Urine concentration and dilution in hypokalemic and hypercalcemic dogs.

The urine-concentrating mechanism was studied in chronic hypokalemia (seven dogs given a low K(+), high NaCl diet plus injections of deoxycorticosterone acetate [DOCA]) and chronic hypercalcemia (seven dogs given vitamin D). In the potassium-depleted dogs, muscle, serum, and urine K(+) fell markedly, but glomerular filtration rate (GFR) and body weight varied little. Maximum urine osmolality fell in all dogs (mean decrease = 45%); however, solute-free water reabsorption (T(CH2O)) at high rates of solute excretion remained normal in three of four dogs. Free water excretion (C(H2O)) increased normally or supranormally as a function of increasing Na(+) delivery to Henle's loop in six dogs so tested. Hypercalcemia of several weeks duration caused a decrease in both GFR (mean 36%) as well as in maximum urine osmolality (mean 57%). Maximum T(CH2O) was not invariably depressed; in fact, when the values were adjusted for the reduced number of functioning nephrons (T(CH2O)/C(In)), four of seven studies were normal. C(H20)/C(In) increased normally (or supranormally) with increasing fractional Na delivery to Henle's loop in four of five dogs.I conclude that the lowered maximum urine osmolality in these hypokalemic and hypercalcemic dogs was not related to abnormal water reabsorption from the collecting ducts. Although not specifically measured in this study, it is very likely that solute accumulation in the renal medulla was reduced. This probably was not caused by abnormal delivery of sodium to, nor reabsorption of sodium from Henle's loop. It is likely that a more subtle defect exists in the countercurrent mechanisms for establishing a steep concentration gradient in the renal medulla. In the few hypercalcemic dogs in whom GFR was very low, I believe that injury to, and blockage of medullary tubules could account for most of the reduction in maximum U(Osm). Although not specifically ruled out, there is no evidence here to suggest that high serum Ca(+) or low serum K(+) per se causes a defect in sodium and water reabsorption in the mammalian nephron.