Synergic Interaction of Vitamin D Deficiency and Renal Hyperfiltration on Mortality in Middle-Aged Men

Vitamin D deficiency and renal hyperfiltration (RHF) are prevalent conditions both recently linked with mortality. The two conditions are interrelated, but their combined effect and interaction on mortality have not been studied. The objective of this study was to assess the combined effect and interaction of vitamin D deficiency and RHF on all-cause, cardiovascular (CV), and non-CV mortality in nondiabetic middle-aged men.

Middle-aged nondiabetic men (n = 1,959) were followed up for a median of 28 years. With adjustment for age, body mass index (BMI), smoking, BMI-smoking interaction, healthy Nordic diet (HND), alcohol consumption, and hypertension, we fitted Cox proportional hazard models to estimate the hazard ratios (HRs) of all-cause-, CV-, and non-CV mortality with respect to vitamin D deficiency and RHF. We evaluated the effect of interaction between RHF and vitamin D on the outcomes on the additive and multiplicative scales.

Vitamin D deficiency and RHF, both individually and combined, are associated with a high hazard of mortality. The HRs for all-cause- and non-CV mortality were highest among men with coexisting vitamin D deficiency and RHF (HR, 3.02; 95% CI, 1.90 to 4.79; and HR, 3.63; 95% CI, 2.07 to 6.36; respectively). We found a synergic interaction between vitamin D deficiency and RHF in respect to all-cause (RERI, 1.47; 95% CI, 0.03 to 2.9) and non-CV mortality (RERI, 2.09; 95% CI, 0.02 to 4.16) of type positive multiplicative, positive additive.

The synergic interaction of vitamin D deficiency and RHF on mortality might have importance in the global burden of the two conditions. Further studies investigating cause-specific mortality are needed to highlight underlying mechanisms by which vitamin D deficiency and RHF interact.