Bibliogr. s. 1589

Oxazaphosphorines (cyclophosphamide ñ CP, ifosfamide ñ IF) are alkylating cytostatics used in chemotherapy of cancer and autoimmune diseases. They have numerous adverse effects, including uro- and nephrotoxic, dependent of the type of drug, time of therapy and presence of any coexistent nephrotoxic factors in a treated patient. Purpose of this study was to estimate the renal function and the level of urinary bladder dysfunction occurring in rats following administration of a single, large CP/IF dose. The experiment involved 30 rats who were administered a single intraperitoneal dose of 150 mg/kg b.w. of CP (group 1) or IF (group 2) or normal saline (group 3 ñ control), respectively. Following the administration animals were placed in individual metabolic cages. 24 h later rats were sacrificed, blood collected and nephrectomy and cystectomy performed in order to prepare specimens for histopathological analysis. Circadian diuresis was also assessed, along with a qualitative urine assessment with strip tests and laboratory renal function parameters in plasma and urine: sodium, urea, creatinine and uric acid levels, and circadian elimination of sodium, potassium, urea, creatinine, uric acid and protein. Creatinine clearance, urea clearance and fractionated sodium elimination (FENa) and renal failure index (RFI) were also calculated. An increased diuresis and acidification of urine with reduced circadian elimination of potassium and a significant proteinuria, as well as increased plasma levels of creatinine and urea were found in the group of rats that received a single dose of CP, compared to control animals. Rats treated with IF also demonstrated acidification of urine, reduced circadian potassium elimination, a significant proteinuria and increased plasma creatinine and urea levels, but their diuresis was comparable to that observed in control animals. IF-treated animals were also characterized by reduced urea clearance, FENa and RFI. Histopathological analysis confirmed presence of inflammatory changes in urinary bladders in both groups 1 and 2, and absence of any significant morphological disorders in kidneys. Obtained results suggest a dysfunction of distal tubules and collective tubules developing as a result of administration of a single nephrotoxic dose of IF/CP. FENa and RFI results indicate also a higher nephrotoxic potential of IF administered as a single dose.