Aldosterone antagonists for preventing the progression of chronic kidney disease

Abstract

Aldosterone antagonists reduced proteinuria and blood pressure in adults who had mild to moderate CKD and were treated with ACEi or ARB (or both), but increase hyperkalaemia and gynaecomastia. Whether adding aldosterone antagonists to ACEi or ARB (or both) reduced the risk of major cardiovascular events or ESKD in this population is unknown.

Finerenone Attenuates Endothelial Dysfunction and Albuminuria in a Chronic Kidney Disease Model by a Reduction in Oxidative Stress

“…The beneficial effect of finerenone on the restoration of endothelial function in MWF by an increase in peNOS Ser1177 /eNOS, and thus in both basal and stimulated NO availability, is in accordance with previous data demonstrating that MR signaling contributes to endothelial dysfunction ( Quaschning et al, 2001 ; Virdis et al, 2002 ; Sanz-Rosa et al, 2005 ; Bolignano et al, 2014 ). Moreover, finerenone has demonstrated beneficial effects on the endothelium, reducing endothelial cell apoptosis and re-endothelialization in a model of neointima formation ( Dutzmann et al, 2017 ).…”

Finerenone Attenuates Endothelial Dysfunction and Albuminuria in a Chronic Kidney Disease Model by a Reduction in Oxidative Stress

“…The beneficial effect of finerenone on the restoration of endothelial function in MWF by an increase in peNOS Ser1177 /eNOS, and thus in both basal and stimulated NO availability, is in accordance with previous data demonstrating that MR signaling contributes to endothelial dysfunction ( Quaschning et al, 2001 ; Virdis et al, 2002 ; Sanz-Rosa et al, 2005 ; Bolignano et al, 2014 ). Moreover, finerenone has demonstrated beneficial effects on the endothelium, reducing endothelial cell apoptosis and re-endothelialization in a model of neointima formation ( Dutzmann et al, 2017 ).…”

Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis

“…Data from the ONTARGET study showed that combination ACE–I and ARB increased risk of dialysis, doubling of creatinine or death and combination treatment is not recommended in clinical guidelines [44]. We show an average potassium increase of 0.19 mmol/L at end of treatment (similar to previous data [15, 16]) and three times greater risk of hyperkalaemia in patients receiving MRA in addition to ACE-I and/or ARB. It is essential to consider that this does not necessarily equate to risk of developing clinically significant hyperkalaemia requiring treatment, rather of developing a serum potassium level above the predefined study upper limit, which in many trials was 5.5–6 mmol/L.…”

“…These findings are in keeping with previous published meta-analyses [15, 16, 20]. By using additional unpublished summary results from a number of authors, we ensure that our protein/albumin excretion data are more comprehensive and hence more accurate.…”

Effects of Spironolactone and Chlorthalidone on Cardiovascular Structure and Function in Chronic Kidney Disease

“…The effect of chlorthalidone on office systolic BP in this study was similar to that observed in participants with CKD treated with chlorthalidone in the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in whom systolic BP was reduced by approximately 11 mm Hg over a 6-year treatment period (36). Several recent meta-analyses of the effects of mineralocorticoid receptor blockers in stage 3–4 CKD have shown similar reductions in BP to those seen in this study with spironolactone (37 –39). In addition, these studies suggest possible beneficial effects on kidney function with consistent reductions in proteinuria, although there were small excess risks of hyperkalemia (38 –40).…”

Finerenone Attenuates Endothelial Dysfunction and Albuminuria in a Chronic Kidney Disease Model by a Reduction in Oxidative Stress

“…The beneficial effect of finerenone on the restoration of endothelial function in MWF by an increase in peNOS Ser1177 /eNOS, and thus in both basal and stimulated NO availability, is in accordance with previous data demonstrating that MR signaling contributes to endothelial dysfunction ( Quaschning et al, 2001 ; Virdis et al, 2002 ; Sanz-Rosa et al, 2005 ; Bolignano et al, 2014 ). Moreover, finerenone has demonstrated beneficial effects on the endothelium, reducing endothelial cell apoptosis and re-endothelialization in a model of neointima formation ( Dutzmann et al, 2017 ).…”

Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis

“…Data from the ONTARGET study showed that combination ACE–I and ARB increased risk of dialysis, doubling of creatinine or death and combination treatment is not recommended in clinical guidelines [44]. We show an average potassium increase of 0.19 mmol/L at end of treatment (similar to previous data [15, 16]) and three times greater risk of hyperkalaemia in patients receiving MRA in addition to ACE-I and/or ARB. It is essential to consider that this does not necessarily equate to risk of developing clinically significant hyperkalaemia requiring treatment, rather of developing a serum potassium level above the predefined study upper limit, which in many trials was 5.5–6 mmol/L.…”

“…These findings are in keeping with previous published meta-analyses [15, 16, 20]. By using additional unpublished summary results from a number of authors, we ensure that our protein/albumin excretion data are more comprehensive and hence more accurate.…”

Effects of Spironolactone and Chlorthalidone on Cardiovascular Structure and Function in Chronic Kidney Disease

“…The effect of chlorthalidone on office systolic BP in this study was similar to that observed in participants with CKD treated with chlorthalidone in the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in whom systolic BP was reduced by approximately 11 mm Hg over a 6-year treatment period (36). Several recent meta-analyses of the effects of mineralocorticoid receptor blockers in stage 3–4 CKD have shown similar reductions in BP to those seen in this study with spironolactone (37 –39). In addition, these studies suggest possible beneficial effects on kidney function with consistent reductions in proteinuria, although there were small excess risks of hyperkalemia (38 –40).…”

Finerenone Attenuates Endothelial Dysfunction and Albuminuria in a Chronic Kidney Disease Model by a Reduction in Oxidative Stress

“…The beneficial effect of finerenone on the restoration of endothelial function in MWF by an increase in peNOS Ser1177 /eNOS, and thus in both basal and stimulated NO availability, is in accordance with previous data demonstrating that MR signaling contributes to endothelial dysfunction ( Quaschning et al, 2001 ; Virdis et al, 2002 ; Sanz-Rosa et al, 2005 ; Bolignano et al, 2014 ). Moreover, finerenone has demonstrated beneficial effects on the endothelium, reducing endothelial cell apoptosis and re-endothelialization in a model of neointima formation ( Dutzmann et al, 2017 ).…”

Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis

“…Data from the ONTARGET study showed that combination ACE–I and ARB increased risk of dialysis, doubling of creatinine or death and combination treatment is not recommended in clinical guidelines [44]. We show an average potassium increase of 0.19 mmol/L at end of treatment (similar to previous data [15, 16]) and three times greater risk of hyperkalaemia in patients receiving MRA in addition to ACE-I and/or ARB. It is essential to consider that this does not necessarily equate to risk of developing clinically significant hyperkalaemia requiring treatment, rather of developing a serum potassium level above the predefined study upper limit, which in many trials was 5.5–6 mmol/L.…”

“…These findings are in keeping with previous published meta-analyses [15, 16, 20]. By using additional unpublished summary results from a number of authors, we ensure that our protein/albumin excretion data are more comprehensive and hence more accurate.…”

Effects of Spironolactone and Chlorthalidone on Cardiovascular Structure and Function in Chronic Kidney Disease

“…The effect of chlorthalidone on office systolic BP in this study was similar to that observed in participants with CKD treated with chlorthalidone in the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in whom systolic BP was reduced by approximately 11 mm Hg over a 6-year treatment period (36). Several recent meta-analyses of the effects of mineralocorticoid receptor blockers in stage 3–4 CKD have shown similar reductions in BP to those seen in this study with spironolactone (37 –39). In addition, these studies suggest possible beneficial effects on kidney function with consistent reductions in proteinuria, although there were small excess risks of hyperkalemia (38 –40).…”