Failure of successful renal transplant to produce appropriate levels of 1,25-dihydroxyvitamin D

Bone metabolism disturbances following renal transplantation (RT) are complex and multifactorial in origin. Abnormalities in 1,25-dihydroxyvitamin D levels in RT patients under treatment at our Bone Center prompted this retrospective study.

Parameters of vitamin D metabolism were compared in RT patients and a cohort of patients with primary hyperparathyroidism (PHTP) who mimicked the hyperparathyroid state of the RT patients. Thirty-one RT recipients (from 300 reviewed) matched our inclusion criteria with a stable graft function for more than 1 year and a glomerular filtration rate (GFR) >50 mL/min per 1.73 m² (Group A); these were compared with 42 consecutive patients with PHTP who had been referred to the same Bone Center for treatment for over 1 month (Group B). Statistical analysis included the chi-square or Fisher’s exact tests for categorical data and the Wilcoxon rank sum test for quantitative measures.

The mean (±SD) 1,25-dihydroxyvitamin D level was significantly lower (p < 0.001) in Group A patients (29.8 ± 16.2) than in Group B patients (70.2 ± 25.9) despite non-significant differences in the levels of parathyroid hormone (PTH) (mean: 184.0 vs.101.1;p < 0.29), phosphorus (mean: 3.2 vs. 3.1; p < 0.3) and 1,25-vitamin D (mean: 19.5 vs. 25.2; p < 0.06). Group A patients had lower levels (p < 0.05) of mean serum calcium and calculated GFR (9.3 mg/dL, 65.7 mL/min) than Group B patients (10.6 mg/dL, 97.6 mL/min). 1,25-Dihydroxyvitamin D significantly correlated with calcium (p < 0.001), 25-vitamin D (p < 0.005) and GFR (p < 0.001) in both groups, but there was a notable lack of association between 1,25-dihydroxyvitamin D and PTH (p < 0.64) or phosphorus (p < 0.26) in Group A patients. In this group, 1,25-dihydroxyvitamin D was not influenced by the type of immunosuppresion regimen (p < 0.06), use of biphosphonates (p < 0.73), presence of diabetes (p < 0.59), menopause in women (p < 0.08), season (p < 0.43) or race (p < 0.31). Our data indicate that 1,25-dihydroxyvitamin D metabolism remains disturbed for a considerable time after successful RT, with the result that the level of 1,25-dihydroxyvitamin D in RT patients is lower despite physiological signals that should stimulate its production. Our analysis of many clinical variables was unable to elucidate the underlying mechanism(s) for this disturbance.

Successful RT may not produce appropriate levels of 1,25-dihydroxyvitamin D commensurate to the elevated levels of PTH. This abnormality along with sustained hyperparathyroidism may contribute to bone loss following transplantation.