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Clinical Outcomes with Active versus Nutritional Vitamin D Compounds in Chronic Kidney Disease

Kamyar Kalantar-Zadeh^*,,, and Csaba P. Kovesdy^,||

^* Harold Simmons Center for Chronic Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California; David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Epidemiology, UCLA School of Public Health, Los Angeles, California; Division of Nephrology, Salem Veterans Affairs Medical Center, Salem Virginia; and ^|| Department of Medicine, University of Virginia, Charlottesville, Virginia

Correspondence: Dr. Kamyar Kalantar-Zadeh, Harold Simmons Center for Chronic Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, C1-Annex, Torrance, CA 90509-2910. Phone: 310-222-3891; Fax: 310-782-1837; E-mail: kamkal{at}ucla.edu

Increasing confusion exists as to which vitamin D compounds are more appropriate for persons with chronic kidney disease (CKD). Some opinion-based guidelines recommend administration of such nutritional vitamin D agents as ergocalciferol or cholecalciferol as the first therapy in hyperparathyroidism associated with low circulating levels of 25-hydroxy vitamin D (<30 ng/ml) in nondialysis dependent CKD patients. Insufficient to deficient levels of 25-hydroxy vitamin D have been reported in the majority of individuals with CKD, including both nondialysis dependent and maintenance dialysis patients. Epidemiologic studies have almost consistently indicated the survival benefit of active vitamin D agents across all stages of CKD, including among dialysis patients with 25-hydroxy vitamin D deficiency. To date, no large observational or interventional studies have shown any survival advantage of nutritional vitamin D in CKD patients. Several recent (postguideline) small studies have yielded mixed results regarding the potential benefits of ergocalciferol in CKD, including satisfactory to inadequate lowering of PTH level to target ranges, improving response to erythropoietin stimulating agents, and salutary effects on glycemic controls. Compared with nutritional vitamin D agents, active vitamin D compounds appear to more effectively lower the circulating levels of alkaline phosphatase, a conveniently available biomarker associated with increased mortality and coronary artery calcification in CKD patients. The ideal vitamin D therapy for CKD patients should be the one that improves survival irrespective of suggested or imposed target ranges for arbitrary or opinion-based surrogate end points. Randomized controlled trials are needed to verify which agents offer superior survival advantages.