Tubular Atrophy and Low Netrin-1 Gene Expression Are Associated With Delayed Kidney Allograft Function

Successful long-term kidney allograft survival with parallel reduction of complications resulting from prolonged immunosuppressive treatment is a goal in kidney transplantation. We studied the immune changes in cell phenotypes and gene expression induced by kidney transplantation. Our goal was to find a phenotypic and/or transcriptional pattern that might be considered prognostic for the kidney transplant outcome. The analysis was performed prospectively on 36 KTx recipients sampled during the first year and followed for five years after transplantation and on 40 long-term KTx recipients (7.9±2.2 y. post-KTx). The research involved flow cytometry assessment of lymphocyte subpopulations (including Tregs and CD3+CD8+CD28− lymphocytes) and gene expression analysis of immune-related genes (CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGFB, and TNFA). The analysis of patterns observed over the first post-KTx year was confronted with control, pretransplant, and long-term transplant results. Treg counts at months one and three post-KTx correlated positively with the current and future allograft function. FOXP3 gene expression at month one post-KTx was also associated with long-term allograft function. The KTx-induced CD3+CD8+CD28− population correlated with GZMB and PRF1 expression and suggested their cytotoxic properties. The size of the Treg population and regulatory FOXP3 gene expression in the early period after transplantation are associated with kidney transplant outcome. The outlined predictive power of the Treg population needs to be investigated further to be confirmed as one of the immune monitoring strategies that may help achieve the best long-term kidney allograft outcomes.

Download Full-text

P1687ASSOCIATION OF URINARY MICRORNA-21-5P WITH INTERSTITIAL FIBROSIS AND TUBULAR ATROPHY (IFTA) IN RENAL TRANSPLANT RECIPIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1687 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Michal Gniewkiewicz ◽

Izabela Paszkowska ◽

Jolanta Gozdowska ◽

Katarzyna Czerwinska ◽

Anna Sadowska-Jakubowicz ◽

...

Keyword(s):

Renal Transplant ◽

Renal Allograft ◽

Interstitial Fibrosis ◽

Clinicopathological Parameters ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Tubular Atrophy ◽

Kidney Allograft ◽

Expression Levels ◽

Allograft Function

Abstract Background and Aims One of the most limiting factors of long-term graft survival is chronic renal allograft dysfunction (CAD). The major hallmarks of CAD are interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs (miRNAs) are 19-25 nucleotides, small, noncoding molecules involved in the regulation of gene expression. MiRNAs have a role in various immunological processes, including inflammation and fibrosis. Particularly, microRNA-21-5p (miR-21) is reported to be strongly associated with pathogenesis regarding tubulointerstitium. The aim of this study was to analyse expression levels of urinary miR-21 in the renal transplant recipients and evaluate their application in the assessment of IFTA and kidney allograft function. Method The expression levels of urinary miR-21 were measured in 31 renal transplant recipients with biopsy-evaluated IFTA (IFTA 0+I: n=17; IFTA II+III: n=14) by quantitative PCR. Protocolar biopsies were performed 1 or 2 years after renal transplantation. Urine samples were collected at the time of biopsy procedure. MicroRNA-191-5p was used as reference gene. Correlations between the clinicopathological parameters and the level of expression of miR-21 were assessed. Results Relative expression level of miR-21 was significantly increased in IFTA II+III group compared to IFTA 0+I group. MiR-21 correlated positively with serum concentration of creatinine and negatively with eGFR. ROC analysis showed diagnostic value of miR-21 with an area under curve (AUC) of 0.80, high sensitivity and specificity. Conclusion MiR-21 is associated with IFTA and dysfunction of kidney allograft. It may be considered as potential non-invasive biomarker of renal allograft function.

Download Full-text

Fibrous Intimal Thickening at Implantation Adversely Affects Long-Term Kidney Allograft Function

Transplantation Journal ◽

10.1097/tp.0b013e31818bbe06 ◽

2009 ◽

Vol 87 (1) ◽

pp. 72-78 ◽

Cited By ~ 22

Author(s):

Annemie T. Woestenburg ◽

Gert A. Verpooten ◽

Dirk K. Ysebaert ◽

Eric A. Van Marck ◽

Dierik Verbeelen ◽

...

Keyword(s):

Intimal Thickening ◽

Kidney Allograft ◽

Allograft Function

Download Full-text

High urinary interleukin-2 in late post-transplant period portends a risk of decline in kidney allograft function: a preliminary study

BMC Research Notes ◽

10.1186/s13104-017-2936-7 ◽

2017 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Andriy V. Trailin ◽

Marina V. Pleten ◽

Tetyana I. Ostapenko ◽

Nadiia F. Iefimenko ◽

Olexandr S. Nykonenko

Keyword(s):

Interleukin 2 ◽

Kidney Allograft ◽

Post Transplant ◽

Allograft Function ◽

Preliminary Study

Download Full-text

Adverse effect of donor vasopressor support on immediate and one-year kidney allograft function

Surgery ◽

10.1016/s0039-6060(96)80014-6 ◽

1996 ◽

Vol 120 (4) ◽

pp. 663-666 ◽

Cited By ~ 40

Author(s):

Renee marshall ◽

Nasimul Ahsan ◽

Saleena Dhillon ◽

Michael Holman ◽

Harold C. Yang

Keyword(s):

Adverse Effect ◽

Kidney Allograft ◽

Vasopressor Support ◽

Allograft Function ◽

One Year

Download Full-text

Pre-Transplant Histological Assessment Provides a Useful Predictor of Subsequent Kidney Allograft Function

Transplantation Journal ◽

10.1097/01.tp.0000543076.52776.db ◽

2018 ◽

Vol 102 ◽

pp. S340-S341

Author(s):

Adam Brayne ◽

Patrick Trotter ◽

Daniel Hart ◽

Gavin Pettigrew ◽

Menna Clatworthy

Keyword(s):

Kidney Allograft ◽

Histological Assessment ◽

Allograft Function

Download Full-text

P1639DEVELOPMENT OF SELF-LIMITED LOW-LEVEL BK VIREMIA/VIRURIA SUGGESTS IDEAL IMMUNOSUPPRESSION TO SUPPRESS T-CELL AND ANTIBODY-MEDIATED REJECTION AND PRESERVE KIDNEY ALLOGRAFT FUNCTION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1639 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Bettina Näf ◽

Thomas Müller ◽

Rudolf Peter Wuthrich ◽

Thomas Schachtner

Keyword(s):

Lower Incidence ◽

De Novo ◽

Allograft Survival ◽

Kidney Allograft ◽

Low Level ◽

Antibody Mediated Rejection ◽

Maintenance Immunosuppression ◽

Allograft Function ◽

High Level ◽

Egfr Slope

Abstract Background and Aims Polyomavirus BK (BKV) viremia has been suggested as a surrogate marker of overimmunosuppression. Due to recent advances in monitoring strategies and pre-emptive therapy, progression to BKV-associated nephropathy (BKVN) has been reduced. Reduction of maintenance immunosuppression during BKVN, however, has been associated with both T-cell mediated rejection (TCMR), antibody-mediated rejection (ABMR), and inferior kidney allograft outcomes. Although the administration of intravenous immunoglobulins (IVIG) failed to treat BKVN, IVIG may have properties to reduce allosensitization. Method We studied 860 kidney transplant recipients (KTRs) predominantly under tacrolimus-based triple-drug maintenance immunosuppression from 2009 to 2018. We identified 130 KTRs (15.1%) with high-level BK viremia >10,000 copies/mL (presumptive BKVN), 180 KTRs (20.9%) with low-level BK viremia <10,000 copies/mL, 85 KTRs (9.9%) with isolated BK viruria, and 465 KTRs (54.1%) with no BK viruria/viremia. Kidney allograft outcomes with respect to TCMR, ABMR, development of de novo donor-specific antibodies (DSA), kidney allograft survival, and estimated glomerular filtration rate (eGFR) slope were analysed. Due to the increased incidence of TCMR and ABMR among KTRs with presumptive BKVN, 48 of 130 KTRs (36.9%) with high-level BK viremia starting from 2015 received IVIG (0.5 g/kg of body weight) on a biweekly basis during BKV replication. Results Very interestingly, KTRs with low-level BK viremia/viruria showed a significantly lower incidence of TCMR compared to KTRs with no BK viremia/viruria and KTRs with high-level BK viremia (p<0.05). In addition, KTRs with low-level BK viremia/viruria showed a significantly lower incidence of ABMR compared to KTRs with high-level BK viremia (p<0.05). No differences were observed with respect to the development of de novo DSA (MFI>5000) between KTRs with low-level BK viremia/viruria, KTRs with no BK viremia/viruria, and KTRs with high-level BK viremia (p>0.05). KTRs with low-level BK viremia/viruria showed superior kidney allograft survival and lower eGFR slope compared to KTRs with no BK viremia/viruria and KTRs with high-level BK viremia (p<0.05). The administration of IVIG during high-level BK viremia didn’t impact the development of TCMR, ABMR, development of de novo DSA, eGFR slope, and kidney allograft survival (p<0.05). Conclusion Our results show that low-level BK viremia/viruria is associated with suppression of TCMR and ABMR in the early period posttransplantation, and preservation of kidney allograft function in the long-term. The administration of IVIG didn’t prove beneficial to reduce allosensitization among KTRs with high-level BK viremia.

Download Full-text