Spironolactone Add-on for Preventing or Slowing the Progression of Diabetic Nephropathy: A Meta-analysis

• Published in: Clinical therapeutics Vol. 37; no. 9; pp. 2086 - 2103.e10
• Main Authors: Hou, Jing, MS, Xiong, Weiquan, MS, Cao, Ling, MS, Wen, Xiangqiong, MS, Li, Ailing, MS
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2015; Elsevier Limited
• Subjects: albuminuria; Albuminuria - urine; Antihypertensive Agents - therapeutic use; Blood pressure; Blood Pressure - drug effects; Creatinine - urine; Diabetes; Diabetic Nephropathies - complications; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - prevention & control; diabetic nephropathy; Disease Progression; Drug Therapy, Combination; Glomerular Filtration Rate - drug effects; Humans; hyperkalemia; Hyperkalemia - chemically induced; Hypertension - drug therapy; Hypoglycemic Agents - therapeutic use; Internal Medicine; Kidney diseases; Medical Education; Meta-analysis; Mineralocorticoid Receptor Antagonists - adverse effects; Mineralocorticoid Receptor Antagonists - therapeutic use; Plasma; Potassium; Potassium - blood; proteinuria; Rodents; spironolactone; Spironolactone - adverse effects; Spironolactone - therapeutic use; Studies; albuminuria; blood pressure; spironolactone; proteinuria; diabetic nephropathy; hyperkalemia
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2015.05.508

Abstract Purpose The aim of this meta-analysis was to evaluate the benefits and potential adverse effects of adding spironolactone to standard antidiabetic/renoprotective/antihypertensive (AD/RP/AHT) treatment in patients with diabetic nephropathy (DN). Methods PubMed/MEDLINE and Web of Knowledge were searched for relevant randomized, controlled studies (RCTs) or quasi-RCTs of the effects of adding spironolactone to standard AD/RP/AHT treatment in patients with DN. Results were summarized with a random-effects model or a fixed-effects model. Findings According to the outcomes measured (benefits and risks of adding spironolactone to standard AD/RP/AHT treatment), compared with controls, the addition of spironolactone significantly decreased end-of-treatment (EOT) 24-hour urinary albumin/protein excretion and significantly increased percentage reduction from baseline in urinary albumin/creatinine ratio (UACR), although it did not significantly affect EOT UACR. The addition of spironolactone further led to a significantly greater reduction from baseline in glomerular filtration rate (GFR)/estimated (e) GFR, although it did not significantly affect EOT GFR/eGFR. Further, the addition of spironolactone significantly reduced EOT in-office, 24-hour, and daytime systolic and diastolic blood pressure (SBP and DBP, respectively) and led to significantly greater reductions from baseline in in-office SBP and DBP, although it did not significantly affect nighttime SBP or DBP. Finally, the addition of spironolactone significantly increased mean serum/plasma potassium levels and the risk for hyperkalemia. Implications Spironolactone could be added to preexisting AD/RP/AHT therapy in patients with DN to prevent or slow DN progression by reducing proteinuria. The addition of spironolactone would likely provide even more beneficial effect in patients with DN and hypertension due to the BP reduction associated with spironolactone use. However, the beneficial effects of spironolactone add-on should be weighed against its potential risks, especially hyperkalemia. The long-term effects of spironolactone add-on on renal outcomes and mortality need to be studied.