PROGRESSION OF RENAL-FAILURE IN THE HAN-SPRD POLYCYSTIC KIDNEY RAT

The Han: SPRD Pkd rat mutant is an autosomal dominant rat model with i ncomplete penetration of polycystic renal transformation. Progressive renal failure occurs in heterozygous male animals. The mechanisms of p rogression have not been elucidated. To identify some pathogenetic fac tors involved we subjected male SPRD Pkd rats (and their non-affected littermates as controls) to uninephrectomy (UNX), castration or enalap ril treatment. To assess progression S-urea at age 150 days was chosen as endpoint. (i) In uninephrectomized male Han: SPRD Pkd (n = 12 anim als per group) S-urea at age 150 days was consistently above 300 mg/dl , while it was 245 mg/dl (191-290) in control Han: SPRD Pkd. (ii) In c astrated male Han: SPRD median S urea at 150 days was 100 mg/dl (69-21 1) compared to sham-operated male Plan: SPRD controls (245; 191-290). Castration did not, however, prevent accelerated progression after uni nephrectomy. (iii) Enalapril (50 mg/l) in the drinking fluid did not s ignificantly lower median systolic blood pressure (by plethysmography) in animals on 0.2% sodium diet (at 185 days 160 mmHg; 140-170 versus 170: 140-195 in non-enalapril controls). although circulating ACE was significantly inhibited (17 U; 11-33 versus 89; 52-108 in controls). S -urea at age 185 days was not significantly different in the 2 groups. In conclusion, the Han: SPRD Pkd model differs from human ADPKD to so me extent. Uninephrectomy accelerates renal failure in the rat, but no t in humans. On the other hand, in contrast to human ADPKD the renin s ystem is suppressed in the rat model and ACE inhibition does not affec t the course of renal failure.