Evaluation of the effect of desmopressin on urinary tract infections

SUMMARY Objective: To evaluate the effects of exogenously administered antidiuretic doses of desmopressin acetate (DDAVP) on urinary tract infections in rats by biochemical, microbiologic and histopathologic parameters. Materials and methods: Eight different groups of 56 Wistar rats were studied. At the beginning, the urine analysis and bacterial urine cultures were performed with mid stream void urine samples; urinary volume and density were assessed with 24-hour urine collection for ail rats. After urine cultures resulted negative at the beginning of the study, 0.1 mL of solution containing Escherichia coli (£. coli) (1010/mL) was injected into both two kidneys of 28 Wistar rate and another 28 Wistar rats underwent urethral catheterization and intravesical instillation of 0.3 mL of the same bacterial solution. When the urine cultures obtained one day after bacterial inoculation resulted positive for £ Coli, 8 equal groups, each containing 7 rats were formed. Group I, II, III, IV had pyelonephritis, and Group V, VI, VII, VIII had cystitis. In Group II, IV, VI, VIII DDAVP (2 ng/dose daily) was injected intramuscularly for 7 days, starting at one day after bacterial inoculation; in Group I, III, V, VII saline solution (0,9% NaCI 0.5 ml daily) was injected intramuscularly for 7 days, starting at one day after bacterial inoculation. The urine analysis and bacterial urine cultures were performed with mid stream void urine samples; urinary volume and density were assessed with 24-hour urine collection for ail rats at 1s1, 3th, 5th and 7th days of DDAVP or saline injection; additionally in Group III, IV, VII, VIII these studies were performed at 14th, 21st and 28th days. Blood samples of all rats were obtained to determine serum creatinine levels at 7th days of saline or DDAVP injection, additionally blood samples of rats that in Group III, IV, VII, VIII were obtained at 28th days of saline or DDAVP injection. Rats in Group I, II, V, VI were sacrificed 8 days after bacterial inoculation and rate in Group III, IV, VII, VIII were sacrificed 29 days after bacterial inoculation, and both kidneys and urinary bladder were examined histopathologically for inflamation and fibrosis, and were graded subjectively. Results: There was no significant difference in mean daily urine volumes between DDAVP and saline injected pyelonephritis groups, during the first week of the study. In DDAVP injected cystitis groups, mean daily urine volumes were lower than saline injected cystitis groups and DDAVP injected pyelonephritis groups, during the firstweek of the study; differences between these groups disappeared after DDAVP administration was stopped at 7th day of the study. The urine density results of rats were found contradictory and inconsistent with the current medical reports. The positive results of urine leukocyte esterase assessment with dipstick test, the presence of bacteria in urine with microscopic urine examination and the daily urine culture results for E. coli based on colony forming unit per mililiter (cfu/mL) were found similar between DDAVP or saline injected rats in cystitis groups and pyelonephritis groups. The serum creatinine levels were found in normal ranges for all rats at 7th and 28th day of the study. Neither renal inflammation and fibrosis scores nor urinary bladder inflammation scores were found different at the end of the first week and at the end of the 4th week of the study, between DDAVP or saline injected rate in pyelonephritis groups. Similarly neither renal inflammation and fibrosis scores nor urinary bladder inflammation scores were found different at the end of the first week and at the end of the 4th week of the study, between DDAVP or saline injected rats in cystitis groups. No fibrosis was found in any of the urinary bladder histopathologic examination. The histopathologic scores showed no correlation with the daily urine volume, the positive test results for urine leukocyte esterase with dipstick test, the urine culture results for E. coli based on colony forming unit per mililiter or serum creatinine levels in both the pyelonephritis and cystitis groups. Conclusion: In this study it was shown that daily 2 ug fixed dose of DDAVP administration to rats that had pyelonephritis or cystitis performed with using E. coli, did not increase serum creatinine levels above normal ranges; had no effect on daily urine culture results for bacterial growth based on colony forming unit per mililiter and had no effect on renal, urinary bladder inflammation and fibrosis process. Furthermore, we showed that under preexisting urinary tract infection, the antidiuretic doses of DDAVP administration had no adverse affect in either the infection process in the kidneys and urinary bladder or the serum creatinine level which was assessed for the evaluation of renal functions, and the renal histopathologic injury. Keywords: Desmopressin acetate, pyelonephritis, cystitis, rat