10-year surveillance biopsy studies (Nankivell,2003 & Stegall,2017) and podometric studies are compatible with progressive glomerulosclerosis (GS) contributing to long-term allograft loss-of-function.Thus one would expect to see a correlation between long-term allograft function decline and accelerated podocyte detachment.

To test this hypothesis,we randomly collected urine samples from 174 kidney transplant (TP) recipients. Available urine samples for each allograft were averaged (mean n=4.7±2.6, range 2-15/allograft). Allografts were divided into “short-term” where urine sample collection was within 1-year post TP (mean 0.56±0.25years,n=117), “intermediate-term" where urine collection was between 1-4 years (mean=2.4±0.7years,n=34) and “long-term” where urine collection begun >4 years post TP (mean 7.7±0.3years,n=23).

In the long-term group, high correlations were noted between [Delta]eGFR (eGFR decrease,ml/min/1.73m²/yr) and urine protein:creatinine ratio (UProtCr) and urine podocin mRNA:creatinine ratio (UPodCr, rate of podocyte detachment). Proteinuria was highly correlated with both podocyte markers (podocin, nephrin) as well as urine aquaporin mRNA:creatinine ratio (tubular marker). No relationship was observed between UTGFbeta1 mRNA and [Delta]eGFR or proteinuria.

These findings strengthen the hypothesis that long-term allograft function decline is driven by progressive GS caused by accelerated podocyte detachment. Further investigation into accelerators of podocyte loss may uncover mechanisms that drive post-TP glomerular disease and long term allograft failure.

CITATION INFORMATION: Naik A., Aqeel J., Cibrik D., Samaniego M., Chowdhury M., Wang S., Afshinnia F., Wiggins R. Urine Pellet Podocyte mRNAs Correlate Closely with Late Kidney Allograft Loss-of-Function Am J Transplant. 2017;17 (suppl 3).

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