Incident heart failure and decline in kidney function are often linked conditions; both are prevalent in older individuals and are associated with high morbidity and mortality. Previous studies have demonstrated an association between lower concentrations of 25-hydroxyvitamin D and progression of chronic kidney disease (CKD), heart failure, and mortality; diabetes, higher blood pressure, and inflammation are also key risk factors for heart failure and kidney disease.
However, according to Umet Selamet, MD, and colleagues, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for optimal biologic effects. There are few data available on whether there is an association between concentrations of calcitriol and clinically relevant outcomes. Further, there are no data on whether the ratio of 24, 25-hydroxyvitamin D to 25-hydroxyvitamin D (the vitamin D metabolite ratio [VMR]) is associated with renal or heart failure outcomes; no studies to date have compared these associations with those with calcitriol.
Dr. Selamet et al. conducted a case-cohort study to assess associations of calcitriol concentrations and VMR with major decline in kidney function, incident heart failure, and death. The cohort included well-functioning community-dwelling older adults who participated in the Health ABC (Health, Aging, and Body Composition) study. The researchers sought to test the hypothesis that there would be an independent association between lower concentrations of calcitriol and decline in kidney function, incident heart failure, and death. Study results were reported in the American Journal of Kidney Diseases [2018;72(3):419-428].
The Health ABC study enrolled 3075 participants, who ranged in age from 70 to 79 years at study inception. Enrollment continued from April 1997 to June 1998 at two study sites in Pittsburgh, Pennsylvania, and Memphis, Tennessee. The current analysis was conducted on data from a subcohort of 479 randomly selected participants.
The primary predictor was serum calcitriol, measured using positive ion electrospray ionization-tandem mass spectrometry. The outcomes of interest were major kidney function decline, defined as ≥30% decline in estimated glomerular filtration rate (eGFR) from baseline; incident heart failure; and all-cause mortality during 10 years of follow-up
Of the 479 persons in the subcohort, mean age was 74 years, 52% were male, and 61% were white. Mean 25-hydroxyvitamin D concentration was 21.5 ng/mL, mean calcitriol concentration was 40.6 pg/mL, mean VMR was 4.81, and mean eGFR was 73 mL/min/1.73 m2.
Participants were stratified into quartiles by calcitriol concentration. Compared with those in the highest quartile of calcitriol concentration (>52 pg/mL), those in the lowest quartile (<34 pg/mL) were more likely to be male, white, and more educated. They were also more likely to have diabetes and to smoke, and were less likely to be hypertensive. Their total and high-density lipoprotein cholesterol concentrations were lower, while their triglyceride concentrations were higher.
The lowest quartile participants also had lower eGFRs and concentrations of serum calcium and intact parathyroid hormone (iPTH). Concentrations of fibroblast growth factor 23 (FGF-23) were higher in the lowest quartile; concentrations of phosphate were similar across quartiles.
During a mean 8.6 years of follow-up, 44% of those in the subcohort (n=212) died. Following adjustment, there was an association between each 1-standard deviation lower calcitriol concentration and a 30% higher risk for major kidney function decline (95% confidence interval [CI], 1.03-1.65; P=.03). There was no significant association between calcitriol and incident heart failure (hazard ratio [HR], 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.10; 95% CI, 0.81-1.26). There were no significant interactions between calcitriol status, baseline intact PTH, or FGF-23.
Study limitations cited by the authors included the observational design of the study, precluding the ability to ascribe cause-effect relationships; limiting the participants to adults 70 to 79 years of age and to either black or white race, perhaps affecting the generalizability of the findings to younger populations or other races/ethnicities; taking measurements of calcitriol at a single time point; and the possibility of bias due to those who died during follow-up or were too sick to return to follow-up visits.
The researchers said, “In community-dwelling older adults with preserved kidney function, lower calcitriol concentrations are independently associated with major kidney function decline. If these findings are confirmed, future studies should determine whether serum calcitriol measurement provides a surrogate for kidney tubule function and may facilitate assessment of nonglomerular aspects of kidney health.”
- Researchers conducted a case-cohort study to examine the associations of calcitriol concentrations with major kidney function decline, incident heart failure, and mortality.
- The participants of the current analysis were well-functioning, community-dwelling participants 70 to 79 years of age who participated in the Heart, Aging, and Body Composition study.
- In fully adjusted analysis, there was an association between each 1-standard deviation in lower calcitriol concentration and a 30% higher risk for major kidney function decline.