Maternal renal insufficiency alters plasma composition and renal function in the fetal sheep

Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia Submitted 16 March 2006 ; accepted in final form 16 October 2006 To determine the effects of chronic maternal renal insufficiency on fetal renal function, we studied nine fetuses whose mothers underwent subtotal nephrectomy at least 2 mo before mating (STNxF) and seven fetuses from intact ewes (IntF) (126–128 days of gestation, term 150 days). STNxF had lower hematocrit ( P < 0.05), plasma chloride ( P < 0.01), and creatinine levels ( P < 0.01), and the length-to-width ratio of their kidneys was reduced ( P < 0.05). They excreted twice as much urine ( P < 0.05) and sodium ( P < 0.01). Total ( P = 0.01) and proximal fractional sodium reabsorptions ( P < 0.05) were lower in STNxF; distal delivery of sodium ( P < 0.05) and distal fractional sodium reabsorption ( P < 0.05) were higher. They tended to have suppressed renin levels ( P = 0.06). Infusions of amino acids (alanine, glycine, proline, and serine at 0.32 mmol/min for 1 h and 0.64 mmol/min for 2 h intravenously), known to stimulate renal blood flow and glomerular filtration rate in fetal sheep, did so in IntF ( P < 0.01). Arterial pressure also increased ( P < 0.01). These effects were not observed in STNxF. In summary, chronic maternal renal insufficiency was associated with profound alterations in fetal renal excretion of fluid and electrolytes and impaired renal hemodynamic and glomerular responses to amino acid infusion. Whether these marked changes in the renal function of fetuses carried by STNx ewes are associated with alterations in renal function in postnatal or adult life remains to be determined. glomerular filtration; amino acid infusions; hypochloremia; hyponatremia; renin Address for reprint requests and other correspondence: K. Gibson, Dept. of Physiology and Pharmacology, School of Medical Sciences, Univ. of New South Wales, Sydney, NSW, 2052 Australia (e-mail: K.Gibson{at}unsw.edu.au )