BACKGROUND AND OBJECTIVES:Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the cornerstones of pharmacologic therapy in diabetic nephropathy. Mineralocorticoid receptor blockers reduce proteinuria as single agents or add-on therapy to other renin-angiotensin-aldosterone system-inhibiting drugs in these patients. The long-term benefits and ultimate role of mineralocorticoid receptor blockers in diabetic nephropathy remain unknown. A clinical trial previously showed that the kalemic effect of spironolactone is higher than losartan when added to lisinopril in patients with diabetic nephropathy. The purpose of this study was to investigate if renal potassium handling was primarily responsible for that observation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a blinded, randomized, three-arm placebo-controlled clinical trial, 80 participants with diabetic nephropathy taking lisinopril (80 mg) were randomized to spironolactone (25 mg daily), losartan (100 mg daily), or placebo (trial dates from July of 2003 to December of 2006). Serum potassium, aldosterone, and 24-hour urine sodium, potassium, and creatinine were measured over 48 weeks. Differences were analyzed with repeated measures mixed models. RESULTS: Mean follow-up serum potassium was 5.0 mEq/L for spironolactone, 4.7 mEq/L for losartan (P=0.05 versus spironolactone), and 4.5 mEq/L for placebo (P<0.001 versus spironolactone; P=0.03 versus losartan). The difference in serum potassium was 0.23 mEq/L for losartan versus placebo (P=0.02), 0.43 mEq/L for spironolactone versus placebo (P<0.001), and 0.2 mEq/L for spironolactone versus losartan (P=0.05). Serum and urine potassium excretion and secretion rates were similar between groups throughout the study. CONCLUSION:Spironolactone raised serum potassium more than losartan in patients with diabetic nephropathy receivinglisinopril, despite similar renal sodium and potassium excretion. This finding suggests that extrarenal potassium homeostasis contributes to hyperkalemia in these patients. A better understanding of extrarenal potassium homeostasis will provide an opportunity to use this drug more safely in patients with diabetic nephropathy as well as other patient populations.
RCT Entities:
BACKGROUND AND OBJECTIVES: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the cornerstones of pharmacologic therapy in diabetic nephropathy. Mineralocorticoid receptor blockers reduce proteinuria as single agents or add-on therapy to other renin-angiotensin-aldosterone system-inhibiting drugs in these patients. The long-term benefits and ultimate role of mineralocorticoid receptor blockers in diabetic nephropathy remain unknown. A clinical trial previously showed that the kalemic effect of spironolactone is higher than losartan when added to lisinopril in patients with diabetic nephropathy. The purpose of this study was to investigate if renal potassium handling was primarily responsible for that observation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a blinded, randomized, three-arm placebo-controlled clinical trial, 80 participants with diabetic nephropathy taking lisinopril (80 mg) were randomized to spironolactone (25 mg daily), losartan (100 mg daily), or placebo (trial dates from July of 2003 to December of 2006). Serum potassium, aldosterone, and 24-hour urine sodium, potassium, and creatinine were measured over 48 weeks. Differences were analyzed with repeated measures mixed models. RESULTS: Mean follow-up serum potassium was 5.0 mEq/L for spironolactone, 4.7 mEq/L for losartan (P=0.05 versus spironolactone), and 4.5 mEq/L for placebo (P<0.001 versus spironolactone; P=0.03 versus losartan). The difference in serum potassium was 0.23 mEq/L for losartan versus placebo (P=0.02), 0.43 mEq/L for spironolactone versus placebo (P<0.001), and 0.2 mEq/L for spironolactone versus losartan (P=0.05). Serum and urine potassium excretion and secretion rates were similar between groups throughout the study. CONCLUSION:Spironolactone raised serum potassium more than losartan in patients with diabetic nephropathy receiving lisinopril, despite similar renal sodium and potassium excretion. This finding suggests that extrarenal potassium homeostasis contributes to hyperkalemia in these patients. A better understanding of extrarenal potassium homeostasis will provide an opportunity to use this drug more safely in patients with diabetic nephropathy as well as other patient populations.
Authors: E J Lewis; L G Hunsicker; W R Clarke; T Berl; M A Pohl; J B Lewis; E Ritz; R C Atkins; R Rohde; I Raz Journal: N Engl J Med Date: 2001-09-20 Impact factor: 91.245
Authors: B M Brenner; M E Cooper; D de Zeeuw; W F Keane; W E Mitch; H H Parving; G Remuzzi; S M Snapinn; Z Zhang; S Shahinfar Journal: N Engl J Med Date: 2001-09-20 Impact factor: 91.245
Authors: G L Bakris; M Siomos; D Richardson; I Janssen; W K Bolton; L Hebert; R Agarwal; D Catanzaro Journal: Kidney Int Date: 2000-11 Impact factor: 10.612
Authors: Bertram Pitt; Willem Remme; Faiez Zannad; James Neaton; Felipe Martinez; Barbara Roniker; Richard Bittman; Steve Hurley; Jay Kleiman; Marjorie Gatlin Journal: N Engl J Med Date: 2003-03-31 Impact factor: 91.245
Authors: Raquel Esteras; Maria Vanessa Perez-Gomez; Laura Rodriguez-Osorio; Alberto Ortiz; Beatriz Fernandez-Fernandez Journal: Ther Adv Drug Saf Date: 2015-08
Authors: Edmund Ym Chung; Marinella Ruospo; Patrizia Natale; Davide Bolignano; Sankar D Navaneethan; Suetonia C Palmer; Giovanni Fm Strippoli Journal: Cochrane Database Syst Rev Date: 2020-10-27