Sir,
Secondary hyperparathyroidism (SHPT) and its associated bone and vascular complications are highly prevalent in patients undergoing renal replacement therapy. Whether successful kidney transplantation corrects SHPT in the majority of patients with a functioning graft is unclear. In the context of an ongoing, randomized study on the effects of vitamin D therapy in post-transplant patients, we reviewed the clinical data of 150 consecutive kidney or kidney–pancreas transplant recipients with a functioning graft a minimum of 1 year after transplantation at our institution. Table 1 presents patients’ characteristics displayed according to a pre-transplantation iPTH level < or ≥65 pg/ mL (upper limit of normal). As shown, despite a similar and acceptable post-transplant eGFR and optimal serum levels of calcium and phosphate, only 17% of the patients in the higher iPTH category regressed to normal, while 24% of the patients with low iPTH before transplantation moved to the higher category over time. In a multivariable model that included nine variables [age, gender, diabetes mellitus, iPTH< or ≥65 pg/mL at time of transplantation, most recent serum calcium (albumin corrected), most recent serum phosphorus, most recent creatinine, most recent eGFR and haemodialysis], we identified male gender [beta coefficient 2.67 (1.12–6.38); P < 0.03], pre-transplant haemodialysis [beta coefficient 2.25 (0.95–5.30); P = 0.06] and iPTH ≥65 pg/mL prior to transplantation [beta coefficient 11.48 (4.79–27.53); P < 0.001] as independent variables predicting iPTH ≥65 pg/mL at follow-up (model X2 = 46.56; P < 0.001). The limited available literature suggests that the risk of persistent SHPT post-transplantation is associated with high serum levels of calcium and phosphorus prior to transplantation and sub-optimal graft function post-transplantation [1]. However, when we repeated our multivariable analyses including pre-transplantation serum calcium and phosphorus, the results did not change. Some investigators suggested that 25% [2] to 50% [3] of transplant recipients demonstrate elevated iPTH long term, although our data would suggest a much higher incidence. Potential explanations include adenomatous transformation of parathyroid nodules that may be only partially reversible, reduced intestinal absorption of calcium induced by steroid therapy and persistent relative vitamin D deficiency. Despite the known dissociation between iPTH levels and bone histology, early intervention to reduce the incidence of SHPT in post-transplantation with vitamin D receptor activators or calcimimetics may be very important to reduce the incidence of osteoporotic fractures and vasculopathy in these patients [4].
Table 1.
Patients’ characteristics according to pre-transplantation iPTH levels
| Intact parathyroid hormone pre-transplant | |||
|---|---|---|---|
| Variable | ≥65 pg/mL (N = 95) | <65 pg/mL (N = 55) | P value |
| Age (years) | 49.8 ± 14.3 | 45.0 ± 15.5 | 0.08 |
| Male gender, N (%) | 54 (57) | 20 (36) | 0.02 |
| African American, N (%) | 45 (48) | 20 (36) | |
| Caucasian, N (%) | 38 (40) | 31 (56) | 0.19 |
| Other, N (%) | 11 (12) | 4 (8) | |
| Diabetes mellitus, N (%) | 22 (24) | 13 (26) | 0.81 |
| Hypertension, N (%) | 66 (71) | 42 (82) | 0.13 |
| Donor type, N (%) | |||
| Cadaveric donor | 70 (74) | 36 (65) | 0.29 |
| Living donor | 25 (26) | 19 (34) | |
| Time from transplant (months) | 41.7 ± 40.5 | 49.5 ± 30.8 | 0.27 |
| Time on dialysis (years) | 4.6 ± 11.7 | 2.8 ± 2.9 | 0.41 |
| Haemodialysis | 74% | 47% | 0.001 |
| Peritoneal dialysis | 21% | 29% | 0.49 |
| Pre-emptive transplant | 5% | 24% | 0.002 |
| Serum creatinine (mg/dL) | 1.93 ± 1.68 | 1.51 ± 1.17 | 0.14 |
| eGFR (mL/min/1.73 m2) | 52.8 ± 22.4 | 56.6 ± 20.8 | 0.36 |
| Most recent corrected serum calcium (mmol/L) | 2.3 ± 0.3 | 2.3 ± 0.2 | 0.24 |
| Pre-transplant corrected serum calcium (mmol/L) | 2.3 ± 0.4 | 2.2 ± 0.3 | 0.68 |
| Most recent serum phosphorus (mmol/L) | 1.06 ± 0.42 | 1.16 ± 0.29 | 0.14 |
| Pre-transplant serum phosphorus (mmol/L) | 1.74 ± 0.58 | 1.77 ± 0.61 | 0.90 |
| Serum albumin (g/dL) | 3.6 ± 0.5 | 3.5 ± 0.6 | 0.33 |
| Pre-transplant iPTH pg/mL | 191 ± 203 (range 65–1613) | 42 ± 11 (range 3–62) | 0.0001 |
| Follow-up iPTH pg/mL | 239 ± 249 (range 28–1493) | 107 ± 134 (range 13–739) | 0.0001 |
| Change in iPTH category | 17 (18%) | 12 (24%) | 0.0001 |
Numbers are expressed as absolute values, percentages, mean ± SD and range where indicated.
Conflict of interest statement. Dr. E. Rojas is supported by a training grant from Genzyme Therapeutics; Dr. Paolo Raggi has received research grants from and he is part of a Medical Advisory Board for Genzyme Therapeutics.
References
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