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

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.

Urine and blood samples were collected from adult male HPK rats and phenotypically normal littermates at 70 days of age for measurements of urea-nitrogen 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.

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.

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.