Is Calcitriol Life-Protective for Patients with Chronic Kidney Disease?

Abstract

In nephrology we are frequently confronted with association studies reporting novel biomarkers or mediators. Which among the myriad of potential candidates are amenable to intervention and, thereafter, which do we carry forward into clinical trials? Our group and others have considered the potential of vitamin D. Before commenting on vitamin D in chronic kidney disease, lessons learned from Alfred Sommer's initial observational studies and subsequent clinical trials with vitamin A—a journey of humility and perseverance—are worthy of reminder. Alfred Sommer, Dean Emeritus of the Johns Hopkins Bloomberg School of Public Health, received the Lasker Award in 1997 for his seminal work showing vitamin A deficiency is linked to increased risk of mortality and for demonstrating that correcting this deficiency reduces mortality. His series of studies started as simple observations, which led to community-based randomized trials. When Sommer initiated his work, vitamin A deficiency was highly prevalent, yet the connection between vitamin A deficiency and mortality had not been established. With the intent of examining night-blindness and dry eyes, Sommer and his colleagues stumbled across the observation that death rates in children with these ophthalmic conditions were several-fold higher than children without these conditions.1 When Sommer first published his prospective observational study linking vitamin A deficiency with a 16% increased risk in mortality,2 the field hardly took notice. As he articulated in a commentary written at the time of winning the Lasker, “The initial report associating vitamin A deficiency with increased mortality was received with deafening silence.”1 This response, as we know all too well, is common. Treatment with activated vitamin D, or calcitriol [1,25(OH)2D3], has been used for over three decades to manage the secondary hyperparathyroidism and hypocalcemia accompanying chronic renal disease.3–6 This intervention markedly changed the management of renal …