Urinary Podocin mRNA as Predictor of Renal Allograft Function Decline

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Conference Proceeding

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Publication Title

Am J Transplant


Purpose: Traditional biomarkers (such as proteinuria, lyear eGFR) as well as validated risk prediction tools such as the Birmingham Risk Score predict risk of ESRD. However the ideal biomarker is one that is associated with smaller changes in allograft function such that early intervention is likely to be beneficial in retarding progression. In addition, biomarkers that are nephron segment specific will allow to delineate mechanistic processes driving allograft dysfunction. Methods: 125 consenting kidney transplant recipients had urines collected over the first year (2012-2015). Patients were followed till June 2017, graft failure or death whichever was earlier. Demographic and clinical data including EGFR was collected. Urines were analyzed for proteinuria as well as absolute mRNA quantification for podocin, nephrm (podocyte specific markers), Aquaporm2 (distal collecting tubule) and TGFbetal (measure of profibrotic activity). Absolute mRNA data was normalized to urine creatinine. Data on glomerulosclerosis (GS) and Interstitial Fibrosis Tubular Atrophy (TFTA) was obtained from year surveillance biopsies or last biopsy in the first year. Linear regressions were used to determine slope of EGFR decline for individual patient from time of first urine collection to end of follow-up. "Progres-sors" were defined as those in whom EGFR declined by >3 ml/mm/year. K-fold cross validation techniques were used to split data into derivation and validation cohorts. Results: Overall 10, 327 follow up EGFR observations and 547 urine samples were available for analysis. Twenty grafts were lost in follow up with 10 due to death. Table below highlights comparison of selected urine mRNA markers with traditionally used predictors clinical and histological predictors. Urine mRNA markers outper-formed proteinuria, renal function and histological parameters in predicting risk of progression. Among urine mRNA markers only podocm and TGFbetal predicted risk of progression (LCL of 95%CI was >0. 5). [Figure Presented] Other predators that were tested and not significant: Rejection, CMV and BKV infections. Nephrin was excluded due to collinearity with podocin. Conclusions: The average first year urine podocin mRNA is a good biomarker for predicting allograft function decline (of >3 ml/mm/year over a median 4. 5years) compared to traditionally used biomarkers. Further internal and external validation studies as well as comparison with other mRNA markers are needed to establish clinical utility.



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