We examined the effects of cisplatin (5 mg/kg BW) on renal function in rats. Three days after administration of cisplatin whole kidney clearance of inulin fell and 24-h urine volume increased. Maximal urine osmolality and papillary solute content were reduced. Superficial nephron glomerular filtration rate measured along the proximal tubule, where no leak of inulin could be demonstrated, was reduced in cisplatin-treated animals. Differences between superficial nephron glomerular filtration rate determined in proximal and distal tubules were greater in cisplatin-treated rats than in control rats. Neither a change in fluid or sodium movement along superficial nephrons nor a reduced early distal tubule transepithelial sodium gradient explain the polyuria. Urea was reabsorbed from, not added to, the loop fluid in cisplatin-treated animals. Morphologic changes were evident in the S3 segment of the proximal tubule in cisplatin-treated animals but the glomeruli were normal. Polyuria occurred despite diminished glomerular filtration rate in cisplatin nephrotoxicity. The diminished concentration of salt and urea in the papilla as a result of abnormal function of the collecting duct or pars recta portion of the proximal tubule contributed to the defect in concentrating ability.

In a study of 56 alcoholics with liver cirrhosis, 18 (32%) had decreased bone density and low levels of serum 25-hydroxyvitamin D (25-OH-D) (less than 20 ng per ml). To compare the efficacy of vitamin D2 and 25-OH-D treatment in correcting the metabolic bone disease in alcoholic cirrhosis, the 18 patients were randomized in the following manner, in groups of six patients each: Group 1, control (received no supplemental vitamin D treatment); Group 2, given vitamin D2 (50,000 IU p.o.) two to three times weekly, and Group 3, treated with 25-OH-D (20 to 50 mg p.o.) daily as required to attain normal serum 25-OH-D levels. The study period lasted 6 to 12 months (mean, 10.7 months). Initial histomorphometric study of transiliac bone biopsy with double tetracycline labeling in nine patients in whom biopsy was feasible showed only osteoporosis without evidence of osteomalacia. By the end of the study, serum 25-OH-D levels in the control group (Group 1) raised slightly while showing marked improvement in Groups 2 and 3. Bone density results remained unchanged in control patients but demonstrated a significant increase in both treatment groups. Vitamin D2 and 25-OH-D were equally effective in increasing bone density measurements. Posttreatment biopsies were performed in three patients of Group 2 and two patients of Group 3. While the histomorphometric results in Group 3 were not conclusive, in Group 2 improvement in static measures of bone remodeling was noted. Osteoporosis is the usual form of bone disease in alcoholic cirrhosis and a response to either vitamin D2 or 25-OH-D treatment is suggested.