Reduced nephron endowment is associated with development of renal and cardiovascular disease. We hypothesised this may be attributable to impaired sodium homeostasis by the remaining nephrons. This study investigated whether a nephron deficit, induced by fetal uninephrectomy at 100d gestation (term=150 days), resulted in 1) altered renal sodium handling both under basal conditions and in response to an acute 0.9% saline load, (50 ml/kg/30minutes); 2) hypertension; and 3) altered expression of renal channels/transporters in male sheep at 6 months of age. Uninephrectomised animals had significantly elevated arterial pressure (90.1±1.6 vs 77.8±2.9; P<0.001) whilst glomerular filtration rate and renal blood flow (per gram of kidney weight) were 30% lower than that of the sham animals. Total kidney weight was similar between the groups. Renal gene expression of apical NHE3, ENaC (β and γ) subunits and basolateral Na+/K+ ATPase (β and γ) subunits were significantly elevated in uninephrectomised animals whilst ENaC α expression was reduced. Urine flow rate and sodium excretion increased in both groups in response to salt loading but this increase in sodium excretion was delayed by approximately 90 min in the uninephrectomised animals, whilst total sodium output was 12% in excess of the infused load (P<0.05). This study shows that animals with a congenital nephron deficit have alterations in tubular sodium channels/transporters and cannot rapidly correct for variations in sodium intake likely contributing to the development of hypertension. This suggests that people born with a nephron deficit should be monitored for early signs of renal and cardiovascular disease.
The rest is here:
Reduced nephron endowment due to fetal uninephrectomy impairs renal sodium handling in male sheep
