Low nephron endowment increases susceptibility to salt-induced elevation of blood pressure in mice

OBJECTIVES: Humans born preterm have low nephron endowment and an increased risk for hypertension and chronic kidney disease (CKD) later in life. The risks of these sequelae are augmented by a higher incidence of postnatal kidney injury from ischemic, hypoxic and/or nephrotoxic insults. METHODS: To test the hypothesis that congenital nephron deficits in the absence of other renal insults are a risk factor for hypertension, and that salt intake modifies this response, we performed continuous ambulatory blood pressure (BP) monitoring before and after high salt diet in a novel mouse model of low nephron endowment (named Ret UB del ). RESULTS: We discovered that adult Ret UB del mice and controls have similar systolic and diastolic BP. After high salt diet, Ret UB del males and females had a greater rise in systolic BP, and Ret UB del females had a greater rise in diastolic BP than controls. In contrast, Ret UB del males had less of a rise in diastolic BP, revealing possible sex dimorphisms in mice with low nephron endowment. In females, salt loading was accompanied by less suppression of juxtaglomerular renin and a blunted rise in fractional excretion of urinary sodium, although sample stratification reduced the power to detect significant male-female differences. Ret UB del males had more of a CKD phenotype, suggesting that CKD did not contribute to salt-sensitivity. CONCLUSIONS: This study shows the impact of a modifiable dietary factor on the development of hypertension in mice with low nephron endowment.