Effects of mineralocorticoid receptor antagonists on the progression of diabetic nephropathy

Abstract

Aims/introduction: We aimed to evaluate the potential benefits and adverse effects of adding a mineralocorticoid receptor antagonist (MRA) to angiotensin-converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB), as standard treatment in patients with diabetic nephropathy.

Materials and methods: We scanned the Embase, PubMed and Cochrane Central Register of Controlled Trials databases for human clinical trials published in English until June 2016, evaluating renal outcomes in patients with diabetic nephropathy.

Results: A total of 18 randomized controlled trials involving 1,786 patients were included. Compared with ACEI/ARB alone, co-administration of MRA and ACEI/ARB significantly reduced urinary albumin excretion and the urinary albumin-creatinine ratio (mean difference -69.38, 95% confidence intervals -103.53 to -35.22, P < 0.0001; mean difference -215.74, 95% confidence intervals -409.22 to -22.26, P = 0.03, respectively). A decrease of blood pressure was also found in the co-administration of MRA and ACEI/ARB groups. However, we did not observe any improvement in the glomerular filtration rate. There was a significant increase in the risk of hyperkalemia on the addition of MRA to ACEI/ARB treatment (relative risk 3.74, 95% confidence intervals 2.30-6.09, P < 0.00001).

Conclusions: These findings suggest that co-administration of MRA and ACEI/ARB has beneficial effects on renal outcomes with increasing the incidence of hyperkalemia.

Keywords: Diabetic nephropathy; Meta- analysis; Mineralocorticoid receptor antagonist.

Figure 1

Study flow chart for the process of selecting the final 18 randomized controlled trials (RCT).

Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study. Green refers to a low risk of bias, yellow refers to an unclear risk of bias, and red refers to a high risk of bias.

Figure 4

Forest plot of therapeutic effect on proteinuria in patients with diabetic nephropathy, pooled mean difference and 95% confidence interval (CI) for mineralocorticoid receptor antagonist (MRA) plus angiotensin‐converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB) therapy vs ACEI/ARB monotherapy. (a) Urinary albumin excretion (UAE) value at the end of the study. (b) Urinary albumin–creatinine ratio (UACR) value at the end of the study. (c) UACR percentage change from the baseline.

Figure 5

Forest plot of therapeutic effect on glomerular filtration rate (GFR) in patients with diabetic nephropathy, pooled mean difference and 95% confidence interval (CI) for mineralocorticoid receptor antagonist (MRA) plus angiotensin‐converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB) monotherapy. (a) GFR value at the end of the study. (b) GFR change from the baseline to the end of the study.

Figure 6

Forest plot of therapeutic effect on blood pressure in patients with diabetic nephropathy, pooled mean difference and 95% confidence interval (CI) for mineralocorticoid receptor antagonist (MRA) plus angiotensin‐converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB) monotherapy. (a) Systolic blood pressure value at the end of the study. (b) Diastolic blood pressure value at the end of the study. (c) Systolic blood pressure change from baseline to the end of the study. (d) Diastolic blood pressure change from baseline to the end of the study.

Figure 7

Forest plot of therapeutic effect on adverse events of hyperkalemia in patients with diabetic nephropathy, pooled relative risk and 95% confidence interval (CI) for mineralocorticoid receptor antagonist (MRA) plus angiotensin‐converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB) monotherapy.