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INCIDENCE AND SOME FUNCTIONAL CHARACTERISTICS OF HYDRONEPHROSIS IN BRATTLEBORO RATS

The present report concerns spontaneous hydronephrosis in Brattleboro rats. The usual criteria and definitions regarding this strain of rat are employed: DI-rats homozygous for the trait of diabetes insipidus; HZ-rats heterozygous for the condition.’ In addition, the defective gene responsible for diabetes insipidus of Brattleboro rats has been eliminated by successive HZ crosses to produce a “wild-type’’ Brattleboro rat. Hydronephrosis is a generic term used to define a condition wherein there is a progressive dilatation of the renal pelvis, usually associated with degenerative changes (atrophy, destruction, or compression) of renal medullary tissue. Obstruction of urine flow at any site between pelvis and urethra is the usual cause, although the pathogenesis is far from uniform. The condition can be produced experimentally in a variety of ways, the most common being to partially occlude the ureter. There is, however, strong evidence at least in laboratory rodents, and possibly man, that heritable factors affecting the kidney and/or ureter are involved in the appearance of hydronephrosis.2-i In the Brattleboro rats, the severe hydronephrosis in some cases leads to almost total destruction of the kidney (FIGURE 1 ) . The colony initiated from two DI males and six HZ females (courtesy of Professor J. C. Sloper, Charing Cross Hospital Medical School, London) began to display hydronephrosis after approximately 30 generations. The incidence in subsequent generations is given for a random selection of rats in FIGURE 2. A breeding program is presently underway crossing DI with the Long Evans rat-the strain from which the Brattleboros were originally derived R-to eliminate the hydronephrosis. It is however premature to speculate upon the genetics of the disease and its relationship to the inheritance or otherwise of diabetes insipidus. The most salient features of the data presented in FIGURE 2 include: hydronephrosis affects the right kidney more than the left; male rats are more susceptible than females to hydronephrosis-moreover it is apparently absent from “wild-type” females; hydronephrosis is present from an early age, although its severity may increase. Weanling male DI rats display the condition and certainly bilateral hydronephrosis is more often present in older than younger rats; and the pattern of incidence of the condition in general excludes dietary or infectious causes and to date frank ureteral occlusions (spermatic vessels in males, for example) and other anatomical variations have not been detected.