Aldosterone antagonists for preventing the progression of chronic kidney disease

Evidence Summaries

Level of Evidence = D
Aldosterone antagonists might possibly reduce proteinuria in patients with chronic kidney disease who are already on angiotensin converting enzyme inhibitors and angiotensin receptor blockers although the evidence is insufficient and long-term effects on renal outcomes, mortality and safety are unknown. They appear to increase the risk of hyperkalaemia.

A Cochrane review 1 included 27 studies with a total of 1,549 subjects. Compared to angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) plus placebo, non-selective aldosterone antagonists (spirololactone) combined with ACEi and/or ARB (or both) significantly reduced 24 hour proteinuria (MD -0.61 g, 95% CI -1.08 to -0.13;11 studies, n=596; significant heterogeneity, I²= 76%). There was a significant reduction in both systolic (MD -3.44 mm Hg, 95% CI -5.05 to -1.83; 10 studies, n=556) and diastolic (MD -1.73 mm Hg, 95% CI -2.83 to -0.62; 9 studies, n=520) blood pressure with the addition of non-selective aldosterone antagonists to ACEi and/or ARB. This did not translate into a clear improvement in glomerular filtration rate (MD -2.55 mL/min/1.73 m², 95% CI -5.67 to 0.51; 9 studies, n=528). There was a significant increase in the risk of hyperkalaemia with the addition of non-selective aldosterone antagonists to ACEi and/or ARB (RR 2.00, 95% CI 1.25 to 3.20; 11 studies, n=632; number needed to treat for an additional harmful outcome (NNH): 7.2, 95% CI 3.4 to ∞) and increased the risk of gynaecomastia compared to ACEi or ARB (or both) (RR 5.14, 95% CI 1.14 to 23.23; 4 studies, n=281;NNH: 14.1, 95% CI 8.7 to 37.3).

Comment: The quality of evidence is downgraded by study quality (lack of blinding and inadequate intention-to-treat adherence), by indirectness (short follow-up time and only surrogate outcomes), and by imprecise results (limited study size for each comparison).

References

1. Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev 2009;(3):CD007004 [Review content assessed as up-to-date: 30 January 2013].  [PMID:19588415]


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