The Prevalence and Outcome of Parathyroid Disorder After Renal Transplantation: A Prospective Observational Study

Dear Editor,

There is a well-recognized association between chronic kidney disease (CKD) and mineral bone disease. Renal transplantation restores calcium, phosphorous, and vitamin D levels leading to decline in levels of serum parathyroid hormone (PTH). The prevalence of parathyroid disorder in post-transplant recipients is variable.^1-4 There are few Indian data regarding the prevalence of parathyroid disorder in kidney transplant recipients. This prospective, observational study aimed to assess the prevalence of parathyroid disorder in renal transplant recipients during 12 months of transplantation and identify the association of parathyroid disorder with demographics/clinical variables. The study protocol was approved by institutional ethics committee.

Demographic characteristics of 52 post-transplant recipients are shown in Supplementary Table 1. Of 52 patients, two were lost to follow-up and one expired after 3 months, and one patient expired after 6 months of transplantation. Analysis was done considering 52, 49, and 48 patients, respectively at 3, 6, and 12 months after transplantation.

At baseline serum iPTH <65 and ≥65 pg/ml were found in 8 (15.38%) and 44 (84.61%) patients, respectively. At 3-month, 43 (82.7%) had hyperparathyroidism, and 9 (17.30%) had normal PTH levels. At 6-month, 45 (91.8%) had hyperparathyroidism, and 4 (8.2%) had normal PTH levels. At 12-month, 38 (79.2%) had hyperparathyroidism, and 10 (20.8%) had normal PTH levels. Pre-transplantation mean iPTH levels were 370.496 ± 419.26 pg/ml, and post-transplantation, these values were 237.496 ± 244.13 pg/ml, 184.420 ± 165.59 pg/ml, and 205.975 ± 250.09 pg/ml, at 3, 6, and 12 months, respectively. Table 1 outlines the levels of biochemical parameters at baseline and post-transplantation. Supplementary Figure 1 shows the trend of changes in glomerular filtration rate (eGFR), serum PTH, calcium, phosphorus, and vitamin D post-transplantation. Table 2 presents the association of post-transplant hyperparathyroidism months with demography/clinical variables. Supplementary Figure 2 depicts scatter plots for all significant associations. The mean iPTH levels were significantly higher in patients with eGFR <60 ml/min/1.73 m² than ≥60 ml/min/1.73 m² (310.694 pg/ml vs. 143.143 pg/ml, P = 0.023). More details are available in Supplementary Materials and Methods.

The pre-transplantation mean serum iPTH levels, in our study, are comparable to values reported by Gomes et al.⁵ (300 pg/ml) and Wolf et al.⁶ (423.4 ± 340.1 pg/ml). The prevalence of hyperparathyroidism (defined as ≥65 pg/ml) was 82.7%, 91.8%, and 79.2%, respectively, at 3-, 6-, and 12-month post-transplantation, which are approachable to figures reported in two Indian studies. The first study published by Rathi et al.,^S7 showed the prevalence of 42.7% and 51.3%, respectively, at 12- and 24-week post-renal transplantation. Aggarwal et al.^S8 showed the high, normal, and low PTH levels (as per the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines for the range of eGFR) in 69%, 22%, and 9% of cases. Our patients had achieved normal post-transplantation serum calcium and phosphorus levels. At 12-month, the incidence of hypercalcemia was less (4.17%) than observed in studies published by Gomes et al.⁵ (24%) and Torres et al.^S9 (75%). High prevalence of vitamin D deficiency is most likely attributable to less events of hypercalcemia in our population.

Post-transplant PTH levels (at 3-, 6-, and 12-month) correlated with pre-transplant PTH levels. Disease duration and dialysis vintage showed a significant effect in the early post-transplantation period at 3-month, which was not observed on further follow-up. This could be explained by that pre-transplant factors (i.e. duration of disease) may be decisive in early post-transplantation period; however, as time progresses, post-transplant factors (i.e. eGFR) play a crucial role in severity of hyperparathyroidism. GFR is generally considered as the best index for graft function.^S10 Our cohort achieved relatively good graft functions with mean estimated GFR of 79.44 ml/min/1.73 m², 72.80 ml/min/m², and 71.29 ml/min/m² at 3-, 6-, and 12-month post-transplantation. Comparatively, Bleskestad et al.^S11 and Gomes et al.⁵ reported the mean eGFR of 70.9 ml/min/m² and 58.1 ± 18.7 ml/min/mm², respectively, at 1-year post-transplantation. Recent Indian study by Aggarwal et al.^S8 stated almost patients achieved eGFR >60 ml/min/m². Post-renal transplant recipients had eGFR ≈ 30–60 mL/min/1.73 m², hinting some degree of reduced kidney function resulting in CKD-related hyperparathyroidism.^S12 We discovered that hyperparathyroidism was not correlated with serum creatinine and eGFR at 3- and 6-month, but it was correlated at 12-month. These findings suggest the role of post-transplant factors (i.e. serum creatinine and eGFR) as a long-term predictor for hyperparathyroidism; however, further studies are warranted to validate this claim.

Our study was limited by small sample size and short follow-up. Further, the fibroblast growth factor (FGF) 23 levels and bone mineral density were not assessed. In conclusion, hyperparathyroidism continued up to 12-month post-transplantation. Vitamin D deficiency/ insufficiency was common in post-transplant recipients. Pre-transplantation factors affected the parathyroid status in the early post-transplantation period, while post-transplantation factors impacted the parathyroid status in the late post-transplant period.