Pam Harrison

June 06, 2014

AMSTERDAM — A blood test that measures the propensity of kidney transplant recipients to develop vascular calcification can be used to identify which patients are at greatest risk for all-cause mortality and graft failure, new research shows.

"Renal transplantation improves the prognosis of patients with end-stage renal disease, but the risk of cardiovascular events in these patients remains high, compared with the general population," said investigator Charlotte Keyzer, MD, from the University Medical Center Groningen in the Netherlands.

Because results from the new nanoparticle-based overall calcification propensity assay are strongly associated with all-cause mortality and graft failure, individual patient survival can be predicted more effectively than current models allow.

Dr. Keyzer presented the study here at the European Renal Association-European Dialysis and Transplant Association 51st Congress.

Calcification Propensity Assay

The assay determines the propensity for calcification in an individual by measuring the maturation time (T50) of calciprotein particles, which prevent the precipitation of calcium and phosphate in serum.

When the maturation time is long, "defense against calcification is intact," Dr. Keyzer explained. "Reduced time indicates a high calcification propensity."

She and her team evaluated 699 patients who had undergone kidney transplantation and were stable for at least 1 year.

Mean serum T50 in the cohort was 286 minutes. Values were divided by T50 tertiles: less than 262 minutes, from 262 to 311 minutes, and more than 311 minutes.

During the median follow-up period of period 3.1 years, 81 patients (12%) died and 45 patients (6%) developed graft failure.

Multivariate linear regression analysis demonstrated that patients with T50 in the lowest tertile, signifying the highest calcification propensity, had the lowest survival rate and the highest risk for graft failure during follow-up.

Specifically, mortality risk was 41% lower in the highest T50 tertile than in the lowest tertile (P < .001). And the risk for graft failure was 62% lower in the highest tertile than in the lowest tertile (P < .001).

"We found that serum T50 was inversely associated with the risk of mortality and graft failure, independent of known risk factors and T50 determinants," Dr. Keyzer reported.

Prediction Model

The investigators combined predictions of all-cause mortality and graft failure obtained from the T50 test with those calculated using a model that took into account age, sex, and renal function.

"When we took all the numbers together, we could see that improvement of reclassification [for at-risk patients] was 14%, indicating that 1 of 7 renal transplant recipients can be better classified for mortality risk and graft failure with the addition of serum T50," Dr. Keyzer said.

When patients are identified as being at high risk for vascular calcification, it might be possible to provide supplemental magnesium or reduce phosphate load, she told Medscape Medical News.

"Renal transplant recipients all have normal phosphate levels in their serum, but still, patients in the upper range of normal phosphate are at risk for vascular calcification. I think we need to aim for lower phosphate loads even when serum is still in the normal range," she explained.

"This is a really important assay that I think will be useful moving forward," said Geoffrey Block, MD, from Denver Nephologists, who has worked with the principle investigator of the T50 study, Andreas Pasch, MD, from University Hospital of Bern in Switzerland.

Dr. Block told Medscape Medical News that he "completely endorses" Dr. Keyzer's suggestion that changing phosphate will, in fact, change the T50.

The study was supported by the Dutch Kidney Foundation, among other renal organizations. Dr. Keyzer and Dr. Block have disclosed no relevant financial relationships.

European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 51st Congress: Abstract 4064. Presented June 2, 2014.

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