NEPHRON OBSTRUCTION IN NORDIHYDROGUAIARETIC ACID-INDUCED RENAL CYSTIC-DISEASE

Studies were performed to characterize conditions in rat kidneys whose nephrons were made cystic by feeding 2% nordihydroguaiaretic acid (NDGA) to the animals. Using two micropipettes, we monitored intratubular hydrostatic pressures while perfusing single surface nephrons in NDGA-exposed (5 to 7 weeks) and normal rat kidneys. The introduction of 50 nl of Ringers solution labeled with 3H-inulin at a flow rate of 25 nl/min was associated with a significant mean (± SEM) increase (167 ±61%; P < 0.02) in pressure in cystic but not in nondilated (-0.5 ± 27.2%) or normal (31 ± 23%)nephrons, respectively. The relative amount of 3H-inulin excreted in 40 min from cystic (4.0 ± 2.0%) was less than that excreted from either nondilated (19± 7%; P < 0.05) or normal (105 ± 26%, P < 0.01) nephrons. Intralumenal pressures in nondilated but not other nephron groups correlated with urinary flow rates (r=0.51; P < 0.02). Single nephron filtration rates and tubular-fluid-to-plasma 3H-inulin ratios in additional rats were similar among all groups of tubules. Concluding that these data reflected increased resistance to out-flow from cystic nephrons, we examined these and additional NDGA-exposed (1 to 24 weeks) kidneys. 3H-thymidine radioautography demonstrated maximum collecting tubular cell hyperplasia (13% labeling) at 2 to 3 weeks of NDGA-exposure. Microscopy and microdissection demonstrated tiny mural polyps along outer medullary segments of collecting tubules. Thirteen tubules were traced to their outlets; polyps impinging on outflow lumens were found in all 13 instances. We conclude that partial nephron obstruction exists in NDGA-exposed kidneys and that obstruction is a likely contributor to cyst formation in this model.