Lúcia H. Kudo

Renal Involvement in Leptospirosis: A Pathophysiologic Study

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%, p < 0.05). 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%, p < 0.05, and 43.6 +/- 9.0%, p < 0.05, 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.

Renal Concentration Defect Induced by Cisplatin

The effects of cisplatin (5 mg/kg BW given intraperitoneal^) on renal concentration mechanism were evaluated initially by clearance studies in rats 5–7 days after cisplatin administration and compared

Effect of atrial natriuretic factor and cyclic guanosine monophosphate on water and urea transport in the inner medullary collecting duct

We examined the action of high (2×10−8M) and low (6×10−9M) concentrations of atrial natriuretic factor (ANF) on water and urea transport in the rat inner medullary collecting duct (IMCD) using the in vitro microperfusion technique. We measured the hydraulic conductivity (Lp ×10−6 cm/atm per second) and both lumen-to-bath (Pu(lb)) and bath-to-lumen (Pu(bl)) 14C-urea permeabilities (Pu× 10−5 cm/s) in the absence and in the presence of vasopressin (VP). High concentrations of ANF were able to inhibit the maximum activity of (50 μU/ml) VP-stimulated Lp but physiological concentration of ANF inhibit only submaximum activity (10 μU/ml) of VP-stimulated Lp. The hydrosmotic effect of dibutyryl-cyclic 3,5 adenosine monophosphate (cAMP) (10−4M) was unchanged by high concentrations of ANF (2×10−8M). Also we found that high (10−4M) and low (10−6M) concentrations of exogenous cyclic 3,5-guanosine monophosphate (GMP) while unable to change the Lp in the absence of VP, decreased the maximum activity of VP-stimulated Lp significantly. We also found that ANF inhibits partially and in a reversible manner the VP-stimulated Pu(lb) but not the VP-stimulated Pu(bl). These results demonstrated that plasma concentrations of ANF observed during volume expansion (10−10M) are able to inhibit submaximum activity of VP-stimulated (10 μU/ml) Lp in the rat IMCD, this effect seems to occur before cAMP formation and it appears to be mediated by cGMP. ANF (6× 10−9M) also reduced the VP-stimulated urea outflux. Therefore, the increase in water excretion produced by ANF could be explained, at least in part, by the inhibition by ANF of vasopressin effects on water and urea transport in the IMCD.

Renal concentrating defect in protein malnutrition: the role of the thick ascending limb of Henle and inner medullary collecting duct.

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 less than 0.051), although the fractional distal delivery of sodium did not differ from normal. Throughout hypertonic saline diuresis the free-water reabsorption (TcCH20) corrected by inulin clearance was lower in malnourished rats (6.62 +/- 0.64%) than in control animals (9.25 +/- 0.62, p less than 0.05). Moreover, when TcH20 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 x 10(5) cm/s to 71.3 +/- 5.4 x 10(5) cm/s by adding maximum effective concentration (50 microU/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 x 10(-6) cm/atm/s, a mean value not significantly different from that observed in the IMCD of normal rats (35.2 +/- 4.3 x 10(-6) cm/atm/s).(ABSTRACT TRUNCATED AT 250 WORDS)

Phosphate transport in isolated rat inner medullary collecting duct

Phosphate transport by the inner medullary collecting duct of normal rats was studied using an in vitro microperfusion technique. Net (Jnet), lumen-to-bath (Jlb) and bath-to-lumen (Jbl) phosphate fluxes were measured using 32PO4 as tracer, in the absence of net water absorption. A net absorption of phosphate (22.3 ±3.3 pmol cm−2 s−1) was observed by direct determination, and was similar to the difference between the Jlb and Jbl (57.7±8.2 and 32.2±1.5 pmol cm−2 s−1 respectively). The addition of amiloride (10 μM) to the perfusate did not change the Jlb of phosphate but blocked the efflux of sodium. Also, the withdrawal of sodium from the bath and perfusion solution did not change the Jlb of phosphate. In parallel, the addition of ouabain (10 mM) to the bath fluid decreased the Jlb of sodium more (37%) than the Jlb of phosphate (12%) and did not change the Jbl of phosphate. The addition of arsenate (10 μM) to the perfusate both in the presence and in the absence of sodium caused a decrease in Jlb, but Jbl remained unchanged, and parathyroid hormone (10 U) added to the bath did not change the Jlb. The increase in pH of the bath and perfusion fluid was associated with an increase in the Jlb of phosphate, and the decrease in pH was similarly followed by a decrease in phosphate efflux. The Jbl did not change with the pH alterations. These data demonstrate that a net phosphate absorption takes place in rat inner medullary collecting duct perfused in vitro and that this transport appears to be independent of sodium absorption and the action of parathyroid hormone. Moreover, a decrease in luminal and bath pH induces a decrease in phosphate efflux.