Table 2.
Clinical studies of the correlation between vitamin D and allograft function
| Study | Design | Study population and use of Vitamin D | Outcome and notes |
|---|---|---|---|
| Observational studies | |||
| Falkiewicz et al, 2009 (38) | Prospective study of adult transplant recipients (n = 90) with measured 1,25(OH)2D3 on day 3, month 1, 6, 12, 18 and 24 post-transplant | Patients were followed-up for 24 months. | All patients had received alfalcalcidol as part of routine care pre-transplant. Despite this, severe 1,25(OH)2D3 deficiency was present in 83% on day 3. In only 50% the concentration rose to normal levels during follow-up. |
| The effect of 1,25(OH)2D3 levels on outcomes (incidence of acute rejection, graft function, de novo malignancy and cardiovascular events) was analyzed. | The incidence of delayed graft function was higher in those with 1,25(OH)2D3 deficiency. There was a negative correlation between initial and 1 month 1,25(OH)2D3 levels and graft function during follow-up. Those with 1,25(OH)2D3 deficiency had poorer outcomes (death from cardiovascular events, acute rejection episodes, graft loss and cancer). | ||
| Wesseling-Perry et al 2011 (41) | Prospective analysis of pediatric transplant recipients with stable transplant function at recruitment (n = 68) | Associative study analyzing link between mineral ion abnormalities and GFR/acute rejection over a 2 year follow-up period. Measurement of 25(OH)D3, 1,25(OH)2D3 and FGF-23 was made at mean ± s.d. 4.9 ± 0.5 years post-transplant and correlated with transplant outcomes over the next 2 years. | 4 patients were lost to follow-up, so only 64 were included in the analysis. |
| VitD levels do not, but FGF-23 levels do, correlate with number of episodes of acute rejection and decline in eGFR over 2 year follow-up. | |||
| Kim et al 2012 (39) | Observational study of adult transplant recipients (n = 106) with known VitD levels prior to transplantation. | Measurement of 25(OH)D3 pre and post-transplantation with exclusion of osteoporotic patients. Patients were followed up every 6 months for 36 months. | Pre-transplant VitD deficiency was identified in multiple logistic regression analysis as a significant independent risk factor for decline in eGFR over 36 months post-transplantation. |
| Bienaimé et al 2013 (40) | Prospective cohort study of adult transplant recipients (n = 634) with measured 25(OH)D3 levels at 3 months post-transplant. | Measured 25(OH)D3 levels at 3-months post transplantation were correlated with clinical variables over a median follow-up of 48.6 months. | 19 patients were lost to follow-up and 30 had lost their graft, 28 had died with a functioning graft |
| There was no association between 3 month VitD levels and either graft loss or death during the follow-up period. | |||
| 25(OH)D3 level at 3 months was an independent predictor of mGFR and progression of IF/TA at 12 months. | |||
| Interventional studies | |||
| Tanaci et al 2003 (42) | Retrospective cohort analysis of adult patients (n = 92) treated, or not, with VitD | Outcomes of 43 transplant recipients in whom VitD was prescribed for clinically detectable osteoporosis (500 ng daily calcitriol) were compared to 49 patients without osteoporosis and not receiving VitD | 8 patients in the treatment arm were excluded from analysis due to non-compliance with treatment. |
| The group treated with VitD had more acute rejection episodes before treatment that control group; after treatment rejection episodes between treatment and control groups were the same. There was no difference in mean graft survivals between the two groups. | |||
| Follow-up ranged from 3-28 months | |||
| Uyar et al 2006 (44) | Retrospective interventional study of adult transplant recipients (n =110) treated, or not, with VitD | Outcomes of transplant recipients treated (n = 59) or not (n = 51) with calcitriol were compared. Calcitriol (dose not stated) was initiated at mean (±s.d) 24 ± 19.1 months post-transplantation. | By 3rd year of follow-up, patients given calcitriol had significantly lower creatinine and required fewer steroid pulses. |
| There was no difference in the number of acute rejection episodes. | |||
| Courbebaisse et al 2011 (45) | Retrospective cohort analysis of adult transplant recipients (n = 64) treated, or not, with VitD | 49 patients with serum 25(OH)D3 levels below 30ng/mL received cholecalciferol 100,000IU fortnightly from months 4 to 6, then every 2 months until 12 months post-transplantation. They were compared to 47 historical control patients with 25(OH)D3 levels below 30 ng/mL that had not received cholecalciferol. In the final analysis, due to exclusion criteria, only n = 32 patients in each group were analyzed. | Due to exclusion criteria, data from only 68% of the initial cohort were analyzed (n = 32 in each group). |
| There was no difference between the two groups in renal function (mGFR), proteinuria nor epithelial phenotypic changes by 12 months. Urinary PIIINP/Creatinine ratio, a surrogate marker of renal fibrosis, was no different between the two groups. Banff scoring for renal fibrosis (IF/TA) was also no different between the two groups. | |||
| Özdemir et al 2011 (43) | Retrospective cohort analysis of adult transplant recipients (n = 102) treated, or not, with VitD | 102 patients who had undergone transplant renal biopsy were studied. 40 had received calcitriol (dose not given) for 12 months from mean ± s.d 18 ± 6 months post-transplant. They were compared to 62 that had not had calcitriol | Calcitriol-treated patients experienced fewer episodes of acute rejection. On renal biopsy they had significantly lower tubular and interstitial HLA-DR expression and less peritubular capillary destruction than control subjects. This was reflected by better 5-year graft survival in calcitriol-treated patients and a multiple logistic regression model in which calcitriol-treatment had an independent (beneficial) effect on graft survival. |
VitD, Vitamin D; 25(OH)D3, 25-hydroxyvitamin D; 1,25(OH)2D3, 1,25-Dihroxyvitamin D; IU, international units; mGFR, measured (iohexol clearance) glomerular filtration rate; PIIINP, procollagen III aminoterminal propeptide; IF/TA, interstitial fiobrosis/tubular atrophy.