ROLE OF OBSTRUCTION IN AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE IN RATS

Kidney micropuncture and microdissection studies were carried out on h eterozygous 2- to 4-month-old female and male Han:SPRD rats with autos omal dominant polycystic kidney disease (ADPKD) and on normal controls , to determine whether cysts are obstructed. Pressures in proximal tub ules and cysts were determined using a servo null device and were reco rded before, during, and after intraluminal infusion of an isotonic eq uilibrium solution at 15 and 50 nl/min. Initial cyst pressures in nine cystic rats averaged 18.5 +/- 5.9 (SD) mm Hg, N = 49, significantly ( P < 0.01) higher than in normal proximal tubules in four control rats, 14.3 +/- 1.6 mm Hg, N = 36. Pressures in non-cystic tubules in cystic rats, 16.8 +/- 4.4 mm Hg, N = 25, were not significantly different fr om pressures in control kidneys or in cysts. When proximal tubules wer e microinfused at 15 nl/min in control rats, tubule pressure increased by 3.8 +/- 1.2 mm Hg, N = 24. In cysts, the response was highly varia ble. Twenty out of 33 microinfused cysts (61%) showed responses simila r to normal tubules and were considered to be nonobstructed; 13 (39%) showed large pressure increases upon microinfusion, sometimes to value s over 100 mm Hg (obstructed cysts). Left kidney inulin clearance (in mu l/min . 100 g body wt) averaged 335 +/- 65 (N = 4) in control rats and 344 +/- 144 (N = 9) in cystic rats; at this early stage of the dis ease no decline in GFR was seen. Weights of cystic kidneys were twice those of normal animals. Microdissection and scanning electron microsc opy revealed the presence of intraluminal casts and debris and constri ctions between cysts that would impede fluid flow. We conclude that ob struction is a frequent, early event in PKD and, when present, promote s cyst enlargement. Since many cysts are not obstructed, we suggest th at factors other than fixed obstruction initiate cyst formation.