Amelioration of polycystic kidney disease by modification of dietary protein intake in the rat

Polycystic kidney disease is the most common potentially lethal single- gene inherited disease in man. There is no specific therapy. Previous studies in the pcy mouse model of polycystic kidney disease have shown amelioration of cystic change by reduction in dietary protein intake. The Han:SPRD-cy rat is a model of autosomal dominant polycystic kidney disease that closely resembles human disease in its histology and clinical course. We compared the morphometric assessment of cystic change and standard laboratory measures of renal function in heterozygous Han: SPRD-cy rats that received isocaloric diets containing either 8% or 20% protein as casein. This level of dietary protein restriction was associated with a significant reduction of mean body weight in the 8% protein group (358 g) compared with 20% protein (490 g; P = 0.027). Mean renal volume, adjusted for the difference in body weight, was significantly lower in the 8% protein group (6.2 mL/kg) compared with the 20% protein group (11.6 mL/kg; P = 0.016). The major component in this reduction was a reduction in total cyst volume to a mean 0.47 mL in the 8% protein group from 2.68 mL in the 20% protein group (P0.0001). All 8% protein diet animals survived to 6 months of age, but 3 of 11 20% protein diet animals died between 5 and 6 months of age. Mean serum creatinine and urea levels were significantly lower in the 8% protein group (118 mmol/L and 15.6 mmol/L) compared with the 20% protein group (272 mmol/L, P = 0.0033, and 81.5 mmol/L, P = 0.0002, respectively). Dietary protein restriction is a potent method for modifying the course of polycystic kidney disease in the Han:SPRD-cy/+ rat. These findings emphasize the potential for diet to alter the physiology of the renal tubulointerstitium.