Evaluation of spironolactone plus hydrochlorothiazide in reducing proteinuria in type 2 diabetic nephropathy (original) (raw)
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Diabetes Care, 2005
OBJECTIVE-The objective of this study was to evaluate the safety and short-term effect of adding spironolactone to conventional antihypertensive treatment including diuretics and maximally recommended doses of an ACE inhibitor or an angiotensin II receptor blocker (ARB) on albuminuria and blood pressure in type 2 diabetic patients with nephropathy. RESEARCH DESIGN AND METHODS-Twenty-one type 2 diabetic patients with nephropathy were enrolled in a randomized, double-masked, cross-over study. Patients were treated in random order with spironolactone 25 mg once daily and matched placebo for 8 weeks, respectively, in addition to ongoing antihypertensive treatment including diuretics and maximally recommended doses of an ACE inhibitor and/or an ARB. At the end of each treatment period, albuminuria, 24-h ambulatory blood pressure (ABP), and glomerular filtration rate (GFR) were determined. RESULTS-During the addition of placebo, values were as follows: albuminuria (geometric mean [range]) 1,566 [655-7,762] mg/24 h, ABP (mean Ϯ SE) 138 Ϯ 3/71 Ϯ 1 mmHg, and GFR (mean Ϯ SE) 74 Ϯ 6 ml/min per 1.73 m 2. During the addition of spironolactone, albuminuria was reduced by 33% (95% CI 25-41) (P Ͻ 0.001), fractional clearance of albumin by 40% (24-53) (P Ͻ 0.001), and 24-h ABP by 6 mmHg (2-10) for systolic and 4 mmHg (2-6) for diastolic (P Ͻ 0.001 for both). The change in albuminuria did not correlate with the change in systolic 24-h ABP (r ϭ 0.19, P ϭ 0.42) or diastolic 24-h ABP (r ϭ 0.01, P ϭ 0.96). Spironolactone treatment induced an insignificant reversible reduction in GFR of 3 ml/min per 1.73 m 2 (Ϫ0.3 to 6) (P ϭ 0.08). One patient was excluded from the study due to hyperkalemia. Otherwise treatment was well tolerated. CONCLUSIONS-Our study suggests that spironolactone safely adds to the reno-and cardiovascular protective benefits of treatment with maximally recommended doses of ACE inhibitor and ARB by reducing albuminuria and blood pressure in type 2 diabetic patients with nephropathy.
Nephro-Urology Monthly, 2014
Background: Diabetic nephropathy is the most important cause of end stage renal disease (ESRD). Aldosterone is involved in renal damage through induction of fibrosis, inflammation and necrosis in the kidney tissue. Previous studies have demonstrated that the combination of angiotensin receptor blocker (ARB) and spironolactone (an anti-aldosterone drug) are efficient for albuminuria reduction. Objectives: This study was designed to evaluate the effect of spironolactone alone on diabetic nephropathy. Patients and Methods: In this double blind randomized clinical trial, 60 type II diabetic patients with microalbuminuria were enrolled. They were divided into two groups: case group (spironolactone 25 mg and placebo, 30 cases) and control (spironolactone 25 mg plus losartan 25 mg, 30 cases). The treatment success rate (more than 50% reduction in microalbuminuria) was compared between the two groups. Results: After three months, successful treatment was seen in 70% (95% CI: 52-83) and 83.3% (CI 95%: 66-93) of case and control groups, respectively (P = 0.4). Mean ± SD of serum potassium levels after three months in case and control groups were 4.56 ± 0.38 and 4.39 ± 0.34 mEq/L, respectively (P = 0.08). Mean ± SD of systolic blood pressures in case and control groups were 129.67 ± 9.4 and 130.97 ± 9.4 mmHg, respectively (P = 0.6). Mean ± SD of serum creatinine levels at the end of the study were 0.95 ± 0.15 in case and 0.90 ± 0.22 mg/dL in control group (P = 0.4). Conclusions: Spironolactone alone is as effective as the combination of spironolactone and losartan on albuminuria reduction in type 2 diabetic patients and can be used alone as an effective drug for diabetic nephropathy.
Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy
Kidney International, 2006
Reduction of nephrotic range albuminuria is associated with markedly improved renal and cardiovascular outcome in patients with diabetic nephropathy. Aldosterone has been suggested to play a role in the progression of diabetic nephropathy. We therefore aimed to evaluate the short-term effect of aldosterone antagonism with spironolactone on nephrotic range albuminuria and blood pressure in diabetic nephropathy. Twenty Caucasian patients with diabetic nephropathy and nephrotic range albuminuria (42500 mg/ 24 h) despite recommended antihypertensive treatment completed this double-masked, randomized crossover trial. Patients were treated in random order with spironolactone 25 mg once daily and matched placebo for 2 months, on top of ongoing antihypertensive treatment, including an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker in maximally recommended doses. Median (range) number of antihypertensive drugs was 3 (2-5). After each treatment period, albuminuria, 24-h ambulatory blood pressure, and glomerular filtration rate (GFR) were determined. Spironolactone on top of recommended renoprotective treatment induced a 32% (95% confidence interval (CI): 21-42%) reduction in albuminuria from (geometric mean (95% CI)) 3718 (2910-4749) mg/24 h on placebo treatment (Po0.001). There was a significant reduction in 24-h blood pressure of 6 (2-10)/4 (2-6) mm Hg and day blood pressure of 7 (3-12)/5 (3-7) mm Hg (Po0.01), whereas night blood pressure remained unchanged. Spironolactone induced an insignificant reversible reduction in GFR of 3 ml/min/1.73 m 2 from 64 (27) ml/min/1.73 m 2 . No patients were excluded due to adverse events. Our results suggest that spironolactone treatment on top of recommended renoprotective treatment including maximal renin-angiotensin system blockade may offer additional renoprotection in patients with diabetic nephropathy and nephrotic range albuminuria.
Clinical and experimental nephrology, 2015
Several studies have demonstrated that spironolactone has an anti-albuminuric property in diabetic nephropathy. As an adverse event, spironolactone often induces the elevation of creatinine levels with hypotension and hyperkalemia. Therefore, we aimed to evaluate the efficacy and safety of spironolactone in Japanese patients with type 2 diabetes treated with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Fifty-two Japanese patients with diabetic nephropathy and albuminuria (100 mg/gCr-2000 mg/gCr) treated with renin-angiotensin system (RAS) blockade were enrolled in a prospective, randomized, open-label study. The patients were subjected to add-on treatment with spironolactone 25 mg once daily and compared with matched controls for 8 weeks. The primary outcome was a reduction in the rate of albuminuria at 8 weeks compared with the baseline value. This study was registered with UMIN Clinical Trials Registry (000008016). Albuminuria was reduced by 33...
Caspian journal of internal medicine, 2013
Early diagnosis of albuminuria and the prevention of its progression to macroalbuminuria and diabetic nephropathy are crucial. Angiotensin converting enzyme inhibitors (ACEIs) and antagonists of angiotensin II receptors type I (ARBs) are currently used as first-line treatment for albuminuria in these patients. The present study was conducted to assess the efficacy of addition of spironolactone to ACEIs or ARB in the prevention of diabetic nephropathy. Sixty patients were selected from the patients who referred to a Diabetes Clinic in this randomized clinical trial study. The control group received enalapril and the case group took additive therapy with spironolactone for 12 weeks. Blood pressure, concentrations of creatinine and albumin in the serum and urine, urinary albumin/creatinine ratio, serum potassium were determined for each patient in the beginning of and every 4-6 weeks until the end of the study. This clinical trial was registered in the Iranian Registry of Clinical Tria...
Jundishapur Journal of Natural Pharmaceutical Products, 2015
Background: Chronic kidney disease is a persistent disorder in kidney function. This is a progressive disorder characterized by arterial hypertension, glomerular hypertension, proteinuria and some other signs; controlling any of them can reduce the progression of chronic kidney disease. In chronic kidney disease, proteinuria is used as a measure for monitoring nephron injuries and its response to treatment. Angiotensin converting enzyme inhibitors and Angiotensin receptor blockers can reduce the progression of chronic kidney disease by inhibition of Renin-Angiotensin-Aldosterone system and reduction of glomerular pressure and controlling proteinuria. However, none of them can control plasma aldosterone level appropriately. Aldosterone produces Transforming growth factor-b (TGF-b), which induces proliferation of fibroblasts and glomerulosclerosis and accelerates chronic kidney disease. Aldosterone antagonist can increase useful effects of angiotensin-converting-enzyme inhibitor (ACEI) and Angiotensin receptor blockers (ARB) Drugs. Objectives: The study was designed to assess the effects of spironolactone as the aldosterone antagonist combined with ACEI or ARB drugs to reduce proteinuria in chronic kidney disease to prevent its progression. Patients and Methods: This was a semi-experimental without control study. Eighty patients treated for at least two months with ACEI or ARB with uncontrolled proteinuria above 0.9g/dL were treated with 25mg/d spironolactone for two months. 24-hour urine protein and some other variables were measured at the beginning of the study, after two months treatment and one month after discontinuing the treatment. Results: Administration of 25 mg/d spironolactone combined with ACEI or ARB for two months led to mean reduction of 24 h-urine protein from 2796.1 to 1857.4. No hyperkalemia or change in glomerular filtration rate occurred. One month after discontinuation of spironolactone, proteinuria returned to baseline level. Persistence of reduction in proteinuria in patients receiving ARBs was more than those taking ACEIs. Conclusions: Spironolactone combined with ACEIs or ARBs leads to reduction of proteinuria in chronic kidney disease and therefore reduction of progression of the disease.
Kidney International, 2006
Experimental evidence suggests that aldosterone contributes to progressive kidney disease. Angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor antagonists suppress the renin-angiotensin system but they do not effectively reduce plasma aldosterone. Hence, administration of aldosterone receptor antagonists may provide additional renal protection. In the present prospective randomized open-label study, we evaluated the effects of spironolactone (25 mg/day for 1 year) on proteinuria and estimated glomerular filtration rate in 83 patients with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists. Eighty-two patients were treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists alone and served as controls. After 1 year of therapy, proteinuria decreased from 2.170.08 to 0.8970.06 g/g creatinine (Po0.001) in patients treated with spironolactone, but it did not change in control patients. Baseline aldosterone levels were significantly correlated with proteinuria (r ¼ 0.76, Po0.0001), and predicted the degree of reduction in proteinuria with spironolactone (r ¼ 0.42, Po0.0002). Baseline estimated glomerular filtration rate was similar in patients treated with spironolactone and controls (62.472.4 and 62.272.1 ml/min/1.73 m 2 , respectively). After 1 month of therapy with spironolactone, estimated glomerular filtration rate decreased more in patients treated with spironolactone than in controls. However, by the end of 1 year the monthly rate of decrease in estimated glomerular filtration rate from baseline was lower in patients treated with spironolactone than in controls (0.32370.044 vs 0.47470.037 ml/min/ 1.73 m 2 , Po0.01). Spironolactone caused a significant rise in serum potassium levels (from 4.270.04 at baseline to 5.070.05 mEq/l after 12 months of treatment, Po0.001). In conclusion, this study has shown that spironolactone may reduce proteinuria and retard renal progression in chronic kidney disease patients.
Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy
Clinical Journal of the American Society of Nephrology, 2014
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.
New modalities for treatment of diabetic nephropathy: a mini review
International journal of epidemiologic research, 2015
Background and aims: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure which could increase the risk of cardiovascular disease and morbidity and mortality in patients. The aim of this study was to investigate new modalities for treatment of diabetic nephropathy. Methods:This study was a mini-review research to investigate drugs that are used for DN treatment. Results: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptors blocker (ARB) are the bases of DN treatment during recent decades. Due to some of adverse reactions of these drugs like hyperkalemia and chronic cough, other drugs such as non dihydropridin Ca channel blockers, uric acid lowering drugs, renin antagonists, lipid lowering agents, oral hypoglycemic agents such as Thiazolidinediones, Vitamin D and selective endothelin receptor antagonists have been used in some studies for decreasing proteinuria and slowing progression of DN. The results of these studies are different and ...