Assessing the effect of activated vitamin D on all-cause mortality and clinical outcomes in hemodialysis patients

Abstract

Abstract Background: The reported incidence rate of end-stage renal disease (ESRD) patients receiving dialysis therapy in Taiwan remained highest across the world and the number of prevalent dialysis patients continued to rise Patients with ESRD have a high mortality rate that far exceeds the mortality rate for the general population The most common causes of death are cardiovascular disease and infection Activated vitamin D plays an important role in the treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD) which encompasses vitamin D deficiency derangement of mineral metabolism hyperparathyroidism renal osteodystrophy and vascular calcification In addition many potential benefits of activated vitamin D have been suggested including suppression of renin synthesis inhibition of vascular calcification and modification of immune response However tertiary hyperparathyroidism hypercalcemia and vascular calcification all confine the prescriptions of activated vitamin D to patients with relatively normal serum calcium and phosphorus levels The utilization pattern of activated vitamin D has not been determined in Taiwan The long-term impact of activated vitamin D use on clinical hard outcomes is still controversial Objective: We aimed to determine the real world prescribing pattern patient characteristics hospital accreditation levels and urbanizations which may influence prescription of activated vitamin D in incident hemodialysis patients in Taiwan Then we evaluated the effect of activated vitamin D use on overall survival and the associated clinical hard outcomes in these patients Method: The national survey of oral activated vitamin D for hemodialysis patients was done using the National Health Insurance Research Database from 2000 through 2010 We used the registry of catastrophic illness certificate to confirm the ESRD status of these incident hemodialysis patients Then we used multivariate Cox proportional hazard regression to assess the association of activated vitamin D use with all-cause mortality in these patients We also used competing risk analysis to evaluate the impact of activated vitamin D use on the hazards of acute myocardial infarction ischemic stroke amputation and infection respectively Results: Of 61 485 incident hemodialysis patients from 2001 through 2010 25% received activated vitamin D over the follow-up period The prescription of activated vitamin D was more prevalent in medical centers than in regional or district hospitals and more in urban than in suburban or rural hospitals The first time of activated vitamin D prescription varied widely There were 8 151 vitamin D users and 44 606 non-users according to prescription of vitamin D or not before the 360th day of hemodialysis initiation Patients prescribed vitamin D were younger and had fewer baseline comorbidities Vitamin D users were associated with a significantly lower risk of death in the multivariate adjusted Cox model (HR 0 91 [95% CI 0 87-0 95]) and propensity score matching analysis (HR 0 94 [95% CI 0 90-0 98]) respectively High dose users were associated with a lower risk of death compared with conventional dose users and non-users The result of competing risk analysis using subdistribution hazard regression with death as competing events showed that vitamin D users were associated with a lower risk of amputation (subdistribution hazard ratio SHR 0 84 [95% CI 0 74-0 96]) and infection (SHR 0 91 [95% CI 0 88-0 95]) but not acute myocardial infarction (SHR 1 04 [95% CI 0 93-1 16]) or ischemic stroke (SHR 0 91 [95% CI 0 82-1 01]) In subgroup analyses the survival advantage associated with activated vitamin D was prominent in younger patients and those without heart failure The reduced subdistribution hazards of amputation and infection were consistent across all subgroups analyzed Moreover a trend toward a lower subdistribution hazard of amputation and infection was observed in high dose users Conclusion: Compared with other countries activated vitamin D prescribing was less prevalent in Taiwan Use of activated vitamin D in incident hemodialysis patients is associated with a lower risk of all-cause death amputation and infection Evidence from the real world practice has also suggested survival benefits in the high dose vitamin D users The cause of death in ESRD patients is complex and multifactorial Prescription of activated vitamin D is inexpensive and associated with multiple potential benefits It could be considered an integral part in the care of these patients unless contraindicated

Date of Award	2019
Original language	English
Supervisor	Yea-Huei Kao (Supervisor)