Effects of Sex on Intra-Individual Variance in Urinary Solutes in Stone-Formers Collected from a Single Clinical Laboratory

Abstract

Background/AimsOur work in a rodent model of urinary calcium suggests genetic and gender effects on increased residual variability in urine chemistries. Based on these findings, we hypothesized that sex would similarly be associated with residual variation in human urine solutes. Sex-related effects on residuals might affect the establishment of physiological baselines and error in medical assays.MethodsWe tested the effects of sex on residual variation in urine chemistry by estimating coefficients of variation (CV) for urinary solutes in paired sequential 24-h urines (≤72 hour interval) in 6,758 females and 9,024 males aged 16–80 submitted to a clinical laboratory.ResultsFemales had higher CVs than males for urinary phosphorus overall at the False Discovery Rate (P<0.01). There was no effect of sex on CV for calcium (P>0.3). Males had higher CVs for citrate (P<0.01) from ages 16–45 and females higher CVs for citrate (P<0.01) from ages 56–80, suggesting effects of an extant oestral cycle on residual variance.ConclusionsOur findings indicate the effects of sex on residual variance of the excretion of urinary solutes including phosphorus and citrate; differences in CV by sex might reflect dietary lability, differences in the fidelity of reporting or genetic differentiation in renal solute consistency. Such an effect could complicate medical analysis by the addition of random error to phenotypic assays. Renal analysis might require explicit incorporation of heterogeneity among factorial effects, and for sex in particular.

Current update and future directions on gut microbiome and nephrolithiasis

“…[ 37 ] Lower gut microbiome reserve can partly explain the higher prevalence of nephrolithiasis in males and in those with high body mass index,[ 37 63 ] although in males, lower urinary citrate excretion after puberty can be another risk factor. [ 65 ] Those exposed to multiple antibiotics such as patients with cystic fibrosis[ 46 ] or inflammatory bowel disease[ 61 ] may not get enough time in between the antibiotic exposures for the microbiome to recover. [ 63 64 ] The long-term consequences of antibiotic exposure were also supported by in vivo studies which linked antibiotics to systemic diseases such as obesity, diabetes, and atherosclerosis.…”

Reply to: Calcium/Citrate Ratio and Risk of Kidney Stone

“…In that letter, the authors acknowledge that our findings are in accordance with the literature, especially the study by DeFoor et al 2 However, they also highlight that there is sexual variation for urine citrate. 3 In adults and older adolescents, there clearly is a higher urinary citrate excretion in women as compared with that in men. 3 Sex differences of the urinary citrate/creatinine ratio have since then been confirmed in adolescents.…”

“…3 In adults and older adolescents, there clearly is a higher urinary citrate excretion in women as compared with that in men. 3 Sex differences of the urinary citrate/creatinine ratio have since then been confirmed in adolescents. 4 These sex differences start with the onset of puberty and may explain the higher prevalence of kidney stones in men.…”