OBJECTIVES : Secondary hyperparathyroidism (SHPT) is a common major complication in non-dialysis chronic kidney disease (ND-CKD), increasing risk of morbidity and mortality. The objective of this analysis was to systematically review the clinical efficacy of treatments for controlling SHPT in ND-CKD.

METHODS : The PUBMED database was searched for randomized controlled trials (RCTs) using a predefined search strategy. Only English publications were included, and no restriction was imposed on publication year. The search included disease specific terms (CKD and SHPT), treatment options (nutritional vitamin D (cholecalciferol, ergocalciferol), calcitriol, vitamin D receptor activators (paricalcitol, alfacalcidol, doxercalciferol), calcifediol (extended or immediate release), calcimimetics (cinacalcet)) and outcomes (including changes in parathyroid hormone (PTH), Vitamin D metabolites (25(OH)D or 1,25(OH)2D), calcium and phosphate and the events hypercalcemia and hyperphosphatemia).

RESULTS : The search strategy produced a total of 952 hits. After a screening of titles, abstracts and full-texts by two independent researchers, 44 articles were included. Most RCTs (n=32) were placebo controlled. The most commonly investigated intervention was paricalcitol (n=15) and the least common was immediate release calcifediol (n=1). The most commonly reported results were changes in PTH, 25(OH)D, calcium and phosphate; mean intervention-arm changes in PTH and 25(OH)D across studies ranged from -60% (paricalcitol) to +21% (calcitriol) and -11% (calcitriol) to +302% (extended release calcifediol), respectively. Changes in calcium and phosphate levels were generally minor. The highest incidence of hypercalcemia was 43.3% (paricalcitol) and of hyperphosphatemia was 52% (placebo).

CONCLUSIONS : Coverage of the relevant interventions and outcomes varied considerably in the identified literature. Paricalcitol, calcitriol and cholecalciferol and reporting of changes in PTH, 25(OH)D, calcium and phosphate were the most common. The effects of treatment on PTH and 25(OH)D varied noticeably both across interventions and within interventions. A more sophisticated synthesis of the results would be needed to draw any conclusions regarding relative effectiveness and safety.