Evaluation of spironolactone plus hydrochlorothiazide in reducing proteinuria in type 2 diabetic nephropathy

Abstract

Introduction: Inhibitors of the renin-angiotensin aldosterone system (RAAS) are the basic drugs for treatment of diabetic nephropathy, as to some extent is spironolactone. The aim of the study was to evaluate the effect of spironolactone versus spironolactone plus hydrochlorothiazide in decreasing proteinuria in type 2 diabetic mellitus (T2DM) patients. Methods: In a double-blind clinical trial, 60 T2DM patients with nephropathy randomly assigned to three equal groups were enrolled. Spironolactone (50 mg/day) plus placebo, spironolactone (50 mg/day) plus hydrochlorothiazide (25 mg/day), and hydrochlorothiazide (25 mg/day) plus placebo were prescribed, respectively. The duration of treatment was three months for all patients. Urine protein was measured at the beginning and end of the study and analysis of data was performed. Results: Twenty-six of the patients were male, with a total mean age of 56.8±8.3 years. Mean 24-h urine protein was reduced in patients in groups 1 and 2 compared to the third group (p < 0.001). Serum potassium in the first group showed a significant increase of 0.26 meq/lit with mean 4.64 ± 0.28 meq/lit (p=0.002), but it did not change in the second and third groups. Conclusion: Our results showed that spironolactone plus hydrochlorothiazide is an effective and inexpensive modality in the treatment of diabetic nephropathy without increasing serum potassium.

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

“…From a total of 236 potentially eligible studies, 220 were excluded because they were not relevant to the study objectives; were reviews, meeting abstracts, case-only studies (ie, a control group [in which control medication or placebo was added to standard AD/RP/AHT treatment] was not included); or contained no detailed, usable data necessary for the meta-analysis. A total of 16 studies 23,28,34,35,[42][43][44][45][46][47][48][49][50][51][52][53] were included in the present metaanalysis and are described in the table (see also Supplemental Tables 1A-3B in the online version 28,34,43,45,47,49,52,53 ; and hyperkalemia, 12 studies (spironolactone, 319; control, 295). 28,34,35,[43][44][45][46]48,49,50,52,53 Effects of the Addition of Spironolactone on Urinary Protein/Albumin Excretion Compared with controls, the addition of spironolactone to standard AD/RP/AHT treatment significantly reduced end-of-treatment 24-hour urinary albumin/protein excretion (MD = -61.48; 95% CI, -96.74 to -26.23; P = 0.0006) (Figure 2A).…”

“…First, most of the included studies were short-term, and long-term studies were lacking. For example, only 1 35 of the 8 studies included in the analysis of the effects of the addition of spironolactone on EOT urinary albumin/protein excretion was long-term (41 year), whereas the other 7 studies 28,34,43,45,[49][50][51] were all short-term (a couple of months). Thus, the long-term effects of the addition of spironolactone are still unclear.…”

Impact of vitamin D therapy on decreasing of proteinuria in type 2 diabetic patients

“…In addition to angiotensin converting enzyme inhibitors and angiotensin receptor blockers, other drugs such as spironolactone (aldosterone receptor blocker)(14), non- dihydropyridine calcium channel blockers (diltiazem), antihyperlipidemic agents (20), allopurinol (12) were used in the treatment of DN. …”

“…Spironolactone an aldosterone receptor blocker probably has renoprotective effect due to its anti-inflammatory property (13). In addition, combination of spironolactone and hydrochlorothiazide may be effective in DN treatment (14). …”

Efficacy and safety of mineralocorticoid receptor antagonists with ACEI/ARB treatment for diabetic nephropathy: A meta‐analysis

“…Fortunately, a newly developed third-generation drugs of MRAs, finerenone, was associated with a fewer episodes of hyperkalaemia. 15 Two studies have analyzed the effects of adding MRAs to patients with DN, 16,17 but the included trials [18][19][20][21] evaluated difference between the clinical effects of MRAs plus ACEI/ARB and other drugs (thiazide, furosemide and ACEI, etc) plus ACEI/ARB. Treatments of thiazide/furosemide/ACEI certainly caused an extra influence on renal outcomes, for example, blood pressure, compared with placebo.…”