Renal Transplant Failure Linked To Elevated Pre-Transplant iPTH

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ST. JOHN'S, NEWFOUNDLAND—Renal transplant recipients who had elevated pre-transplant levels of intact parathyroid hormone (iPTH) are at increased risk of post-transplant hypercalcium and graft rejection, according to findings presented at the Canadian Society of Nephrology's 2012 annual meeting.

“The association of pre-transplant iPTH level with outcome is interesting and clearly suggests mineral metabolism is important in post-transplant outcome,” lead investigator John Gill, MD, told Renal & Urology News. “The mechanisms which underlie this association need further study.”

Dr. Gill, a transplant nephrologist at St. Paul's Hospital in Vancouver, B.C., and his co-investigators made this discovery when gathering information about the increasingly common phenomena of hyperparathyroidism and hypercalcemia in kidney transplant patients. The researchers reviewed information from 1,352 consecutive adults who received kidneys alone between January 2000 an August 2007 in two of Canada's largest transplant centers, St. Paul's Hospital and the Toronto General Hospital.

A “striking” 40% of the patients had at least one episode of hypercalcemia—defined as albumin-corrected serum calcium level of 2.6 mmol/L or greater—within a year of transplantation, according to the investigators. Furthermore, 162 patients (12%) had post-transplant hypercalcemia throughout the first post-transplant year. Hypercalcemia resolved within two years in 25% of patients with this condition, and it resolved within three and five years post-transplant in 36% and 54%, respectively, of the affected cohort. Twenty-one (13%) of hypercalcemic patients required surgical parathyroidectomy.

Patients with post-transplant hypercalcemia experienced an average 1.81 mL/min/1.73 m2/year drop in estimated glomerular filtration rate, compared with a 0.22 mL/min/1.73 m2/year increase among those who did not develop post-op hypercalcemia.

Post-transplant hypercalcemia was significantly associated with age. Compared with individuals younger than 40 years, those aged 40-49, 50-59, and aged 60 and older had an 89%, 75%, and 114% increased risk of post-transplant hypercalcemia, respectively.

A pre-transplant iPTH level of 10.6-53 pmol/L was associated with a fourfold higher risk of hypercalcemia compared with a level below 10.6 pmol/L, whereas an iPTH level above 53 pmol/L was associated with an 11-fold higher risk.

Duration of dialysis prior to transplantation was another factor associated with post-transplant hypercalcemia. Compared with patients who were on dialysis for less than one year prior to transplantation, those on pre-transplant dialysis for more than five years had a 2.7 times increased risk.

Additionally, patients with pre-transplant calcium levels greater than 2.6 mmol/L had a 5.7 times increased risk of post-transplant hypercalcemia compared with patients who had normal serum calcium levels.

Post-transplant hypercalcemia was not associated with graft failure, but researchers observed an 80% higher probability of graft failure among patients with pre-transplant iPTH levels above 53 pmol/L compared with patients whose pre-transplant levels were below 10.6 pmol/L. The researchers could not determine whether post-transplant iPTH levels are associated with graft failures because these levels are not routinely measured.

Prevention and treatment of hyperparathyroidism may be important in patients who are about to receive a kidney transplant, Dr. Gill concluded.

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