Protective Effect of Urinary Alkalinization on Gentamicin Nephrotoxicity in Rats

We investigated the effect of urinary alkalinization accomplished by intraperitoneal injection of sodium bicarbonate and acetazolamide on gentamicin nephrotoxicity in male Fisher 344rats. Forty rats (body weight 200-300g) were divided into four groups: control (gentamicin 20mg/kg, bid), high sodium load (gentamicin 20mg/kg, 25cc of saline, bid), low bicarbonate (gentamicin 20mg/kg, 25cc of sodium bicarbonate 100mEq/L, 2.5mg of Diamox, bid) and high bicarbonate (gentamicin 20mg/kg, 10cc of sodium bicarbonate 250mEq/L, 2.5mg of Diamox, bid) groups. All drugs and electrolyte solutions as mentioned above were administered intraperitoneally twice a day for seven days and changes in renal functions were studied. While salt loading failed to influence the severity of gentamicin nephrotoxicity, urinary alkalinization induced by bicarbonate and acetazolamide injection showed remarkable ameliorating effects on gentamicin nephrotoxicity. The high bicarbonate group exhibited more beneficial effects than the low bicarbonate group on gentamicin nephrotoxicity. So, urinary alkalinization seems to be an effective method for the prevention of gentamicin nephrotoxicity in rats.

Phosphorus and Calcium Homeostasis in Chronic Subtotally Nephrectomized Parathyroidectomized Rats

Calcium and phosphorus balance studies were carried out in subtotally nephrectomized rats (NX), with or without parathyroidectomy (NX-PTX; NX sham-PTX) in order to determine the ability of the remnant kidney to regulate excretion of these elements in the absence of parathyroid hormone. The rats were fed three different phosphorus diets, and calcium intake was also varied. We found that the NX-PTX rats adapted to the three different phosphorus diets in a manner indistinguishable from the NX sham-PTX rats. The per cent of ingested phosphorus excreted in the urine increased as dietary phosphorus increased. When supplementary calcium was added to the diet urinary phosphorus excretion fell and fecal phosphorus increased, in an identical fashion in the NX-PTX and NX sham-PTX animals. Urinary calcium excretion decreased as dietary phosphorus increased, and UCaV increased when supplementary calcium was provided in the diet. Total body calcium and phosphorus balance (intake-(urine+feces)) varied with intake, but was not significantly different between the NX-PTX and NX sham-PTX rats. These experiments demonstrate that subtotally nephrectomized rat have a parathyroid-independent mechanism(s) for regulating both urinary and fecal calcium and phosphorus excretion. The mechanism is not revealed by the present study, but may relate to changes in serum calcium and/or phosphorus which occur following parathyroidectomy.