Hypertension after neonatal uninephrectomy in rats precedes glomerular damage

The present study was designed to determine whether adult hypertension caus ed by a reduced number of nephrons from birth is due to preceding glomerula r damage. Newborn male Sprague-Dawley rat pups were uninephrectomized durin g the first 24 hours after birth (UNX rats). At 20 weeks of age, chronicall y instrumented UNX animals were hypertensive on a normal-sodium (0.20%) die t compared with sham-operated controls (142+/-2 versus 124+/-2 min Hg in co ntrols). Body weights and the total kidney-to-body weight ratio were not si gnificantly different in adult UNX animals compared with controls. Glomerul ar filtration rate (GFR) was reduced by 49% in UNX rats (1.85+/-0.24 versus 3.65+/-0.22 mL/min). Urine protein excretions were higher in UNX rats (20/-2 versus 7+/-1 mg/d in controls). On a high-sodium (3.15%) diet, arterial pressure increased more in UNX than in controls (28+/-9 versus 3+/-1 mmHg) . In contrast, in animals studied at 8 weeks of age, GFR was only reduced b y 26% in UNX animals (2.02+/-0.06 versus 2.73+/-0.07 mL/min). Their hyperte nsion (125+/-2 versus 117+/-2 mmHg) was also salt sensitive (increase on hi gh-sodium diet of 35+/-11 versus 8+/-2 mmHg in controls) but was not associ ated with proteinuria or histological signs of glomerular disease. Number o f glomeruli per kidney in UNX animals was not different from controls, but individual glomerular volume increased by 41%. Thus, surgical removal of 50 % of the nephrons, when done during development, causes reduced renal funct ion and salt-sensitive hypertension in adulthood. Hypertension is present e arlier in life than signs of glomerular disease, which suggests that hypert ension is a major contributor to rather than primarily resulting from onset of renal disease.