scholarly journals Effects of canagliflozin on hyperkalaemia and serum potassium in people with diabetes and chronic kidney disease: insights from the CREDENCE trial

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
B L Neuen ◽  
M Oshima ◽  
V Perkovic ◽  
C Arnott ◽  
G Bakris ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Serum Potassium ◽  
Sglt2 Inhibitor ◽  
Renin Angiotensin System ◽  
Renin Angiotensin ◽  
Post Hoc Analysis ◽  
Intention To Treat ◽  
Potassium Binders ◽  
Post Hoc

Abstract Background Hyperkalaemia is a common complication of type 2 diabetes mellitus (T2DM) and limits the optimal use of agents that block the renin-angiotensin aldosterone system (RAAS), particularly in patients with chronic kidney disease (CKD). In patients with CKD, sodium glucose cotransporter 2 (SGLT2) inhibitors provide cardiorenal protection, but whether they affect the risk of hyperkalaemia remains uncertain. Purpose We sought to assess the effect of canagliflozin on hyperkalaemia and other potassium-related outcomes in people with T2DM and CKD by conducting a post-hoc analysis of the CREDENCE trial. Methods The CREDENCE trial randomized 4401 participants with T2DM and CKD to the SGLT2 inhibitor canagliflozin or matching placebo. In this post-hoc analysis using an intention-to-treat approach, we assessed the effect of canagliflozin on a composite outcome of time to either investigator-reported hyperkalaemia or the initiation of potassium binders. We also analysed effects on central laboratory-determined hyper- and hypokalaemia (serum potassium ≥6.0 and <3.5 mmol/L, respectively) and change in serum potassium. Results At baseline the mean serum potassium in canagliflozin and placebo arms was 4.5 mmol/L; 4395 (99.9%) participants were receiving renin angiotensin system blockade. Canagliflozin reduced the risk of investigator-reported hyperkalaemia or initiation of potassium binders (HR 0.78, 95% CI 0.64–0.95, p=0.014; Figure 1). The incidence of laboratory-determined hyperkalaemia was similarly reduced (HR 0.77, 95% CI 0.61–0.98, p=0.031; Figure 2); the risk of hypokalaemia (HR 0.92, 95% CI 0.71–1.20, p=0.53) was not increased. Mean serum potassium over time with canagliflozin was similar to that of placebo. Conclusion Among patients treated with RAAS inhibitors, SGLT2 inhibition with canagliflozin may reduce the risk of hyperkalaemia in people with T2DM and CKD without increasing the risk of hypokalaemia. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

scholarly journals Effect of sodium bicarbonate supplementation on the renin-angiotensin system in patients with chronic kidney disease and acidosis: a randomized clinical trial

2020 ◽  
Author(s):  
Dominique M. Bovée ◽  
Lodi C. W. Roksnoer ◽  
Cornelis van Kooten ◽  
Joris I. Rotmans ◽  
Liffert Vogt ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Sodium Chloride ◽  
Kidney Disease ◽  
Sodium Bicarbonate ◽  
Renin Angiotensin System ◽  
Ammonium Excretion ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Endothelin 1 ◽  
Plasma Bicarbonate

Abstract Background Acidosis-induced kidney injury is mediated by the intrarenal renin-angiotensin system, for which urinary renin is a potential marker. Therefore, we hypothesized that sodium bicarbonate supplementation reduces urinary renin excretion in patients with chronic kidney disease (CKD) and metabolic acidosis. Methods Patients with CKD stage G4 and plasma bicarbonate 15–24 mmol/l were randomized to receive sodium bicarbonate (3 × 1000 mg/day, ~ 0.5 mEq/kg), sodium chloride (2 × 1,00 mg/day), or no treatment for 4 weeks (n = 15/arm). The effects on urinary renin excretion (primary outcome), other plasma and urine parameters of the renin-angiotensin system, endothelin-1, and proteinuria were analyzed. Results Forty-five patients were included (62 ± 15 years, eGFR 21 ± 5 ml/min/1.73m2, plasma bicarbonate 21.7 ± 3.3 mmol/l). Sodium bicarbonate supplementation increased plasma bicarbonate (20.8 to 23.8 mmol/l) and reduced urinary ammonium excretion (15 to 8 mmol/day, both P < 0.05). Furthermore, a trend towards lower plasma aldosterone (291 to 204 ng/L, P = 0.07) and potassium (5.1 to 4.8 mmol/l, P = 0.06) was observed in patients receiving sodium bicarbonate. Sodium bicarbonate did not significantly change the urinary excretion of renin, angiotensinogen, aldosterone, endothelin-1, albumin, or α1-microglobulin. Sodium chloride supplementation reduced plasma renin (166 to 122 ng/L), and increased the urinary excretions of angiotensinogen, albumin, and α1-microglobulin (all P < 0.05). Conclusions Despite correction of acidosis and reduction in urinary ammonium excretion, sodium bicarbonate supplementation did not improve urinary markers of the renin-angiotensin system, endothelin-1, or proteinuria. Possible explanations include bicarbonate dose, short treatment time, or the inability of urinary renin to reflect intrarenal renin-angiotensin system activity. Graphic abstract

scholarly journals Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors

2016 ◽  
Vol 90 (3) ◽  
pp. 696-704 ◽  
Author(s):  
Matthew R. Weir ◽  
George L. Bakris ◽  
Coleman Gross ◽  
Martha R. Mayo ◽  
Dahlia Garza ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Stopping Renin-Angiotensin System Inhibitors in Chronic Kidney Disease: Predictors of Response

2011 ◽  
Vol 119 (4) ◽  
pp. c348-c354 ◽  
Author(s):  
Anderson Roman Gonçalves ◽  
Arif Khwaja ◽  
Aimune K. Ahmed ◽  
Mohsen El Kossi ◽  
Meguid El Nahas
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Predictors Of Response

Analysing the impact of a guideline for the use of new potassium binders for treatment of chronic hyperkalaemia to maximise inhibition of renin–angiotensin–aldosterone system (RAAS) within the general nephrology clinic?

2020 ◽  
Author(s):  
Priyank Patel ◽  
Andrew Frankel
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Ckd Stage ◽  
The Mean ◽  
Potassium Binders ◽  
The Impact ◽  
Chronic Use

Abstract Background Renin–angiotensin–aldosterone system (RAAS) inhibitors provide significant cardiorenal benefits with improved long-term outcomes for patients. This is most significant for patients receiving maximal RAAS inhibition, but some patients are unable to tolerate this therapy because of hyperkalaemia. Recently published National Institute for Health and Care Excellence (NICE) technology appraisal guidance recommended using sodium zirconium cyclosilicate (SZC) and patiromer for patients with chronic kidney disease (CKD) stage 3b to 5 or heart failure with reduced ejection fraction, who are not taking an optimised dosage of RAAS inhibitor because of hyperkalaemia. Objective Determine the impact of a locally produced guideline on effective implementation of NICE recommendation for use of SZC or patiromer to help maximise inhibition of the renin–angiotensin–aldosterone system within the general nephrology clinic. Methods A local guideline to practically support the implementation of recommendations made by NICE in the chronic use of new potassium binders was produced. One hundred sequential patients in a general nephrology clinic with non-immune chronic kidney disease (CKD 3 to 5) had their electronic records reviewed. Those with an indication for RAAS inhibition were identified. Results Of the 100 consecutive patients audited, 46 were female and 54 were male. The mean age of these patients was 64 and the mean estimated glomerular filtration rate (eGFR) was 33. Sixty-eight patients had an indication for being on RAAS inhibition with only 10 on maximal doses. Of the remaining 58 patients, 26 (45%) were limited by hyperkalaemia. Of these 26 patients, 12 of these patients (46%) had hyperkalaemia associated with an episode of acute kidney injury (AKI). Therefore, 14% of patients attending a general nephrology clinic were identified suitable for SZC and patiromer. Conclusions A significant proportion (14%) of unselected patients attending a general nephrology clinic were not on optimum RAAS inhibition due to hyperkalaemia. These patients would meet the criteria established within a working guideline for the implementation of the chronic use of SZC or patiromer and are likely to attain prognostic long-term benefit by using these new potassium binders to maximise RAAS inhibition. This analysis has implications for renal centres across the UK.

Increased heart rate is associated with intrarenal renin–angiotensin system activation in chronic kidney disease patients

2019 ◽  
Vol 23 (9) ◽  
pp. 1109-1118 ◽  
Author(s):  
Naro Ohashi ◽  
Shinsuke Isobe ◽  
Sayaka Ishigaki ◽  
Taro Aoki ◽  
Takashi Matsuyama ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Heart Rate ◽  
Kidney Disease ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
System Activation

scholarly journals Finerenone and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes

Circulation ◽  
2020 ◽  
Author(s):  
Gerasimos Filippatos ◽  
Stefan D. Anker ◽  
Rajiv Agarwal ◽  
Bertram Pitt ◽  
Luis M. Ruilope ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renin Angiotensin System ◽  
Mineralocorticoid Receptor Antagonist ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
History Of

Background: The FIDELIO-DKD trial evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) with optimized renin-angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and CV outcomes. We report the effect of finerenone on individual CV outcomes and in patients with and without history of atherosclerotic CV disease (CVD). Methods: This randomized, double-blind, placebo-controlled trial included patients with T2D and urine albumin-to-creatinine ratio 30-5000 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m 2 , treated with optimized renin-angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive finerenone or placebo. The composite CV outcome included time to CV death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified CV analyses included analyses of the components of this composite and outcomes according to CVD history at baseline. Results: Between September 2015 and June 2018, 13,911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0-3.4 years), finerenone reduced the risk of the composite CV outcome compared with placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.99; P=0.034), with no significant interaction between patients with and without CVD (HR, 0.85; 95% CI, 0.71-1.01 in patients with a history of CVD; HR, 0.86; 95% CI, 0.68-1.08 in patients without a history of CVD; P-value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone vs 0.8% with placebo in patients with CVD and 2.2% with finerenone vs 1.0% with placebo in patients without CVD). Conclusions: Among patients with CKD and T2D, finerenone reduced incidence of the composite CV outcome, with no evidence of differences in treatment effect based on pre-existing CVD status. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02540993 (Funded by Bayer AG)

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