Effect of Aging on Kidney Function in Male Intrauterine Growth Restricted Rats

Abstract

Epidemiological studies show a correlation between low birth weight (LBW), reduced nephron number, and an increased risk of kidney disease later in life. We hypothesized that LBW males would have lower nephron numbers and diminished kidney function compared to their age‐matched controls. To test this hypothesis, our lab performed a reduced uterine perfusion or sham surgery on day 14 of gestation in timed pregnant rats to induce intrauterine growth restriction (IUGR). Their male offspring were aged to 18 months. Metabolic studies were performed to collect 24‐hr albuminuria data. Rats were then instrumented with jugular catheters and allowed to recover overnight. FITC‐sinistrin was infused intravenously in conscious rats to calculate glomerular filtration rate (GFR) by transcutaneous clearance measurements, and the right kidney was harvested to calculate nephron number through a semi‐quantitative acid maceration technique. Albuminuria was remarkably high in both groups, but there was no significant difference in IUGR (206.6±29.2 mg/day) compared to control (286.3±50.7 mg/day)(n=12/group). GFR examined in a subset was not significantly decreased in IUGR (0.48±0.07) compared to control (0.69±0.11)(p‐value=0.16, n=4/group). Nephron number was not statistically different in IUGR (75,000±4,074) compared to control (96,400±8,298) although there was a trend towards significance (p‐value=0.055, n=4/group). These data indicate that males have kidney injury and a reduction in kidney function that is independent of developmental programming effects by 18 months of age. However, this does not provide evidence about the time course of development of kidney injury or the susceptibility of IUGR offspring to secondary renal insults. Therefore, one future aim is to measure kidney function in younger males to determine whether there is a difference in the age of onset of GFR reduction and albuminuria in these animals. We will also study the effect of uni‐nephrectomy as a second hit in the progression of renal injury.Support or Funding InformationNIH 074927, T32HL105324, AHA GRNT1990004