FACTORS INFLUENCING PROGRESSION OF RENAL-FAILURE IN AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE

Autosomal dominant polycystic kidney disease (ADPKD) frequently leads to end-stage renal failure (ESRF) in the sixth decade of life, but con siderable heterogeneity exists in the rate of progression of renal fai lure, The respective contribution of genetic factors and of potentiall y amendable factors, such as blood pressure control or protein intake limitation, on the rate of progression in ADPKD patients is still deba ted. To evaluate the role of factors influencing the rate of progressi on of renal failure in ADPKD, we retrospectively analyzed the annual r ate of decline of creatinine clearance (Ccr) in 109 ADPKD patients fol lowed from the time a Ccr value of 30 to 50 mt per min/1.73 m(2) was m easured until ESRD and need for hemodialysis (Study A), and in 48 undi alyzed ADPKD patients followed for at least 4 yr from the time a Ccr v alue of 50 to 60 mt per min/1.73 m(2) was measured (Study B). In Study A, the decline in Ccr (Delta Ccr) (mean +/- SE) was 5.8 +/- 0.2 mt pe r min/1.73 m(2) per year in the whole series, and was lower in females than in males (5.0 +/- 0.2 versus 6.4 +/- 0.2, P < 0.001). Accordingl y, ESRF was reached at a later age in female patients (55,1 +/- 1.2 ve rsus 50.6 +/- 1.2 yr, P < 0.01). The age at ESRF in male patients was lower when the disease was transmitted by mother than by father (46.3 +/- 1.9 versus 54.1 +/- 1.8 yr, P < 0.01), whereas no significant effe ct of the gender of the affected parent was apparent in female patient s. By regression analysis, there was a positive but weak relationship between Delta Ccr and mean arterial pressure (average value during fol low-up, 107 +/- 1 mm Hg, r = 0.224, P < 0.05) but not with dietary pro tein intake (mean value in follow-up, 0.87 +/- 0.03 g/kg per day, r = 0.10, P = 0.33) nor with proteinuria at baseline, which was lower than 0.3 g/day in 104 cases (r = 0.10, P = 0.28), There was a negative rel ationship between age at ESRF and Delta Ccr (r = 0.245, P < 0.05), wit h a later and slower progression in older subjects. In Study B, the me an decline in renal function during follow-up was 5.3 +/- 0.4 mL/min/1 .73 m(2) per year, a value close to that observed in Study A. By multi ple regression analysis of the overall population (studies A and B com bined), only MAP, age and gender were independent predictive factors o f Delta Ccr but all studied parameters taken together accounted for at best 20% of Delta Ccr variation. We conclude that the rate of progres sion of renal failure in ADPKD patients is mainly determined by gene e xpression, with female gender and older age associated with a slower p rogression, whereas blood pressure control, but not protein intake, ex erts a limited beneficial influence on the rate of progression in pati ents with advanced polycystic kidney disease who already have signific ant renal insufficiency.