hestia Chair in Integrated Health and Social Care, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain
| | - Josep Comin-Colet
- Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
- Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain
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Takkar C, Nassar T, Qunibi W. An evaluation of sodium zirconium cyclosilicate as a treatment option for hyperkalemia. Expert Opin Pharmacother 2020; 22:19-28. [PMID: 32892634 DOI: 10.1080/14656566.2020.1810234] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Hyperkalemia, defined as serum potassium level > 5.0 mEq/l, is associated with serious cardiac dysrhythmias, sudden death and increased mortality risk. It is common in patients with chronic kidney disease (CKD), diabetes (DM) and heart failure (HF), particularly in those treated with the renin-angiotensin-aldosterone system (RAAS) inhibitors or potassium-sparing diuretics. Although these drugs have documented renal and cardiac protective benefits, frequent hyperkalemia associated with their use often dictates administration of suboptimal doses or their discontinuation altogether. Treatment for chronic hyperkalemia in these settings has been challenging; however, the recent introduction of two new potassium-binding resins has revolutionized our approach to treating hyperkalemia. AREAS COVERED We review key clinical data relating to the pharmacokinetics, efficacy and safety of sodium zirconium cyclosilicate (SZC) as a treatment option for hyperkalemia. EXPERT OPINION SZC and Patiromer are promising new agents for lowering serum potassium in hyperkalemic patients, including those with CKD, with and without DM or HF, facilitating the use of the RAAS inhibitors for renal and cardiac protection. Recent randomized clinical trials have shown that SZC effectively lowers serum potassium and maintains normokalemia in most hyperkalemic patients. Clinical trials showed that SZC lowers serum potassium within 1 h, although it is not approved for treating acute hyperkalemia. SZC was well tolerated and associated with minimal adverse effects.
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Affiliation(s)
- Chandan Takkar
- Internal Medicine, Division of Nephrology, University of Texas Health Science Center at San Antonio , San Antonio, USA
| | - Tareq Nassar
- Division of Nephrology, University of Texas Health Science Center at San Antonio, Internal Medicine , San Antonio, USA
| | - Wajeh Qunibi
- Internal Medicine, Division of Nephrology, University of Texas Health Science Centre and Texas Diabetes Institute , San Antonio, USA
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