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Jeon J, Shin DW, Park SH, Jung JH, Lee K, Lee JE, Huh W, Han K, Jang HR. Kidney and Cardiovascular Outcomes in Older Population with Mildly to Moderately Decreased Kidney Function: A Nationwide Cohort Study. Am J Nephrol 2024:1-13. [PMID: 39462486 DOI: 10.1159/000541832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 07/24/2024] [Accepted: 10/02/2024] [Indexed: 10/29/2024]
Abstract
INTRODUCTION Although the prevalence of chronic kidney disease (CKD) is increasing in the aging population, the clinical relevance of the CKD definition (glomerular filtration rate [GFR] <60 mL/min/1.73 m2) in older populations remains debatable. We investigated the clinical outcomes in older populations with mildly to moderately decreased GFR (45-59 mL/min/1.73 m2, CKD stage 3A). METHODS A total of 7,789,242 participants aged ≥40 years with estimated GFR (eGFR) ≥45 mL/min/1.73 m2 in national health screening examination from 2012 to 2017 were included in this retrospective cohort study using the Korean National Health Insurance Service database. The main outcomes included kidney failure, cardiovascular disease (CVD), and all-cause death. Cox regression hazard models were used to estimate the hazard ratios. RESULTS The proportion of participants with eGFR 45-59 mL/min/1.73 m2 was 10.0% and 16.3% in the old (65-74 years) and very old (75≥ years) groups, respectively. Mildly to moderately decreased eGFR was associated with a higher risk of kidney failure, CVD, and all-cause death compared with eGFR 60-89 mL/min/1.73 m2 in the old and very old groups, regardless of proteinuria (adjusted hazard ratio [95% confidence interval] in the very old group without proteinuria: kidney failure 3.048 [2.495-3.722], CVD 1.103 [1.066-1.142], and all-cause death 1.172 [1.144-1.201]). CONCLUSION Mildly to moderately decreased eGFR was associated with an increased risk of kidney failure, CVD, and all-cause death in the older population, regardless of proteinuria, suggesting the importance of appropriate monitoring and management in this population.
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Affiliation(s)
- Junseok Jeon
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea,
| | - Dong Wook Shin
- Department of Family Medicine/Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Park
- Department of Family Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jin-Hyung Jung
- Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
| | - Kyungho Lee
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jung Eun Lee
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Wooseong Huh
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Hye Ryoun Jang
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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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] [Academic Contribution 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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Luo X, Xu J, Zhou S, Xue C, Chen Z, Mao Z. Influence of SGLT2i and RAASi and Their Combination on Risk of Hyperkalemia in DKD: A Network Meta-Analysis. Clin J Am Soc Nephrol 2023; 18:1019-1030. [PMID: 37256921 PMCID: PMC10564376 DOI: 10.2215/cjn.0000000000000205] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 12/22/2022] [Accepted: 05/24/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND This network meta-analysis investigated the effect of various combined regimens of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and renin-angiotensin-aldosterone system inhibitors (RAASis) on the occurrence of hyperkalemia in diabetic kidney disease. METHODS The risk of hyperkalemia was compared using the random-effects model of network meta-analysis, with results expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The comparative effects of all medications and their combinations with placebo were ranked using the surface under the cumulative ranking probabilities. RESULTS In total, 27 eligible studies involving 43,589 participants with diabetic kidney disease were included. Major findings showed that the use of mineralocorticoid receptor antagonists (MRAs) on top of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) prominently increased hyperkalemia incidence when compared with placebo (OR, 6.08; 95% CI, 2.30 to 16.08), ACEI (OR, 3.07; 95% CI, 1.14 to 8.31), ARB (OR, 2.57; 95% CI, 1.10 to 6.02), SGLT2i (OR, 9.22; 95% CI, 2.99 to 28.46), renin inhibitors+ACEI/ARB (OR, 2.23; 95% CI, 1.14 to 4.36), or SGLT2i+ACEI/ARB (OR, 4.10; 95% CI, 2.32 to 7.26). Subgroup analysis among different generations of MRA found that spironolactone had the strongest effect in combination with ACEI/ARB, even higher than the combined use of ACEI and ARB (OR, 2.89; 95% CI, 1.26 to 6.63). In addition, SGLT2i had a significantly lower incidence of hyperkalemia compared with ACEI (OR, 0.33; 95% CI, 0.12 to 0.91), ARB (OR, 0.28; 95% CI, 0.13 to 0.61), dual RAASi (ACEI combined with ARB; OR, 0.17; 95% CI, 0.06 to 0.47), or MRA or renin inhibitors combined with ACEI/ARB (OR, 0.11; 95% CI, 0.04 to 0.33; OR, 0.24; 95% CI, 0.08 to 0.76, respectively). Moreover, adding SGLT2i to the combination of MRA and ACEI/ARB, as well as the combinations of different RAASis, markedly reduced the occurrence of hyperkalemia. CONCLUSIONS Among the therapeutic drugs with the potential risk of increasing serum potassium in patients with diabetic kidney disease, MRA added an extra risk of hyperkalemia while SGLT2i had the opposite effect and could even reverse the elevation of serum potassium caused by the combined regimen, including MRAs.
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Affiliation(s)
- Xiaoling Luo
- Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jing Xu
- Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China
- State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
| | - Shoulian Zhou
- Division of Hemodialysis Center, Naval Hospital of Eastern Theater of PLA, Zhoushan, Zhejiang, China
| | - Cheng Xue
- Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Zewei Chen
- Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Zhiguo Mao
- Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China
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Villain C, Metzger M, Liabeuf S, Hamroun A, Laville S, Mansencal N, Combe C, Fouque D, Frimat L, Jacquelinet C, Laville M, Ayav C, Briançon S, Pecoits-Filho R, Hannedouche T, Stengel B, Massy ZA. Effectiveness and Tolerance of Renin-Angiotensin System Inhibitors With Aging in Chronic Kidney Disease. J Am Med Dir Assoc 2021; 23:998-1004.e7. [PMID: 34856172 DOI: 10.1016/j.jamda.2021.10.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 03/19/2021] [Revised: 10/22/2021] [Accepted: 10/23/2021] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Renin-angiotensin system inhibitors (RASi) are recommended for slowing chronic kidney disease (CKD) progression to kidney failure. Their effectiveness and tolerance as patients age remain uncertain because older patients have often been excluded from clinical trials. DESIGN CKD-REIN cohort study. SETTING AND PARTICIPANTS We studied 2762 patients with CKD stages 3 and 4 and a clinical indication for RASi enrolled between 2013 and 2016 in 40 nephrology clinics nationally representative in France. METHODS The primary outcome was the occurrence of kidney failure or death. The secondary outcomes were the occurrence of cardiovascular events and hospitalizations with acute kidney injury (AKI) or hyperkalemia. A propensity score analysis was performed. We used Cox models to estimate hazard ratios (HRs) for each outcome associated with RASi prescription and tested interactions with age. RESULTS Patients' mean age was 67 years, including 841 (30%) aged 75 years and older; 2178 (79%) were prescribed RASi's. During a median follow-up of 4.6 years, 33% of patients reached kidney failure or died. RASi prescription was associated with a lower risk of kidney failure or death (HR 0.79, 95% CI 0.66, 0.95), an association not modified by age (P for interaction = .72). It was not significantly associated with cardiovascular events. During the first 3 years of follow-up, 14% of patients were hospitalized with AKI or hyperkalemia, but risk was not higher among those prescribed RASi's (HR 0.75, 95% CI 0.55-1.02) and age did not modify its effect (P for interaction = .28). CONCLUSIONS AND IMPLICATIONS This study shows that aging does not appear to modify either RASi's beneficial effects on major CKD outcomes or their potential adverse effects.
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Affiliation(s)
- Cédric Villain
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France; Service de Gériatrie, CHU de Caen, Normandie Université UNICAEN, Caen, France.
| | - Marie Metzger
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France
| | - Sophie Liabeuf
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France; Service de Pharmacologie Clinique, Département de Recherche Clinique, CHU d'Amiens, Université de Picardie Jules Verne, INSERM U-1088, Amiens, France
| | - Aghilès Hamroun
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France
| | - Solene Laville
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France
| | - Nicolas Mansencal
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France; Service de Cardiologie, CHU Ambroise Paré, APHP, Boulogne-Billancourt, Université de Versailles-Saint Quentin (UVSQ), France
| | - Christian Combe
- Service de Néphrologie Transplantation Dialyse Aphérèses, CHU de Bordeaux, Bordeaux, France; INSERM Unité 1026, Université de Bordeaux, Bordeaux, France
| | - Denis Fouque
- Université de Lyon, Service de Néphrologie, CarMeN INSERM 1060, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
| | - Luc Frimat
- Service de Néphrologie, Université de Lorraine, APEMAC, CHRU de Nancy-Hôpitaux de Brabois, Nancy, France
| | - Christian Jacquelinet
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France; Agence de Biomédecine, La Plaine Saint-Denis, France
| | - Maurice Laville
- Université de Lyon, Service de Néphrologie, CarMeN INSERM 1060, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
| | - Carole Ayav
- CIC 1433 Epidémiologie Clinique, INSERM, CHRU, Université de Lorraine, CHRU de Nancy-Hôpitaux de Brabois, Nancy, France
| | - Serge Briançon
- CIC 1433 Epidémiologie Clinique, INSERM, CHRU, Université de Lorraine, CHRU de Nancy-Hôpitaux de Brabois, Nancy, France
| | | | - Thierry Hannedouche
- Service de Néphrologie-Hémodialyse, Hôpitaux Universitaires de Strasbourg, Faculté de Médecine de Strasbourg, Strasbourg, France
| | - Bénédicte Stengel
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France
| | - Ziad A Massy
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France; Service de Néphrologie-Dialyse, CHU Ambroise Paré, APHP, Boulogne-Billancourt, France
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Wadhwa NK, Kline JA, Adapa SR. The Role of Patiromer in Delaying the Onset of Renal Replacement Therapy in Patients with Advanced Renal Failure. Case Rep Nephrol 2021; 2021:6987456. [PMID: 34532145 PMCID: PMC8440084 DOI: 10.1155/2021/6987456] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 07/07/2021] [Accepted: 08/30/2021] [Indexed: 11/22/2022] Open
Abstract
Patients with chronic kidney disease (CKD) are at an increased risk of developing hyperkalemia, which can be potentially life threatening. Hyperkalemia is frequently encountered with renin-angiotensin-aldosterone system inhibitor (RAASi) therapy use in patients with CKD and often results in the underdosing or discontinuation of these drugs. RAASi therapy has been proven to delay the progression of CKD, ameliorate proteinuria, and reduce the overall risk of cardiovascular morbidity and mortality. Patiromer is a sodium-free, potassium-binding polymer used for the treatment of hyperkalemia. We present a case series of four patients with Stage 4 or 5 CKD in whom the initiation of dialysis was delayed with the use of patiromer. For one patient, dialysis was delayed by 18 months, whereas the remaining three patients, in whom hyperkalemia was one of the main complications, remain dialysis independent to date.
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Affiliation(s)
| | - Jason A. Kline
- Cooper Medical School of Rowan University, Camden, NJ, USA
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Tanaka K, Saito H, Iwasaki T, Oda A, Watanabe S, Kanno M, Kimura H, Shimabukuro M, Asahi K, Watanabe T, Kazama JJ. Association between serum potassium levels and adverse outcomes in chronic kidney disease: the Fukushima CKD cohort study. Clin Exp Nephrol 2021; 25:410-417. [PMID: 33411113 DOI: 10.1007/s10157-020-02010-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 08/14/2020] [Accepted: 12/01/2020] [Indexed: 11/24/2022]
Abstract
BACKGROUND Serum potassium disorders, commonly observed in chronic kidney disease (CKD), are reportedly associated with higher mortality, but their impact on renal outcomes is still controversial. METHODS The present study used the longitudinal data of the Fukushima CKD cohort study to investigate the relationships between hypokalemia and hyperkalemia and adverse outcomes such as renal outcomes and all-cause mortality in Japanese patients with non-dialysis-dependent CKD. The study involved 1330 CKD patients followed-up for 2.8 years. The primary endpoint of the present study was a kidney event, defined as a combination of doubling of baseline serum creatinine and end-stage kidney disease. RESULTS Hyperkalemia (≥ 5.0 mmol/L) was noted in 10.6% and hypokalemia (< 4.0 mmol/L) in 16.4% of the study population. Significant U-shaped associations were observed between potassium levels and both kidney events and all-cause mortality on univariate Cox regression analyses. After adjustment for covariates, both hypokalemia and hyperkalemia were significantly associated with an increased risk of kidney events, with the lowest risk at a serum potassium of 4.0-4.4 mmol/L. Compared with a reference level of 4.0-4.4 mmol/L, the adjusted hazard ratio for kidney events was 2.49 (1.33-4.66) for serum potassium < 4.0 mmol/L, 1.72 (1.00-2.96) for 4.5-4.9 mmol/L, and 2.16 (1.15-4.06) for ≥ 5.0 mmol/L. There was no significant association between serum potassium levels and mortality after multivariate adjustment. CONCLUSION Hypokalemia and hyperkalemia were associated with an increased risk of CKD progression, but not with mortality in Japanese patients with non-dialysis-dependent CKD.
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Affiliation(s)
- Kenichi Tanaka
- Department of Nephrology and Hypertension, Fukushima Medical University, 1, Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan. .,Department of Chronic Kidney Disease Initiatives, Fukushima Medical University, Fukushima, Japan.
| | - Hirotaka Saito
- Department of Nephrology and Hypertension, Fukushima Medical University, 1, Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Tsuyoshi Iwasaki
- Department of Nephrology and Hypertension, Fukushima Medical University, 1, Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Akira Oda
- Department of Nephrology and Hypertension, Fukushima Medical University, 1, Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Shuhei Watanabe
- Department of Nephrology and Hypertension, Fukushima Medical University, 1, Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Makoto Kanno
- Department of Nephrology and Hypertension, Fukushima Medical University, 1, Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan.,Department of Chronic Kidney Disease Initiatives, Fukushima Medical University, Fukushima, Japan
| | - Hiroshi Kimura
- Department of Nephrology and Hypertension, Fukushima Medical University, 1, Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Michio Shimabukuro
- Department of Chronic Kidney Disease Initiatives, Fukushima Medical University, Fukushima, Japan.,Department of Diabetes, Endocrinology and Metabolism, Fukushima Medical University, Fukushima, Japan
| | - Koichi Asahi
- Department of Chronic Kidney Disease Initiatives, Fukushima Medical University, Fukushima, Japan.,Division of Nephrology and Hypertension, Iwate Medical University, Yahaba, Japan
| | - Tsuyoshi Watanabe
- Department of Chronic Kidney Disease Initiatives, Fukushima Medical University, Fukushima, Japan
| | - Junichiro J Kazama
- Department of Nephrology and Hypertension, Fukushima Medical University, 1, Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan.,Department of Chronic Kidney Disease Initiatives, Fukushima Medical University, Fukushima, Japan
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7
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Seliger SL. Hyperkalemia in patients with chronic renal failure. Nephrol Dial Transplant 2020; 34:iii12-iii18. [PMID: 31800076 DOI: 10.1093/ndt/gfz231] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 09/10/2019] [Indexed: 12/14/2022] Open
Abstract
Although hyperkalemia is much more common in patients with chronic kidney disease (CKD), the reported frequency of hyperkalemia varies markedly across studies, primarily due to differences in the ascertainment of hyperkalemia and the severity of CKD. Major risk factors for hyperkalemia among CKD patients include lower estimated glomerular filtration rate (eGFR), use of renin-angiotensin-aldosterone system inhibitors (RAASis), diabetes, older age and male gender. The use of two drugs to inhibit RAAS in diabetic CKD markedly increases the risk of hyperkalemia, as demonstrated in large multicenter clinical trials. Hyperkalemia has consistently been associated with an increased risk of adverse events compared with normokalemia, including all-cause mortality and cardiovascular morbidity and mortality. This risk is not explained by differences in comorbidity or estimated GFR, nor concomitant metabolic abnormalities such as acidosis among those with hyperkalemia. Sodium polystyrene sulfonate has been used commonly for decades to treat hyperkalemia in CKD patients, but without any high-quality clinical data to support its efficacy and with an increased risk of rare but serious colonic complications. The newer oral potassium-binding agents, patiromer and sodium zirconium cyclosilicate, have been shown to be effective and safe for the non-emergent treatment of hyperkalemia in CKD patients, including patients treated with RAASis. Although the long-term use of these medications may permit continuation of RAASis in CKD patients with hyperkalemia, the overall impact of this approach (as compared with down-titration of RAASis and/or up-titration of diuretics) on long-term morbidity, mortality and quality of life remains uncertain.
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Affiliation(s)
- Stephen L Seliger
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
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8
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Taylor KS, Mclellan J, Verbakel JY, Aronson JK, Lasserson DS, Pidduck N, Roberts N, Fleming S, O'Callaghan CA, Bankhead CR, Banerjee A, Hobbs FR, Perera R. Effects of antihypertensives, lipid-modifying drugs, glycaemic control drugs and sodium bicarbonate on the progression of stages 3 and 4 chronic kidney disease in adults: a systematic review and meta-analysis. BMJ Open 2019; 9:e030596. [PMID: 31542753 PMCID: PMC6756484 DOI: 10.1136/bmjopen-2019-030596] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE To evaluate the effects of drug interventions that may modify the progression of chronic kidney disease (CKD) in adults with CKD stages 3 and 4. DESIGN Systematic review and meta-analysis. METHODS Searching MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, International Clinical Trials Registry Platform, Health Technology Assessment, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index and Clinical Trials Register, from March 1999 to July 2018, we identified randomised controlled trials (RCTs) of drugs for hypertension, lipid modification, glycaemic control and sodium bicarbonate, compared with placebo, no drug or a drug from another class, in ≥40 adults with CKD stages 3 and/or 4, with at least 2 years of follow-up and reporting renal function (primary outcome), proteinuria, adverse events, maintenance dialysis, transplantation, cardiovascular events, cardiovascular mortality or all-cause mortality. Two reviewers independently screened citations and extracted data. For continuous outcomes, we used the ratio of means (ROM) at the end of the trial in random-effects meta-analyses. We assessed methodological quality with the Cochrane Risk of Bias Tool and confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS We included 35 RCTs and over 51 000 patients. Data were limited, and heterogeneity varied. Final renal function (estimated glomerular filtration rate) was 6% higher in those taking glycaemic control drugs (ROM 1.06, 95% CI 1.02 to 1.10, I2=0%, low GRADE confidence) and 4% higher in those taking lipid-modifying drugs (ROM 1.04, 95% CI 1.00 to 1.08, I2=88%, very low GRADE confidence). For RCTs of antihypertensive drugs, there were no significant differences in renal function. Treatment with lipid-modifying drugs led to a 36% reduction in cardiovascular disease and 26% reduction in all-cause mortality. CONCLUSIONS Glycaemic control and lipid-modifying drugs may slow the progression of CKD, but we found no pooled evidence of benefit nor harm from antihypertensive drugs. However, given the data limitations, further research is needed to confirm these findings. PROSPERO REGISTRATION NUMBER CRD42015017501.
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Affiliation(s)
- Kathryn S Taylor
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Julie Mclellan
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Jan Y Verbakel
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
| | - Jeffrey K Aronson
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Daniel S Lasserson
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Nicola Pidduck
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Nia Roberts
- Bodleian Health Care Libraries, University of Oxford, Oxford, UK
| | - Susannah Fleming
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | | | - Clare R Bankhead
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Amitava Banerjee
- Farr Institute of Health Informatics Research, University College London, London, UK
| | - Fd Richard Hobbs
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Rafael Perera
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
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9
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Garlo KG, Bates DW, Seger DL, Fiskio JM, Charytan DM. Association of Changes in Creatinine and Potassium Levels After Initiation of Renin Angiotensin Aldosterone System Inhibitors With Emergency Department Visits, Hospitalizations, and Mortality in Individuals With Chronic Kidney Disease. JAMA Netw Open 2018; 1:e183874. [PMID: 30646338 PMCID: PMC6324397 DOI: 10.1001/jamanetworkopen.2018.3874] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Indexed: 12/25/2022] Open
Abstract
IMPORTANCE Renin angiotensin aldosterone system inhibitors (RAASIs) benefit individuals with chronic kidney disease (CKD). Elevations in serum creatinine and potassium levels are common reasons for discontinuation of this therapy, but their incidence and risks are not well characterized in community practice. OBJECTIVE To evaluate associations of increased creatinine levels, hyperkalemia, and therapy continuation with the risk of emergency department (ED) visits, hospitalizations, and mortality within 1 year after RAASI therapy initiation in individuals with CKD. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study included 4661 individuals with nondialysis CKD newly prescribed a RAASI or a diuretic who were treated at 36 outpatient primary care offices affiliated with Brigham & Women's Hospital and Massachusetts General Hospital, Boston, from January 1, 2009, through December 31, 2011. Individuals receiving a new prescription for a diuretic were used to provide context. All participants had a baseline measure of renal function and at least 1 follow-up measurement of creatinine and potassium levels within 90 days of the prescription. Data were analyzed from January 1, 2009, through December 31, 2012. EXPOSURES Changes in creatinine and potassium levels within 90 days after the prescription date and therapy discontinuation. MAIN OUTCOMES AND MEASURES Emergency department visits, hospitalizations, and mortality within 1 year. RESULTS A total of 4661 individuals were included in the analysis (2506 [53.8%] women; mean [SD] age, 71 [14]; 3931 [84.3%] white; and 4198 [90.1%] with CKD stage 3). Of these, 2354 individuals (50.5%) received RAASIs and 2307 (49.5%) received diuretics. Creatinine level increase of at least 30% after RAASI therapy initiation was found in 158 of 2354 individuals (6.7%); hyperkalemia of greater than 5.0 mEq/L, in 251 of 2354 (10.7%). Increases in creatinine level of at least 30% (unadjusted odds ratio [OR], 1.40; 95% CI, 0.89-2.21), hyperkalemia (unadjusted OR, 1.15; 95% CI, 0.64-2.06), and therapy discontinuation (unadjusted OR, 1.01; 95% CI, 0.71-1.46) were not associated with ED visits or hospitalizations, which was consistent with results from competing risk analyses. Initial increases in creatinine level of at least 30% were associated with mortality in the total cohort (adjusted OR [aOR], 2.17; 95% CI, 1.45-3.25). However, the effect was only independent for diuretics (aOR, 2.27; 95% CI, 1.41-3.66) and not for RAASIs (aOR, 1.82; 95% CI, 0.83-3.99). CONCLUSIONS AND RELEVANCE Acute creatinine and potassium level disturbances after initiation of RAASI therapy in individuals with CKD appear to be sustained often often not sustained and not associated with ED visits or hospitalizations, despite therapy continuation. Findings from this study suggest that increases in creatinine level were independently associated with mortality among individuals prescribed diuretics but not RAASIs. Structured laboratory monitoring during RAASI therapy initiation may guide appropriate continuation of therapy in the outpatient setting.
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Affiliation(s)
- Katherine G. Garlo
- Department of Medicine, Renal Division, Brigham & Women’s Hospital, Boston, Massachusetts
| | - David W. Bates
- The Center for Patient Safety Research and Practice, Division of General Internal Medicine and Primary Care, Brigham & Women’s Hospital, Boston, Massachusetts
- Clinical and Quality Analysis, Partners HealthCare, Somerville, Massachusetts
| | - Diane L. Seger
- The Center for Patient Safety Research and Practice, Division of General Internal Medicine and Primary Care, Brigham & Women’s Hospital, Boston, Massachusetts
- Clinical and Quality Analysis, Partners HealthCare, Somerville, Massachusetts
| | - Julie M. Fiskio
- The Center for Patient Safety Research and Practice, Division of General Internal Medicine and Primary Care, Brigham & Women’s Hospital, Boston, Massachusetts
- Clinical and Quality Analysis, Partners HealthCare, Somerville, Massachusetts
| | - David M. Charytan
- Department of Medicine, Renal Division, Brigham & Women’s Hospital, Boston, Massachusetts
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10
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Raman M, Green D, Middleton RJ, Kalra PA. Comparing the impact of older age on outcome in chronic kidney disease of different etiologies: a prospective cohort study. J Nephrol 2018; 31:931-939. [PMID: 30187380 PMCID: PMC6244557 DOI: 10.1007/s40620-018-0529-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/17/2018] [Accepted: 08/22/2018] [Indexed: 11/30/2022]
Abstract
Background In older patients with chronic kidney disease (CKD), the risk of progression to end stage renal disease and cardiovascular death both differ compared to younger patients. This likely reflects differences in case mix and co-morbid burdens. We sought to establish the extent to which age itself is an independent biomarker of adverse outcome in CKD. Methods This was an analysis of the Salford Kidney Study, a prospective, longitudinal, observational study of 2,667 patients with eGFR < 60 ml/min/1.73 m2. Patients were divided into four age groups (< 55, 55–65, 65–75 and > 75 years). Within group adjusted hazard ratios for death in older compared to younger patients were calculated for different primary renal diseases. A competing risk model of death and renal replacement therapy (RRT) as outcomes was performed. Results The median age of the cohort was 67.1 years [interquartile range (IQR): 55.6–75.3] and median eGFR 30.8 ml/min/1.73 m2 (IQR: 20.6–43.2). Follow up was 3.5 ± 2.9 years. Overall, the adjusted HR for death in patients aged > 75 years compared to those < 55 years was 4.4 (95% CI 3.4–5.9), p < 0.001. The HR for death differed between primary renal diseases and CKD stages. In diabetic nephropathy, the HR was 3.0 (1.8–5.3, p < 0.001), in glomerulonephritis the HR was 12.2 (5.6–25.5, p < 0.001). The cumulative incidence of RRT was < 0.1 at 10 years for patients > 75 years, compared with 0.50 in those < 55 years. Death was more likely at 20 months in those aged 75 years or older (0.17) than at 10 years in those aged < 55 years (0.10). Conclusion This study demonstrates that the risk associated with older age shows significant variability between primary renal diseases. This is whilst acknowledging that observational studies carry the risk of hidden bias not adjusted for in the statistical model. Electronic supplementary material The online version of this article (10.1007/s40620-018-0529-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Maharajan Raman
- Vascular Research Group, Department of Renal Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Darren Green
- Vascular Research Group, Department of Renal Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK. .,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
| | - Rachel J Middleton
- Vascular Research Group, Department of Renal Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Philip A Kalra
- Vascular Research Group, Department of Renal Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
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11
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Messinger-Rapport BJ, Little MO, Morley JE, Gammack JK. Clinical Update on Nursing Home Medicine: 2016. J Am Med Dir Assoc 2017; 17:978-993. [PMID: 27780573 DOI: 10.1016/j.jamda.2016.09.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 09/07/2016] [Accepted: 09/07/2016] [Indexed: 12/31/2022]
Abstract
This is the tenth clinical update. It covers chronic kidney disease, dementia, hypotension, polypharmacy, rapid geriatric assessment, and transitional care.
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Affiliation(s)
| | - Milta O Little
- Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, MO
| | - John E Morley
- Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, MO.
| | - Julie K Gammack
- Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, MO
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12
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Kamada T, Hayashi M, Fujiwara W, Yoshikawa D, Mukaide D, Sugishita Y, Yoshinaga M, Itoh T, Yokoi H, Ishii J, Watanabe E, Ozaki Y, Izawa H. Antihypertensive efficacy and safety of the angiotensin receptor blocker azilsartan in elderly patients with hypertension. Drug Chem Toxicol 2016; 40:110-114. [PMID: 27424785 DOI: 10.1080/01480545.2016.1188301] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/13/2023]
Abstract
OBJECTIVES The number of elderly patients with hypertension has been steadily increasing. However, there are limited data on the safety and efficacy of the new angiotensin type 1 receptor blocker (ARB) azilsartan in elderly patients with hypertension. We investigated the clinical efficacy and safety of azilsartan in this population. METHODS The study population comprised 56 ambulatory patients with essential hypertension. We evaluated the reduction in blood pressure and safety after 12 weeks of treatment with azilsartan in 29 hypertensive patients ≥65 years of age (aged group) in comparison with the findings in 27 patients <65 years of age (non-aged group). RESULTS Systolic blood pressure in the aged group declined significantly from 155 ± 18 mmHg at baseline to 138 ± 11 mmHg after 12 weeks of treatment with azilsartan, and that in the non-aged group also declined significantly from 152 ± 20 mmHg at baseline to 142 ± 13 mmHg after 12 weeks of treatment with azilsartan. There were no significant differences in the magnitude of change in blood pressures from pre-treatment to post-treatment with azilsartan between the non-aged and aged groups. There were no changes in clinical laboratory findings, including serum levels of creatinine, potassium, lipids, and other metabolic variables, after 12 weeks of treatment with azilsartan in both groups. CONCLUSIONS Our findings suggest that azilsartan is effective in lowering blood pressure in elderly patients and may be safe. Therefore, azilsartan could be a valuable option for treating hypertension in elderly and non-elderly patients.
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Affiliation(s)
- Tomohito Kamada
- a Department of Cardiology , Fujita Health University, Banbuntane Hotokukai Hospital , Nagoya , Japan and.,b Department of Cardiology , Fujita Health University , Toyoake , Japan
| | - Mutsuharu Hayashi
- a Department of Cardiology , Fujita Health University, Banbuntane Hotokukai Hospital , Nagoya , Japan and
| | - Wakaya Fujiwara
- a Department of Cardiology , Fujita Health University, Banbuntane Hotokukai Hospital , Nagoya , Japan and
| | - Daiji Yoshikawa
- a Department of Cardiology , Fujita Health University, Banbuntane Hotokukai Hospital , Nagoya , Japan and
| | - Daisuke Mukaide
- a Department of Cardiology , Fujita Health University, Banbuntane Hotokukai Hospital , Nagoya , Japan and
| | - Yoshinori Sugishita
- a Department of Cardiology , Fujita Health University, Banbuntane Hotokukai Hospital , Nagoya , Japan and
| | - Masataka Yoshinaga
- a Department of Cardiology , Fujita Health University, Banbuntane Hotokukai Hospital , Nagoya , Japan and
| | - Takehiro Itoh
- a Department of Cardiology , Fujita Health University, Banbuntane Hotokukai Hospital , Nagoya , Japan and
| | - Hiroatsu Yokoi
- a Department of Cardiology , Fujita Health University, Banbuntane Hotokukai Hospital , Nagoya , Japan and
| | - Junichi Ishii
- b Department of Cardiology , Fujita Health University , Toyoake , Japan
| | - Eiichi Watanabe
- b Department of Cardiology , Fujita Health University , Toyoake , Japan
| | - Yukio Ozaki
- b Department of Cardiology , Fujita Health University , Toyoake , Japan
| | - Hideo Izawa
- a Department of Cardiology , Fujita Health University, Banbuntane Hotokukai Hospital , Nagoya , Japan and
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13
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Raman M, Green D, Middleton RJ, Kalra PA. OLDER PEOPLE WITH CHRONIC KIDNEY DISEASE: DEFINITION, AND INFLUENCE OF BIOMARKERS AND MEDICATIONS UPON CARDIOVASCULAR AND RENAL OUTCOMES. J Ren Care 2016; 42:150-61. [PMID: 27364740 DOI: 10.1111/jorc.12164] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Chronic kidney disease (CKD) is a global problem. With an ageing population the burden on the health services has increased due to the growing number of older people with CKD. This group of individuals is far different to the younger CKD population and their risk of cardiovascular death is far greater than the risk of progressing to end stage kidney disease (ESKD). OBJECTIVE In this review we explore the role of certain biomarkers and medications in predicting the risk of progression to ESKD and death in old people with CKD. METHODS An electronic literature search of EMBASE and MEDLINE databases was performed using Healthcare Databases Advanced Search (HDAS) in December 2014. RESULTS Albuminuria is a key biomarker in predicting the risk of death and progression to ESKD. Cystatin C appears to be superior in predicting the risk of cardiovascular and non-cardiovascular death compared to GFR or creatinine. Several inflammatory biomarkers can be used to predict the risk of death and progression to CKD but measuring and monitoring them in routine clinical practice will be expensive and impractical. The effects of long-term RAAS inhibition in older people are not well established. Older people especially those with CKD receive suboptimal secondary preventive measures. Due to multiple comorbidities older people with CKD are usually receiving a number of medications. This can potentially lead to significant adverse drug events (ADE) due to drug interactions. CONCLUSION Novel non-traditional risk factors like albuminuria, Cystatin C and inflammatory biomarkers play an important role in predicting their risk of death and progression to ESKD. The efficacy and safety of medications in older people with CKD is not well established and requires more extensive, focused study.
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Affiliation(s)
- Maharajan Raman
- Vascular Research Group, Salford Royal NHS Foundation Trust, Salford, UK.,Institute of Population Health, University of Manchester, Manchester, UK
| | - Darren Green
- Vascular Research Group, Salford Royal NHS Foundation Trust, Salford, UK.,Institute of Population Health, University of Manchester, Manchester, UK
| | - Rachel J Middleton
- Vascular Research Group, Salford Royal NHS Foundation Trust, Salford, UK.,Institute of Population Health, University of Manchester, Manchester, UK
| | - Philip A Kalra
- Vascular Research Group, Salford Royal NHS Foundation Trust, Salford, UK.,Institute of Population Health, University of Manchester, Manchester, UK
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14
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Corsonello A, Fusco S, Bustacchini S, Chiatti C, Moresi R, Bonfigli AR, Di Stefano G, Lattanzio F. Special considerations for the treatment of chronic kidney disease in the elderly. Expert Rev Clin Pharmacol 2016; 9:727-37. [PMID: 26885869 DOI: 10.1586/17512433.2016.1155448] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 12/12/2022]
Abstract
Chronic kidney disease (CKD) is common in older adults, and its burden is expected to increase in older populations. Even if the knowledge on the approach to older patient with CKD is still evolving, current guidelines for pharmacological management of CKD does not include specific recommendations for older patients. Additionally, decision-making on renal replacement therapy (RRT) for older patients is far from being evidence-based, and despite the improvement in dialysis outcomes, RRT may cause more harm than benefit compared with conservative care when prognostic stratification is not carefully assessed. The use of comprehensive geriatric assessment tools could help clinicians in applying a more informed decision-making. Finally, physical exercise and rehabilitation interventions also represents a promising therapeutic strategy.
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Affiliation(s)
- Andrea Corsonello
- a Italian National Research Center on Aging, Unit of Geriatric Pharmacoepidemiology , Research Hospital of Cosenza , Cosenza , Italy
| | - Sergio Fusco
- a Italian National Research Center on Aging, Unit of Geriatric Pharmacoepidemiology , Research Hospital of Cosenza , Cosenza , Italy
| | - Silvia Bustacchini
- b Scientific Direction , Italian National Research Center on Aging , Ancona , Italy
| | - Carlos Chiatti
- b Scientific Direction , Italian National Research Center on Aging , Ancona , Italy
| | - Raffaella Moresi
- b Scientific Direction , Italian National Research Center on Aging , Ancona , Italy
| | - Anna Rita Bonfigli
- b Scientific Direction , Italian National Research Center on Aging , Ancona , Italy
| | | | - Fabrizia Lattanzio
- b Scientific Direction , Italian National Research Center on Aging , Ancona , Italy
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15
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Clinical Practice Guideline on management of patients with diabetes and chronic kidney disease stage 3b or higher (eGFR <45 mL/min). Nephrol Dial Transplant 2015; 30 Suppl 2:ii1-142. [PMID: 25940656 DOI: 10.1093/ndt/gfv100] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 02/06/2023] Open
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16
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Suzuki H, Kikuta T, Inoue T, Hamada U. Time to re-evaluate effects of renin-angiotensin system inhibitors on renal and cardiovascular outcomes in diabetic nephropathy. World J Nephrol 2015; 4:118-26. [PMID: 25664254 PMCID: PMC4317622 DOI: 10.5527/wjn.v4.i1.118] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 09/18/2014] [Revised: 11/13/2014] [Accepted: 12/03/2014] [Indexed: 02/06/2023] Open
Abstract
The use of renin-angiotensin system (RAS) inhibitors, such angiotensin converting enzyme inhibitors/angiotensin-II receptor blockers, to slow progression of chronic kidney disease (CKD) in a large group dominated by elderly people in the real world is not supported by available evidence. Large-scale clinical trials had many faults, among them a lack of focus on the elderly. However, it would be difficult to conduct clinical trials of a similar scale in elderly CKD patients. Besides, progression of kidney disease is often slow in elderly persons, and the vast majority of older adults with CKD will die before reaching end stage renal disease. Moreover, since it is not clear that progression of kidney disease, and even of proteinuric diabetic nephropathy, is not inhibited through the use of RAS inhibitors, the most patient-centric goal of therapy for many elderly individuals should be individualized.
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17
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Becquemont L, Bauduceau B, Benattar-Zibi L, Berrut G, Bertin P, Bucher S, Corruble E, Danchin N, al-Salameh A, Derumeaux G, Doucet J, Falissard B, Forette F, Hanon O, Pasquier F, Pinget M, Ourabah R, Piedvache C. Association between Cardiovascular Drugs and Chronic Kidney Disease in Non-Institutionalized Elderly Patients. Basic Clin Pharmacol Toxicol 2015; 117:137-43. [DOI: 10.1111/bcpt.12376] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 11/13/2014] [Accepted: 01/05/2015] [Indexed: 12/20/2022]
Affiliation(s)
- Laurent Becquemont
- Pharmacology Department; Faculty of Medicine Paris-Sud; APHP; Bicêtre university Hospital; University Paris-Sud; Le Kremlin Bicêtre France
| | | | | | - Gilles Berrut
- Clinical Gerontology; Nantes university hospital; Nantes France
| | - Philippe Bertin
- Rheumatology Department; Limoges University Hospital; Limoges France
| | - Sophie Bucher
- General Practice Department; Faculty of Medicine Paris-Sud; University Paris-Sud; Le Kremlin-Bicêtre France
| | - Emmanuelle Corruble
- INSERM U 669; Faculty of Medicine Paris-Sud; Department of Psychiatry; Bicêtre University Hospital; APHP; University Paris-Sud; Le Kremlin Bicêtre France
| | | | - Abdallah al-Salameh
- Pharmacology Department; Faculty of Medicine Paris-Sud; APHP; Bicêtre university Hospital; University Paris-Sud; Le Kremlin Bicêtre France
| | - Geneviève Derumeaux
- Cardiovascular Functional Exploration; Louis Pradel Hospital; HCL; Bron France
| | - Jean Doucet
- Internal Medicine, Geriatrics and Therapeutics; Saint Julien University Hospital; Rouen University; Rouen France
| | - Bruno Falissard
- INSERM U 669; Faculty of Medicine Paris-Sud; Biostatistics Department; APHP; Hôpital Paul Brousse; University Paris-Sud; Le Kremlin-Bicêtre France
| | - Francoise Forette
- National Foundation of Gerontology; University Paris Descartes; Paris France
| | - Olivier Hanon
- Geriatrics Department; EA 4468, AP-HP; Broca university hospital; University Paris Descartes; Paris France
| | - Florence Pasquier
- UDSL; EA 1046, CHU; University of Lille Nord de France; Lille France
| | - Michel Pinget
- Endocrinology, Diabetes and Diseases of Nutrition; University Hospital of Strasbourg; European Centre for the Study of Diabetes (CeeD); University of Strasbourg; Strasbourg France
| | - Rissane Ourabah
- General Practice Department; Faculty of Medicine Paris-Sud; University Paris-Sud; Le Kremlin-Bicêtre France
| | - Celine Piedvache
- Pharmacology Department; Faculty of Medicine Paris-Sud; APHP; Bicêtre university Hospital; University Paris-Sud; Le Kremlin Bicêtre France
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18
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Sheen SS, Park RW, Yoon D, Shin GT, Kim H, Park IW. The Model for End-stage Liver Disease score is potentially a useful predictor of hyperkalemia occurrence among hospitalized angiotensin receptor blocker users. J Clin Pharm Ther 2014; 40:48-54. [PMID: 25328056 DOI: 10.1111/jcpt.12224] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 11/28/2013] [Accepted: 09/17/2014] [Indexed: 12/28/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Angiotensin receptor blockers (ARBs) are medications commonly used for treating conditions such as hypertension. However, ARBs are frequently associated with hyperkalemia, a potentially critical adverse event, in high-risk patients. Although both the liver and the kidney are major elimination routes of ARBs, the relationship between hepatorenal function and ARB-related hyperkalemia has not yet been investigated. The purpose of this study was to evaluate the risk of hyperkalemia, in terms of various hepatorenal functions, for hospitalized patients newly initiated on ARB treatment. METHODS We evaluated ARB-related hyperkalemia in a cohort of 5530 hospitalized patients, who had not previously used ARBs, between 12 April 2004 and 31 May 2012. Hepatorenal function was assessed by the Model for End-stage Liver Disease (MELD) score. Hyperkalemia risk was assessed by hepatorenal function, risks were categorized into the four MELD scoring groups, and the groups were compared with one another. RESULTS AND DISCUSSION The MELD score was significantly different between the hyperkalemic and non-hyperkalemic groups (independent t-test, P < 0.001). The MELD score 10-14, 15-19 and ≥ 20 groups showed higher risks of hyperkalemia than the lowest MELD score group {log-rank test, P < 0.001; multiple Cox proportional hazard model, hazard ratios 1.478 (P = 0.003), 2.285 (P < 0.001) and 3.024 (P < 0.001), respectively}. WHAT IS NEW AND CONCLUSION The MELD score showed a stronger predictive performance for hyperkalemia than either serum creatinine or estimated glomerular filtration rate alone. Furthermore, the MELD score showed good predictive performance for ARB-related hyperkalemia among hospitalized patients. The clinical implications and reasons for these findings merit future investigation.
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Affiliation(s)
- S S Sheen
- Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Korea
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Abstract
Chronic kidney disease (CKD) is increasingly being recognized as a disease of elderly individuals. In recent years the definition and categorization of kidney disease has been standardized. There are concerns that this standardization has led to an increase in the number of older individuals labeled as having CKD. This article addresses the definitions of CKD, recently published revised CKD stages with risk stratifications, and limitations of using formulas to assess renal function in the elderly. Also discussed are management of common risk factors of progression CKD, nonrenal-related outcomes, prognosis of CKD in older individuals, and criteria for referral to nephrology.
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Affiliation(s)
- Thin Thin Maw
- Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
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Turgut F, Yesil Y, Balogun RA, Abdel-Rahman EM. Hypertension in the elderly: unique challenges and management. Clin Geriatr Med 2014; 29:593-609. [PMID: 23849010 DOI: 10.1016/j.cger.2013.05.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 12/28/2022]
Abstract
Elderly individuals, worldwide, are on the rise, posing new challenges to care providers. Hypertension is highly prevalent in elderly individuals, and multiple challenges face care providers while managing it. In addition to treating hypertension, the physician must treat other modifiable cardiovascular risk factors in patients with or without diabetes mellitus or chronic kidney disease to reduce cardiovascular events and mortality. This review discusses some of the unique characteristics of high blood pressure in the elderly and provides an overview of the challenges facing care providers, as well as the current recommendations for management of hypertension in the elderly.
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Affiliation(s)
- Faruk Turgut
- Department of Nephrology, School of Medicine, Mustafa Kemal University, 31034, Hatay, Turkey
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Park IW, Sheen SS, Yoon D, Lee SH, Shin GT, Kim H, Park RW. Onset time of hyperkalaemia after angiotensin receptor blocker initiation: when should we start serum potassium monitoring? J Clin Pharm Ther 2013; 39:61-8. [PMID: 24262001 DOI: 10.1111/jcpt.12109] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 10/11/2013] [Accepted: 10/14/2013] [Indexed: 12/19/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Angiotensin receptor blockers (ARBs) frequently induce hyperkalaemia in high-risk patients. Early detection of hyperkalaemia can reduce the subsequent harmful effects. This study was performed to examine the onset time of hyperkalaemia after ARB therapy. METHODS We carried out a retrospective analysis to determine the onset time of hyperkalaemia (serum potassium >5·5 mm) among hospitalized patients newly starting ARB therapy between 2004 and 2012, in a tertiary teaching hospital. Predefined possible risk factors and concomitant medications were evaluated. RESULTS AND DISCUSSION During the 97-month study period, a total of 4267 hospitalized patients started ARBs as new drugs and 225 patients showed hyperkalaemia. A significantly increased risk of hyperkalaemia was detected among patients with a high baseline potassium [odds ratio (OR) 6·0] and those who took non-potassium-sparing diuretics (OR 2·2) or potassium supplements (OR 1·6). A high glomerular filtration rate (GFR) was associated with a lower risk of hyperkalaemia (OR 0·992). Fifty-two percentage of hyperkalaemic events occurred within the first week after initiation of ARB therapy. The highest frequency of hyperkalaemia occurred on the first day after initiation of ARBs. Hyperkalaemia occurred earlier in patients with a high baseline serum potassium level, reduced GFR, diabetes and in those without heart failure. WHAT IS NEW AND CONCLUSION Hyperkalaemia occurs most frequently at the beginning of ARB therapy in hospitalized patients. Monitoring of serum potassium and estimated GFR after initiation of ARBs should be started within a few days or not later than 1 week, especially in patients with risk factors.
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Affiliation(s)
- I-W Park
- Department of Nephrology, Ajou University School of Medicine, Suwon, Korea
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Abstract
The renin-angiotensin system (RAS) is involved in hepatic fibrosis. To date there is no known effective treatment for hepatic fibrosis. Modulation of the RAS with angiotensin converting enzyme inhibitors and angiotensin receptor blockers may be a promising therapeutic option for the treatment of hepatic fibrosis. This review provides an update about the role of RAS in hepatic fibrosis, and treatment of hepatic fibrosis in the light of different studies in animals and humans is also updated. RAS induces key steps involved in hepatic fibrosis, such as activation of hepatic stellate cells and expression of transforming growth factor β1. Treatment with angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers attenuate fibrosis progression in both animal and human studies. Further, controlled studies are required to evaluate the role of RAS inhibitors and angiotensin-converting enzyme 2 in patients with chronic liver diseases in whom the causative agent cannot be removed.
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Abstract
The treatment of diabetic nephropathy in elderly individuals is based primarily on data from younger age groups. However, the assumption that the same treatment approaches for the younger age groups can be uniformly applied to elderly individuals is likely to be incorrect. The cornerstones of aggressive therapy for diabetic kidney disease in general may have drawbacks in elderly patients. For example, significant risks of tight glycemic control have emerged in recent studies. Excessive decrease of blood pressure to existing targets may be unsafe in elderly individuals. Limited data do indicate that renin-angiotensin blockade may be as effective and no riskier than in middle-aged diabetic kidney patients. Until further studies are carried out, it is prudent to treat the elderly patient with similar approaches as in younger patients, but tempered by the issues reviewed in this article. There is a growing need for the development of clinical guidelines to retool CKD management in the elderly diabetic population using both current and emerging therapies.
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Caldeira D, David C, Sampaio C. Tolerability of angiotensin-receptor blockers in patients with intolerance to angiotensin-converting enzyme inhibitors: a systematic review and meta-analysis. Am J Cardiovasc Drugs 2012; 12:263-77. [PMID: 22587776 DOI: 10.1007/bf03261835] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Between 5% and 20% of patients treated with angiotensin-converting enzyme inhibitors (ACE inhibitors) develop intolerance. Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) can be used as an alternative treatment. OBJECTIVE In this study we aimed to evaluate the tolerability of ARBs in patients with intolerance to ACE inhibitors. DATA SOURCES The electronic databases PubMed, MEDLINE/EMBASE via Dialog, CENTRAL, and ISI Web of Knowledge were searched. STUDY SELECTION Randomized controlled trials (RCTs) evaluating ARBs in patients with intolerance to ACE inhibitors were selected. DATA SYNTHESIS Risk ratio (RR) and 95% confidence intervals (CIs) were estimated assuming the random effects method. We found 11 RCTs comparing ARBs with ACE inhibitors, diuretics, or placebo, and one RCT comparing high-dose versus low-dose ARB. RESULTS ARBs had fewer cough events versus ACE inhibitors (RR 0.37; 95% CI 0.28, 0.48). ARBs had drug discontinuation (RR 0.99; 95% CI 0.84, 1.17) and cough risk (RR 1.01; 95% CI 0.74, 1.39) rates similar to placebo. Angioedema risk with ARBs was also similar to placebo (RR 1.62; 95% CI 0.17, 15.79). Compared with placebo, hypotension (RR 2.63; 95% CI 1.77, 3.92), renal dysfunction (RR 2.07; 95% CI 1.45, 2.95) and hyperkalemia (RR 3.37; 95% CI 1.60, 7.11) were more frequent with ARBs. CONCLUSIONS ACE inhibitor rechallenge should be discouraged in patients with previous intolerance to ACE inhibitors due to a higher risk of cough. ARBs had cough and angioedema incidences similar to placebo. Despite a significantly higher incidence of hypotension, renal dysfunction and hyperkalemia, discontinuation of ARBs was similar to placebo.
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Park I, Sheen SS, Lim HS, Yoon D, Park MY, Lee SH, Shin GT, Kim H, Park RW. Comparison of hyperkalemic risk in hospitalized patients treated with different angiotensin receptor blockers: a retrospective cohort study using a Korean clinical research database. Am J Cardiovasc Drugs 2012; 12:255-62. [PMID: 22799614 DOI: 10.1007/bf03261834] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND AND AIM Clinical use of angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) is associated with hyperkalemia as an adverse drug reaction. Although it has significant clinical implications, the incidence and relative risks of hyperkalemia with various ARBs have not yet been fully evaluated. The purpose of this study was to determine the risk of hyperkalemic events in hospitalized patients treated with different ARBs and to compare the risk among them. METHODS We constructed a retrospective cohort composed of hospitalized adult patients who took ARBs in a single tertiary teaching hospital between April 2004 and March 2010. We estimated the incidence of hyperkalemia (serum potassium level >5.5 mEq/L) with various ARBs, and then compared the risk between them using a multivariate Cox proportional hazard model based on age, sex, Charlson co-morbidity score, baseline serum potassium, underlying diseases, and concomitant drugs. RESULTS We identified 6992 evaluable intervals from 5449 patients treated with one of the seven ARBs during hospitalization over the 71-month study period with 2521.6 patient-months. We found 381 hyperkalemic events (5.4%) during the study period and an overall event rate of 15.1/100 patient-months. Moderate to fatal hyperkalemia was relatively rare (>6.0 mEq/L, 2.1% [moderate]; >6.5 mEq/L, 0.9% [severe]; >7.0 mEq/L, 0.3% [fatal]). After adjustment for covariates, telmisartan showed a lower risk of hyperkalemia (hazard ratio 0.67; 95% confidence interval 0.51, 0.89) compared with all other ARBs. CONCLUSION The risk of hyperkalemic events in hospitalized patients treated with different ARBs was defined. Telmisartan showed a relatively lower hyperkalemic risk profile in hospitalized patients compared with other ARBs.
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Akerman C, Kirk A, Hewitt J. Diabetic renal disease in older people. PRACTICAL DIABETES 2012. [DOI: 10.1002/pdi.1669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 11/11/2022]
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Cernes R, Mashavi M, Zimlichman R. Differential clinical profile of candesartan compared to other angiotensin receptor blockers. Vasc Health Risk Manag 2011; 7:749-59. [PMID: 22241949 PMCID: PMC3253768 DOI: 10.2147/vhrm.s22591] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/13/2023] Open
Abstract
The advantages of blood pressure (BP) control on the risks of heart failure and stroke are well established. The renin-angiotensin system plays an important role in volume homeostasis and BP regulation and is a target for several groups of antihypertensive drugs. Angiotensin II receptor blockers represent a major class of antihypertensive compounds. Candesartan cilexetil is an angiotensin II type 1 (AT[1]) receptor antagonist (angiotensin receptor blocker [ARB]) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. Oral candesartan 8–32 mg once daily is recommended for the treatment of adult patients with hypertension. Clinical trials have demonstrated that candesartan cilexetil is an effective agent in reducing the risk of cardiovascular mortality, stroke, heart failure, arterial stiffness, renal failure, retinopathy, and migraine in different populations of adult patients including patients with coexisting type 2 diabetes, metabolic syndrome, or kidney impairment. Clinical evidence confirmed that candesartan cilexetil provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. Candesartan cilexetil, one of the current market leaders in BP treatment, is a highly selective compound with high potency, a long duration of action, and a tolerability profile similar to placebo. The most important and recent data from clinical trials regarding candesartan cilexetil will be reviewed in this article.
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Affiliation(s)
- Relu Cernes
- The Brunner Institute for Cardiovascular Research, Wolfson Medical Center and Tel Aviv University, Tel Aviv, Israel
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Renin-angiotensin system blockade in older adults with chronic kidney disease: a review of the literature. Curr Opin Nephrol Hypertens 2010; 19:413-9. [PMID: 20539228 DOI: 10.1097/mnh.0b013e32833b8d6b] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/13/2023]
Abstract
PURPOSE OF REVIEW We have reviewed the literature examining the benefits and harms of renin-angiotensin system (RAS) blockade in older adults, using studies which included patients with chronic kidney disease (CKD) as well as those which included a broader patient population. RECENT FINDINGS We review the results of key trials which evaluate the impact of RAS blockade on renal outcomes, and those which address the impact of RAS blockade on more global outcomes (cardiovascular events and mortality). Many trials examining renal outcomes of RAS blockade excluded older patients or did not present age-stratified results, whereas trials which examined global outcomes often excluded patients with CKD. Most older patients with CKD have nonproteinuric nondiabetic CKD, thus differing from participants in trials which examined renal outcomes, which often included only patients with diabetes or proteinuria. Most studies did not address alternate outcomes which may carry greatest import for older patients, such as worsening comorbid illness or changes in functional status. SUMMARY The role of RAS inhibition for older patients with CKD remains unclear. Information on age-specific effects of RAS blockade on a range of different outcomes among older patients with CKD would improve our ability to assess the benefits and harms of RAS inhibition in this population.
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Cardiovascular risk reduction with Renin-Angiotensin aldosterone system blockade. Nurs Res Pract 2010; 2010:101749. [PMID: 21994809 PMCID: PMC3169243 DOI: 10.1155/2010/101749] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 10/02/2009] [Revised: 05/13/2010] [Accepted: 05/25/2010] [Indexed: 01/13/2023] Open
Abstract
This paper examines the evidence supporting treatments within the renin-angiotensin aldosterone system (RAS), the role cardioprotection plays within the management of hypertension, considerations around medication adherence, and the role of the nurse or nurse practitioner in guiding patients to achieve higher hypertension control rates. A large body of data now exists to support the use of angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) which act on RAS, in the management of hypertension and their effect on cardiovascular risk reduction. Current evidence suggests that inhibition of the RAS is an important target for cardioprotection. RAS inhibition controls blood pressure and also reduces target-organ damage. This is especially important in populations at high-risk for damage including patients with diabetes and those with chronic kidney disease. Both ARBs and ACEIs target the RAS offering important reductions in both BP and target organ damage.
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Rifkin DE, Winkelmayer WC. Medication issues in older individuals with CKD. Adv Chronic Kidney Dis 2010; 17:320-8. [PMID: 20610359 DOI: 10.1053/j.ackd.2010.03.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 02/05/2010] [Revised: 03/13/2010] [Accepted: 03/16/2010] [Indexed: 01/10/2023]
Abstract
Older US adults bear a substantial burden of chronic disease and take an average of five prescription and non-prescription medications per day. Recent data suggest that over 20% of older adults have chronic kidney disease (CKD) as defined by an impaired glomerular filtration rate. These individuals often have multiple comorbidities, including diabetes, hypertension, and cardiovascular disease. Although patients with CKD may receive substantial benefits from prescribed medications, they are also at high risk for adverse drug events and polypharmacy. In this review, we outline the risks and benefits of medication use in the CKD population as a specific case within geriatric pharmacoepidemiology as a framework.
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Scuteri A, Tesauro M. Management of Global Cardiovascular Risk in Older Subjects with Diabetes Mellitus. High Blood Press Cardiovasc Prev 2010. [DOI: 10.2165/11311800-000000000-00000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 11/02/2022] Open
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Turgut F, Balogun RA, Abdel-Rahman EM. Renin-angiotensin-aldosterone system blockade effects on the kidney in the elderly: benefits and limitations. Clin J Am Soc Nephrol 2010; 5:1330-9. [PMID: 20498247 DOI: 10.2215/cjn.08611209] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 12/31/2022]
Abstract
The proportion of the population that is elderly (age>or=65 years) is growing across the world. The increasing longevity of humans results in a higher number of elderly patients' presenting with multiple chronic diseases such as hypertension, diabetes, and chronic kidney disease (CKD). These problems increase morbidity and mortality in the elderly. Overactivity of the renin-angiotensin-aldosterone system (RAAS) is associated with the development of hypertension, cardiovascular events, and CKD, so targeting the RAAS is a logical therapeutic approach. Elderly patients present special concerns regarding the benefits versus risks of using RAAS blockers. Plasma renin activity declines with age, which has been attributed to the effect of age-associated nephrosclerosis. Plasma aldosterone is also reduced with age, resulting in a greater risk for hyperkalemia in older individuals, especially when coupled with the age-associated decline in GFR. Moreover, the elderly have a higher frequency of concurrent conditions and are on many medications, which may further increase the risk for adverse effects of RAAS blocking agents. Unfortunately, there is a paucity of literature that is specifically aimed at studying elderly using the RAAS blockers. We present in our in-depth review data regarding benefits and limitations of the use of the RAAS blockades on the various sites along the RAAS pathway for elderly patients. Specific attention was given to the role of combination RAAS blockade therapy and higher monotherapy dosing in the treatment of hypertension in the elderly.
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Affiliation(s)
- Faruk Turgut
- Department of Medicine, University of Virginia Health System, P.O. Box 800133, Charlottesville, VA 22908, USA.
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Abstract
Both in the United States and many regions of the world, chronic kidney disease and end-stage renal disease (ESRD) in patients with diabetes mellitus have reached epidemic proportions in recent years. The large prevalent diabetic ESRD population in the US involves remarkable risk in African Americans and an increasing population of elderly diabetic patients, including many octogenarians. In the US and globally, over 90% of diabetic ESRD patients have type 2 diabetes. The multinational epidemic of diabetic ESRD has been linked to increases in the prevalence of diabetes in many populations, related to obesity, ageing, and physical inactivity. It is anticipated that the worldwide prevalence of diabetes over the next 20 years will reach a level twice that of the year 2000. The excessive morbidity and mortality of the diabetic ESRD population are well documented. However, the growth in incidence and prevalence rates for diabetic ESRD has remained somewhat stable in the US in recent years, and new data suggest that the incidence of ESRD expressed per diabetic population may finally be declining, suggesting that proven therapies are making "progress on progression."
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Affiliation(s)
- Mark E Williams
- Department of Medicine, Harvard Medical School, Joslin Diabetes Center and Beth Israel Deaconess Medical Center, Boston, MA, USA.
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Pappoe LS, Winkelmayer WC. ACE Inhibitor and Angiotensin II Type 1 Receptor Antagonist Therapies in Elderly Patients with Diabetes Mellitus. Drugs Aging 2010; 27:87-94. [DOI: 10.2165/11316430-000000000-00000] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 11/02/2022]
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Is angiotensin system blockade indicated in the elderly? Nat Rev Nephrol 2010; 6:11-2. [DOI: 10.1038/nrneph.2009.206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 11/08/2022]
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Cigolle CT, Blaum CS, Halter JB. Diabetes and Cardiovascular Disease Prevention in Older Adults. Clin Geriatr Med 2009; 25:607-41, vii-viii. [DOI: 10.1016/j.cger.2009.09.001] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 11/15/2022]
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Abstract
The kidneys are among the most prominent body organs affected by the process of aging, as both kidney morphology and function are known to change with age. However, special challenges emerge when the elderly patient also has diabetes complicated by kidney disease. Cases frequently progress from the early stages of diabetic nephropathy to advanced kidney impairment and end-stage renal disease, and the majority of patients suffer cardiovascular complications. However, many elderly patients with diabetes will lack the classic clinical features of diabetic kidney disease. Neither the efficacy nor safety of general treatment goals such as glycemic control, hypertension management and renin–angiotensin blockade have been adequately addressed in the aging diabetic kidney patient. These basic treatments for diabetic kidney disease are extrapolated from studies of mostly middle-aged individuals. Diabetic kidney guidelines do not adequately distinguish between age groups. Aggressive management must be measured against life expectancy in the elderly. The physician should be aware of these risks. Unfortunately, many elderly diabetic chronic kidney disease/end-stage renal disease patients are not prescribed the treatments that are available. Over a third of new end-stage renal disease cases among the elderly are due to diabetic kidney disease. Prognosis is poor, even for those who receive a kidney transplant.
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Affiliation(s)
- Mark E Williams
- Renal Unit, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA
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Sadjadi SA, McMillan JI, Jaipaul N, Blakely P, Hline SS. A comparative study of the prevalence of hyperkalemia with the use of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers. Ther Clin Risk Manag 2009; 5:547-52. [PMID: 19707264 PMCID: PMC2710386 DOI: 10.2147/tcrm.s5176] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/13/2023] Open
Abstract
Background and objectives Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are increasingly used in a variety of settings including heart failure, renal failure, arterial hypertension, and diabetic nephropathy. The objective of this study was to investigate the prevalence of hyperkalemia with ACEI and ARB use, in a population of the United States veterans. Design, settings, material, and measurements Retrospective observational cohort study of 1163 patients on ACEIs and 1168 patients on ARBs in a single Veterans Affairs Medical Center. Electronic medical records were reviewed over a 12-month period with data collected on various demographic, laboratory, comorbidity, and medication related variables. Results Hyperkalemia (>5 mEq/L) was observed in 20.4% of patients on ACEIs and 31.0% on ARBs. Severe hyperkalemia (6 mEq/L or higher), was observed in 0.8% of ACEI and 2.8% of ARB users. In univariate logistic regression analyses, diabetes mellitus; serum glucose, total carbon dioxide content, creatinine, and estimated glomerular filtration rate (GFR) were significantly associated with hyperkalemia. ARB use, when compared to ACEI, was associated with a 42% increase in odds of hyperkalemia (odds ratio [OR] = 1.42; p = 0.001) in a model including adjustment for GFR and a 56% increase in odds of hyperkalemia (OR = 1.56; p < 0.001) in a model including adjustment for serum creatinine. Conclusions Hyperkalemia, associated with the use of ACEIs and ARBs, is usually mild and severe hyperkalemia is rare. Hyperkalemia is more common with ARBs than ACEIs. ARB use, when compared to ACEI use, may significantly and independently be associated with increased odds of hyperkalemia.
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Affiliation(s)
- Seyed Ali Sadjadi
- Section of Nephrology (111N), Jerry L Pettis Memorial Veterans Medical Center, Loma Linda, CA, USA
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Heagerty AM, Mallion JM. Olmesartan Medoxomil in Elderly Patients with Essential or Isolated Systolic Hypertension. Drugs Aging 2009; 26:61-76. [DOI: 10.2165/0002512-200926010-00005] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/11/2023]
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Ueno H, Yoshimura M, Nakayama M, Yamamuro M, Nishijima T, Kusuhara K, Nagayoshi Y, Kojima S, Kaikita K, Sumida H, Sugiyama S, Ogawa H. Clinical factors affecting serum potassium concentration in cardio-renal decompensation syndrome. Int J Cardiol 2008; 138:174-81. [PMID: 18804879 DOI: 10.1016/j.ijcard.2008.08.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 02/25/2008] [Revised: 07/03/2008] [Accepted: 08/08/2008] [Indexed: 11/18/2022]
Abstract
BACKGROUND Renin-angiotensin-aldosterone system (RAAS) inhibitors are currently indispensable for the treatment of heart failure. It is well known that hyperkalemia is likely to occur in renal failure; however, it has not yet been clarified how the serum potassium concentration changes as heart failure progresses. Currently, the cardio-renal decompensation syndrome holds that the serum potassium concentration is altered similarly by both heart failure and renal failure; however, there are no definitive reports on this. In order to use RAAS inhibitors more safely and effectively in heart failure, it is necessary to understand the factors affecting serum potassium concentration in the clinical setting. METHODS AND RESULTS We examined the clinical factors affecting serum potassium concentration in 1035 consecutive patients with cardiovascular disease who were hospitalized in our institution. Multiple regression analysis showed that the independent factors associated with an elevated serum potassium concentration were renal insufficiency evaluated by estimated glomerular filtration rate (eGFR) (P<0.0001), diabetes mellitus evaluated by HbA(1c) (P=0.0005) and the use of RAAS inhibitors (P=0.0010). The independent factors associated with a decreased serum potassium concentration were mean blood pressure (P<0.0001), heart failure evaluated by log BNP (P=0.0164) and the use of diuretics (P=0.0232). CONCLUSIONS The serum potassium concentration decreases with the severity of heart failure if renal function is preserved. From the perspective of potassium homeostasis, we could use the RAAS inhibitors more aggressively in patients with heart failure who do not have renal failure.
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Affiliation(s)
- Hirofumi Ueno
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan
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