Objectives Vitamin D deficiency, elevated fibroblast growth factor 23 (FGF23) and elevated parathyroid hormone (PTH) have each been associated with increased mortality in people with chronic kidney disease (CKD). Previous studies have focused on the effects of FGF23 in relatively advanced CKD. This study aims to assess whether FGF23 is similarly a risk factor in people with early CKD, and how this risk compares to that associated with vitamin D deficiency or elevated PTH.
Design Prospective cohort study.
Setting Thirty-two primary care practices.
Participants One thousand six hundred and sixty-four people who met Kidney Disease: Improving Global Outcomes (KDIGO) definitions for CKD stage 3 (two measurements of estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 at least 90 days apart) prior to study recruitment.
Outcome measures All-cause mortality over the period of study follow-up and progression of CKD defined as a 25% fall in eGFR and a drop in GFR category, or an increase in albuminuria category.
Results Two hundred and eighty-nine participants died during the follow-up period. Vitamin D deficiency (HR 1.62, 95% CI 1.01 to 2.58) and elevated PTH (HR 1.42, 95% CI 1.09 to 1.84) were independently associated with all-cause mortality. FGF23 was associated with all-cause mortality in univariable but not multivariable analysis. Fully adjusted multivariable models of CKD progression showed no association with FGF23, vitamin D status or PTH.
Conclusions In this cohort of predominantly older people with CKD stage 3 and low risk of progression, vitamin D deficiency and elevated PTH were independent risk factors for all-cause mortality but elevated FGF23 was not. While FGF23 may have a role as a risk marker in high-risk populations managed in secondary care, our data suggest that it may not be as important in CKD stage 3, managed in primary care.
Trial registration number National Institute for Health Research Clinical Research Portfolio Study Number 6632.
- cardiovascular mortality
- chronic kidney disease
- fibroblast growth factor 23
- Vitamin D
- parathyroid hormone
- all-cause mortality
- chronic kidney disease progression
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Contributors AS: design of these analyses, data collection (year 5 study visits), analysed the data, wrote the manuscript, produced the figures. NJM: initial study design, participant recruitment, data collection (Baseline and Y1 study visits), critically reviewed and approved manuscript. RJF: initial study design, critically reviewed and approved manuscript. CWM: initial study design, critically reviewed and approved manuscript. MWT: initial study design, design of these analyses, wrote the manuscript.
Funding The RRID study is currently funded by a Research Project Grant (R302/0713) from the Dunhill Medical Trust. Previous study funding includes a joint British Renal Society and Kidney Research UK fellowship (to NJM), and an unrestricted educational grant from Roche Products Ltd. No pharmaceutical company had any input into study design, data collection or analysis. The data are wholly owned by the investigators.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Nottingham REC 1.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Anonymised data can be made available to researchers who meet the conditions of the ethics approval and research governance policy that applies to this study. Researchers may apply for data access by contacting Dr. Teresa Grieve, Research and Development Manager, Derby Teaching Hospitals NHS Foundation Trust (firstname.lastname@example.org).
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