Vitamin D and Secondary Hyperparathyroidism in Chronic Kidney Disease: A Critical Appraisal of the Past, Present, and the Future

Abstract

The association between vitamin D deficiency and especially critical shortage of active vitamin D (1,25-dihydroxyvitamin D, calcitriol) with the development of secondary hyperparathyroidism (sHPT) is a well-known fact in patients with chronic kidney disease (CKD). The association between sHPT and important clinical outcomes, such as kidney disease progression, fractures, cardiovascular events, and mortality, has turned the prevention and the control of HPT into a core issue of patients with CKD and on dialysis. However, vitamin D therapy entails the risk of unwanted side effects, such as hypercalcemia and hyperphosphatemia. This review summarizes the developments of vitamin D therapies in CKD patients of the last decades, from calcitriol substitution to extended-release calcifediol. In view of the study situation for vitamin D insufficiency and sHPT in CKD patients, we conclude that the nephrology community has to solve three core issues: (1) What is the optimal parathyroid hormone (PTH) target level for CKD and dialysis patients? (2) What is the optimal vitamin D level to support optimal PTH titration? (3) How can sHPT treatment support reduction in the occurrence of hard renal and cardiovascular events in CKD and dialysis patients?

Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS)

“…A further limitation of the present Position Statement is that we decided not to face the problems of the need for vitamin D supplementation as related to the prevention of autoimmunity and in patients with inflammatory bowel disorders. Recent data seem to suggest a possible link between hypovitaminosis D and both autoimmunity [ 169 , 170 ] and inflammatory bowel disease [ 171 , 172 ]. Notwithstanding these recent data, our decision has been based on the fact that for the use of vitamin D in these disorders, data in the literature, in terms of large controlled and randomized intervention clinical trials, are lacking.…”

Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines

“…It is clear, then, that there is conflicting evidence on the optimal levels of VD (with disagreement on both the lower normal limit and an undefined upper limit), not only in the general population but also in CKD patients [ 76 ]. Correspondingly, the evidence regarding the safety and efficacy of high-dose VD supplementation in patients with CKD remains discordant [ 37 ], and periodic measurement of serum calcium and phosphate should be considered, especially for patients who are using calcium-based phosphate binders and/or VD active analogues [ 74 ].…”

“…Although controversies still exist [ 30 , 35 , 36 , 37 , 38 ], diagnosis and treatment of VD deficiency [with either nutritional (native) or active forms of VD] have not yet been excluded from nephrology practice and guidelines [ 22 , 31 , 39 , 40 ], and despite the poor quality of available evidence, much data may still support VD use in populations with VD deficiency or certain special characteristics, such as CKD patients [ 36 , 39 , 40 ]. Furthermore, when an optimized prediction tool was recently developed using machine-learning techniques, both parathyroid hormone (PTH) and calcidiol were found to be among the seven variables identified as having the best predictive value for 2-year all-cause mortality in patients with CKD G4-G5 [ 41 ].…”

Secondary hyperparathyroidism in diabetic kidney disease patients treated with hemodialysis

“…Це може бути викликано порушенням синтезу вітаміну Д у шкірі, дієтичними обмеженнями, зниженням доступності попередників 25-гідроксивітаміну Д холекальциферолу/ергокальциферолу. Крім того, ХХН пригнічує 1α-гідроксилазу CYP27B1, яка каталізує активацію 25-гідроксивітаміну Д, порушується біосинтез вітаміну Д, а протеїнурія та уремія сприяють втраті білків, що зв'язують вітамін Д [15].…”