Congenital Heart Disease and Autosomal Dominant Polycystic Kidney Disease

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Chedid M, Hanna C, Zaatari G, Mkhaimer Y, Reddy P, Rangel L, Zubidat D, Kaidbay D.H.N, Irazabal M.V, Connolly H.M, Senum S.R, Madsen C.D, Hogan M.C, Zoghby Z, Harris P.C, Torres V.E, Johnson J.N, Chebib F.T: Congenital Heart Disease in Adults with Autosomal Dominant Polycystic Kidney Disease. Am J Nephrol DOI 10.1159/000522377

The optimum dosage and preparation of renin-angiotensin system inhibitors (RASi) for slowing the progression of progressive proteinuric CKD remains somewhat uncertain, although it is generally appreciated that these agents exert their beneficial effects lately via lowering of systemic arterial and intra-glomerular capillary blood pressure. Both of these effects play a role in lowering the magnitude of proteinuria, and thus the rate of progression.

Suehiro and co-workers examined the relative effects of azilsartan and candesartan (both angiotensin receptor blockers; ARBs) on proteinuria and systemic arterial pressure in 111 patients with CKD (14% with diabetic kidney disease, 53% with chronic glomerulonephritis, and 28% with “hypertensive” nephropathy). The baseline proteinuria (urine protein to creatinine ratio; UPCR) was 1.8 ± 1.8 g/gCr and the eGFR was 42 ± 20 mL/min/1.73 m2. The average baseline blood pressure was 131/71 mm Hg. The dosage was 20 mg/day for azilsartan and 6 mg/day for candesartan. The trial was a randomized, cross-over design and the follow-up was 3 months. The primary endpoint was the percentage change in UPCR from baseline. Sodium chloride intake was not controlled.

At the end of study, the mean percentage change in UPCR was +6.1% in the azilsartan group and +25.8% in the candesartan group. Adverse events were similar. Average systolic blood declined at the end of the study in the azilsartan group and increased in the candesartan group. The change in UPCR was correlated with the decline in systemic arterial blood pressure.

This study confirms the generally well-known superior efficacy of azilsartan for blood pressure control, but only one dose (20 mg/day) was compared to one dose (6 mg/day) of candesartan. In the absence of a dose ranging study it is unknown whether the effects of higher doses of either agent would confirm this superiority of azilsartan over the entire range of commonly used dosages. Also, the lack of controlling for sodium chloride intake is a confounder in this study. The benefits on proteinuria track with the systemic anti-hypertensive effects, so it is unknown whether the superior anti-proteinuric effects of azilsartan are due to a systemic or an intra-renal effect (or both). The short duration of the study precluded any conclusions concerning beneficial effects on CKD progression. Nevertheless, this study does indicate that azilsartan might be the preferred agent for achieving blood pressure control and reducing proteinuria in patients with “generic” CKD. Larger and longer studies will be required to confirm this hypothesis and the beneficial effects may differ between the categories of CKD defined by etiology (particularly diabetic vs. glomerulo-nephritic CKD).

Richard Glassock

Quoted Karger Article

Congenital Heart Disease in Adults with Autosomal Dominant Polycystic Kidney Disease