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The present study was carried out to examine the effect of chronic dietary protein restriction on renal water handling in the rat. During hypotonic saline infusion, the malnourished rats showed a lower free-water clearance, corrected by inulin clearance (7.2 ± 0.4%), than normal rats (13.6 ± 2.5%, p H2o) corrected by inulin clearance was lower in malnourished rats (6.62 ± 0.64%) than in control animals (9.25 ± 0.62, p H2o was referred to the osmolar clearance, malnourished animals showed lower values than normal. These results suggest a defect in NaCl transport in the thick ascending limb of Henle. In vitro measurements of diffusional water permeability (PDW) in the inner medullary collecting duct (IMCD) obtained from malnourished rats showed an increase from 40.0 ± 5.4 × 10-5 cm/s to 71.3 ± 5.4 × 10-5 cm/s by adding maximum effective concentration (50 μU/ml) of arginine vasopressin (VP) to the bath. These values were not different from the PDW observed in the IMCD of normal rats. In another series of microperfusion experiments, the hydraulic conductivity in IMCD of malnourished rats measured also in the presence of maximum effective concentration of VP was 29.7 ± 3.4 × 10-6 cm/atm/s, a mean value not significantly different from that observed in the IMCD of normal rats (35.2 ± 4.3 × 10-6 cm/atm/s). However, the Lp stimulated by submaximum effective doses of VP (1 and 10 μU/ml) was significantly lower in the IMCD of malnourished than normal rats. These findings indicate that the concentration defect observed in malnourished rats was due to a defect in NaCl transport in the thick ascending limb of Henle, and a partial resistance of IMCD to VP-stimulated water permeability.

The renal effects of acyclovir (100 mg/kg body weight i.p. for 7 days) were studied in rats. All animals became polyuric and presented an increase in blood urea nitrogen and fractional excretion of sodium and potassium. During hypotonic saline infusion, the acyclovir-treated rats showed higher distal fractional delivery compared to normal rats (27.8 +/- 4.7 vs. 11.3 +/- 0.9%, p less than 0.01) and a lower ratio of free-water clearance to distal sodium delivery (33.5 +/- 7.8 vs. 57.2 +/- 3.9%, p less than 0.02). Following hypertonic saline infusion, the ratio of osmolar to inulin clearance was higher in acyclovir rats (47.8 +/- 7.4%) than in normal rats (27.0 +/- 4.8%), whereas the ratio of free-water reabsorption to osmolar clearance was lower in the acyclovir rats (13.6 +/- 4.6 vs. 38.2 +/- 3.2%, p less than 0.01). These findings suggest an effect of acyclovir on the proximal tubule, thick ascending limb and/or inner medullary collecting duct (IMCD). In vitro measurements of 3H2O permeability of perfused IMCD of normal rats showed that vasopressin (50 microU/ml) added to the bath increased the diffusional water permeability (43.4 +/- 4.8 vs. 105.6 +/- 9.1 x 10(-5) cm/s), while in acyclovir rats, the control value (58.8 +/- 9.1 x 10(-5) cm/s) did not increase significantly in the presence of vasopressin (71.3 +/- 13.6 x 10(-5) cm/s). These results suggest that high doses of acyclovir produce azotemia and an abnormal function of the proximal tubule and thick ascending limb associated with resistance to vasopressin of the IMCD.

The kidney involvement in leptospirosis appears to be a special form of acute renal failure due to a higher frequency of polyuric forms and the presence of hypokalemia with an elevated urinary fractional excretion of potassium. Using a clearance technique, we detected higher fractional urinary potassium excretion in leptospirotic guinea pigs (26.5 +/- 4.7%) than in normal animals (14.1 +/- 2.8%, p0.05). After blocking distal NaCl reabsorption with furosemide, it was observed that in leptospirotic animals both fractional sodium excretion (40.0 +/- 7.4%) and fractional potassium excretion (136.3 +/- 32.7%) were higher than in normal animals (20.4 +/- 3.8%, p0.05, and 43.6 +/- 9.0%, p0.05, respectively). Microperfusion studies showed that the normal and leptospirotic medullary thick ascending limb had both identical transepithelial potential difference (+3.7 +/- 0.4 vs. 3.9 +/- 0.2 mV) and relative sodium-to-chloride permeability. The same technique showed that the osmotic water permeability (Posm; 0.9 +/- 0.4 x 10(-5) cm/s.atm) and diffusional permeability (34.7 +/- 6.6 x 10(-5) cm/s) observed in the leptospirotic inner medullary collecting duct (IMCD) in the presence of vasopressin were unchanged, as was also the case for urea permeability (3.74 +/- 0.7 x 10(-5) cm/s). These data show that acute renal failure in leptospirosis is characterized by tubular changes leading to potassium secretion probably due to a decrease in proximal sodium reabsorption. Furthermore, the inability to concentrate urine evidenced by the low P(o)sm present in leptospirotic animals is due, at least in part, to IMCD resistance to vasopressin.

Acute renal failure induced by leptospirosis was studied in 56 patients. A higher frequency of nonoliguric renal failure was observed with lower morbidity and mortality rates than in oliguric forms. In addition, 45% of the patients in this series were hypokalemic, and no hyperkalemic patients were seen. A prospective study in 11 patients showed an initially elevated urinary fractional potassium excretion that fell simultaneously with the high urinary fractional sodium excretion and the urinary K/Na ratio, suggesting an increased distal potassium secretion due to an increased distal sodium delivery consequent to functional impairment of the proximal reabsorption of sodium.

The present study was carried out to examine the effect of potassium depletion in rat kidneys subjected to a temporary ischemic event produced by clamping of left renal artery. The postischemic kidneys of rats on a normal diet with adequate potassium intake showed an increase in H2O, Na and K excretion, with no change in inulin clearance whereas significant differences were found in potassium-deprived rats. Potassium depletion was brought about by dietary K deprivation for 10 days. K-depleted rats (serum K = 2.5 +/- 0.1 mEq/l) had a decrease in inulin clearance of the postischemic kidney from 1.01 +/- 0.10 to 0.43 +/- 0.05 ml/min (p less than 0.01), and a greater increase in fractional excretion of H2O, Na and K when compared to normal rats. The postischemic kidney from both normal and hypokalemic rats showed a decrease in Na-K-ATPase of the inner stripe of the outer medulla. These data indicate that short-term ischemia produces polyuria, increases natriuresis and kaliuresis, associated, at least in part, with a decrease in Na-K-ATPase in the inner stripe of the outer medulla (probably the thick ascending limb of Henle) and that K depletion potentiates ischemic renal failure.