Predialysis Vitamin D Receptor Activator Treatment and Cardiovascular Events after Dialysis Initiation: A Multicenter Observational Study

Abstract

Background: Vitamin D receptor activator (VDRA) administration has been linked with a reduced incidence of cardiovascular disease (CVD). However, it is unclear whether VDRA administration during the predialysis stage is associated with CVD incidence after dialysis initiation in patients with chronic kidney disease. Therefore, we examined the association between VDRA use and CVD events. Methods: This multicenter observational study included 1,516 patients; they were divided into 2 groups: those who did and did not receive oral VDRA for at least 3 months before dialysis initiation. The CVD incidence was compared between these groups. Factors that impacted CVD incidence were extracted through a multivariate analysis. Subgroups were created based on prior CVD history and serum CRP levels. Results: The incidence of CVD was significantly lower in the VDRA group (log-rank test, p = 0.014). Stepwise multivariate analyses identified age, gender, diabetes, CVD history, calcium-channel blockers, beta-blockers, loop diuretics, anti-platelet agents, phosphate binders, VDRA, erythropoiesis stimulating agents, and cardiothoracic ratio as factors affecting CVD incidence. In the group with no CVD history, VDRA use was associated with a low incidence of CVD (HR 0.35). In the group with serum CRP levels <1.0 mg/dl, VDRA use was associated with a low incidence of CVD (HR 0.47). Conclusion: Administration of VDRA during predialysis was associated with a low incidence of CVD onset after dialysis initiation.

Vitamin D in Chronic Kidney Disease and Dialysis Patients

“…In a recent meta-analysis of CKD, Li et al reported that VDRAs reduced the incidence of cardiovascular events and reduced proteinuria, but resulted in an increased probability of hypercalcemia when paricalcitol was used [107]. In an observational study performed in Japan, it was reported that VDRA prescriptions during the late stages of CKD are associated with fewer cardiovascular diseases during the early dialysis stage [108]. Survival analysis in some observational cohorts from North America show advantages for patients treated with a synthetic analog (Paricalcitol), which is thought to be less hypercalcemic than calcitriol [100,102].…”

Vitamin D Receptor: A Novel Therapeutic Target for Kidney Diseases

“…Studies in various clinical trials have demonstrated that VDR stimulation by VDRAs protects against cardiovascular death risk in CKD patients. A multicenter study with 1,516 patients showed that administration of VDRA during predialysis can decrease the incidence of cardiovascular disease onset after dialysis initiation [ 173 ]. Oral calcitriol, even in low doses, can reduce overall and cardiovascular mortality and increase the survival rates in dialyzed patients [ 174 , 175 ].…”

Association between stopping renin-angiotensin system inhibitors immediately before hemodialysis initiation and subsequent cardiovascular events

“…The estimated glomerular filtration rate (eGFR) was calculated using the Japanese Society of Nephrology’s equation: eGFR = 194 × serum creatinine –1.094 × age –0.287 (×0.739 for women). The use of diuretics before dialysis initiation included regular loop diuretics, thiazide-type diuretics, or spironolactone [ 14 , 15 ]. The use of RASIs was defined as the use of ACEIs or ARBs.…”

“…The study outcomes were all-cause mortality and CV events after HD initiation. CV events were defined as heart failure, acute coronary syndrome, stroke, or peripheral artery disease requiring hospitalization [ 15 ]. Outcome data of all patients in this cohort were collected by reviewing the medical records of the AICOPP group or by sending letters to each dialysis clinic where patients were transferred for maintenance HD.…”