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Calcitriol and FGF-23, but neither PTH nor sclerostin, are associated with calciuria in CKD

  • Nephrology - Original Paper
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Abstract

Purpose

The recent observation that urinary calcium excretion (UCE) drops considerably with CKD and that this effect may occur beyond compensation for reduced intestinal calcium absorption suggests that CKD per se is a state of sustained positive calcium balance, a mechanism likely to contribute to vascular calcification and CVD in CKD. However, the determinants of UCE reduction in CKD are not well understood and there is a lack of clinical studies, particularly in the CKD population. Therefore, in this study, we aimed to evaluate variables associated with UCE in a CKD cohort.

Methods

Baseline data on 356 participants of the Progredir Study, Sao Paulo, Brazil, essentially composed of CKD G3a–G4, were analyzed according to UCE (24 h urine collection).

Results

Median 24 h UCE was 38 mg/day (IQR 21–68 mg/day) and 0.48 mg/kg/day (IQR 0.28–0.82 mg/kg/day). In univariate analysis, UCE was inversely related to age, phosphorus, 1-84 PTH, FGF-23 and sclerostin, and positively associated with eGFR, DBP, 1,25(OH)2-vitamin D, calcium, bicarbonate, total calorie intake and spironolactone use. After adjustments for age, sex and eGFR, only 1,25(OH)2-vitamin D, calcium, FGF-23, bicarbonate and total calorie intake remained associated with it, but not PTH nor sclerostin. Lastly, in a multivariable model, eGFR, serum 1,25(OH)2-vitamin D, calcium, and FGF-23 remained associated with UCE. Similar results were observed when calcium fractional excretion was used instead of UCE, with eGFR, 1-25-vitamin D and FGF-23 remaining as independent associations.

Conclusion

Our results showed that CKD is associated with very low levels of UCE and that 1,25(OH)2-vitamin D, serum calcium and FGF-23 were independently associated with UCE in this population, raising the question whether these factors are modulators of the tubular handling of calcium in CKD.

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Acknowledgements

DiaSorin, Minnesota, USA, performed pro-bono the 1,25(OH)2D, 25-OH-vitamin D, 1-84 PTH, and FGF-23 measurements and did not interfere in any process of this manuscript. This study was supported by FAPESP and CNPq.

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Authors and Affiliations

  1. Nephrology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, 255 Av Dr Enéas de Carvalho Aguiar, Sao Paulo, SP, 05403-000, Brazil

    J. Ramalho, E. M. Petrillo, A. P. M. Takeichi, R. M. A. Moyses & S. M. Titan

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  1. J. Ramalho
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  2. E. M. Petrillo
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  3. A. P. M. Takeichi
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  4. R. M. A. Moyses
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Correspondence to J. Ramalho.

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Ethical statement

All subjects included in this study have given informed written consent, and the study protocol was approved by two local Ethics Committees (Ethics in Research Committee—University Hospital, Sao Paulo University, no. 11,147/11; and Ethics Commission for Analysis of Research Projects, Hospital das Clínicas, Medical School, Sao Paulo University, no. 0798/11).

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Ramalho, J., Petrillo, E.M., Takeichi, A.P.M. et al. Calcitriol and FGF-23, but neither PTH nor sclerostin, are associated with calciuria in CKD. Int Urol Nephrol 51, 1823–1829 (2019). https://doi.org/10.1007/s11255-019-02215-0

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