RNA Signature for Noninvasive Diagnosis of Fibrosis in Kidney Transplants

Tubulointerstitial fibrosis (fibrosis) is a histologic feature associated with a failing kidney allograft. It is currently diagnosed by an invasive allograft biopsy, which is costly and subject to sampling errors and possible complications. Early diagnosis is also a challenge.

Cornell inventors have developed a noninvasive diagnostic method by using a quantitative polymerase chain reaction (qPCR) assay to measure messenger RNA levels (mRNA) from urine samples from biopsied allograft patients. Urine specimens from 114 patients were divided into a discovery set and a validation set. Levels of 22 mRNAs were measured by qPCR in the 76 samples from the discovery set. Four genes, vimentin, NKCC2, E-cadherin and 18S rRNA, were selected to be included in the multigene prediction model of fibrosis diagnosis.

The composite score based on this four-gene model was highly associated with the diagnosis of fibrosis by biopsy. This composite score predicted fibrosis in the discovery set with a sensitivity of 93.8% and a specificity of 84.1% and in the validation set with a sensitivity of 77.3% and a specificity of 87.5%.

Advantages

• Noninvasive diagnosis
• May serve as an anticipatory biomarker

Potential Applications

• Noninvasive diagnosis of human renal allograft fibrosis
• May also be developed to predict fibrosis from chronic kidney diseases