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Disorders in bone-mineral parameters and the risk of death in persons with chronic kidney disease stages 4 and 5: the PECERA study

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Abstract

Background

Abnormalities of bone mineral parameters are associated with increased mortality in patients on dialysis, but their effects and the optimal range of these biomarkers are less well characterized in non-dialysis chronic kidney disease (CKD).

Methods

PECERA (Collaborative Study Project in Patients with Advanced CKD) is a 3-year, prospective multicenter, open-cohort study of 966 adult patients with non-dialyzed CKD stages 4–5 enrolled from 12 centers in Spain. Associations between levels of serum calcium (Ca) (corrected for albumin), phosphate (P), and intact parathyroid hormone (iPTH) with all-cause mortality (primary outcome) and cardiovascular mortality (secondary outcome) were examined using time-dependent Cox proportional hazards models and penalized splines analysis adjusted by demographics and comorbidities, treatments and biochemical values collected every 6 months for 3 years.

Results

After a median follow-up of 29 months (IQR: 13–36 months) there were 181 deaths (19%). The association of calcium with all-cause mortality was J-shaped, with an increased risk for all-cause mortality at levels > 10.5 mg/dL. For phosphate and iPTH levels, the association was U-shaped. The serum values associated with the minimum risk of mortality were 3.8 mg/dL for phosphate and 70 pg/mL for iPTH, being the lowest risk ranges between 2.8 and 5.0 mg/dL, and between 38 and 112 pg/mL for phosphate and iPTH, respectively.

Conclusions

Our study provides evidence on the non-linear association of serum calcium, phosphate and iPTH levels with mortality in stage 4 and 5 CKD patients, and suggests potential survival benefits for controlling bone mineral parameters in this population, as previously reported for dialysis patients.

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Acknowledgements

The PECERA study was sponsored by the Valencian Society of Nephrology, the Spanish Society of Nephrology, and the Tomás de Osma Renal Foundation. Logistics (meetings, developing of Web site for data entry, etc.) were financially supported by Abbott, Hoffmann-La Roche, and Boehringer Ingelheim. The authors wish to thank all the co-investigators and participating centers of the PECERA study: MD Albero (Hospital Virgen de los Lirios. Alcoy), L Álvarez (Hospital Virgen de los Lirios. Alcoy), A Antolín (Hospital Francesc de Borja), MA Aparicio (Hospital de la Ribera), E Bea (Hospital de la Ribera), S Bea (Hospital General Universitario de Valencia), Y Blanco (Hospital de la Ribera), C Climent (Hospital Francesc de Borja), C Del Pozo (Hospital Virgen de los Lirios. Alcoy), JE Fernández-Nájera (Hospital de Manises), C García-Aparicio (Hospital de Villajoyosa), A García Hervás (Hospital Universitari Dr Peset), E Garrigós (Hospital Universitario La Fe), M González-Rico (Hospital Clínico Universitario de Valencia), JL Górriz (Hospital Clínico Universitario de Valencia), JM Graña (Hospital de la Ribera), R López-Menchero (Hospital Virgen de los Lirios), J Martín-Rivas (Hospital de Elda), P Molina (Hospital Universitari Dr Peset), C Montoyo (Hospital de la Marina Alta. Denia), E Muñoz de Bustillo (Hospital de Villajoyosa), LM Pallardó (Hospital Universitari Dr Peset), A Peris (Hospital Universitario La Fe), F Ramos (Hospital de Denia), L Sánchez (Hospital Virgen de los Lirios. Alcoy), MP Sánchez-Pérez (Hospital Universitario La Fe), A Soldevila (Hospital Universitario La Fe), J Torralba (Hospital General Univesitario de Alicante), V Valverde (Hospital de Elda).

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Authors and Affiliations

  1. Department of Nephrology, Hospital Universitari Dr Peset, FISABIO, Avda. Gaspar Aguilar, 90, 46017, Valencia, Spain

    Pablo Molina, Luis M. Pallardó & Verónica Escudero

  2. Department of Medicine, Universitat de València, Valencia, Spain

    Pablo Molina, Luis M. Pallardó & José L. Górriz

  3. Department of Mathematics, Universidad de Alicante, Alicante, Spain

    Mariola D. Molina

  4. Department of Nephrology, Hospital General Universitario, Alicante, Spain

    Javier Torralba

  5. Section of Nephrology, Hospital Virgen de Los Lirios, Alcoi, Spain

    Luis Álvarez

  6. Department of Nephrology, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    Ana Peris & Pilar Sánchez-Pérez

  7. Department of Nephrology, Hospital Clínico Universitario, INCLIVA, Valencia, Spain

    Miguel González-Rico, María J. Puchades, Elena Giménez-Civera, Luis D’Marco & José L. Górriz

  8. Department of Nephrology, Hospital de Manises, Valencia, Spain

    José E. Fernández-Nájera

  9. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Juan J. Carrero

Authors
  1. Pablo Molina
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Contributions

All authors contributed important intellectual content during manuscript drafting or revision and accept accountability for the overall work. The individual contribution of each co-author is as follows: research idea and study design: JLG, LMP, PM, MPS; patient recruitment and clinical information gathering: PM, JLG, JT, VE, LA, AP, MPS, MG, MJP, JEF, EG, LD; statistical analysis: MDM, PM, JJC; data analysis/interpretation: PM, MDM, JLG, JJC; supervision and mentorship: JLG, LMP, JJC.

Corresponding author

Correspondence to Pablo Molina.

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Conflicts of interest

The results presented in this paper have not been published previously in whole or part, except in abstract format. JJC acknowledges support from the Swedish Research Council (grant number 2019-01059). The authors declare no other conflicts of interest that might be perceived as affecting the objectivity of this study.

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The study was conducted in agreement with the Declaration of Helsinki, and the Hospital Ethics Committees approved the study.

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Molina, P., Molina, M.D., Pallardó, L.M. et al. Disorders in bone-mineral parameters and the risk of death in persons with chronic kidney disease stages 4 and 5: the PECERA study. J Nephrol 34, 1189–1199 (2021). https://doi.org/10.1007/s40620-020-00916-9

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  • DOI: https://doi.org/10.1007/s40620-020-00916-9

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