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Decoding the Troubled Allograft: Proteinuria within the 1st Post-Transplant Year Associates with and Risk Stratifies Inflamed Renal Transplants

A. Cherukuri, R. Mehta, A. Tevar, R. Munjal, K. Kalra, C. Puttarajappa, P. Sood, C. Wu, S. Hariharan

Starzl Transplantation Institute, UPMC, Pittsburgh, PA

Meeting: 2020 American Transplant Congress

Abstract number: 455

Keywords: Graft failure, Proteinuria, Rejection

Session Information

Session Name: Kidney Complications: Immune Mediated Late Graft Failure

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:45pm

 Presentation Time: 4:27pm-4:39pm

Location: Virtual

*Purpose: The relationship between progression of proteinuria and allograft histology through the 1st year with clinical outcomes is unclear.

*Methods: Here, we systematically studied proteinuria {early (<4mo) or late (at 1yr) using uPCR} and allograft histology in 1000 patients transplanted between 2013-17. Patients were divided into 4 groups based on proteinuria evolution (Gp-I: <0.5g thru 1yr; Gp-II: >0.5g early &<0.5g by 1yr; Gp-III: <0.5g early & >0.5g by 1yr; Gp-IV: proteinuria>0.5g thru 1yr). IS utilized Thymo followed by Tac+MMF. Patients underwent 2 protocol biopsies (Bx) at 3mos & 1yr and any for-cause Bx. Importantly uPCR was assessed at each Bx. Patients with de novo or recurrent GN were excluded

*Results: Proteinuria: Of the 800 patients with 1287 matched Bx to proteinuria, 78% were in Gp-I, while 7% were in Gp-II and 7.5% each in Gp-III & IV. Thus 15% of the patients had either evolving or persistent proteinuria. Gp III & IV was associated with worse graft loss at 5yrs compared to Gp I & II independent of sCr at 1yr (HR, 3.8, 95% CI 2.4-6.1, p<0.0001), thus representing a high-risk category (Fig1A/B). Proteinuria and Histology: Gp III/IV was associated with significantly worse t, i, g & ptc Banff scores both early and late when compared to Gp I/II. This translated not only to 2 X increased TCMR in Gp III/IV at both time points compared to Gp-I/II (Early: 45% vs. 23%, p<0.0001; Late: 58% vs. 27%, p<0.0001) but also greater severity. Further, Gp-III/IV was associated with a 3.9 X increased odds of recurrent/recalcitrant TCMR compared to Gp-I/II (95% CI 1.7-9.1, p=0.0006) despite therapy. Next, Gp-III/IV was associated with worse IFTA compared to Gp-I/II (IFTA score: 1.8 vs. 2.72, p<0.0001; IFTA≥3, Gp I/II 15% vs. Gp III/IV 29%, p<0.0001). Thus persistent/evolving proteinuria associates with worse allograft inflammation through the 1st year and increased scarring at 1yr. Histology, proteinuria and outcomes: Allograft inflammation (TCMR), in combination with Gp III/IV proteinuria was associated with markedly worse outcomes independent of potential confounders including serum sCr at 1yr (overall graft survival, HR, 6.5, 95% CI 3.2-13.2, p<0.0001; death censored graft survival, HR 6.8, 95% CI 2.8-16.1, p<0.0001) (Fig 1C/D).

*Conclusions: Early proteinuria >0.5g associates with worse allograft inflammation and in combination identifies a sub-group of patients at risk for poor graft outcomes. Such patients could represent a target population for future clinical trials with novel agents aimed at improving outcomes.

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To cite this abstract in AMA style:

Cherukuri A, Mehta R, Tevar A, Munjal R, Kalra K, Puttarajappa C, Sood P, Wu C, Hariharan S. Decoding the Troubled Allograft: Proteinuria within the 1st Post-Transplant Year Associates with and Risk Stratifies Inflamed Renal Transplants [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/decoding-the-troubled-allograft-proteinuria-within-the-1st-post-transplant-year-associates-with-and-risk-stratifies-inflamed-renal-transplants/. Accessed May 11, 2025.

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