EXPERIMENTAL STUDIES ON THE CHEMOTHERAPEUTIC EFFECT ON RETROGRADE PROTEUS PYELONEPHRITIS IN RATS

Abstract

The effect of chemotherapy on experimental pyelonephritis in rats was investigated by initiating treatment at various intervals after induction of the disease. An experimental model of pyelonephritis was produced by transurethral inoculation of Proteus mirabilis 24 hours after producing chemical cystitis by instilling 0.5ml of 0.75% acetic acid into bladder transurethrally. The bacterial inoculum was 0.5ml of heart infusion broth containing 10⁶ cells/ml of P, mirabilis isolated from a 33-year-old woman with bilateral chronic pyelonephritis and renal stones. The animals were administered 100mg of ampicillin per kilogram of body weight intramuscularly twice daily for 7 days from 1, 3, 5, 7 and 10 days after inoculation. At 4 weeks after inoculation, urinary concentrating ability, renal histology, serum antibody titer and urinary tract stone formation were examined.
The results obtained were as follows.
1) The incidence of pyelonephritis with this experimental model was 94.0%, including rats that died in the observation period. In controls not pretreated with acetic acid prior to P, mirabilis inoculation, the incidence of pyelonephritis was 71.7%. This difference was significant (p<0.01). Serum antibody titer measured by bacterial agglutination displayed a dramatic rise from 1 to 2 weeks after inoculation and increased gradually thereafter.
2) Disturbances of urinary concentrating ability were mildest in rats in which treatment was initiated 1 day after inoculation. The longer the interval between inoculation and the commencement of treatment, the more severe were disturbances of urinary concentrating ability.
3) Histological changes of the kidney were mildest in rats in which treatment was initiated 1 day after inoculation. The longer the interval between inoculation and the commencement of treatment, the more pronounced were histological changes.
4) Serum antibody titer was low in each group in which treatment was initiated within 7 days of inoculation compared to that of nontreated group.
5) A significant correlation between impaired urinary concentrating ability (urinary osmolarity after withdrawing all water for 24 hours) and serum antibody titer was seen in each of group with the exception of that in which treatment was initiated 1 day after inoculation.
6) There was no stone formation of urinary tract in rats in which treatment was initiated 1 and 3 days after inoculation.
The results of this experiment indicate that the prompt treatment of pyelonephritis by suitable chemotherapeutic means is of vital importance as suggested by renal function, renal histology, and serum antibody titer. Furthermore, urinary concentrating ability and serum antibody titer were considered to be important parameter in the diagnosis and treatment of pyelonephritis.