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

Letter to: Does the Urinary Calcium/Citrate Ratio Add to the Diagnostic Workup of Children at Risk of Kidney Stones? A Cross-Sectional Study Journal of Child Science 2019; 09(01): e1-e6 DOI: 10.1055/s-0039-1677818 Calcium/Citrate Ratio and Risk of Kidney Stone Does the Urinary Calcium/Citrate Ratio Add to the Diagnostic Workup of Children at Risk of Kidney Stones? A Cross-Sectional Study We recently published our article entitled “Does the Urinary Calcium/Citrate (UCa/UCi) Ratio Add to the Diagnostic Workup of Children at Risk of Kidney Stones?” in your prestigious journal.[ 1 ] We have received a letter to the editor by Beuy Joob and Viroj Wiwanikit. 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.[ 4 ] These sex differences start with the onset of puberty and may explain the higher prevalence of kidney stones in men.[ 4 ] Interestingly, the substantial increase of nephrolithiasis in children and adolescents, however, is among adolescent girls.[ 5 ] [ 6 ] Our study by Lee M et al[ 1 ] involved 56 males with a median (25th, 75th percentile) age of 8 (3, 15) years and 41 females with a median age of 10 (6.8, 15) years, which was not statistically different ( p = 0.2720, Mann Whitney U test). The details of the patients are listed in [ Table 1 ]. This means that most of the patients were prepubertal. As pointed out, the sex differences begin with the onset of puberty.[ 4 ] The proposed cutoff for assessing the stone risk therefore holds in our patient cohort and the main conclusion that “ U Ca /U Ci rather than U Ci /U Cr may be more predictive in the clinical setting when evaluating for nephrolithiasis” remains adequate as we did not observe any sex differences for the urinary citrate/creatinine ratio ([ Fig. 1 ]). Unfortunately, our cohort of patients was too small to perform a subanalysis of adolescents, and we did not routinely obtain the Tanner stage to precisely determine the onset of puberty. Therefore, we do acknowledge that more work is needed to assess the utility of the urinary U Ca /U Ci as a predictor for nephrolithiasis or urolithiasis in pubertal adolescents. We agree with the conclusion in Joob and Wiwanitkit's letter to the editor that the sex variation should be kept in mind in interpreting U Ca /U Ci in adolescents. We do see many adolescent girls with kidney stones who have normal U Ci /U Cr but abnormal U Ca /U Ci . The reasons for the substantial increase of kidney stones in adolescent girls remain a main question for our ongoing research. Fig. 1 Comparison of urinary citrate/creatinine ratio in the aforementioned study.[ 1 ] There was no significant difference between both sexes. Table 1 Patient characteristics and comparison of parameters Group SF NSF Comparison Test Number of patients 51 46 Age (years, median and IQR) 8 (3,15) 10 (6.8, 15) 0.1755 Mann Whitney Female (%) 19 (37.3%) 22 (47.8%) 0.3074 Fisher's exact test Urinary citrate (mmol/L, median and IQR) 1.55 (0.95, 2.32) 1.675 (0.79, 3.13) 0.7743 Mann Whitney Urinary calcium (mmol/L, median and IQR) 1.87 (1.21, 4.29) 1.0 (0.26, 2.3) 0.0021 Mann Whitney Urinary sodium (mmol/L, median and IQR) 77 (30, 121) 107 (48, 154) 0.0963 Mann Whitney Urinary potassium (mmol/L, median and IQWR) 42 (28, 101) 48 (19, 80) 0.9895 Mann Whitney Urinary creatinine (µmol/L, median and IQR) 3.4 (1.5, 6.8) 4.6 (1.9, 9.0) 0.3878 Mann Whitney Urinary oxalate (µmol/L, median and IQR) 189 (111, 291) 134 (38, 290) 0.1438 Mann Whitney Urinary urate (µmol/L, median and IQR) 1.9 (1, 5.7) 2.3 (1, 12) 0.2544 Mann Whitney Urinary pH (mean ± SD) 6.6 ± 0.91 6.5 ± 0.98 0.7366 t-test Urinary specific gravity (median and IQR) 1.010 (1.005, 1.020) 1.015 (1.005, 1.020) 0.1842 Mann Whitney Urinary citrate/creatinine (mmol/mmol, median and IQR) 0.48 (0.21, 0.90) 0.38 (0.21, 0.86) 0.8784 Mann Whitney Urinary calcium/creatinine (mmol/mmol, median and IQR) 0.67 (0.31, 1.37) 0.24 (0.11, 0.73) 0.0029 Mann Whitney Urinary calcium/citrate (mmol/mmol, median and IQR) 1.30 (0.73, 2.78) 0.68 (0.29, 1.83) 0.0114 Mann Whitney Urinary sodium/potassium (mmol/mmol, mean ± SD) 2.08 ± 1.92 2.50 ± 1.36 0.3185 t -test Abbreviations: IQR, interquartile range (25th and 75th percentiles); NSF, non-stone formers; SD, standard deviation, SF, stone formers. Note: Statistically significant differences are in boldface. The comparison column represents the p -value, and in the test column, the test that was used is listed (based on the distribution and data type). Letter to this article: Calcium/Citrate Ratio and Risk of Kidney Stone Journal of Child Science 2019; 09(01): e90-e90 DOI: 10.1055/s-0039-1697944

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