Urine Proteins May Identify Failure of Kidney Transplantation

By Laurie Barclay, MD
Medscape Medical News

November 26, 2008 — A noninvasive test that analyzes proteins in the urine can correctly identify patients whose transplanted kidneys are failing, according to the results of a proof-of-concept study reported in the November 26 issue of the Journal of the American Society of Nephrology.

"Despite optimal immunosuppressive therapy, more than 50% of kidney transplants fail because of chronic allograft dysfunction," write Luis F. Quintana, from the University of Barcelona in Spain, and colleagues. "A noninvasive means to diagnose chronic allograft dysfunction may allow earlier interventions that could improve graft half-life."

The investigators used mass spectrometry to analyze differences in the urinary polypeptide patterns of 32 patients with chronic allograft dysfunction and in 18 control subjects. Of the 32 patients with chronic allograft dysfunction (CAD), 14 had pure interstitial fibrosis and tubular atrophy, and 18 had chronic active antibody-mediated rejection. The control subjects consisted of 8 stable transplant recipients and 10 healthy subjects.

Unsupervised hierarchical clustering demonstrated good segregation of samples in groups that corresponded relatively well to these 4 clinical conditions. Furthermore, the composition of the proteome in the group with pure interstitial fibrosis and tubular atrophy differed from that of the chronic active antibody-mediated rejection group. These results were confirmed in an independent validation set.

Using the 14 protein ions that best discriminated between these 2 groups allowed correct classification of 100% of the patients with pure interstitial fibrosis and tubular atrophy and 100% of the patients with chronic active antibody-mediated rejection.

"This study establishes a pattern for two histologic lesions associated with distinct graft outcomes and constitutes a first step to designing a specific, noninvasive diagnostic tool for chronic allograft dysfunction," the study authors write. "The combination of protocol graft biopsies with simultaneous proteomic analyses at different times after renal transplantation could provide more accurate information on the exact mechanisms involved in the development of CAD. This information could be very helpful not only for an early diagnosis of CAD but also in the treatment and prevention of the leading cause of graft loss."

The main study limitation was small sample size.

"Additional studies including a larger and more diverse transplant recipient population are required to confirm our data," the study authors conclude. "Reproduction of these patterns in future studies would represent a step forward in identifying each protein and in translating this relatively intricate procedure into a biochemical test of clinical utility."

The Fondo de Investigaciones Sanitarias and an Emili Letang Fellowship award from Hospital Clinic in Barcelona supported this study. The authors have disclosed no relevant financial relationships.

J Am Soc Nephrol. Published online November 26, 2008.