Glomerular hyperfiltration and hypertrophy in the rat hypoplastic kidney as a model of oligomeganephronic disease

Abstract

Background. Rat male hypogonadisim (hgn/hgn) is accompanied by bilateral hypoplastic kidney (HPK). The HPK contains a reduced number of nephrons that progress to chronic renal failure. In this study, we describe the renal pathophysiology in adult HPK rats as a potential model of oligomeganephronic disease. Methods. Urine and blood samples were collected from adult male HPK rats and phenotypically normal littermates at 70 days of age for measurements of ureanitrogen and creatinine clearances (Cun and Ccr). Glomerular number (GN) and glomerular projective area were determined using the maceration method. Blood pressure was measured. Urinary protein and renal histology were examined. Urinary albumin concentration was determined at early postnatal ages. Results. Renal weight was significantly smaller in adult HPK males than in normal males. Polyuria and polydipsia were observed in HPK rats. Ccr and Cun were low in HPK rats compared with those in normal rats. The HPK contained only 20% of the nephrons present in normal kidneys. The Cun and Ccr divided by GN (average values of single nephron Cun and Ccr) of HPK rats were about two and four times greater than normal levels, respectively. This hyperfiltration was not accompanied by systemic hypertension, but was associated with marked glomerular hypertrophy and glomerulosclerosis, which were observed mainly in the inner cortex. A considerable heterogeneity of glomerular size was found in HPK and most glomeruli of surface nephrons retained normal size and histology. A remarkable leakage of albumin into urine was found at 35 and 70 days of age. Conclusions. The HPK rat is a useful model for studying the pathophysiology of oligomeganephronic disease as well as glomerular hyperfiltration and hypertrophy induced by severe congenital reduction of nephrons.

Reduced Mitotic Activity and Increased Apoptosis of Fetal Sertoli Cells in Rat Hypogonadic (hgn/hgn) Testes

“…The slides were incubated with 3,3'-diaminobenzidine tetrahydrochloride (DAB), counterstained with hematoxylin and examined under a light microscope (BX50; Olympus). Microscopic images were obtained using a Penguin 600CL digital camera system (Pixera Corporation, Osaka, Japan) attached to the microscope [6,7,[17][18][19].…”

“…Moreover, their ovaries are hypoplastic at birth, and they have reduced fertility [5]. These animals have one quarter the number of nephrons present in the normal kidney, and their individual nephrons are extremely hypertrophied [6]. Thus, hgn/hgn rats can be used a s a n e x p e r i m e n t a l m o d e l o f h u m a n oligomeganephronia, which progresses to renal insufficiency with advancing age [7].…”

Duplicated insertion mutation in the microtubule-associated protein Spag5 (astrin/MAP126) and defective proliferation of immature Sertoli cells in rat hypogonadic (hgn/hgn) testes

“…Genomic DNA was isolated from the livers of the rats derived from the HDH, HGN , and HGNII (hgn-inbred strain derived from Wistar-Imamichi closed colony) (Suzuki et al 2005) strains. All had been genotyped by test mating.…”

“…We have described the pathophysiological characters of these hgn/hgn rats, in which testicular dysplasia was used to study testes development , 1993, 2004b, Yagi et al 2006). In addition, we have used the renal hypoplasia occurring in these rats as a model of oligomeganephronia and chronic renal failure (Suzuki & Suzuki, 1995Suzuki et al 1991Suzuki et al , 2005Suzuki et al , 2006. Since no other knockout mouse or mutant rat showing a similar phenotype has been reported, we started linkage analysis in 1997 and located the responsible gene on rat chromosome 10 (Suzuki et al 1999).…”

“…Male hypogonadic (hgn/hgn) rats are characterized by male sterility resulting from testicular dysplasia , 1993, 2004b, a short female reproductive life resulting from ovarian hypoplasia (Suzuki et al 1992), progressive renal insufficiency resulting from renal hypoplasia (Suzuki & Suzuki 1995, Suzuki et al 1991, 2005, and body growth retardation (Suzuki et al 1992). All of these effects are controlled by a single recessive allele (hgn) located on chromosome 10 (Suzuki et al 1999(Suzuki et al , 2004a.…”