Prevalence of abnormal serum vitamin D, PTH, calcium and phosphorus in CKD
To examine the role of vitamin D deficiency as it relates to eGFR and hyperparathyroidism by examining the relationships of circulating vitamin D, PTH, Calcium, and Phosphorus in CKD patients.
Study Design and Population:
This is a cross-sectional, cohort study of CKD patients from 153 US-based centers across the United States. The study describes the cross-sectional analysis of baseline data in the SEEK study. Patients over 40 with an eGFR less than 60ml/min on initial screening were included. Patients were excluded if they were on renal replacement therapy, had a history of primary parathyroid disease or had been on prescription vitamin D in the previous 12 months. Blood tests were collected between June and October to ensure consistent sunlight intensity across the US.
Intervention and Observations
Lab values of Ca, P, PTH, 1,25 OH2D3 and 25(OH)D3 were measured and analyzed to determine their relationship to eGFR.
1814 CKD patients were included in the analysis. Initially 5255 subjects were screened and 1903 patients met the study criteria however 89 subjects were missing creatinine levels leaving 1814 subjects. 71% of patients were over 65.
The mean eGFR was 47ml/min. Twenty three percent (n=405) had an eGFR>60ml/min/1.73m2 due to a discrepancy between the eGFR calculated from the screening and the eGFR calculated from the serum creatinine measured at baseline.
PTH, Ca and P were analyzed by eGFR intervals and it was noted that Ca and P remained within the normal range until eGFR was <20mL/min. Increases in PTH were noted much sooner at eGFR levels of 45mL/min. The prevalence of hyperparathyroidism increased across declining eGFR deciles.
Vitamin D metabolites were assessed across the spectrum of eGFR deciles. It was observed that a statistically significant relationship existed between 1,25 OH2D3 and eGFR but not between 25(OH)D3 and eGFR. Looking at prevalence of combinations of abnormalities, it was determined that 49% of those with low 1,25 levels had high iPTH whereas only 35% of those with low 25(OH) levels had high iPTH levels.
Multivariate analysis revealed that diabetes mellitus, increased UACR and decreased eGFR were predictive of lower 1,25 OH2 D3.
This was a very large observational study. The cross-sectional design of the study does not allow causal relationships to be determined but it does provide a significant amount of information about the prevalence of abnormalities of vitamin D metabolites and parathyroid hormone. Specifically the early prevalence of 1,25 OH2D3 deficiency raises questions about potential therapeutic uses.
The majority of the subjects were over 65 years old and the results may not be generalizable to younger patients. A weakness of this study is that kidney disease was defined by a single creatinine measure to calculate eGFR, thus 22% of patients had an eGFR >60mL/min at enrollment.
Impact on Practice:
The study highlights a need for longitudinal studies relating these data to clinical outcomes and for interventional studies. The early rise in iPTH and decline in 1,25 OH2 D3 independent of changes in calcium and phosphorus leads to questions about the optimal metabolite to measure in CKD however routine screening of vitamin D metabolites is not recommended at this time. Guidelines for vitamin D supplementation in the general population would appear to apply for the CKD population until further evidence is available.