BACKGROUND: Recurrence of immunoglobulin A nephropathy (IgAN) limits graft survival in kidney transplantation. However, predictors of a worse outcome are poorly understood. METHODS: Among 442 kidney transplant recipients (KTRs) with IgAN, 83 (18.8%) KTRs exhibited biopsy-proven IgAN recurrence between 1994 and 2020 and were enrolled in the derivation cohort. A multivariable Cox model predicting allograft loss based on clinical data at the biopsy and a web-based nomogram were developed. The nomogram was externally validated using an independent cohort (n = 67). RESULTS: Patient age <43 years {hazard ratio [HR] 2.20 [95% confidence interval (CI) 1.41-3.43], P < .001}, female gender [HR 1.72 (95% CI 1.07-2.76), P = .026] and retransplantation status [HR 1.98 (95% CI 1.13-3.36), P = .016] were identified as independent risk factors for IgAN recurrence. Patient age <43 years [HR 2.77 (95% CI 1.17-6.56), P = .02], proteinuria >1 g/24 hours [HR 3.12 (95% CI 1.40-6.91), P = .005] and C4d positivity [HR 2.93 (95% CI 1.26-6.83), P = .013] were found to be associated with graft loss in patients with IgAN recurrence. A nomogram predicting graft loss was constructed based on clinical and histological variables, with a C statistic of 0.736 for the derivation cohort and 0.807 for the external validation cohort. CONCLUSIONS: The established nomogram identified patients with recurrent IgAN at risk for premature graft loss with good predictive performance.

• Keywords
• IgA nephropathy, glomerulonephritis, kidney transplantation, nomogram, recurrence,
• MeSH
• Allografts pathology   MeSH
• Adult MeSH
• Glomerulonephritis, IGA * complications   surgery   MeSH
• Kidney pathology   MeSH
• Humans MeSH
• Nomograms MeSH
• Graft Survival MeSH
• Prognosis MeSH
• Recurrence MeSH
• Retrospective Studies MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Molecular assessment of renal allografts has already been suggested in antibody-mediated rejection (ABMR), but little is known about the gene transcript patterns in particular renal compartments. We used laser capture microdissection coupled with quantitative RT-PCR to distinguish the transcript patterns in the glomeruli and tubulointerstitium of kidney allografts in sensitized retransplant recipients at high risk of ABMR. The expressions of 13 genes were quantified in biopsies with acute active ABMR, chronic active ABMR, acute tubular necrosis (ATN), and normal findings. The transcripts were either compartment specific (TGFB1 in the glomeruli and HAVCR1 and IGHG1 in the tubulointerstitium), ABMR specific (GNLY), or follow-up specific (CXCL10 and CX3CR1). The transcriptional profiles of early acute ABMR shared similarities with ATN. The transcripts of CXCL10 and TGFB1 increased in the glomeruli in both acute ABMR and chronic active ABMR. Chronic active ABMR was associated with the upregulation of most genes (SH2D1B, CX3CR1, IGHG1, MS4A1, C5, CD46, and TGFB1) in the tubulointerstitium. In this study, we show distinct gene expression patterns in specific renal compartments reflecting cellular infiltration observed by conventional histology. In comparison with active ABMR, chronic active ABMR is associated with increased transcripts of tubulointerstitial origin.

• Keywords
• antibody-mediated rejection, gene expression, kidney transplantation, laser capture microdissection, renal compartments,
• MeSH
• Biopsy MeSH
• Chronic Disease MeSH
• Adult MeSH
• Kidney Glomerulus immunology   metabolism   pathology   MeSH
• HLA Antigens immunology   MeSH
• Isoantibodies immunology   MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Laser Capture Microdissection MeSH
• Kidney immunology   metabolism   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Graft Rejection genetics   immunology   metabolism   pathology   MeSH
• Aged MeSH
• Gene Expression Profiling MeSH
• Case-Control Studies MeSH
• Transcriptome * MeSH
• Kidney Transplantation adverse effects   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• HLA Antigens MeSH
• Isoantibodies MeSH