Vitamin D compounds for people with chronic kidney disease not requiring dialysis

People with lower kidney function (chronic kidney disease; CKD) develop changes in circulating blood levels of calcium and phosphorus. The kidney gradually loses the ability to remove phosphorus from the blood and cannot activate adequate amounts of vitamin D to maintain normal levels of calcium. The parathyroid gland senses these changes and compensates to increase calcium by elevating production and release of parathyroid hormone (PTH). These metabolic changes alter bone metabolism to release calcium and accordingly lead to bone abnormalities including altered bone production. In turn, bony changes may result in bone deformation, bone pain, and altered risks of fracture.

Treatment for these mineral changes in CKD include replacing activated vitamin D to suppress parathyroid hormone release. Earlier activated vitamin D preparations (calcitriol and alfacalcidol) were associated with increased circulating calcium and phosphorus through their direct action on the vitamin D receptor. Newer agents have since been developed that similarly suppress parathyroid hormone but limit changes in calcium and phosphorus. Avoidance of increased calcium and phosphorus is considered important as these minerals may activate calcification in arteries and tissues, potentially leading to heart disease and tissue damage.

We identified 16 studies of vitamin D preparations in people with CKD and not requiring dialysis (less severe CKD) involving 894 people. No studies were designed to understand the effect of vitamin D therapy on risks of premature cardiovascular disease or mortality. Vitamin D agents lowered PTH significantly compared with no treatment, however also increased both calcium and phosphorus levels. Newer vitamin D therapies have not been compared with older vitamin compounds in CKD directly; whether they are associated with increased calcium and phosphorus is uncertain. In the future, new studies are required to assess outcomes important to patients, such as life expectancy and premature heart disease. It will also be important to know if vitamin D therapy should be used differently (differing target levels of PTH) in differing stages of CKD.

Authors' conclusions: 

There are not sufficient data to determine the effect of vitamin D compounds on mortality and cardiovascular outcomes in people with CKD not requiring dialysis. While vitamin D compounds reduce serum PTH (49.3 pg/mL (5.6 pmol/L)) compared with placebo, the relative clinical benefits of PTH lowering versus treatment-related increases in serum phosphorus and calcium remain to be understood.

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Background: 

Vitamin D compounds are used to suppress elevated serum parathyroid hormone (PTH) in people with chronic kidney disease (CKD).

Objectives: 

To assess the efficacy of vitamin D therapy on biochemical, bone, cardiovascular, and mortality outcomes in people with CKD and not requiring dialysis.

Search strategy: 

We searched The Cochrane Renal Group's specialised register, Cochrane's Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and reference lists of retrieved articles.

Selection criteria: 

Randomised controlled trials (RCTs) comparing different forms, schedules, or routes of administration of vitamin D compounds for people with CKD not requiring dialysis were included. Vitamin D compounds were defined as established (calcitriol, alfacalcidol, 24,25(OH)2vitamin D3) or newer (doxercalciferol, maxacalcitol, paricalcitol, falecalcitriol) vitamin D compounds.

Data collection and analysis: 

Data were extracted by two authors. Statistical analyses were performed using the random effects model. Results were summarized as risk ratio (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes with 95% confidence intervals (CI).

Main results: 

Sixteen studies (894 patients) were included. No formulation, route, or schedule of vitamin D compound was found to alter the mortality risk or need for dialysis. Vitamin D compounds significantly lowered serum PTH (4 studies, 153 patients: MD -49.34 pg/mL, 95% CI -85.70 to -12.97 (-5.6 pmol/L, 95% CI -9.77 to -1.48)) and were more likely to reduce serum PTH > 30% from baseline value (264 patients: RR 7.87, 95% CI 4.87 to 12.73). Vitamin D treatment was associated with increased end of treatment serum phosphorus (3 studies, 140 patients: MD 0.37 mg/dL, 95% CI 0.09, 0.66 (0.12 mmol/L, 95% CI 0.03, 0.21)) and serum calcium (5 studies, 184 patients: MD 0.20 mg/dL, 95% CI 0.17 to 0.23 (0.05 mmol/L, 95% CI 0.04 to 0.06)). Few data were available comparing intermittent with daily vitamin D administration, or other schedules of dosing.

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