Abstract: FR-PO1189
Urinary Transcriptomics Reveals a Novel Connection Between Tubulointerstitial Fibrosis and Albuminuria in Kidney Transplant Recipients
Session Information
- Transplantation: Clinical - Rejection, Biomarkers, and Pharmacology
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Oguntuwase, Elizabeth Feyikemi, Weill Cornell Medicine, New York, New York, United States
- Li, Carol Y., Weill Cornell Medicine, New York, New York, United States
- Muthukumar, Thangamani, Weill Cornell Medicine, New York, New York, United States
- Suthanthiran, Manikkam, Weill Cornell Medicine, New York, New York, United States
Background
Albuminuria is prognostic in chronic kidney disease. Understanding the underlying molecular mechanisms may help identify therapeutic targets and inform treatment decisions.
Methods
We studied 137 biopsy-matched urine specimens from 127 kidney allograft recipients with indication or surveillance biopsies who did not have acute rejection as per the Banff criteria. Urine albimun:creatinine ration (UACR) was categorized as normal (<30 mg/g; 41 urines, 40 recipients), microalbuminuria (30-299 mg/g; 49 urines, 44 recipients), or macroalbuminuria (≥300 mg/g; 47 urines, 43 patients).
We used a hypothesis driven gene panel (CD3E, CD20, CD25, CD46, CD103, CD105, granzyme B [GZMB], perforin [PRF1], CTLA4, FOXP3, CXCL9, CXCL10, TLR4, TGFB1, PAI-1, and Vimentin) in a customized RT-qPCR assay to quantify urinary cell mRNAs. Banff lesion scores and urinary cell mRNA levels were analyzed across UACR strata.
Results
Acute Banff lesion scores (glomerulitis, peritubular capillaritis, interstitial infiltration, tubulitis, intimal arteritis) and transplant glomerulopathy scores were low (median <0.5; KW P>0.05) across UACR groups. In contrast, tubular atrophy increased with worsening albuminuria (median scores 0.325, 0.734, 1.174; Kruskal-Wallis P= 0.0002; Spearmen r=0.35, P<0.0001), as did interstitial fibrosis (median scores 0.25, 0.694, 0.935; KW P=0.0006; Spearmen r=0.34, P<0.0001).
Albuminuria correlated with urinary mRNA abundance of inflammatory mediators GZMB (P=0.006, r=0.298, P=0.0004), PRF1 (P= 0.002, r=313, P=0002), CXCL9 (P=0.012, r=0.222, P=0.009), CXC10 (P=0.003, r=0.223, P=0.008), and TLR4 (P=0.025, r=0.209, P= 0.016) and fibrogenic markers TGFB1 (P=0.028, r=0.248, P=0.003), PAI-1 (P=0.002, r=0.344, P<0.0001), vimentin (P=0.0002, r=0.421, P<0.0001), and CD105 (P=0.002, r=0.336, P<0.0001).
Conclusion
In kidney recipients without histologic evidence of rejection, albuminuria is associated with interstitial fibrosis and tubular atrophy. This finding challenges the paradigm that albuminuria mainly reflects glomerular damage. A distinct urinary cell mRNA signature of inflammatory mediators (TLR-4, CXCL9, CXCL10, PRF1, GZM) and fibrogenic transcripts (TGFB1, CD105, PAI-1, vimentin) links immune activation and tubulointerstial injury to albuminuria. These findings provide a molecular rationale for targeting immune-fibrotic pathways to improve long-term outcomes.