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.