Reduced nephron endowment is associated with development of renal and cardiovascular disease. We hypothesized this may be attributable to impaired sodium homoeostasis by the remaining nephrons. The present study investigated whether a nephron deficit, induced by fetal uninephrectomy at 100 days gestation (term=150 days), resulted in (i) altered renal sodium handling both under basal conditions and in response to an acute 0.9% saline load (50 ml·kg−1 of body weight·30 min−1); (ii) hypertension and (iii) altered expression of renal channels/transporters in male sheep at 6 months of age. Uninephrectomized animals had significantly elevated arterial pressure (90.1±1.6 compared with 77.8±2.9 mmHg; P<0.001), while glomerular filtration rate and renal blood flow (per g 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 (type 3 Na+/H+ exchanger), ENaC (epithelium Na+ channel) β and γ subunits and basolateral Na+/K+ ATPase β and γ subunits were significantly elevated in uninephrectomized animals, while ENaC α subunit 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 uninephrectomized animals, while total sodium output was 12% in excess of the infused load (P<0.05). In conclusion, the present 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 probably 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.
Reduced nephron endowment due to fetal uninephrectomy impairs renal sodium handling in male sheep
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Reetu R. Singh, Kate M. Denton, John F. Bertram, Andrew J. Jefferies, Karen M. Moritz; Reduced nephron endowment due to fetal uninephrectomy impairs renal sodium handling in male sheep. Clin Sci (Lond) 1 June 2010; 118 (11): 669–680. doi: https://doi.org/10.1042/CS20090479
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