Date: Tuesday, June 5, 2018
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
Increasing data supports the hypothesis that long term allograft loss-of-function is associated with progressive glomerulosclerosis (GS). In models of progressive GS the ratio of two podocyte-specific markers (urine podocin:nephrin mRNA ratio,uPNR) is related to disease progression reflecting relative down-regulation of nephrin mRNA in response to podocyte stress (PMID:22863839).We recently observed increased glomerular podocin:nephrin transcript ratio under conditions of nephrectomy-induced hypertrophic stress associated with accelerated podocyte detachment,progressive GS and ESKD (PMID:28720684).As allografts represent a single kidney state (reverse nephrectomy) where loss of function is associated with accelerated podocyte detachment,we assessed whether uPNR would be elevated in long-term allografts losing function.
Methods: Urine pellet podocyte mRNA markers were analyzed in 57 kidney allograft recipients who had >1 urine sample collected (mean 4.7±2.6 samples,range 2-15 urine samples/allograft) at greater than 1-year post-transplant (mean 4.6±2.6 years).A tertile analysis was done by allograft loss of function.
Results: Among the allografts that were losing function most rapidly,uPNR was significantly elevated in association with an increased level of proteinuria (uProtCR) and increased rates of podocyte detachment (urine podocin and nephrin mRNA to creatinine ratios,uPodCR and uNepCR).
|Rate of GFR decline analyzed by tertiles for samples collected >1year after transplantation|
|Tertile||Lowest tertile||Intermediate tertile||Highest tertile||p value|
|eGFR decline (ml/min/yr)||1.6±1.3||-1.9±0.8||-12.5±9.9||0.0001|
|UPodCR||2.6e-05 ± 2.3e-05||3.1e-05 ± 4.9e-05||1.2e-04 ± 1.5e-04||0.002|
|UNepCR||1.4e-04 ± 8.5e-05||2.3e-04 ± 2.9e-04||5.5e-04 ± 5.8e-04||0.008|
|PNR||0.20 ± 0.16||0.18 ± 0.20||0.38 ± 0.30||0.03|
Conclusion: uPNR was significantly elevated (2-fold) in allografts losing function.The ratio of two podocyte-specific markers avoids many biases inherent in urine markers related to urine concentration etc.Larger long term studies are necessary to assess the potential utility of uPNR as a non-invasive biomarker specifically reflecting podocyte stress in allografts.
CITATION INFORMATION: Naik A., Aqeel J., Cibrik D., Samaniego M., Wang S., Chowdhury M., Afshinnia F., Wiggins R. Urine Podocin mRNA to Nephrin mRNA Ratio as a Marker of "Podocyte Stress" among Kidney Allografts Losing Function Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Naik A, Aqeel J, Cibrik D, Samaniego M, Wang S, Chowdhury M, Afshinnia F, Wiggins R. Urine Podocin mRNA to Nephrin mRNA Ratio as a Marker of "Podocyte Stress" among Kidney Allografts Losing Function [abstract]. https://atcmeetingabstracts.com/abstract/urine-podocin-mrna-to-nephrin-mrna-ratio-as-a-marker-of-podocyte-stress-among-kidney-allografts-losing-function/. Accessed September 19, 2020.
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