Rat Hypoplastic Kidney (hpk/hpk) Induces Renal Anemia, Hyperparathyroidism, and Osteodystrophy at the End Stage of Renal Failure.

Abstract

ABSTRACT. In rats with genetically hypoplastic kidneys (hpk/hpk) and associated hypogonadism (hgn/hgn), their kidneys contain only onequarter the number of nephrons that are found in those of normal rats [26]. Not surprisingly, therefore, renal excretive function has been shown to be depressed in hpk/hpk rats [26]. In the study presented here, we have examined the process of the progression of renal failure and the development of renal secondary disease in hpk/hpk rats. The plasma concentrations of urea-nitrogen and creatinine were significantly higher in adult hpk/hpk rats than in normal rats. These values elevated gradually and the degree of renal histological damage also progressed with advancing age in the hpk/hpk rats. In addition, renal anemia appeared at 140 days of age or later in these rats, and hyperplasia of the parathyroid glands was visible macroscopically at 280 days of age. In the hpk/hpk rats plasma levels of calcium and phosphorus were significantly lower and higher than in normal rats, respectively, at 280 days of age. Pathologically, the left femora of hpk/hpk rats exhibited fibrous osteodystrophy at 280 days of age and the calcium content of the right femora (as a percentage of the dry weight of bone) was significantly lower than in normal rats at both 210 and 280 days of age. These results indicate that the reduced nephrogenesis of the hpk/hpk rats causes progressive renal failure, secondarily inducing anemia, hyperparathyroidism, and osteodystrophy. -KEY WORDS: disease animal model, hyperparathyroidism, osteodystrophy, renal anemia, renal hypoplasia.J. Vet. Med. Sci. 60(10): 1051-1058, 1998 MATERIALS AND METHODS Animals:The animals used in this study were male hpk/ hpk rats and phenotypically normal litter mates (+/hpk or +/+) from the 24th generation of the HGN line maintained in our department [26]. The hpk/hpk males could be identified externally by their hypogonadism [26]. The rats were bred and fed under the same conditions as described in previous reports [24][25][26][27].Hematological examination: Four groups of 4 hpk/hpk and 4 normal animals were used, one group at each of days 70, 140, 210, and 280 after birth. Blood samples were collected from the jugular vein with a plastic syringe moisturized with a small amount of heparin. Red and white blood cells were counted on a hemacytometer with the aid of a light microscope. The counts of reticulocytes and platelets were performed according to the Rees-Ecker method. The hematocrit was determined using a hematocrit tube and the centrifuging method. The concentration of hemoglobin was determined by the methemoglobin method. Plasma samples were obtained by centrifugation and stored at 40°C until they were used to obtain urea-nitrogen, creatinine, calcium, and phosphorus measurements.Histological examination: After collecting blood samples from the rats they were sacrificed by ether overdose. Their kidneys and parathyroid glands with attached tracheas were removed and fixed in 4% neutral formalin, dehydrated in a graded alcohol series, embed...

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