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1
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Blum MF, Neuen BL, Grams ME. Risk-directed management of chronic kidney disease. Nat Rev Nephrol 2025; 21:287-298. [PMID: 39885336 DOI: 10.1038/s41581-025-00931-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2025] [Indexed: 02/01/2025]
Abstract
The timely and rational institution of therapy is a key step towards reducing the global burden of chronic kidney disease (CKD). CKD is a heterogeneous entity with varied aetiologies and diverse trajectories, which include risk of kidney failure but also cardiovascular events and death. Developments in the past decade include substantial progress in CKD risk prediction, driven in part by the accumulation of electronic health records data. In addition, large randomized clinical trials have demonstrated the effectiveness of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists in reducing adverse events in CKD, greatly expanding the options for effective therapy. Alongside angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, these classes of medication have been proposed to be the four pillars of CKD pharmacotherapy. However, all of these drug classes are underutilized, even in individuals at high risk. Leveraging prognostic estimates to guide therapy could help clinicians to prescribe CKD-related therapies to those who are most likely to benefit from their use. Risk-based CKD management thus aligns patient risk and care, allowing the prioritization of absolute benefit in determining therapeutic selection and timing. Here, we discuss CKD prognosis tools, evidence-based management and prognosis-guided therapies.
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Affiliation(s)
- Matthew F Blum
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Brendon L Neuen
- The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Morgan E Grams
- New York University Grossman School of Medicine, New York, NY, USA.
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2
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Copur S, Burlacu A, Kanbay M. Novel approaches in antihypertensive pharmacotherapeutics. Curr Opin Nephrol Hypertens 2025:00041552-990000000-00228. [PMID: 40265521 DOI: 10.1097/mnh.0000000000001081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/24/2025]
Abstract
PURPOSE OF REVIEW The management of hypertension remains suboptimal despite the widespread use of multiple antihypertensive medication groups. We hereby aim to evaluate the novel therapeutic approaches for the management of hypertension. RECENT FINDINGS As the decline in SBP and/or DBP is associated with a significant decline in major adverse cardiovascular events and all-cause mortality, the optimal management of hypertension is at most importance. The high prevalence of resistant hypertension, approximately 10% of hypertensive population, remains a major concern associated with high morbidity and mortality. Recently, multiple novel pharmacotherapeutic approaches have been implicated in the management of hypertension on various pathophysiological mechanisms, including aldosterone synthetase inhibitors, RNA-based therapies such as antisense oligonucleotides and small-interfering RNA, atrial natriuretic peptide analogs, dual endothelin antagonists, intestinal sodium-hydrogen exchanger-3 inhibitors, compound 17b and nonsteroidal mineralocorticoid receptor antagonists. SUMMARY Pharmacotherapeutic management options for hypertension is a growing field of research with potential clinical implications for multiple agents in upcoming years. Such novel approaches have the potential to improve clinical outcomes of hypertension management.
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Affiliation(s)
- Sidar Copur
- Department of Internal Medicine, Division of Internal Medicine, Koç University School of Medicine, Istanbul, Turkey
| | - Alexandru Burlacu
- Faculty of Medicine, University of Medicine and Pharmacy "Grigore T Popa,"
- Institute of Cardiovascular Diseases "Prof. Dr George I.M. Georgescu," Iasi, Romania
| | - Mehmet Kanbay
- Department of Internal Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey
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3
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Gonzalez Suarez ML, Arriola-Montenegro J, Rolón L. Hypertension management in patients with advanced chronic kidney disease with and without dialysis. Curr Opin Cardiol 2025:00001573-990000000-00205. [PMID: 40183393 DOI: 10.1097/hco.0000000000001221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/05/2025]
Abstract
PURPOSE OF REVIEW Hypertension is a common comorbidity in patients with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) on dialysis, contributing significantly to cardiovascular disease and increased mortality. Managing hypertension in this population is complex due to the frequent occurrence of resistant hypertension. This review highlights the recent updates in hypertension management for these patients, especially considering new guidelines and therapeutic options. RECENT FINDINGS Recent literature emphasizes updated KDIGO guidelines, which have lowered blood pressure targets to decrease cardiovascular risks in patients with advanced CKD and ESKD. First-line therapies include diuretics, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers. New pharmacological treatments, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, endothelin receptor antagonists, RNA interference therapeutics, and aldosterone synthase inhibitors, offer promising options for resistant hypertension. Additionally, lifestyle modifications, including a low-salt diet and aerobic exercise, and volume control through ultrafiltration in dialysis patients, are crucial for blood pressure management. SUMMARY The findings suggest that individualized treatment strategies, incorporating both pharmacologic and nonpharmacologic approaches, are essential for optimizing blood pressure control in patients with advanced CKD and ESKD. These strategies can improve cardiovascular outcomes and enhance patient quality of life, with important implications for clinical practice.
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Goraya N, Madias NE, Simoni J, Kahlon M, Aksan N, Wesson DE. Randomized Trial of Dietary Acid Reduction and Acid-Base Status of Patients With CKD and Normal Estimated GFR. Kidney Int Rep 2025; 10:355-374. [PMID: 39990902 PMCID: PMC11843131 DOI: 10.1016/j.ekir.2024.10.032] [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: 10/08/2024] [Accepted: 10/28/2024] [Indexed: 02/25/2025] Open
Abstract
Introduction Modern acid-producing diets in patients with stage G3 to G5 chronic kidney disease (CKD) can cause severe acid accumulation with metabolic acidosis and less severe accumulation causing eubicarbonatemic acidosis in stages G2 to G3, each with kidney injury. The impact of these diets on acid accumulation in those with CKD but normal estimated glomerular filtration rate (eGFR) (CKD G1) is unclear. Methods We assessed whether acid accumulation occurs in patients with CKD and normal eGFR, and if added base-producing fruits and vegetables (F&Vs) or oral sodium bicarbonate (NaHCO3) (HCO3 -) reduces acid accumulation and/or lowers kidney injury. We randomized 153 participants with macroalbuminuric, nondiabetic, CKD stage G1 (mean eGFR = 101 ml/min per 1.73 m2) with hypertension-associated CKD to receive F&Vs in amounts to reduce dietary acid intake by 50% (F&V, n = 51), oral NaHCO3 to match alkali intake of F&V (HCO3 -, n = 51), or usual care (UC, n = 51) for 5 years. We assessed acid accumulation by comparing observed to expected increase in plasma total CO2 (PTCO2) in response to retained bicarbonate (dose - urine bicarbonate excretion) 2 hours after an oral NaHCO3 bolus. Results Baseline acid accumulation, eGFR, urine excretion of albumin, N-acetyl-β-D-glucosamine, and angiotensinogen were not different among groups. Five-year acid accumulation (mean [SD]) was lower in F&V (-1.2 [11.0] mmol] and in HCO3 - (-1.7 [10.8] mmol) than in UC (5.2 [10.3] mmol, P < 0.003), which is consistent with lower acid accumulation in F&V and HCO3 -. Five-year urine excretion of albumin, N-acetyl-β-D-glucosamine, and angiotensinogen were lower in F&V and HCO3 - than in UC, which is consistent with less kidney injury. Conclusions Dietary acid reduction reduces acid accumulation and kidney injury in patients with CKD and normal eGFR.
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Affiliation(s)
- Nimrit Goraya
- Department of Internal Medicine, Baylor Scott and White Health, Temple, Texas, USA
- Department of Internal Medicine, Baylor College of Medicine, Temple, Texas, USA
| | - Nicolaos E. Madias
- St. Elizabeth’s Medical Center and Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Jan Simoni
- Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, Texas; USA
| | - Maninder Kahlon
- Department of Population Health, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA
| | - Nazan Aksan
- Department of Population Health, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA
| | - Donald E. Wesson
- Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA
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Hoekstra T, Dam M, Klaassen G, Bos WJW, van der Boog PJM, Vogt L, van Jaarsveld B, van Dijk S, Navis G, Meuleman Y, ESMO, and SUBLIME study group. Self-Monitoring and Self-Efficacy in Patients with Chronic Kidney Disease During Low-Sodium Diet Self-Management Interventions: Secondary Analysis of the ESMO and SUBLIME Trials. Int J Behav Med 2025; 32:34-44. [PMID: 38066237 DOI: 10.1007/s12529-023-10240-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Collaborators] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/31/2023] [Indexed: 02/05/2025]
Abstract
BACKGROUND Patients with chronic kidney disease are often requested to engage in self-monitoring sodium (i.e. salt) intake, but it is currently unknown how self-monitoring would empower them. This study aims to assess: (1) how frequent self-monitoring tools are being used during low-sodium diet self-management interventions; (2) whether self-efficacy (i.e. trust in own capability to manage the chronic disease) is associated with self-monitoring frequency; and (3) whether higher self-monitoring frequency is associated with an improvement in self-efficacy over time. METHOD Data from two multicenter randomized controlled trials (ESMO [n = 151] and SUBLIME [n = 99]) among adult Dutch patients with chronic kidney disease (eGFR ≥ 20-25 mL/min/1.73 m2) were used. In both studies, routine care was compared to a 3-month low-sodium diet self-management intervention with several self-monitoring tools (online food diary, home blood pressure monitor, and urinary sodium measurement device [only ESMO]). Data was collected on usage frequency of self-monitoring tools. Frequencies during the interventions were compared between low and high baseline self-efficacy groups using the Mann-Whitney U test and T-test and associated with changes in self-efficacy during the interventions using Spearman correlation coefficients. RESULTS Large variations in self-monitoring frequency were observed. In both interventions, usage of self-monitoring tools was highest during the first month with sharp drops thereafter. The online food diary was the most frequently used tool. In the ESMO intervention, low baseline self-efficacy was associated with a higher usage frequency of self-monitoring tools. This finding was not confirmed in the SUBLIME intervention. No significant associations were found between usage frequency of self-monitoring tools and changes in self-efficacy over time. CONCLUSION Patients with low self-efficacy might benefit most from frequent usage of self-monitoring tools when sufficient guidance and support is provided.
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Affiliation(s)
- Tiny Hoekstra
- Department of Nephrology, Amsterdam University Medical Centers, VU University Amsterdam, Amsterdam, The Netherlands.
- Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, Amsterdam, The Netherlands.
| | - Manouk Dam
- Department of Nephrology, Amsterdam University Medical Centers, VU University Amsterdam, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Gerald Klaassen
- Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands
| | - Willem Jan W Bos
- Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands
| | | | - Liffert Vogt
- Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, Amsterdam, The Netherlands
- Nephrology Section, Department of Internal Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Brigit van Jaarsveld
- Department of Nephrology, Amsterdam University Medical Centers, VU University Amsterdam, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Sandra van Dijk
- Department of Health, Medical, and Neuropsychology, Institute of Psychology, Leiden University, Leiden, The Netherlands
| | - Gerjan Navis
- Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands
| | - Yvette Meuleman
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
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Collaborators
Sandra van Dijk, Yvette Meuleman, Friedo W Dekker, Tiny Hoekstra, Gerjan Navis, Liffert Vogt, Paul J M van der Boog, Willem Jan W Bos, Gert A van Montfrans, Elisabeth W Boeschoten, Marion Verduijn, Lucia Ten Brinke, Anke Spijker, Arjan J Kwakernaak, Jelmer K Humalda, Tonnie van Hirtum, Robin Bokelaar, Marie-Louise Loos, Anke Bakker-Edink, Charlotte Poot, Yvette Ciere, Sophie Zwaard, Glenn Veldscholte, Lara Heuveling, Marjolein Storm, Karen Prantl,
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6
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Adamczak M, Kurnatowska I, Naumnik B, Stompór T, Tylicki L, Krajewska M. Pharmacological Nephroprotection in Chronic Kidney Disease Patients with Type 2 Diabetes Mellitus-Clinical Practice Position Statement of the Polish Society of Nephrology. Int J Mol Sci 2024; 25:12941. [PMID: 39684653 PMCID: PMC11641270 DOI: 10.3390/ijms252312941] [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: 10/17/2024] [Revised: 11/20/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
Both chronic kidney disease (CKD) and type 2 diabetes (T2D) are modern epidemics worldwide and have become a severe public health problem. Chronic kidney disease progression in T2D patients is linked to the need for dialysis or kidney transplantation and represents the risk factor predisposing to serious cardiovascular complications. In recent years, important progress has occurred in nephroprotective pharmacotherapy in CKD patients with T2D. In the current position paper, we described a nephroprotective approach in CKD patients with T2D based on the five following pillars: effective antihyperglycemic treatment, SGLT2 inhibitor or semaglutide, antihypertensive therapy, use of RASi (ARB or ACEi), and in selected patients, finerenone, as well as sodium bicarbonate in patients with metabolic acidosis. We thought that the current statement is comprehensive and up-to-date and addresses multiple pathways of nephroprotection in patients with CKD and T2D.
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Affiliation(s)
- Marcin Adamczak
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, 40-027 Katowice, Poland
| | - Ilona Kurnatowska
- Department of Internal Diseases and Transplant Nephrology, Medical University of Lodz, 90-153 Lodz, Poland
| | - Beata Naumnik
- 1st Department of Nephrology, Transplantation and Internal Medicine with Dialysis Unit, Medical University of Bialystok, 15-540 Bialystok, Poland;
| | - Tomasz Stompór
- Department of Nephrology, Hypertension and Internal Medicine, University of Warmia and Mazury in Olsztyn, 10-516 Olsztyn, Poland;
| | - Leszek Tylicki
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, 80-952 Gdansk, Poland
| | - Magdalena Krajewska
- Department of Non-Surgical Clinical Sciences, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland;
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Saka Y, Takahashi H, Naruse T, Watanabe Y. Sacubitril/valsartan reduces proteinuria depending on blood pressure in patients with stage 4-5 chronic kidney disease. Clin Exp Nephrol 2024; 28:1327-1331. [PMID: 39361183 DOI: 10.1007/s10157-024-02561-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 09/05/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND Blood pressure (BP) control is an important factor in the management of chronic kidney disease (CKD). Several studies have shown that BP in many patients with CKD remained uncontrolled even with multiple medications. Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), has been newly approved for treating hypertension in Japan. However, the renoprotective effects remain unclear, particularly in patients with advanced CKD. Here, we investigated the effects on proteinuria of this ARNI in patients with stage 4-5 CKD. METHODS We retrospectively collected data from outpatients with stage 4-5 CKD who started ARNI from January until December 2023. The primary outcome was the change in urine protein creatinine ratio (UPCR) at 6 months after ARNI initiation. Secondary outcomes were systolic and diastolic BP, estimated glomerular filtration rate (eGFR), serum potassium, and serum uric acid (UA). We analyzed factors associated with 50% UPCR reduction by multivariate analysis. RESULTS In total, 47 patients were analyzed. ARNI reduced UPCR from 2.14 g/gCr (interquartile range; 1.09-2.91) to 1.05 g/gCr (0.42-1.95; p < 0.001). Systolic BP fell from 150.0 mmHg (139.5-160.0) to 134.0 mmHg (124.5-140.0; p < 0.001). No significant changes in eGFR, serum potassium, and serum uric acid were observed, except for a slight decrease in eGFR among patients with conversion from a renin-angiotensin system inhibitor to ARNI. In multivariate regression analysis, higher systolic BP (per 10-mmHg increase) was significantly associated with reduced proteinuria (odds ratio 2.51, 95% confidence interval 1.35-4.66; p = 0.004). CONCLUSIONS ARNI reduced proteinuria in patients with stage 4-5 CKD, particularly for those with uncontrolled hypertension.
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Affiliation(s)
- Yosuke Saka
- Department of Nephrology, Kasugai Municipal Hospital, Takakicho 1-1-1, Kasugai, Aichi Prefecture, Japan.
| | - Hiroshi Takahashi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi Prefecture, Japan
| | - Tomohiko Naruse
- Department of Nephrology, Kasugai Municipal Hospital, Takakicho 1-1-1, Kasugai, Aichi Prefecture, Japan
| | - Yuzo Watanabe
- Department of Nephrology, Kasugai Municipal Hospital, Takakicho 1-1-1, Kasugai, Aichi Prefecture, Japan
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8
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Ritter A, Kuhn C, Mohebbi N. [What is confirmed in the treatment of metabolic acidosis in chronic kidney disease?]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2024; 65:1209-1215. [PMID: 39514096 PMCID: PMC11632079 DOI: 10.1007/s00108-024-01806-z] [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] [Accepted: 09/26/2024] [Indexed: 11/16/2024]
Abstract
Precise regulation of the acid-base balance is essential for the functioning of various organs and physiological processes. Acid retention and metabolic acidosis (MA) are frequent complications of chronic kidney disease (CKD) and can also occur following kidney transplantation. In addition to dietary modifications, pharmacological interventions, most notably sodium bicarbonate, are employed to correct MA. While several studies have reported a beneficial effect of MA correction on the progression of CKD, the results remain inconsistent and the magnitude of the treatment effect may be limited. Importantly, no beneficial effect on graft function has been demonstrated after kidney transplantation. The MA is associated with impaired bone quality and although alkali treatment has generally shown positive effects on markers of bone metabolism, consistent changes in bone density have not been observed. Additionally, MA is linked to an increased incidence of cardiovascular events but so far there is a lack of interventional studies with definitive cardiovascular endpoints. Sodium bicarbonate may lead to sodium retention, potentially increasing blood pressure, although the data on this are inconclusive. One interventional study with notable limitations reported a positive effect of alkali treatment on mortality. Correction of MA has been suggested to positively impact protein and muscle catabolism, although no improvement in physical performance was observed in a geriatric population. Limited studies exist on the endocrinological effects of alkali treatment but these indicate a favorable impact on glucose metabolism and potential benefits for thyroid function in predialysis CKD patients. Given the overall low to moderate level of evidence supporting the benefits of alkali treatment, the current guidelines from Kidney Disease: Improving Global Outcomes (KDIGO) propose alkali treatment to prevent serum bicarbonate levels < 18 mmol/l (prior < 22 mmol/l) in adults and the resulting complications.
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Affiliation(s)
- Alexander Ritter
- Klinik für Nephrologie und Transplantationsmedizin, Kantonsspital St. Gallen, St. Gallen, Schweiz
- Klinik für Nephrologie, Universitätsspital Zürich, Zürich, Schweiz
| | - Christian Kuhn
- Klinik für Nephrologie und Transplantationsmedizin, Kantonsspital St. Gallen, St. Gallen, Schweiz
| | - Nilufar Mohebbi
- Praxis und Dialysezentrum Zürich-City, Stockerstrasse 50, Zürich, Schweiz.
- Universität Zürich, Zürich, Schweiz.
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9
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Goraya N, Madias NE, Simoni J, Kahlon M, Aksan N, Wesson DE. Kidney and Cardiovascular Protection Using Dietary Acid Reduction in Primary Hypertension: A Five-Year, Interventional, Randomized, Control Trial. Am J Med 2024; 137:1114-1127.e8. [PMID: 39107215 DOI: 10.1016/j.amjmed.2024.06.006] [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] [Received: 04/23/2024] [Revised: 05/28/2024] [Accepted: 06/05/2024] [Indexed: 08/09/2024]
Abstract
BACKGROUND High fruit and vegetable diets are associated with reduced chronic kidney disease and cardiovascular disease but are infrequently used in hypertension treatment. Low acid diets are also associated with reduced chronic kidney disease and cardiovascular disease, and fruits and vegetables or oral sodium bicarbonate (NaHCO3) lowers dietary acid. METHODS We randomized 153 hypertensive macroalbuminuric patients receiving pharmacologic chronic kidney disease and cardiovascular disease protection to get fruits and vegetables, oral NaHCO3, or Usual Care. We assessed the course of kidney disease progression and cardiovascular disease risk indices over five years. RESULTS Chronic kidney disease progression was slower in participants receiving fruits and vegetables or oral NaHCO3 than Usual Care [mean (SE)] [-1.08 (0.06) and -1.17 (0.07) vs. -1.94 (0.11) mL/min/1.73m2/ year, respectively, P's< .001). Yet, systolic blood pressure was lower, and cardiovascular disease risk indices improved more in participants receiving fruits and vegetables than in those receiving NaHCO3 or Usual Care. These cardiovascular benefits of fruits and vegetables were achieved despite lower doses of pharmacologic chronic kidney disease and cardiovascular disease protection. CONCLUSION The trial supports fruits and vegetables as foundational hypertension treatment to reduce chronic kidney disease progression and cardiovascular disease risk.
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Affiliation(s)
- Nimrit Goraya
- Department of Internal Medicine, Baylor Scott and White Health, Temple, Tex; Department of Internal Medicine, Texas A&M Health Sciences Center College of Medicine, Temple
| | - Nicolaos E Madias
- St. Elizabeth's Medical Center and Department of Medicine, Tufts University School of Medicine, Boston, Mass
| | - Jan Simoni
- Department of Surgery, Texas Tech University Health Sciences Center, Lubbock
| | - Maninder Kahlon
- Department of Population Health, Dell Medical School-The University of Texas at Austin
| | - Nazan Aksan
- Department of Population Health, Dell Medical School-The University of Texas at Austin
| | - Donald E Wesson
- Department of Internal Medicine, Dell Medical School - The University of Texas at Austin.
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Popa IP, Clim A, Pînzariu AC, Lazăr CI, Popa Ș, Tudorancea IM, Moscalu M, Șerban DN, Șerban IL, Costache-Enache II, Tudorancea I. Arterial Hypertension: Novel Pharmacological Targets and Future Perspectives. J Clin Med 2024; 13:5927. [PMID: 39407987 PMCID: PMC11478071 DOI: 10.3390/jcm13195927] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 09/29/2024] [Accepted: 10/02/2024] [Indexed: 10/20/2024] Open
Abstract
Arterial hypertension (HTN) is one of the major global contributors to cardiovascular diseases and premature mortality, particularly due to its impact on vital organs and the coexistence of various comorbidities such as chronic renal disease, diabetes, cerebrovascular diseases, and obesity. Regardless of the accessibility of several well-established pharmacological treatments, the percentage of patients achieving adequate blood pressure (BP) control is still significantly lower than recommended levels. Therefore, the pharmacological and non-pharmacological management of HTN is currently the major focus of healthcare systems. Various strategies are being applied, such as the development of new pharmacological agents that target different underlying physiopathological mechanisms or associated comorbidities. Additionally, a novel group of interventional techniques has emerged in recent years, specifically for situations when blood pressure is not properly controlled despite the use of multiple antihypertensives in maximum doses or when patients are unable to tolerate or desire not to receive antihypertensive medications. Nonetheless, reducing the focus on antihypertensive medication development by the pharmaceutical industry and increasing recognition of ineffective HTN control due to poor drug adherence demands ongoing research into alternative approaches to treatment. The aim of this review is to summarize the potential novel pharmacological targets for the treatment of arterial hypertension as well as the future perspectives of the treatment strategy.
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Affiliation(s)
- Irene Paula Popa
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania (D.N.Ș.)
| | - Andreea Clim
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania (D.N.Ș.)
| | - Alin Constantin Pînzariu
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania (D.N.Ș.)
| | - Cristina Iuliana Lazăr
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania (D.N.Ș.)
| | - Ștefan Popa
- 2nd Department of Surgery–Pediatric Surgery and Orthopedics, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Ivona Maria Tudorancea
- Advanced Research and Development Center for Experimental Medicine (CEMEX), “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115 Iași, Romania
| | - Mihaela Moscalu
- Department of Preventive Medicine and Interdisciplinarity, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Dragomir N. Șerban
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania (D.N.Ș.)
| | - Ionela Lăcrămioara Șerban
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania (D.N.Ș.)
| | - Irina-Iuliana Costache-Enache
- Department of Internal Medicine I, Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania;
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Ionuț Tudorancea
- Department of Morpho-Functional Sciences II, Discipline of Physiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania (D.N.Ș.)
- Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
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11
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Narasaki Y, Siu MK, Nguyen M, Kalantar-Zadeh K, Rhee CM. Personalized nutritional management in the transition from non-dialysis dependent chronic kidney disease to dialysis. Kidney Res Clin Pract 2024; 43:575-585. [PMID: 38738275 PMCID: PMC11467355 DOI: 10.23876/j.krcp.23.142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 08/14/2023] [Accepted: 11/10/2023] [Indexed: 05/14/2024] Open
Abstract
Dialysis has been the dominant treatment regimen in end-stage kidney disease as a means to remove uremic waste products and to maintain electrolyte, acid base, and fluid balance. However, given that dialysis may not always provide a survival benefit nor improved quality of life in certain subpopulations, there is growing recognition of the need for conservative and preservative management as an alternative treatment strategy for advanced chronic kidney disease (CKD). Personalized nutritional management tailored to patient's sociodemographics, social needs, psychological status, health literacy level, and preferences is a key component of conservative and preservative care, as well as in the management of patients transitioning from non-dialysis dependent CKD to dialysis. In this review, we discuss the nutritional and metabolic alterations that ensue in CKD; the rationale for low-protein diets in the conservative and preservative management of advanced CKD; the role of plant-based diets in kidney health; emerging data on dietary potassium and sodium intake on CKD outcomes; and the practical implementation of dietary interventions in advanced kidney disease.
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Affiliation(s)
- Yoko Narasaki
- Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California Irvine, Orange, CA, USA
- Tibor Rubin Veterans Affairs Long Beach Healthcare System, Long Beach, CA, USA
| | - Man Kit Siu
- Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California Irvine, Orange, CA, USA
- Tibor Rubin Veterans Affairs Long Beach Healthcare System, Long Beach, CA, USA
| | - Matthew Nguyen
- Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California Irvine, Orange, CA, USA
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California Irvine, Orange, CA, USA
- Tibor Rubin Veterans Affairs Long Beach Healthcare System, Long Beach, CA, USA
- The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
| | - Connie M. Rhee
- Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California Irvine, Orange, CA, USA
- Tibor Rubin Veterans Affairs Long Beach Healthcare System, Long Beach, CA, USA
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12
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Rosati E, Condello G, Tacente C, Mariani I, Tommolini V, Calvaruso L, Fulignati P, Grandaliano G, Pesce F. Potential Add-On Benefits of Dietary Intervention in the Treatment of Autosomal Dominant Polycystic Kidney Disease. Nutrients 2024; 16:2582. [PMID: 39203719 PMCID: PMC11357151 DOI: 10.3390/nu16162582] [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: 06/17/2024] [Revised: 07/27/2024] [Accepted: 08/02/2024] [Indexed: 09/03/2024] Open
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of renal failure. The pathogenesis of the disease encompasses several pathways and metabolic alterations, including the hyperactivation of mTOR and suppression of AMPK signaling pathways, as well as mitochondrial dysfunction. This metabolic reprogramming makes epithelial cyst-lining cells highly dependent on glucose for energy and unable to oxidize fatty acids. Evidence suggests that high-carbohydrate diets may worsen the progression of ADPKD, providing the rationale for treating ADPKD patients with calorie restriction and, in particular, with ketogenic dietary interventions, already used for other purposes such as in overweight/obese patients or in the treatment of refractory epilepsy in children. Preclinical studies have demonstrated that calorie restriction may prevent and/or slow disease progression by inducing ketosis, particularly through increased beta-hydroxybutyrate (BHB) levels, which may modulate the metabolic signaling pathways altered in ADKPK. In these patients, although limited, ketogenic intervention studies have shown promising beneficial effects. However, larger and longer randomized controlled trials are needed to confirm their tolerability and safety in long-term maintenance and their additive role in the therapy of polycystic kidney disease.
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Affiliation(s)
- Erica Rosati
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (E.R.); (G.C.); (C.T.); (I.M.); (V.T.); (L.C.); (P.F.); (G.G.)
- Unità Operativa Complessa di Nefrologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Giulia Condello
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (E.R.); (G.C.); (C.T.); (I.M.); (V.T.); (L.C.); (P.F.); (G.G.)
- Unità Operativa Complessa di Nefrologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Chiara Tacente
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (E.R.); (G.C.); (C.T.); (I.M.); (V.T.); (L.C.); (P.F.); (G.G.)
- Unità Operativa Complessa di Nefrologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Ilaria Mariani
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (E.R.); (G.C.); (C.T.); (I.M.); (V.T.); (L.C.); (P.F.); (G.G.)
- Unità Operativa Complessa di Nefrologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Valeria Tommolini
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (E.R.); (G.C.); (C.T.); (I.M.); (V.T.); (L.C.); (P.F.); (G.G.)
- Unità Operativa Complessa di Nefrologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Luca Calvaruso
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (E.R.); (G.C.); (C.T.); (I.M.); (V.T.); (L.C.); (P.F.); (G.G.)
- Unità Operativa Complessa di Nefrologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Pierluigi Fulignati
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (E.R.); (G.C.); (C.T.); (I.M.); (V.T.); (L.C.); (P.F.); (G.G.)
- Unità Operativa Complessa di Nefrologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Giuseppe Grandaliano
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (E.R.); (G.C.); (C.T.); (I.M.); (V.T.); (L.C.); (P.F.); (G.G.)
- Unità Operativa Complessa di Nefrologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Pesce
- Division of Renal Medicine, Ospedale Isola Tiberina—Gemelli Isola, 00186 Rome, Italy
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Shimoyama M, Kawamoto S, Nakatani Y, Banba N, Nagashima Y, Tomoe T, Sugiyama T, Ueno A, Kitahara K, Kawabe A, Otani N, Sugimura H, Yasu T. Effects of salt intake reduction by urinary sodium to potassium ratio self-monitoring method. Hypertens Res 2024; 47:1852-1860. [PMID: 38600280 DOI: 10.1038/s41440-024-01655-1] [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: 10/20/2023] [Revised: 02/24/2024] [Accepted: 03/01/2024] [Indexed: 04/12/2024]
Abstract
Effective and feasible educational methods are needed to control salt intake. We performed a single-center, non-randomized controlled study to investigate the effectiveness and feasibility of self-monitoring using a urinary sodium/potassium (Na/K) ratio-measuring device in patients with difficulty in reducing salt intake. This study included 160 patients with hypertension, chronic kidney disease, or heart disease who were followed up in the outpatient clinic of the Dokkyo Medical University Nikko Medical Center. Urinary Na/K ratio measuring Na/K ratio meter were loaned for 2-6 weeks to the treatment (T) group (n = 80) and not to the patients in the control (C) group (n = 80). In the T group, patients were instructed to measure the urinary Na/K ratio at least three times a day and maintain a Na/K ratio below 2.0. Salt reduction education and home blood pressure measurement guidance continued in both groups. The mean device loan period in the T group was 25.1 days, the mean number of measurements was 3.0 times/day, and the proportion of patients achieving three measurements per day was 48.8% (39/80). Self-monitoring using the urinary Na/K ratio meter successfully reduced salt intake by -1.9 g/day at the second visit (p < 0.001) in the T group. In contrast, no change was observed over time in the C group. Self-monitoring using the urinary Na/K ratio meter successfully reduced salt intake in patients with difficulty reducing salt intake.
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Affiliation(s)
- Masahiro Shimoyama
- Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center, 145-1 Moritomo, Nikko, Tochigi, 321 -1298, Japan
| | - Shinya Kawamoto
- Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center, 145-1 Moritomo, Nikko, Tochigi, 321 -1298, Japan.
| | - Yuki Nakatani
- Department of Diabetes and Endocrinology, Dokkyo Medical University Nikko Medical Center, Nikko, Tochigi, Japan
| | - Nobuyuki Banba
- Department of Diabetes and Endocrinology, Dokkyo Medical University Nikko Medical Center, Nikko, Tochigi, Japan
| | - Yasuko Nagashima
- Department of Diabetes and Endocrinology, Dokkyo Medical University Nikko Medical Center, Nikko, Tochigi, Japan
| | - Takashi Tomoe
- Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center, 145-1 Moritomo, Nikko, Tochigi, 321 -1298, Japan
| | - Takushi Sugiyama
- Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center, 145-1 Moritomo, Nikko, Tochigi, 321 -1298, Japan
| | - Asuka Ueno
- Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center, 145-1 Moritomo, Nikko, Tochigi, 321 -1298, Japan
| | - Keijiro Kitahara
- Department of Cardiology, Dokkyo Medical University, Nikko Medical Center, Nikko, Tochigi, Japan
| | - Atsuhiko Kawabe
- Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center, 145-1 Moritomo, Nikko, Tochigi, 321 -1298, Japan
| | - Naoyuki Otani
- Department of Cardiology, Dokkyo Medical University, Nikko Medical Center, Nikko, Tochigi, Japan
| | - Hiroyuki Sugimura
- Department of Cardiology, Dokkyo Medical University, Nikko Medical Center, Nikko, Tochigi, Japan
| | - Takanori Yasu
- Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center, 145-1 Moritomo, Nikko, Tochigi, 321 -1298, Japan
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14
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Duan S, Ma Y, Lu F, Zhang C, Guo H, Zeng M, Sun B, Yuan Y, Xing C, Mao H, Zhang B. High sodium intake and fluid overhydration predict cardiac structural and functional impairments in chronic kidney disease. Front Nutr 2024; 11:1388591. [PMID: 38860161 PMCID: PMC11164051 DOI: 10.3389/fnut.2024.1388591] [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: 02/20/2024] [Accepted: 05/14/2024] [Indexed: 06/12/2024] Open
Abstract
Background High sodium intake and fluid overhydration are common factors of and strongly associated with adverse outcomes in chronic kidney disease (CKD) patients. Yet, their effects on cardiac dysfunction remain unclear. Aims The study aimed to explore the impact of salt and volume overload on cardiac alterations in non-dialysis CKD. Methods In all, 409 patients with CKD stages 1-4 (G1-G4) were enrolled. Daily salt intake (DSI) was estimated by 24-h urinary sodium excretion. Volume status was evaluated by the ratio of extracellular water (ECW) to total body water (TBW) measured by body composition monitor. Recruited patients were categorized into four groups according to DSI (6 g/day) and median ECW/TBW (0.439). Echocardiographic and body composition parameters and clinical indicators were compared. Associations between echocardiographic findings and basic characteristics were performed by Spearman's correlations. Univariate and multivariate binary logistic regression analysis were used to determine the associations between DSI and ECW/TBW in the study groups and the incidence of left ventricular hypertrophy (LVH) and elevated left ventricular filling pressure (ELVFP). In addition, the subgroup effects of DSI and ECW/TBW on cardiac abnormalities were estimated using Cox regression. Results Of the enrolled patients with CKD, the median urinary protein was 0.94 (0.28-3.14) g/d and estimated glomerular filtration rate (eGFR) was 92.05 (IQR: 64.52-110.99) mL/min/1.73 m2. The distributions of CKD stages G1-G4 in the four groups was significantly different (p = 0.020). Furthermore, compared to group 1 (low DSI and low ECW/TBW), group 4 (high DSI and high ECW/TBW) showed a 2.396-fold (95%CI: 1.171-4.902; p = 0.017) excess risk of LVH and/or ELVFP incidence after adjusting for important CKD and cardiovascular disease risk factors. Moreover, combined with eGFR, DSI and ECW/TBW could identify patients with higher cardiac dysfunction risk estimates with an AUC of 0.704 (sensitivity: 75.2%, specificity: 61.0%). The specificity increased to 85.7% in those with nephrotic proteinuria (AUC = 0.713). The magnitude of these associations was consistent across subgroups analyses. Conclusion The combination of high DSI (>6 g/d) and high ECW/TBW (>0.439) independently predicted a greater risk of LVH or ELVFP incidence in non-dialysis CKD patients. Moreover, the inclusion of eGFR and proteinuria improved the risk stratification ability of DSI and ECW/TBW in cardiac impairments in CKD.
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15
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Zhang C, Shi Y, Liu C, Sudesh SM, Hu Z, Li P, Liu Q, Ma Y, Shi A, Cai H. Therapeutic strategies targeting mechanisms of macrophages in diabetic heart disease. Cardiovasc Diabetol 2024; 23:169. [PMID: 38750502 PMCID: PMC11097480 DOI: 10.1186/s12933-024-02273-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 05/08/2024] [Indexed: 05/18/2024] Open
Abstract
Diabetic heart disease (DHD) is a serious complication in patients with diabetes. Despite numerous studies on the pathogenic mechanisms and therapeutic targets of DHD, effective means of prevention and treatment are still lacking. The pathogenic mechanisms of DHD include cardiac inflammation, insulin resistance, myocardial fibrosis, and oxidative stress. Macrophages, the primary cells of the human innate immune system, contribute significantly to these pathological processes, playing an important role in human disease and health. Therefore, drugs targeting macrophages hold great promise for the treatment of DHD. In this review, we examine how macrophages contribute to the development of DHD and which drugs could potentially be used to target macrophages in the treatment of DHD.
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Affiliation(s)
- Chaoyue Zhang
- Cardiovascular Clinical Medical Center, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yunke Shi
- Cardiovascular Clinical Medical Center, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Changzhi Liu
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Shivon Mirza Sudesh
- Faculty of Medicine, St. George University of London, London, UK
- University of Nicosia Medical School, University of Nicosia, Nicosia, Cyprus
| | - Zhao Hu
- Department of Geriatric Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Pengyang Li
- Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA
| | - Qi Liu
- Wafic Said Molecular Cardiology Research Laboratory, The Texas Heart Institute, Houston, TX, USA
| | - Yiming Ma
- Cardiovascular Clinical Medical Center, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Ao Shi
- Faculty of Medicine, St. George University of London, London, UK.
- University of Nicosia Medical School, University of Nicosia, Nicosia, Cyprus.
| | - Hongyan Cai
- Cardiovascular Clinical Medical Center, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
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Natale P, Palmer SC, Navaneethan SD, Craig JC, Strippoli GF. Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev 2024; 4:CD006257. [PMID: 38682786 PMCID: PMC11057222 DOI: 10.1002/14651858.cd006257.pub2] [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: 05/01/2024]
Abstract
BACKGROUND Guidelines suggest that adults with diabetes and kidney disease receive treatment with angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). This is an update of a Cochrane review published in 2006. OBJECTIVES We compared the efficacy and safety of ACEi and ARB therapy (either as monotherapy or in combination) on cardiovascular and kidney outcomes in adults with diabetes and kidney disease. SEARCH METHODS We searched the Cochrane Kidney and Transplants Register of Studies to 17 March 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA We included studies evaluating ACEi or ARB alone or in combination, compared to each other, placebo or no treatment in people with diabetes and kidney disease. DATA COLLECTION AND ANALYSIS Two authors independently assessed the risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS One hundred and nine studies (28,341 randomised participants) were eligible for inclusion. Overall, the risk of bias was high. Compared to placebo or no treatment, ACEi may make little or no difference to all-cause death (24 studies, 7413 participants: RR 0.91, 95% CI 0.73 to 1.15; I2 = 23%; low certainty) and with similar withdrawals from treatment (7 studies, 5306 participants: RR 1.03, 95% CI 0.90 to 1.19; I2 = 0%; low certainty). ACEi may prevent kidney failure (8 studies, 6643 participants: RR 0.61, 95% CI 0.39 to 0.94; I2 = 0%; low certainty). Compared to placebo or no treatment, ARB may make little or no difference to all-cause death (11 studies, 4260 participants: RR 0.99, 95% CI 0.85 to 1.16; I2 = 0%; low certainty). ARB have uncertain effects on withdrawal from treatment (3 studies, 721 participants: RR 0.85, 95% CI 0.58 to 1.26; I2 = 2%; low certainty) and cardiovascular death (6 studies, 878 participants: RR 3.36, 95% CI 0.93 to 12.07; low certainty). ARB may prevent kidney failure (3 studies, 3227 participants: RR 0.82, 95% CI 0.72 to 0.94; I2 = 0%; low certainty), doubling of serum creatinine (SCr) (4 studies, 3280 participants: RR 0.84, 95% CI 0.72 to 0.97; I2 = 32%; low certainty), and the progression from microalbuminuria to macroalbuminuria (5 studies, 815 participants: RR 0.44, 95% CI 0.23 to 0.85; I2 = 74%; low certainty). Compared to ACEi, ARB had uncertain effects on all-cause death (15 studies, 1739 participants: RR 1.13, 95% CI 0.68 to 1.88; I2 = 0%; low certainty), withdrawal from treatment (6 studies, 612 participants: RR 0.91, 95% CI 0.65 to 1.28; I2 = 0%; low certainty), cardiovascular death (13 studies, 1606 participants: RR 1.15, 95% CI 0.45 to 2.98; I2 = 0%; low certainty), kidney failure (3 studies, 837 participants: RR 0.56, 95% CI 0.29 to 1.07; I2 = 0%; low certainty), and doubling of SCr (2 studies, 767 participants: RR 0.88, 95% CI 0.52 to 1.48; I2 = 0%; low certainty). Compared to ACEi plus ARB, ACEi alone has uncertain effects on all-cause death (6 studies, 1166 participants: RR 1.08, 95% CI 0.49 to 2.40; I2 = 20%; low certainty), withdrawal from treatment (2 studies, 172 participants: RR 0.78, 95% CI 0.33 to 1.86; I2 = 0%; low certainty), cardiovascular death (4 studies, 994 participants: RR 3.02, 95% CI 0.61 to 14.85; low certainty), kidney failure (3 studies, 880 participants: RR 1.36, 95% CI 0.79 to 2.32; I2 = 0%; low certainty), and doubling of SCr (2 studies, 813 participants: RR 1.14, 95% CI 0.70 to 1.85; I2 = 0%; low certainty). Compared to ACEi plus ARB, ARB alone has uncertain effects on all-cause death (7 studies, 2607 participants: RR 1.02, 95% CI 0.76 to 1.37; I2 = 0%; low certainty), withdrawn from treatment (3 studies, 1615 participants: RR 0.81, 95% CI 0.53 to 1.24; I2 = 0%; low certainty), cardiovascular death (4 studies, 992 participants: RR 3.03, 95% CI 0.62 to 14.93; low certainty), kidney failure (4 studies, 2321 participants: RR 1.15, 95% CI 0.67 to 1.95; I2 = 29%; low certainty), and doubling of SCr (3 studies, 2252 participants: RR 1.18, 95% CI 0.85 to 1.64; I2 = 0%; low certainty). Comparative effects of different ACEi or ARB and low-dose versus high-dose ARB were rarely evaluated. No study compared different doses of ACEi. Adverse events of ACEi and ARB were rarely reported. AUTHORS' CONCLUSIONS ACEi or ARB may make little or no difference to all-cause and cardiovascular death compared to placebo or no treatment in people with diabetes and kidney disease but may prevent kidney failure. ARB may prevent the doubling of SCr and the progression from microalbuminuria to macroalbuminuria compared with a placebo or no treatment. Despite the international guidelines suggesting not combining ACEi and ARB treatment, the effects of ACEi or ARB monotherapy compared to dual therapy have not been adequately assessed. The limited data availability and the low quality of the included studies prevented the assessment of the benefits and harms of ACEi or ARB in people with diabetes and kidney disease. Low and very low certainty evidence indicates that it is possible that further studies might provide different results.
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Affiliation(s)
- Patrizia Natale
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
- Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy
| | - Suetonia C Palmer
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | | | - Jonathan C Craig
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Giovanni Fm Strippoli
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
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17
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Tang R, Kou M, Wang X, Ma H, Li X, Heianza Y, Qi L. Self-Reported Frequency of Adding Salt to Food and Risk of Incident Chronic Kidney Disease. JAMA Netw Open 2023; 6:e2349930. [PMID: 38153731 PMCID: PMC10755616 DOI: 10.1001/jamanetworkopen.2023.49930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 11/14/2023] [Indexed: 12/29/2023] Open
Abstract
Importance The self-reported frequency of adding salt to foods could reflect a person's long-term salt taste preference, and salt intake has been associated with increased risk of cardiovascular diseases (CVD). Whether self-reported adding of salt to foods is associated with increased risk of chronic kidney disease (CKD) remains unknown. Objective To prospectively examine the association of self-reported frequency of adding salt to foods with incident CKD risk in a general population of adults. Design, Setting, and Participants This population-based cohort study evaluated UK Biobank participants aged 37 to 73 years who were free of CKD at baseline. Participants were enrolled from 2006 to 2010 and prospectively followed up for disease diagnosis. Data were analyzed from October 2022 to April 2023. Exposure Self-reported frequency of adding salt to foods, categorized into never or rarely, sometimes, usually, and always. Main Outcome and Measure Incident CKD cases were defined by diagnostic codes. Hazard ratios (HRs) and 95% CIs were calculated by using Cox proportional hazards models. Models were adjusted for several potential confounders including age, sex, race and ethnicity, Townsend Deprivation Index, estimated glomerular filtration rate (eGFR), body mass index, (BMI), smoking status, alcohol drinking status, regular physical activity, high cholesterol, diabetes, CVD, hypertension, infectious disease, immune disease, and nephrotoxic drugs use at baseline. Results Within a cohort of 465 288 individuals (mean [SD] age 56.32 [8.08] years; 255 102 female participants [54.83%]; 210 186 male participants [45.17%]), participants with higher self-reported frequency of adding salt to foods were more likely to have a higher BMI, higher Townsend Deprivation Index score, and diminished baseline eGFR compared with those who reported a lower frequency of adding salt to foods. Participants who added salt to their foods were also more likely than those who did not add salt to their foods to be current smokers and have diabetes or CVD at baseline. During a median (IQR) follow-up of 11.8 (1.4) years, 22 031 incident events of CKD were documented. Higher self-reported frequency of adding salt to foods was significantly associated with a higher CKD risk after adjustment for covariates. Compared with those who reported never or rarely adding salt to foods, those who reported sometimes adding salt to food (adjusted HR [aHR], 1.04; 95% CI, 1.00-1.07), those who reported usually adding salt to food (aHR, 1.07; 95% CI, 1.02-1.11), and those who reported always adding salt to food (aHR, 1.11; 95% CI, 1.05-1.18) had an increased risk of CKD (P for trend < .001). In addition, eGFR, BMI, and physical activity significantly modified the associations, which were more pronounced among participants with a higher eGFR, lower BMI, or lower level of physical activity. Conclusions and Relevance In this cohort study of 465 288 individuals, a higher self-reported frequency of adding salt to foods was associated with a higher risk of CKD in the general population. These findings suggest that reducing the frequency of adding salt to foods at the table might be a valuable strategy to lower CKD risk in the general population.
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Affiliation(s)
- Rui Tang
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana
| | - Minghao Kou
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana
| | - Xuan Wang
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana
| | - Hao Ma
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana
| | - Xiang Li
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana
| | - Yoriko Heianza
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Lu Qi
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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Georgianos PI, Agarwal R. Hypertension in chronic kidney disease-treatment standard 2023. Nephrol Dial Transplant 2023; 38:2694-2703. [PMID: 37355779 PMCID: PMC10689140 DOI: 10.1093/ndt/gfad118] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Indexed: 06/26/2023] Open
Abstract
Hypertension is very common and remains often poorly controlled in patients with chronic kidney disease (CKD). Accurate blood pressure (BP) measurement is the essential first step in the diagnosis and management of hypertension. Dietary sodium restriction is often overlooked, but can improve BP control, especially among patients treated with an agent to block the renin-angiotensin system. In the presence of very high albuminuria, international guidelines consistently and strongly recommend the use of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker as the antihypertensive agent of first choice. Long-acting dihydropyridine calcium channel blockers and diuretics are reasonable second- and third-line therapeutic options. For patients with treatment-resistant hypertension, guidelines recommend the addition of spironolactone to the baseline antihypertensive regimen. However, the associated risk of hyperkalemia restricts the broad utilization of spironolactone in patients with moderate-to-advanced CKD. Evidence from the CLICK (Chlorthalidone in Chronic Kidney Disease) trial indicates that the thiazide-like diuretic chlorthalidone is effective and serves as an alternative therapeutic opportunity for patients with stage 4 CKD and uncontrolled hypertension, including those with treatment-resistant hypertension. Chlorthalidone can also mitigate the risk of hyperkalemia to enable the concomitant use of spironolactone, but this combination requires careful monitoring of BP and kidney function for the prevention of adverse events. Emerging agents, such as the non-steroidal mineralocorticoid receptor antagonist ocedurenone, dual endothelin receptor antagonist aprocitentan and the aldosterone synthase inhibitor baxdrostat offer novel targets and strategies to control BP better. Larger and longer term clinical trials are needed to demonstrate the safety and efficacy of these novel therapies in the future. In this article, we review the current standards of treatment and discuss novel developments in pathophysiology, diagnosis, outcome prediction and management of hypertension in patients with CKD.
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Affiliation(s)
- Panagiotis I Georgianos
- 2nd Department of Nephrology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Rajiv Agarwal
- Division of Nephrology, Department of Medicine, Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA
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19
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Kang SC, Kang M, Ryu H, Kim S, Kim JH, Kang E, Jeong Y, Kim J, Kim YS, Kim SW, Kim YH, Oh KH. Measured sodium excretion is associated with cardiovascular outcomes in non-dialysis CKD patients: results from the KNOW-CKD study. FRONTIERS IN NEPHROLOGY 2023; 3:1236177. [PMID: 37675361 PMCID: PMC10479682 DOI: 10.3389/fneph.2023.1236177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 08/03/2023] [Indexed: 09/08/2023]
Abstract
Background There are insufficient studies on the effect of dietary salt intake on cardiovascular (CV) outcomes in chronic kidney disease (CKD) patients, and there is no consensus on the sodium (Na) intake level that increases the risk of CV disease in CKD patients. Therefore, we investigated the association between dietary salt intake and CV outcomes in CKD patients. Methods In the Korean cohort study for Outcome in patients with CKD (KNOW-CKD), 1,937 patients were eligible for the study, and their dietary Na intake was estimated using measured 24h urinary Na excretion. The primary outcome was a composite of CV events and/or all-cause death. The secondary outcome was a major adverse cardiac event (MACE). Results Among 1,937 subjects, there were 205 (10.5%) events for the composite outcome and 110 (5.6%) events for MACE. Compared to the reference group (urinary Na excretion< 2.0g/day), the group with the highest measured 24h urinary Na excretion (urinary Na excretion ≥ 8.0g/day) was associated with increased risk of both the composite outcome (hazard ratio 3.29 [95% confidence interval 1.00-10.81]; P = 0.049) and MACE (hazard ratio 6.28 [95% confidence interval 1.45-27.20]; P = 0.013) in a cause-specific hazard model. Subgroup analysis also showed a pronounced association between dietary salt intake and the composite outcome in subgroups of patients with abdominal obesity, female, lower estimated glomerular filtration rate (< 60 ml/min per 1.73m2), no overt proteinuria, or a lower urinary potassium-to-creatinine ratio (< 46 mmol/g). Conclusion A high-salt diet is associated with CV outcomes in non-dialysis CKD patients.
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Affiliation(s)
- Seong Cheol Kang
- Department of Medical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Minjung Kang
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyunjin Ryu
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Seonmi Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Ji Hye Kim
- Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea
| | - Eunjeong Kang
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yujin Jeong
- Department of Biostatistics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jayoun Kim
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yong-Soo Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Soo Wan Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Yeong Hoon Kim
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Republic of Korea
| | - Kook-Hwan Oh
- Kidney Research Institute, Seoul National University Medical Research Center, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
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20
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Mollard R, Cachero K, Luhovyy B, Martin H, Moisiuk S, Mahboobi S, Balshaw R, Collister D, Cahill L, Tennankore KK, Tangri N, MacKay D. Reducing Dietary Acid With Fruit and Vegetables Versus Oral Alkali in People With Chronic Kidney Disease (ReDACKD): A Clinical Research Protocol. Can J Kidney Health Dis 2023; 10:20543581231190180. [PMID: 37560749 PMCID: PMC10408321 DOI: 10.1177/20543581231190180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 06/22/2023] [Indexed: 08/11/2023] Open
Abstract
Background Individuals with chronic kidney disease (CKD) can develop metabolic acidosis which, in turn, is associated with faster progression of CKD and an increased need for dialysis. Oral sodium bicarbonate (the current standard of care therapy for metabolic acidosis) is poorly tolerated leading to low adherence. Base-producing or alkalizing Fruit and vegetables have potential as an alternative treatment for metabolic acidosis as they have been shown to reduce acid load arising from the diet. Objective This trial will evaluate the feasibility of providing base-producing fruit and vegetables as a dietary treatment for metabolic acidosis, compared with oral sodium bicarbonate. Design A 2-arm, open-label, dual-center, randomized controlled feasibility trial. Setting Two Canadian sites: a nephrology clinic in Winnipeg, Manitoba, and a nephrology clinic in Halifax, Nova Scotia. Participants Adult participants with G3-G5 CKD and metabolic acidosis. Measurements Participants will undergo baseline measurements and attend 5 study visits over 12 months at which they will have a measurement of feasibility criteria as well as blood pressure, blood and urine biochemistry, 5-repetition chair stand test (STS5), and questionnaires to assess quality of life and symptoms. Furthermore, participants fill out Automated Self-Administered 24-hour recalls (ASA-24) in the beginning, middle, and end of trial. Methods A total of 40 eligible participants will be randomized 1:1 to either base-producing fruit and vegetables (experimental) group or sodium bicarbonate (control) group, beginning from a daily dose of 1500 mg. Limitations Using self-administered dietary assessments, lack of supervision over the consumption of study treatments and the possible disappointment of the control group for not receiving fruit and vegetables would be considered as limitations for this study. However, we are planning to undertake proper practices to overcome the possible limitations. These practices are discussed throughout the article in detail. Conclusions This study will generate data on base-producing fruit and vegetables consumption as a dietary treatment for metabolic acidosis in CKD. The data will be used to design a future multi-center trial looking at slowing CKD progression in people with metabolic acidosis. Trial Registration This study is registered on clinicaltrials.gov with the identifier NCT05113641.
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Affiliation(s)
- Rebecca Mollard
- Department of Food and Human Nutritional Sciences, Faculty of Agriculture and Food Science, University of Manitoba, Winnipeg, Canada
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, University of Manitoba, Winnipeg, Canada
| | - Katrina Cachero
- Department of Food and Human Nutritional Sciences, Faculty of Agriculture and Food Science, University of Manitoba, Winnipeg, Canada
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, University of Manitoba, Winnipeg, Canada
| | - Bohdan Luhovyy
- Department of Applied Human Nutrition, Mount Saint Vincent University, Halifax, NS, Canada
| | - Heather Martin
- Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
| | - Sharon Moisiuk
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, University of Manitoba, Winnipeg, Canada
| | - Sepideh Mahboobi
- Department of Food and Human Nutritional Sciences, Faculty of Agriculture and Food Science, University of Manitoba, Winnipeg, Canada
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, University of Manitoba, Winnipeg, Canada
| | - Robert Balshaw
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada
| | - David Collister
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, University of Manitoba, Winnipeg, Canada
- Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, Canada
| | - Leah Cahill
- Department of Medicine, Dalhousie University, Halifax, NS, Canada
- Nova Scotia Health Authority, Dalhousie University, Halifax, NS, Canada
| | - Karthik K. Tennankore
- Department of Medicine, Dalhousie University, Halifax, NS, Canada
- Nova Scotia Health Authority, Dalhousie University, Halifax, NS, Canada
| | - Navdeep Tangri
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, University of Manitoba, Winnipeg, Canada
- Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
| | - Dylan MacKay
- Department of Food and Human Nutritional Sciences, Faculty of Agriculture and Food Science, University of Manitoba, Winnipeg, Canada
- Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
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21
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Wesson DE. Does Acid Stress Cause Vascular Dysfunction? J Am Soc Nephrol 2023; 34:1299-1301. [PMID: 37526983 PMCID: PMC10402924 DOI: 10.1681/asn.0000000000000162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/03/2023] Open
Affiliation(s)
- Donald E Wesson
- Department of Internal Medicine, Dell Medical School - The University of Texas at Austin, Austin, Texas
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22
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Tampe D, Baier E, Hakroush S, Tampe B. Serum sodium levels associate with recovery of kidney function in immune checkpoint inhibitor nephrotoxicity. Front Med (Lausanne) 2023; 10:1020691. [PMID: 37547603 PMCID: PMC10399621 DOI: 10.3389/fmed.2023.1020691] [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: 08/16/2022] [Accepted: 07/11/2023] [Indexed: 08/08/2023] Open
Abstract
Background Immune checkpoint inhibitors (ICIs) are novel drugs targeting programmed cell death protein 1-ligand 1 (PD-L1) or its receptor (PD-1). Enhancing the immune system has also been associated with a wide range of immune-related adverse events (irAE). Among them, acute interstitial nephritis (AIN) is a rare but deleterious irAE in the kidney. However, determinants of recovery and long-term kidney function after ICI withdrawal and steroid therapy thereafter remain elusive. Therefore, we here aimed to identify parameters associated with recovery of kidney function in this previous established cohort of AIN in the context of ICI therapy. Methods We here monitored kidney function over a mean follow-up time of 812 days in comparison with clinical, histopathological and laboratory parameters associated with recovery of kidney function after AIN related to ICI nephrotoxicity. Results Abundance of intrarenal PD-L1/PD-1 did not correlate with recovery of kidney function. Furthermore, cumulative steroid dose that was initiated for treatment of AIN related to ICI nephrotoxicity was also not associated with improvement of kidney function. Finally, chronic lesions in the kidney including glomerular sclerosis and interstitial fibrosis/tubular atrophy (IF/TA) did not correlate with eGFR change during the follow-up time. However, we here identified that lower levels of serum sodium at time of kidney biopsy were the strongest independent predictor of renal recovery in ICI-related nephrotoxicity. Conclusion Because low serum sodium levels associated with better improvement of kidney function, these observations might contribute to novel approaches to enhance recovery after AIN related to ICI nephrotoxicity.
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Affiliation(s)
- Désirée Tampe
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Eva Baier
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Samy Hakroush
- Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany
- SYNLAB Pathology Hannover, SYNLAB Holding Germany, Augsburg, Germany
| | - Björn Tampe
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
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23
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Giannese D, D'Alessandro C, Panichi V, Pellegrino N, Cupisti A. Nutritional Treatment as a Synergic Intervention to Pharmacological Therapy in CKD Patients. Nutrients 2023; 15:2715. [PMID: 37375619 DOI: 10.3390/nu15122715] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/03/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
Nutritional and pharmacological therapies represent the basis for non-dialysis management of CKD patients. Both kinds of treatments have specific and unchangeable features and, in certain cases, they also have a synergic action. For instance, dietary sodium restriction enhances the anti-proteinuric and anti-hypertensive effects of RAAS inhibitors, low protein intake reduces insulin resistance and enhances responsiveness to epoetin therapy, and phosphate restriction cooperates with phosphate binders to reduce the net phosphate intake and its consequences on mineral metabolism. It can also be speculated that a reduction in either protein or salt intake can potentially amplify the anti-proteinuric and reno-protective effects of SGLT2 inhibitors. Therefore, the synergic use of nutritional therapy and medications optimizes CKD treatment. Quality of care management is improved and becomes more effective when compared to either treatment alone, with lower costs and fewer risks of unwanted side effects. This narrative review summarizes the established evidence of the synergistic action carried out by the combination of nutritional and pharmacological treatments, underlying how they are not alternative but complementary in CKD patient care.
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Affiliation(s)
- Domenico Giannese
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Claudia D'Alessandro
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Vincenzo Panichi
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Nicola Pellegrino
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Adamasco Cupisti
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
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24
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Jo SM. Understanding and Treatment Strategies of Hypertension and Hyperkalemia in Chronic Kidney Disease. Electrolyte Blood Press 2023; 21:24-33. [PMID: 37434804 PMCID: PMC10329905 DOI: 10.5049/ebp.2023.21.1.24] [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: 11/17/2022] [Revised: 06/10/2023] [Accepted: 06/12/2023] [Indexed: 07/13/2023] Open
Abstract
Hypertension and potassium imbalance are commonly observed in chronic kidney disease (CKD) patients. The development of hypertension would be related to several mechanisms. Hypertension is related to body mass index, dietary salt intake, and volume overload and is treated with antihypertensives. In CKD patients, managing hypertension can provide important effects that can slow the progression of CKD or reduce complications associated with reduced glomerular filtration rate. The prevalence of hyperkalemia and hypokalemia in CKD patients was similar at 15-20% and 15-18%, respectively, but more attention needs to be paid to treating and preventing hyperkalemia, which is related to a higher mortality rate, than hypokalemia. Hyperkalemia is prevalent in CKD due to impaired potassium excretion. Serum potassium level is affected by renin-angiotensin-aldosterone system inhibitors and diuretics and dietary potassium intake and can be managed by potassium restriction dietary, optimized renin-angiotensin-aldosterone system inhibitor, sodium polystyrene sulfonate, patiromer, and hemodialysis. This review discussed strategies to mitigate and care for the risk of hypertension and hyperkalemia in CKD patients.
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Affiliation(s)
- Sang Min Jo
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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25
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Kim HJ, Jung CY, Kim HW, Park JT, Yoo TH, Kang SW, Park SK, Kim YH, Sung SA, Hyun YY, Oh KH, Han SH. Proteinuria Modifies the Relationship Between Urinary Sodium Excretion and Adverse Kidney Outcomes: Findings From KNOW-CKD. Kidney Int Rep 2023; 8:1022-1033. [PMID: 37180512 PMCID: PMC10166734 DOI: 10.1016/j.ekir.2023.02.1078] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 01/10/2023] [Accepted: 02/13/2023] [Indexed: 02/24/2023] Open
Abstract
Introduction High sodium intake is associated with increased proteinuria. Herein, we investigated whether proteinuria could modify the association between urinary sodium excretion and adverse kidney outcomes in patients with chronic kidney disease (CKD). Methods In this prospective observational cohort study, we included 967 participants with CKD stages G1 to G5 between 2011 and 2016, who measured 24-hour urinary sodium and protein excretion at baseline. The main predictors were urinary sodium and protein excretion levels. The primary outcome was CKD progression, which was defined as a ≥50% decline in the estimated glomerular filtration rate (eGFR) or the onset of kidney replacement therapy. Results During a median follow-up period of 4.1 years, the primary outcome events occurred in 287 participants (29.7%). There was a significant interaction between proteinuria and sodium excretion for the primary outcome (P = 0.006). In patients with proteinuria of <0.5 g/d, sodium excretion was not associated with the primary outcome. However, in patients with proteinuria of ≥0.5 g/d, a 1.0 g/d increase in sodium excretion was associated with a 29% higher risk of adverse kidney outcomes. Moreover, in patients with proteinuria of ≥0.5 g/d, the hazard ratios (HRs) (95% confidence intervals[CIs]) for sodium excretion of <3.4 and ≥3.4 g/d were 2.32 (1.50-3.58) and 5.71 (3.58-9.11), respectively, compared with HRs for patients with proteinuria of <0.5 g/d and sodium excretion of <3.4 g/d. In sensitivity analysis with 2 averaged values of sodium and protein excretion at baseline and third year, the results were similar. Conclusion Higher urinary sodium excretion was more strongly associated with an increased risk of adverse kidney outcomes in patients with higher proteinuria levels.
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Affiliation(s)
- Hyo Jeong Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Institute of Kidney Disease Research, Seoul, Republic of Korea
- Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Chan-Young Jung
- Department of Internal Medicine, Yonsei University College of Medicine, Institute of Kidney Disease Research, Seoul, Republic of Korea
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyung Woo Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Institute of Kidney Disease Research, Seoul, Republic of Korea
| | - Jung Tak Park
- Department of Internal Medicine, Yonsei University College of Medicine, Institute of Kidney Disease Research, Seoul, Republic of Korea
| | - Tae-Hyun Yoo
- Department of Internal Medicine, Yonsei University College of Medicine, Institute of Kidney Disease Research, Seoul, Republic of Korea
| | - Shin-Wook Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Institute of Kidney Disease Research, Seoul, Republic of Korea
| | - Sue K. Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
- Department of Biomedical Science, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Yeong Hoon Kim
- Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
| | - Su Ah Sung
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University, Seoul, Republic of Korea
| | - Young Youl Hyun
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Korea
| | - Kook-Hwan Oh
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Seung Hyeok Han
- Department of Internal Medicine, Yonsei University College of Medicine, Institute of Kidney Disease Research, Seoul, Republic of Korea
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26
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Mediterranean Dietary Pattern Adjusted for CKD Patients: The MedRen Diet. Nutrients 2023; 15:nu15051256. [PMID: 36904256 PMCID: PMC10005115 DOI: 10.3390/nu15051256] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 02/04/2023] [Accepted: 02/26/2023] [Indexed: 03/06/2023] Open
Abstract
A number of studies in the general population showed that healthy dietary patterns, such as the Mediterranean Diet, can improve or prevent the development of several chronic diseases and are associated with a significant reduction in all-cause and cardiovascular mortality. The Mediterranean diet may also have favorable effects for the prevention of chronic kidney disease (CKD), but no evidence of renoprotection exists in CKD patients. The Mediterranean Renal (MedRen) diet is an adaptation of the Mediterranean diet recommendations comprising a quantitative reduction in the RDA values of protein, salt and phosphate intake for the general population. Hence, MedRen supplies 0.8 g/Kg of protein, 6 g of salt and less than 800 mg of phosphate daily. Obviously, there is a preference for products of plant origin, which contain more alkali, fibers, unsaturated fatty acids than animal-based food. The MedRen diet can be implemented easily in mild-to-moderate stages of CKD with good results, both in terms of adherence to prescriptions and metabolic compensation. In our opinion, it should be the first step of CKD stage 3 nutritional management. This paper describes the features and reports our experience in the implementation of the MedRen diet as an early nutritional approach to CKD.
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Elsurer Afsar R, Afsar B, Ikizler TA. Sodium Management in Kidney Disease: Old Stories, New Tricks. Semin Nephrol 2023; 43:151407. [PMID: 37639931 DOI: 10.1016/j.semnephrol.2023.151407] [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] [Indexed: 08/31/2023]
Abstract
Excessive dietary sodium intake is associated with an increased risk of hypertension, especially in the setting of chronic kidney disease (CKD). Although implementation of a low-sodium diet in patients with CKD generally is recommended, data supporting the efficacy of this practice is mostly opinion-based. Few controlled studies have investigated the specific association of dietary sodium intake and cardiovascular events and mortality in CKD. Furthermore, in epidemiologic studies, the association of sodium intake with CKD progression, cardiovascular risk, and mortality is not homogeneous, and both low- and high-sodium intake has been associated with adverse health outcomes in different studies. In general, the adverse effects of high dietary sodium intake are more apparent in the setting of advanced CKD. However, there is no established definitive target level of dietary sodium intake in different CKD stages based on glomerular filtration rate and albuminuria/proteinuria. This review discusses the current challenges regarding the rationale of sodium restriction, target levels and assessment of sodium intake, and interventions for sodium restrictions in CKD in relation to clinical outcomes.
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Affiliation(s)
- Rengin Elsurer Afsar
- Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Department of Nephrology, Suleyman Demirel University Faculty of Medicine, Isparta, Turkey
| | - Baris Afsar
- Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Department of Nephrology, Suleyman Demirel University Faculty of Medicine, Isparta, Turkey
| | - Talat Alp Ikizler
- Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Division of Nephrology and Hypertension, Vanderbilt O'Brien Center for Kidney Disease, Nashville, TN; Department of Veteran Affairs, Tennessee Valley Healthcare System, Nashville, TN.
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28
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Saritas T, Floege J. [Retarding progression of chronic kidney disease]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2023; 64:240-246. [PMID: 36723710 DOI: 10.1007/s00108-023-01482-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/23/2023] [Indexed: 02/02/2023]
Abstract
Chronic kidney disease (CKD) affects about 10-15% of the German population with a steady increase. It is assumed that CKD will become the 5th most common cause of death worldwide in 2040. CKD is associated with high risk of mortality, morbidity, related in particular to cardiovascular disease, as well as high healthcare costs. Clinical strategies to manage CKD should encompass extensive life-style modification including weight normalization, reduction of dietary protein and salt intakes, regular exercise and avoidance of nicotine. Pharmacologically it includes inhibition of the renin-angiotensin-aldosterone system (RAAS), sodium-glucose co-transporter‑2 (SGLT-2) inhibitors in both diabetes-related and non-diabetic CKD and strategies to control other risk factors such as proteinuria, hyperglycemia and lipid disturbances. Among the various measures aimed at slowing CKD progression, blood pressure control and in particular RAAS inhibitors have received the most attention. Another therapeutic option includes aldosterone inhibition, be it via classical aldosterone-antagonists or the new mineralocorticoid-receptor antagonists. Avoidance of nephrotoxic agents (e.g. non-steroidal anti-inflammatory drugs) seems self-explanatory. Overall, given the often asymptomatic course of CKD in particular in early phases, patient education and self-empowerment as well as treatment in a multidisciplinary team appear essential to stem the tide of patients with advanced kidney damage.
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Affiliation(s)
- Turgay Saritas
- Klinik für Nieren- und Hochdruckkrankheiten, Uniklinik RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland.
| | - Jürgen Floege
- Klinik für Nieren- und Hochdruckkrankheiten, Uniklinik RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland.
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29
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Haruhara K, Kanzaki G, Tsuboi N. Nephrons, podocytes and chronic kidney disease: Strategic antihypertensive therapy for renoprotection. Hypertens Res 2023; 46:299-310. [PMID: 36224286 PMCID: PMC9899692 DOI: 10.1038/s41440-022-01061-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 08/06/2022] [Accepted: 09/05/2022] [Indexed: 02/07/2023]
Abstract
Chronic kidney disease (CKD) is one of the strongest risk factors for hypertension, and hypertension can exacerbate the progression of CKD. Thus, the management of CKD and antihypertensive therapy are inextricably linked. Research over the past decades has shown that the human kidney is more diverse than initially thought. Subjects with low nephron endowment are at increased risk of developing CKD and hypertension, which is consistent with the theory of the developmental origins of health and disease. Combined with other lifetime risks of CKD, hypertension may lead to a vicious cycle consisting of podocyte injury, glomerulosclerosis and further loss of nephrons. Of note, recent studies have shown that the number of nephrons correlates well with the number of podocytes, suggesting that these two components are intrinsically linked and may influence each other. Both nephrons and podocytes have no or very limited regenerative capacity and are destined to decrease throughout life. Therefore, one of the best strategies to slow the progression of CKD is to maintain the "numbers" of these essential components necessary to preserve renal function. To this end, both the achievement of an optimal blood pressure and a maximum reduction in urinary protein excretion are essential. Lifestyle modifications and antihypertensive drug therapy must be carefully individualized to address the potential diversity of the kidneys.
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Affiliation(s)
- Kotaro Haruhara
- grid.411898.d0000 0001 0661 2073Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Go Kanzaki
- grid.411898.d0000 0001 0661 2073Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Nobuo Tsuboi
- grid.411898.d0000 0001 0661 2073Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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Quiroga B, Torra R. Dietary Aspects and Drug-Related Side Effects in Autosomal Dominant Polycystic Kidney Disease Progression. Nutrients 2022; 14:4651. [PMID: 36364911 PMCID: PMC9658114 DOI: 10.3390/nu14214651] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 11/02/2022] [Accepted: 11/02/2022] [Indexed: 08/30/2023] Open
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease. In the absence of targeted therapies, it invariably progresses to advanced chronic kidney disease. To date, the only approved treatment is tolvaptan, a vasopressin V2 receptor antagonist that has been demonstrated to reduce cyst growth and attenuate the decline in kidney function. However, it has various side effects, the most frequent of which is aquaresis, leading to a significant discontinuation rate. The strategies proposed to combat aquaresis include the use of thiazides or metformin and a reduction in the dietary osmotic load. Beyond the prescription of tolvaptan, which is limited to those with a rapid and progressive decline in kidney function, dietary interventions have been suggested to protect against disease progression. Moderate sodium restriction, moderate protein intake (up to 0.8 g/kg/day), avoidance of being overweight, and increased water consumption are recommended in ADPKD guidelines, though all with low-grade evidence. The aim of the present review is to critically summarize the evidence on the effect of dietary modification on ADPKD and to offer some strategies to mitigate the adverse aquaretic effects of tolvaptan.
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Affiliation(s)
- Borja Quiroga
- Nephrology Department, Hospital Universitario de la Princesa, 28006 Madrid, Spain
| | - Roser Torra
- Inherited Kidney Disorders, Department of Nephrology, Fundació Puigvert, Institut d’Investigació Biomèdica Sant Pau (IIB-SANT PAU), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
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Wesson DE, Mathur V, Tangri N, Hamlett S, Bushinsky DA, Boulware LE. Primary Medical Care Integrated with Healthy Eating and Healthy Moving is Essential to Reduce Chronic Kidney Disease Progression. Am J Med 2022; 135:1051-1058. [PMID: 35576995 DOI: 10.1016/j.amjmed.2022.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/13/2022] [Accepted: 04/14/2022] [Indexed: 11/27/2022]
Abstract
Increasing adverse outcomes in patients with chronic kidney disease reflect growth of patients with early-stage chronic kidney disease and their increasing per population rates of these outcomes. Progression of chronic kidney disease, more than current level of kidney function, is the primary driver of adverse chronic kidney disease-related outcomes. Racial/ethnic minorities progress faster to end-stage kidney disease with greater risk for adverse outcomes. Diabetes and hypertension cause two-thirds of end-stage kidney disease, for which primary medical care integrated with healthy eating and increased physical activity (healthy moving) slows chronic kidney disease progression. Patients with early-stage chronic kidney disease are appropriately managed by primary care practices but most lack infrastructure to facilitate this integration that reduces adverse chronic kidney disease-related outcomes. Individuals of low socioeconomic status are at greater chronic kidney disease risk, and flexible regulatory options in Medicaid can fund infrastructure to facilitate healthy eating and healthy moving integration with primary medical care. This integration promises to reduce chronic kidney disease-related adverse outcomes, disproportionately in racial/ethnic minorities, and thereby reduce chronic kidney disease-related health disparities.
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Affiliation(s)
- Donald E Wesson
- Dell Medical School - The University of Texas at Austin; Donald E Wesson Consulting, LLC, Dallas, Texas.
| | | | - Navdeep Tangri
- Department of Internal Medicine, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada
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de Sá JR, Rangel EB, Canani LH, Bauer AC, Escott GM, Zelmanovitz T, Bertoluci MC, Silveiro SP. The 2021-2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD. Diabetol Metab Syndr 2022; 14:81. [PMID: 35690830 PMCID: PMC9188192 DOI: 10.1186/s13098-022-00843-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 05/03/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021-2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. METHODS The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. RESULTS The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75-89% of agreement; IIb 50-74% of agreement, and III, when most of the panelist recommends against a defined treatment. CONCLUSIONS To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin-angiotensin-aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients' survival.
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Affiliation(s)
- João Roberto de Sá
- Endocrinology Division, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil
| | - Erika Bevilaqua Rangel
- Nephrology Division, UNIFESP, São Paulo, Brazil
- Instituto Israelita de Ensino e Pesquisa Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Luis Henrique Canani
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil
| | - Andrea Carla Bauer
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil
| | - Gustavo Monteiro Escott
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil
| | - Themis Zelmanovitz
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil
| | - Marcello Casaccia Bertoluci
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil
| | - Sandra Pinho Silveiro
- Internal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
- Endocrinology Division, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350-Prédio 12, 4º andar, Porto Alegre, RS, Brazil.
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Martin KE, Thomas BS, Greenberg KI. The expanding role of primary care providers in care of individuals with kidney disease. J Natl Med Assoc 2022; 114:S10-S19. [DOI: 10.1016/j.jnma.2022.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Zhuo M, Kim SC, Patorno E, Paik JM. Risk of hospitalization for heart failure in patients with hyperkalemia treated with sodium zirconium cyclosilicate versus patiromer. J Card Fail 2022; 28:1414-1423. [PMID: 35470055 DOI: 10.1016/j.cardfail.2022.04.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 03/31/2022] [Accepted: 04/04/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Sodium zirconium cyclosilicate (SZC) and patiromer were recently approved to treat hyperkalemia. Whether the initiation of SZC is associated with an increased risk of hospitalization for heart failure (HHF) compared to patiromer in routine practice remains unknown. METHODS AND RESULTS We conducted a new-user cohort study of non-dialysis adults who initiated SZC or patiromer using Optum's de-identified Clinformatics® Data Mart Database from May 2018 to September 2020. We performed propensity score (PS) matching in a variable ratio to match each SZC initiator with up to three patiromer initiators. The primary outcome was HHF. Cox proportional hazards regression models generated hazard ratios (HRs) with 95% confidence intervals (CIs) in the PS-matched groups. The cohort included 1,126 SZC initiators and 2,839 PS-matched patiromer initiators. The mean age was 72 years old, about 30% had a history of heart failure, and 85% had chronic kidney disease stages 3-5. The SZC group had 88 cases of HHF (incidence rate [IR] 35.8 per 100 person-years [PY]), and the patiromer group had 245 cases of HHF (IR 25.1 per 100 PY). The rate of HHF was numerically higher in the SZC initiators than patiromer initiators (HR 1.22, 95%CI 0.95, 1.56), but did not reach statistical significance. Results were consistent across sensitivity and subgroup analyses. CONCLUSIONS Initiation of SZC might be associated with an increased risk of hospitalization for heart failure compared to patiromer in routine practice. Larger comparative studies are needed to evaluate the safety of SZC in routine practice more precisely.
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Affiliation(s)
- Min Zhuo
- Division of Pharmacoepidemiology and Pharmacoeconomics; Division of Kidney (Renal) Medicine; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - Seoyoung C Kim
- Division of Pharmacoepidemiology and Pharmacoeconomics; Division of Rheumatology, Inflammation, and Immunity; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Elisabetta Patorno
- Division of Pharmacoepidemiology and Pharmacoeconomics; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Julie M Paik
- Division of Pharmacoepidemiology and Pharmacoeconomics; Division of Kidney (Renal) Medicine; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; New England Geriatric Research, Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts.
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35
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Cardiorenal protective effects of sodium-glucose cotransporter 2 inhibition in combination with angiotensin II type 1 receptor blockade in salt-sensitive Dahl rats. J Hypertens 2022; 40:956-968. [DOI: 10.1097/hjh.0000000000003099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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36
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Hunter RW, Dhaun N, Bailey MA. The impact of excessive salt intake on human health. Nat Rev Nephrol 2022; 18:321-335. [DOI: 10.1038/s41581-021-00533-0] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/10/2021] [Indexed: 12/19/2022]
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Abstract
OBJECTIVE The benefits of a low-salt diet for patients with chronic kidney disease (CKD) are controversial. We conducted a systematic review and meta-analysis of the effect of a low-salt diet on major clinical outcomes. DESIGN Systematic review and meta-analysis. DATA SOURCES MEDLINE by Ovid, EMBASE and the Cochrane Library databases. ELIGIBILITY CRITERIA FOR SELECTING STUDIES We included randomised controlled trials (RCTs) and cohort studies that assessed the effect of a low-salt diet on the renal composite outcomes (more than 50% decline in estimated glomerular filtration rate (eGFR) during follow-up, doubling of serum creatinine or end-stage renal disease), rate of eGFR decline, change in proteinuria, all-cause mortality events, cardiovascular (CV) events, and changes in systolic blood pressure and diastolic blood pressure. DATA EXTRACTION AND SYNTHESIS Two independent researchers extracted data and evaluated their quality. Relative risks (RRs) with 95% CIs were used for dichotomous data. Differences in means (MDs) or standardised mean differences (SMDs) with 95% CIs were used to pool continuous data. We used the Cochrane Collaboration risk-of-bias tool to evaluate the quality of RCTs, and Newcastle-Ottawa Scale to evaluate the quality of cohort studies. RESULTS We found 9948 potential research records. After removing duplicates, we reviewed the titles and abstracts, and screened the full text of 230 publications. Thirty-three studies with 101 077 participants were included. A low-salt diet produced a 28% reduction in renal composite outcome events (RR: 0.72; 95% CI: 0.58 to 0.89). No significant effects were found in terms of changes in proteinuria (SMD: -0.71; 95% CI: -1.66 to 0.24), rate of eGFR (decline MD: 1.16; 95% CI: -2.02 to 4.33), risk of all-cause mortality (RR: 0.92; 95% CI: 0.58 to 1.46) and CV events (RR: 1.01; 95% CI: 0.46 to 2.22). CONCLUSION A low-salt diet seems to reduce the risk for renal composite outcome events in patients with CKD. However, no compelling evidence indicated that such a diet would reduce the eGFR decline rate, proteinuria, incidence of all-cause mortality and CV events. Further, more definitive studies are needed. PROSPERO REGISTRATION NUMBER CRD42017072395.
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Affiliation(s)
- Honghong Shi
- Renal Division, Shanxi Medical University Second Affiliated Hospital, Taiyuan, Shanxi, China
| | - Xiaole Su
- Renal Division, Shanxi Medical University Second Affiliated Hospital, Taiyuan, Shanxi, China
| | - Chunfang Li
- Renal Divison, Shanxi Cardiovascular Hospital, Taiyuan, Shanxi, China
| | - Wenjuan Guo
- Renal Division, Shanxi Medical University Second Affiliated Hospital, Taiyuan, Shanxi, China
| | - Lihua Wang
- Renal Division, Shanxi Medical University Second Affiliated Hospital, Taiyuan, Shanxi, China
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Banerjee D, Winocour P, Chowdhury TA, De P, Wahba M, Montero R, Fogarty D, Frankel AH, Karalliedde J, Mark PB, Patel DC, Pokrajac A, Sharif A, Zac-Varghese S, Bain S, Dasgupta I. Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021. BMC Nephrol 2022; 23:9. [PMID: 34979961 PMCID: PMC8722287 DOI: 10.1186/s12882-021-02587-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 10/28/2021] [Indexed: 12/31/2022] Open
Abstract
People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes.
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Affiliation(s)
- D Banerjee
- St George's Hospitals NHS Foundation Trust, London, UK
| | - P Winocour
- ENHIDE, East and North Herts NHS Trust, Stevenage, UK
| | | | - P De
- City Hospital, Birmingham, UK
| | - M Wahba
- St Helier Hospital, Carshalton, UK
| | | | - D Fogarty
- Belfast Health and Social Care Trust, Belfast, UK
| | - A H Frankel
- Imperial College Healthcare NHS Trust, London, UK
| | | | - P B Mark
- University of Glasgow, Glasgow, UK
| | - D C Patel
- Royal Free London NHS Foundation Trust, London, UK
| | - A Pokrajac
- West Hertfordshire Hospitals, London, UK
| | - A Sharif
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - S Bain
- Swansea University, Swansea, UK
| | - I Dasgupta
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
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Chang TI, Lerma EV. Optimizing Renin-Angiotensin System Inhibitor Use in CKD. Clin J Am Soc Nephrol 2022; 17:131-133. [PMID: 34789477 PMCID: PMC8763146 DOI: 10.2215/cjn.12950921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- Tara I. Chang
- Stanford University School of Medicine, Palo Alto, California
| | - Edgar V. Lerma
- University of Illinois at Chicago/ Advocate Christ Medical Center Oak Lawn, Berwyn, Illinois
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Damianaki A, Polychronopoulou E, Wuerzner G, Burnier M. New Aspects in the Management of Hypertension in Patients with Chronic Kidney Disease not on Renal Replacement Therapy. High Blood Press Cardiovasc Prev 2021; 29:125-135. [PMID: 34910287 PMCID: PMC8942929 DOI: 10.1007/s40292-021-00495-1] [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: 11/03/2021] [Accepted: 11/30/2021] [Indexed: 11/07/2022] Open
Abstract
With chronic kidney disease (CKD) being a global arising health problem, strategies for delaying kidney disease progression and reducing the high cardiovascular risk inherent to CKD, are the main objectives of the actual management of patients with kidney diseases. In these patients, the control of arterial hypertension is essential, as high blood pressure (BP) is a strong determinant of worst cardiovascular and renal outcomes. Achieving target blood pressures recommended by international guidelines is mandatory and often demands a multiple levels management, including several pharmacological and lifestyle measures. Even in the presence of adequate BP control, the residual cardiovascular risk remains high. In this respect, the recent demonstration that novel agents such as sodium glucose transporter 2 (SGLT2) inhibitors or the new non-steroidal mineralocorticoid antagonist finerenone can retard the progression of kidney diseases and reduce cardiovascular mortality on top of standard of care treatment with renin-angiotensin system inhibitors represent enormous progresses. These studies also demonstrate that cardiovascular and renal protection can be obtained beyond blood pressure control. Other promising novelties are still to come such as renal denervation and endothelin receptor antagonists in the setting of diabetic and non-diabetic kidney diseases. In the present review, we shall discuss the classic and the new aspects for the management of hypertension in CKD, integrating the new data from recent clinical studies.
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Affiliation(s)
- Aikaterini Damianaki
- Service of Nephrology and Hypertension, University Hospital, Rue du Bugnon 17, 1011, Lausanne, Switzerland
| | - Erietta Polychronopoulou
- Service of Nephrology and Hypertension, University Hospital, Rue du Bugnon 17, 1011, Lausanne, Switzerland
| | - Gregoire Wuerzner
- Service of Nephrology and Hypertension, University Hospital, Rue du Bugnon 17, 1011, Lausanne, Switzerland.,Hypertension Research Foundation, Saint-Légier, Switzerland
| | - Michel Burnier
- Service of Nephrology and Hypertension, University Hospital, Rue du Bugnon 17, 1011, Lausanne, Switzerland. .,Hypertension Research Foundation, Saint-Légier, Switzerland.
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Collister D, Ferguson TW, Funk SE, Reaven NL, Mathur V, Tangri N. Metabolic Acidosis and Cardiovascular Disease in CKD. Kidney Med 2021; 3:753-761.e1. [PMID: 34746740 PMCID: PMC8551483 DOI: 10.1016/j.xkme.2021.04.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Rationale & Objective Metabolic acidosis related to chronic kidney disease (CKD) is associated with an accelerated decline in glomerular filtration rate (GFR) and the development of end-stage kidney disease. Whether metabolic acidosis is associated with cardiovascular (CV) events in patients with CKD is unclear. Study Design Retrospective cohort study. Setting & Participants The Optum De-identified Electronic Health Records Dataset, 2007–2017, was used to generate a cohort of patients with non-dialysis-dependent CKD who had at least 3 estimated GFR < 60 mL/min/1.73 m2. Patients with metabolic acidosis (serum bicarbonate 12 to <22 mEq/L) or normal serum bicarbonate (22‒29 mEq/L) at baseline were identified by 2 consecutive measurements 28‒365 days apart. Predictor Serum bicarbonate as a continuous variable. Outcome Primary outcome was a composite of major adverse cardiovascular events (MACE+). Secondary outcomes included individual components of the composite outcome. Analytical Approach Cox proportional hazards models to evaluate the association between 1-mEq/L increments in serum bicarbonate and MACE+. Results A total of 51,558 patients were evaluated, 34% had metabolic acidosis. The median follow-up period was 3.9–4.5 years, depending on the outcome assessed. The adjusted hazard ratio (HR) for MACE+ was 0.964 (95% CI, 0.961–0.968). For the individual components of incident heart failure (HF), stroke, myocardial infarction (MI), and CV death, HRs were 0.98 (95% CI, 0.97–0.98), 0.98 (95% CI, 0.97–0.99), 0.96 (95% CI, 0.96–0.97), and 0.94 (95% CI, 0.93–0.94), respectively, for every 1-mEq/L increase in serum bicarbonate. Limitations Possible residual confounding. Conclusions Metabolic acidosis in CKD is associated with an increased risk of MACE+ as well as the individual components of incident HF, stroke, MI, and CV death. Randomized controlled trials evaluating treatments for the correction of metabolic acidosis in CKD to prevent CV events are needed.
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Affiliation(s)
- David Collister
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Thomas W Ferguson
- Department of Internal Medicine, Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | | | | | | | - Navdeep Tangri
- Department of Internal Medicine, Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
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Tomson CRV, Cheung AK, Mann JFE, Chang TI, Cushman WC, Furth SL, Hou FF, Knoll GA, Muntner P, Pecoits-Filho R, Tobe SW, Lytvyn L, Craig JC, Tunnicliffe DJ, Howell M, Tonelli M, Cheung M, Earley A, Ix JH, Sarnak MJ. Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice Guideline. Ann Intern Med 2021; 174:1270-1281. [PMID: 34152826 DOI: 10.7326/m21-0834] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
DESCRIPTION The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 clinical practice guideline for the management of blood pressure (BP) in patients with chronic kidney disease (CKD) not receiving dialysis is an update of the KDIGO 2012 guideline on the same topic and reflects new evidence on the risks and benefits of BP-lowering therapy among patients with CKD. It is intended to support shared decision making by health care professionals working with patients with CKD worldwide. This article is a synopsis of the full guideline. METHODS The KDIGO leadership commissioned 2 co-chairs to convene an international Work Group of researchers and clinicians. After a Controversies Conference in September 2017, the Work Group defined the scope of the evidence review, which was undertaken by an evidence review team between October 2017 and April 2020. Evidence reviews were done according to the Cochrane Handbook. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to guide the development of the recommendations and rate the strength and quality of the evidence. Practice points were included to provide guidance when evidence was insufficient to make a graded recommendation. The guideline was revised after public consultation between January and March 2020. RECOMMENDATIONS The updated guideline comprises 11 recommendations and 20 practice points. This synopsis summarizes key recommendations pertinent to the diagnosis and management of high BP in adults with CKD, excluding those receiving kidney replacement therapy. In particular, the synopsis focuses on recommendations for standardized BP measurement and a target systolic BP of less than 120 mm Hg, because these recommendations differ from some other guidelines.
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Affiliation(s)
- Charles R V Tomson
- Freeman Hospital, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom (C.R.T.)
| | | | - Johannes F E Mann
- KfH Kidney Center, University Hospital, Friedrich-Alexander University, Erlangen-Nuremberg, Germany (J.F.M.)
| | - Tara I Chang
- Stanford University, Palo Alto, California (T.I.C.)
| | - William C Cushman
- University of Tennessee Health Science Center, Memphis, Tennessee (W.C.C.)
| | - Susan L Furth
- Perelman School of Medicine at the University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (S.L.F.)
| | - Fan Fan Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, China (F.F.H.)
| | - Gregory A Knoll
- The Ottawa Hospital, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada (G.A.K.)
| | - Paul Muntner
- University of Alabama at Birmingham, Birmingham, Alabama (P.M.)
| | - Roberto Pecoits-Filho
- Arbor Research Collaborative for Health, Ann Arbor, Michigan, and Pontifical Catholic University of Paraná, Curitiba, Brazil (R.P.)
| | - Sheldon W Tobe
- University of Toronto, Toronto, and Northern Ontario School of Medicine, Sudbury, Ontario, Canada (S.W.T.)
| | - Lyubov Lytvyn
- MAGIC Evidence Ecosystem Foundation, McMaster University, Hamilton, Ontario, Canada (L.L.)
| | - Jonathan C Craig
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, and Cochrane Kidney and Transplant, Sydney, New South Wales, Australia (J.C.C.)
| | - David J Tunnicliffe
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia (D.J.T., M.H.)
| | - Martin Howell
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia (D.J.T., M.H.)
| | | | | | | | - Joachim H Ix
- University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego, California (J.H.I.)
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Emerging non-pharmacological interventions in ADPKD: an update on dietary advices for clinical practice. Curr Opin Nephrol Hypertens 2021; 30:482-492. [PMID: 34261861 DOI: 10.1097/mnh.0000000000000734] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) reach kidney failure at a median age of 58 years. There has been a strong interest in medical interventions to improve prognosis. With increasing understanding of the underlying pathophysiology, there is also a rationale for non-pharmaceutical interventions. However, these have received little attention. This review, therefore, focuses on dietary interventions in ADPKD. RECENT FINDINGS Recent studies regarding salt, protein and water intake, caloric restriction, BMI, caffeine and alcohol are discussed in this review. In general, these studies suggest that advices do not need to be different from those in chronic kidney disease (CKD). On the basis of research in the general population and CKD, these advices will likely decrease cardiovascular morbidity and mortality. With respect to delaying ADPKD progression, evidence for salt restriction is growing. For increasing water intake and targeting glucose metabolism by intermittent fasting, preclinical studies are promising. Long-term randomized human intervention studies are, however, lacking. SUMMARY In ADPKD, advices regarding dietary interventions can, in general, be the same as in CKD to decrease cardiovascular morbidity and mortality. Whether these interventions also delay disease progression needs further study.
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Trujillo H, Caravaca-Fontán F, Caro J, Morales E, Praga M. The Forgotten Antiproteinuric Properties of Diuretics. Am J Nephrol 2021; 52:435-449. [PMID: 34233330 DOI: 10.1159/000517020] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 04/30/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration. SUMMARY Thiazide diuretics have been shown to reduce proteinuria by >35% in several prospective controlled studies, and these values are markedly increased when combined with a low-salt diet. Thiazide-like diuretics (indapamide and chlorthalidone) have shown similar effectiveness. The antiproteinuric effect of mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) has been clearly established through prospective and controlled studies, and treatment with finerenone reduces the risk of chronic kidney disease progression in type-2 diabetic patients. The efficacy of other diuretics such as amiloride, triamterene, acetazolamide, or loop diuretics has been less explored, but different investigations suggest that they might share the same antiproteinuric properties of other diuretics that should be evaluated through controlled studies. Although the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among diuretics is a controversial issue, their renoprotective and cardioprotective properties, confirmed in various landmark trials, constitute a true revolution in the treatment of patients with kidney disease. Recent subanalyses of these trials have shown that the early antiproteinuric effect induced by SGLT2i predicts long-term preservation of kidney function. Key Message: Whether the early reduction in proteinuria induced by diuretics other than finerenone and SGLT2i, as summarized in this review, also translates into long-term renoprotection requires further prospective and observational studies. In any case, it is important for the clinician to be aware of the antiproteinuric properties of drugs so often used in daily clinical practice.
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Affiliation(s)
- Hernando Trujillo
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain,
| | | | - Jara Caro
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
- Instituto de Investigación Hospital Universitario 12 de Octubre (imas12), Madrid, Spain
| | - Enrique Morales
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
- Instituto de Investigación Hospital Universitario 12 de Octubre (imas12), Madrid, Spain
- Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Manuel Praga
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
- Instituto de Investigación Hospital Universitario 12 de Octubre (imas12), Madrid, Spain
- Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain
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Betz M, Steenes A, Peterson L, Saunders M. Knowledge Does Not Correspond to Adherence of Renal Diet Restrictions in Patients With Chronic Kidney Disease Stage 3-5. J Ren Nutr 2021; 31:351-360. [DOI: 10.1053/j.jrn.2020.08.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 08/03/2020] [Accepted: 08/13/2020] [Indexed: 02/06/2023] Open
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Kang M, Kang E, Ryu H, Hong Y, Han SS, Park SK, Hyun YY, Sung SA, Kim SW, Yoo TH, Kim J, Ahn C, Oh KH. Measured sodium excretion is associated with CKD progression: results from the KNOW-CKD study. Nephrol Dial Transplant 2021; 36:512-519. [PMID: 32582942 DOI: 10.1093/ndt/gfaa107] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 04/07/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Diet is a modifiable factor of chronic kidney disease (CKD) progression. However, the effect of dietary salt intake on CKD progression remains unclear. Therefore, we analyzed the effect of dietary salt intake on renal outcome in Korean patients with CKD. METHODS We measured 24-h urinary sodium (Na) excretion as a marker of dietary salt intake in the prospective, multi-center, longitudinal KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD). Data were analyzed from CKD patients at Stages G3a to G5 (n = 1254). We investigated the association between dietary salt intake and CKD progression. Patients were divided into four quartiles of dietary salt intake, which was assessed using measured 24-h urinary Na excretion. The study endpoint was composite renal outcome, which was defined as either halving the estimated glomerular filtration rate or developing end-stage renal disease. RESULTS During a median (interquartile range) follow-up of 4.3 (2.8-5.8) years, 480 (38.7%) patients developed the composite renal event. Compared with the reference group (Q2, urinary Na excretion: 104.2 ≤ Na excretion < 145.1 mEq/day), the highest quartile of measured 24-h urinary Na excretion was associated with risk of composite renal outcome [Q4, urinary Na excretion ≥192.9 mEq/day, hazard ratio 1.8 (95% confidence interval 1.12-2.88); P = 0.015] in a multivariable hazards model. Subgroup analyses showed that high-salt intake was particularly associated with a higher risk of composite renal outcome in women, in patients <60 years of age, in those with uncontrolled hypertension and in those with obesity. CONCLUSIONS High salt intake was associated with increased risk of progression in CKD.
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Affiliation(s)
- Minjung Kang
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Eunjeong Kang
- Department of Internal Medicine, Ewha Womans University College of Medicine, Ewha Womans University Seoul Hospital, Seoul, Republic of Korea
| | - Hyunjin Ryu
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yeji Hong
- Rehabilitation Medical Research Center, Korea workers' Compensation and Welfare Service Incheon Hospital, Republic of Korea
| | - Seung Seok Han
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Sue K Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Young Youl Hyun
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Republic of Korea
| | - Su Ah Sung
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University, Seoul, Republic of Korea
| | - Soo Wan Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Tae-Hyun Yoo
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea
| | - Jayoun Kim
- Medical Research Collaborating Center, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
| | - Curie Ahn
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Kook-Hwan Oh
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
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Veiras LC, Shen JZY, Bernstein EA, Regis GC, Cao D, Okwan-Duodu D, Khan Z, Gibb DR, Dominici FP, Bernstein KE, Giani JF. Renal Inflammation Induces Salt Sensitivity in Male db/db Mice through Dysregulation of ENaC. J Am Soc Nephrol 2021; 32:1131-1149. [PMID: 33731332 PMCID: PMC8259671 DOI: 10.1681/asn.2020081112] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Accepted: 01/21/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Hypertension is considered a major risk factor for the progression of diabetic kidney disease. Type 2 diabetes is associated with increased renal sodium reabsorption and salt-sensitive hypertension. Clinical studies show that men have higher risk than premenopausal women for the development of diabetic kidney disease. However, the renal mechanisms that predispose to salt sensitivity during diabetes and whether sexual dimorphism is associated with these mechanisms remains unknown. METHODS Female and male db/db mice exposed to a high-salt diet were used to analyze the progression of diabetic kidney disease and the development of hypertension. RESULTS Male, 34-week-old, db/db mice display hypertension when exposed to a 4-week high-salt treatment, whereas equivalently treated female db/db mice remain normotensive. Salt-sensitive hypertension in male mice was associated with no suppression of the epithelial sodium channel (ENaC) in response to a high-salt diet, despite downregulation of several components of the intrarenal renin-angiotensin system. Male db/db mice show higher levels of proinflammatory cytokines and more immune-cell infiltration in the kidney than do female db/db mice. Blocking inflammation, with either mycophenolate mofetil or by reducing IL-6 levels with a neutralizing anti-IL-6 antibody, prevented the development of salt sensitivity in male db/db mice. CONCLUSIONS The inflammatory response observed in male, but not in female, db/db mice induces salt-sensitive hypertension by impairing ENaC downregulation in response to high salt. These data provide a mechanistic explanation for the sexual dimorphism associated with the development of diabetic kidney disease and salt sensitivity.
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Affiliation(s)
- Luciana C. Veiras
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California
| | - Justin Z. Y. Shen
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California
| | - Ellen A. Bernstein
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California
| | - Giovanna C. Regis
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California
| | - DuoYao Cao
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California
| | - Derick Okwan-Duodu
- Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Zakir Khan
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California
| | - David R. Gibb
- Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Fernando P. Dominici
- Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
| | - Kenneth E. Bernstein
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California,Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Jorge F. Giani
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California,Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
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Liu W, Li L, Zhang X, Dong H, Lu M. Efficacy and Safety of Veverimer in the Treatment of Metabolic Acidosis Caused by Chronic Kidney Disease: A Meta-analysis. Front Pharmacol 2021; 12:643128. [PMID: 33995050 PMCID: PMC8117340 DOI: 10.3389/fphar.2021.643128] [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: 12/17/2020] [Accepted: 04/15/2021] [Indexed: 11/13/2022] Open
Abstract
Metabolic acidosis is a common complication of chronic kidney disease (CKD). Veverimer is an orally administrated, free amine polymer with high capacity and binding selectivity to hydrochloric acid from the gastrointestinal tract. This study pooled the current evidence of the efficacy and safety of veverimer for the treatment of metabolic acidosis associated with CKD. We conducted a systematic literature search on PubMed, Embase, and Cochrane Central for relevant randomized controlled trials (RCTs) in June 2020. In this study, three RCTs with 548 patients were included in our analysis. The analysis revealed that veverimer was associated with increased bicarbonate level of patients (weight mean difference [WMD] 3.08, 95% confidence interval [CI] [2.40, 3.77], p < 0.001) and improved physical function compared with placebo measured by Kidney Disease and Quality of Life Short Form 36, question 3 (physical functioning domain) (KDQoL-PFD) score (WMD 5.25, 95% CI [1.58, 8.92], p = 0.005). For safety outcomes, both groups exhibited similar risks for developing headache, diarrhea, flatulence, and hyperkalemia. In conclusion, current clinical evidence indicates that veverimer is efficacious and safe against metabolic acidosis related to CKD compared with placebo. Further research comparing long-term veverimer use with traditional alkali therapy is needed.
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Affiliation(s)
- Wenlin Liu
- Department of Nephrology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Lili Li
- Department of Nephrology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Xuemei Zhang
- Department of Nephrology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Haonan Dong
- Department of Nephrology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Miaomiao Lu
- Department of Nephrology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
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Proteinuria changes in kidney disease patients with clinical remission during the COVID-19 pandemic. PLoS One 2021; 16:e0250581. [PMID: 33891663 PMCID: PMC8064597 DOI: 10.1371/journal.pone.0250581] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 04/08/2021] [Indexed: 01/06/2023] Open
Abstract
Backgrounds Data on how lifestyle changes due to the coronavirus disease 2019 (COVID-19) pandemic have influenced the clinical features of kidney disease patients remain scarce. Methods This study retrospectively analyzed clinical variables in patients with stage G1–G4 chronic kidney disease (CKD) with complete or incomplete remission of proteinuria, who were managed in a nephrology outpatient clinic of a university hospital in Tokyo. The clinical variables during the COVID-19 pandemic (term 1, June–July 2020) were compared to those one year before the pandemic (term 0, June–July 2019). The urinary protein excretion (UPE) was used as the primary outcome measure. Results This study included 325 patients with stage G1–G4 CKD (mean age 58.5 years old, 37.5% female, 80.6% on renin-angiotensin aldosterone system inhibitors [RAASis], 12.0% on maintenance dose immunosuppression therapy) evaluated at term 0. The UPE at terms 0 and 1 was 247 (92–624) and 203 (84–508) mg/day [median (25th–75th percentile)], respectively; the value in term 1 was 18% lower than that in term 0 (p<0.001), with no marked difference in body weight, blood pressure, protein intake or urinary salt excretion. In multivariable analyses, incomplete remission of proteinuria in term 0 (odds ratio [OR] = 2.70, p = <0.001), RAASi use (OR = 2.09, p = 0.02) and decreased urinary salt excretion in term 1 vs. term 0 (OR = 1.94, p = 0.002) were identified as independent variables associated with reduced UPE in term 1 vs. term 0. No significant interactions between the variables were observed. Conclusion In kidney disease patients receiving standard medical care from nephrologists, the UPE after the emergency declaration in relation to the COVID-19 pandemic was lower than before the declaration. The UPE reduction may be associated with reduced dietary salt intake during the pandemic in patients treated with RAASi for insufficient control of proteinuria. Our results support the current proposal to continue therapeutic approaches to these patients, which involve RAASi therapy along with optimizing dietary habits, even while dealing with the COVID-19 pandemic.
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Cheung AK, Chang TI, Cushman WC, Furth SL, Hou FF, Ix JH, Knoll GA, Muntner P, Pecoits-Filho R, Sarnak MJ, Tobe SW, Tomson CR, Mann JF. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int 2021; 99:S1-S87. [PMID: 33637192 DOI: 10.1016/j.kint.2020.11.003] [Citation(s) in RCA: 516] [Impact Index Per Article: 129.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 11/02/2020] [Indexed: 12/19/2022]
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