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Autosomal dominant polycystic kidney disease (ADPKD) frequently leads to end-stage renal failure (ESRF) in the sixth decade of life, but considerable heterogeneity exists in the rate of progression of renal failure. The respective contribution of genetic factors and of potentially amendable factors, such as blood pressure control or protein intake limitation, on the rate of progression in ADPKD patients is still debated. To evaluate the role of factors influencing the rate of progression of renal failure in ADPKD, we retrospectively analyzed the annual rate of decline of creatinine clearance (Ccr) in 109 ADPKD patients followed from the time a Ccr value of 30 to 50 mL per min/1.73 m2 was measured until ESRD and need for hemodialysis (Study A), and in 48 undialyzed ADPKD patients followed for at least 4 yr from the time a Ccr value of 50 to 60 mL per min/1.73 m2 was measured (Study B). In Study A, the decline in Ccr (delta Ccr) (mean +/- SE) was 5.8 +/- 0.2 mL per min/1.73 m2 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). Accordingly, ESRF was reached at a later age in female patients (55.1 +/- 1.2 versus 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 effect of the gender of the affected parent was apparent in female patients. By regression analysis, there was a positive but weak relationship between delta Ccr and mean arterial pressure (average value during follow-up, 107 +/- 1 mm Hg, r = 0.224, P < 0.05) but not with dietary protein 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 relationship between age at ESRF and delta Ccr (r = 0.245, P < 0.05), with a later and slower progression in older subjects. In Study B, the mean decline in renal function during follow-up was 5.3 +/- 0.4 mL/min/1.73 m2 per year, a value close to that observed in Study A. By multiple regression analysis of the overall population (studies A and B combined), only MAP, age and gender were independent predictive factors of delta Ccr but all studied parameters taken together accounted for at best 20% of delta Ccr variation. We conclude that the rate of progression of renal failure in ADPKD patients is mainly determined by gene expression, with female gender and older age associated with a slower progression, whereas blood pressure control, but not protein intake, exerts a limited beneficial influence on the rate of progression in patients with advanced polycystic kidney disease who already have significant renal insufficiency.

The potential role of blood pressure and antihypertensive treatment on the progression of advanced chronic renal failure was analyzed in 223 adult patients (126 males) with well-defined primary chronic renal diseases (glomerulonephritis, n = 73; angionephrosclerosis, n = 24; interstitial nephritis, n = 61; polycystic kidney disease, n = 52, Alport's syndrome, n = 13). Effect of average mean arterial pressure (MAP) obtained during follow-up, antihypertensive treatment (normotensive, conventional antihypertensive treatment, angiotensin-converting enzyme inhibitors [ACEI]), gender, type of the nephropathy, age, body mass index, and protein intake were analyzed using a multivariate analysis of variance. Mean arterial pressure was significantly and independently correlated with duration (r = -0.40, P0.0001) and slope of creatinine clearance (delta Ccr; r = 0.32, P0.0001). Mean arterial pressure and antihypertensive treatment could predict 25% of the variation in duration. Gender, type of the nephropathy, and MAP were able to predict 30% of the variation in delta Ccr. When analyzing results by type of nephropathy, MAP was significantly and inversely correlated with duration in glomerulonephritis (r = 0.29, P0.05), and positively with delta Ccr in angionephrosclerosis and interstitial nephritis (r = 0.49, P0.05 and r = 0.36, P0.01, respectively). In each type of nephropathy, conventional antihypertensive treatment and ACEI had grossly similar effects upon duration and slope except. In conclusion, blood pressure level is an important contributor to progression of chronic renal failure but its effect was more evident in angionephrosclerosis and interstitial nephritis at the extreme values of blood pressure distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND: The respective contribution of the type of nephropathy, gender, and proteinuria, and of the potentially alterable factors blood pressure level and daily protein intake on the rate of progression in non-diabetic renal diseases is debated. METHODS: We retrospectively analysed the influence of primary renal disease, gender, urinary protein excretion, mean arterial pressure (MAP), and dietary protein intake on the rate of decline in creatinine clearance (delta Ccr) in 159 adult patients with well-defined nondiabetic kidney diseases. All patients had been followed from a baseline Crr of 40-50 ml/min/1.73 m2 until endstage renal disease and need for dialysis. RESULTS: Mean (+/- SD) delta Ccr (ml/min/1.73 m2/year) was 9.9 +/- 6.5 in 51 patients (45 males) with chronic glomerulonephritis, 6 +/- 2.5 in 50 patients (26 males) with polycystic kidney disease, 5.5 +/- 2.4 in 17 patients (16 males) with hypertensive angionephrosclerosis, and 3.9 +/- 2 in 41 patients (21 males) with chronic tubulointerstitial nephritis. delta Ccr was higher in males than in females (7.5 +/- 5.2 versus 4.8 +/- 2.5; P < 0.001). Linear regression analysis of the whole population disclosed a strong relationship between delta Ccr and proteinuria (r2 = 0.23; P < 0.001), and a weak relationship between delta Ccr and protein intake (r2 = 0.03; P = 0.02), but no relationship between delta Ccr and MAP (r2 = 0.01; P = 0.23). Stepwise multiple regression analysis identified the type of nephropathy, gender, and proteinuria as independent predictive factors of progression; however, these factors together accounted for only 36% of the variation in delta Ccr, suggesting the contribution of other yet unidentified factors. CONCLUSIONS: Primary kidney disease and urinary protein excretion (reflecting the severity of renal disease in individual cases) appear as the major determinants of the rate of progression, with faster progression in males in all types of nephropathy, whereas potentially alterable factors such as blood pressure and protein intake had only a modest influence in the range of values observed in our patients.

Thirty per cent of patients who started maintenance haemodialysis at our institution between January 1989 and December 1991 had been referred at a very late stage of their renal disease. To assess the causes and consequences of such late referral we retrospectively compared clinical and laboratory features of 65 patients who had been referred less than 1 month prior to first dialysis (late referral, or LR group) and of 153 patients who had been previously followed-up by us for more than 6 months (early referral, or ER group). Age, sex ratio, and socioeconomic status were similar in the two groups. In the LR group, 38 patients had never been referred to a nephrology unit, whereas 27 had discontinued nephrological surveillance. Fluid overload, severe hypertension, and/or pulmonary oedema was present in 57% of LR versus 15% of ER patients (P < 0.001). Mean (+/- 1 SD) systolic and diastolic blood pressure was greater in the LR than the ER group (173 +/- 19/99 +/- 12 versus 147 +/- 15/84 +/- 8 mmHg, P < 0.001). Mean plasma concentration of creatinine, urea and phosphate was significantly greater, whereas bicarbonate, calcium, haematocrit and albumin were less in the LR than the ER group. Most (88%) LR patients started dialysis in emergency conditions through central vein catheterization. Total hospital stay lasted 34.5 +/- 16.3 days in LR versus 5.8 +/- 3.0 days in ER patients (P < 0.0001), resulting in an excess cost of 0.2 million French francs per LR patient.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied 68 families with autosomal dominant polycystic kidney disease (ADPKD) to compare 33 patients who went into end stage renal disease (ESRD) before 45 years of age and 47 patients who went into ESRD over 65 years. The rate of progression to ESRD seems different between early and late evolutive forms of ADPKD. Some environmental and genetic factors might possibly play role.