Sex Differences In Glomerular Filtration Rate Reserve In Healthy Young Adults

Abstract

PURPOSE: The prevalence of chronic kidney disease (CKD), defined as a sustained glomerular filtration rate (GFR) <60 mL/min/1.73m2, is higher in women compared to men. CKD can result from an insufficient number of functional nephrons necessary to maintain a healthy GFR. Functional nephron mass is lower in women compared to men, independent of differences in body size. Thus, women may be more susceptible to chronic reductions in GFR as a result of reductions in relatively fewer functional nephrons. Assessment of GFR reserve, which is defined as the ability to increase GFR in response to a protein load, is used to test the functional capacity of the kidneys to recruit nephrons. Whether GFR reserve differs between men and women is unknown. We tested the hypothesis that GFR reserve is lower in women vs. men. METHODS: Following 2 h of supine rest, healthy young men (n = 12) and women (n = 13, eumenorrheic, tested in the early follicular phase) ingested 1.2 g of whey protein per kg of body weight (fluid volume - men: 295 ± 48, women: 233 ± 27 mL, p < 0.001). Serum (sCr) and urinary (uCr) creatinine were measured pre-protein and 75- and 150-min post-protein ingestion to assess GFR via creatinine clearance (CrCl = uCr x urine flow rate ÷ sCr). Data are presented as mean ± SD RESULTS: Pre-protein, sCr was lower in women vs. men (0.9 ± 0.1 vs. 1.1 ± 0.1 mg/dL, p = 0.029), which was maintained post-protein (p ≤ 0.043). uCr was elevated above pre-protein levels (men: 35.7 ± 12.3, women: 21.8 ± 7.3 mg/dL) in both groups at 75- and 150- min post-protein (p ≤ 0.003), but uCr was higher in men at 150-min post-protein (104.1 ± 30.0 vs. 62.8 ± 24.7 mg/dL, p < 0.001). Urine flow rate decreased from pre- through post- protein (p < 0.001), and there were no differences between groups (p ≥ 0.723). CrCl increased from pre- to 150-min post- protein in men (122 ± 27 vs. 173 ± 89 mL/min, p = 0.002), but CrCl was not different from pre- (88 ± 18 mL/min) at any time post-protein in women (at 150-min post: 85 ± 32 mL/min, p ≥ 0.646), with CrCl at 150-min post-protein being higher in men (p < 0.001). The peak change in CrCl post-protein, independent of time, was greater in men vs. women (+57 ± 67 vs. 17 ± 20 mL/min, p = 0.052). CONCLUSIONS: The increase in CrCl following an oral protein load was lower in women compared to men, supporting that GFR reserve is lower in healthy young women vs. men.