CC BY 4.0 · Journal of Child Science 2019; 09(01): e91-e92
DOI: 10.1055/s-0039-1697922
Letter to the Editor
Georg Thieme Verlag KG Stuttgart · New York

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

Misan Lee
1   Division of Paediatric Nephrology, Department of Paediatrics, Children's Hospital, Mexico City, Mexico
,
Carmen Inés Rodriguez Cuellar
1   Division of Paediatric Nephrology, Department of Paediatrics, Children's Hospital, Mexico City, Mexico
2   Departamento de Nefrología Pediátrica, Instituto Nacional de Pediatría, Mexico City, Mexico
3   Department of Pediatrics, Universidad Nacional Autónoma de México, Mexico City, Mexico
,
Ravneet Nagra
1   Division of Paediatric Nephrology, Department of Paediatrics, Children's Hospital, Mexico City, Mexico
,
Peter Zhan Tao Wang
4   Departments of Surgery, Division of Nephrology, and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
,
Vipin Bhayana
5   Departments of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
,
Guido Filler
1   Division of Paediatric Nephrology, Department of Paediatrics, Children's Hospital, Mexico City, Mexico
5   Departments of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
6   Lilibeth Caberto Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada
7   Departments of Medicine, Division of Nephrology, and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
› Author Affiliations
Further Information

Publication History

25 June 2019

30 June 2019

Publication Date:
16 October 2019 (online)

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 “UCa/UCi rather than UCi/UCr 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 UCa/UCi 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 UCa/UCi in adolescents. We do see many adolescent girls with kidney stones who have normal UCi/UCr but abnormal UCa/UCi. The reasons for the substantial increase of kidney stones in adolescent girls remain a main question for our ongoing research.

Zoom Image
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).


 
  • References

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  • 2 DeFoor W, Jackson E, Schulte M, Alam Z, Asplin J. Calcium-to-citrate ratio distinguishes solitary and recurrent urinary stone forming children. J Urol 2017; 198 (02) 416-421
  • 3 Perry GM, Scheinman SJ, Asplin JR. Effects of sex on intra-individual variance in urinary solutes in stone-formers collected from a single clinical laboratory. PLoS One 2013; 8 (06) e53637
  • 4 Kirejczyk JK, Porowski T, Konstantynowicz J. , et al. Urinary citrate excretion in healthy children depends on age and gender. Pediatr Nephrol 2014; 29 (09) 1575-1582
  • 5 Edvardsson VO, Ingvarsdottir SE, Palsson R, Indridason OS. Incidence of kidney stone disease in Icelandic children and adolescents from 1985 to 2013: results of a nationwide study. Pediatr Nephrol 2018; 33 (08) 1375-1384
  • 6 Rodriguez Cuellar CI, Wang PZT, Freundlich M, Filler G. Educational review: role of the pediatric nephrologists in the work-up and management of kidney stones. Pediatr Nephrol 2019