scholarly journals Urinary MicroRNA-21-5p as Potential Biomarker of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Kidney Transplant Recipients

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 113 ◽  
Author(s):  
Michal S. Gniewkiewicz ◽  
Izabela Paszkowska ◽  
Jolanta Gozdowska ◽  
Katarzyna Czerwinska ◽  
Anna Sadowska-Jakubowicz ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Tubular Atrophy ◽  
Expression Levels ◽  
Allograft Dysfunction ◽  
Potential Biomarker

Chronic renal allograft dysfunction (CAD) is a major limiting factor of long-term graft survival. The hallmarks of progressive CAD are interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs are small, regulatory RNAs involved in many immunological processes. In particular, microRNA-21-5p (miR-21) is considered to be strongly associated with pathogenesis regarding tubulointerstitium. The aim of this study was to assess urinary miR-21 expression levels in the kidney transplant recipients and determine their application in the evaluation of IFTA and kidney allograft function. The expression levels of miR-21 were quantified in the urine of 31 kidney transplant recipients with biopsy-assessed IFTA (IFTA 0 + I: n = 17; IFTA II + III: n = 14) by real-time quantitative PCR. Urine samples were collected at the time of protocolar biopsies performed 1 or 2 years after kidney transplantation. MicroRNA-191-5p was used as reference gene. MiR-21 was significantly up-regulated in IFTA II + III group compared to IFTA 0 + I group (p = 0.003). MiR-21 correlated significantly with serum concentration of creatinine (r = 0.52, p = 0.003) and eGFR (r = −0.45; p = 0.01). ROC analysis determined the diagnostic value of miR-21 with an area under curve (AUC) of 0.80 (p = 0.0002), sensitivity of 0.86 and specificity of 0.71. miR-21 is associated with renal allograft dysfunction and IFTA. Therefore, it could be considered as a potential diagnostic, non-invasive biomarker for monitoring renal graft function.

scholarly journals Preservation of epoxyeicosatrienoic acid bioavailability prevents renal allograft dysfunction and cardiovascular alterations in kidney transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas Duflot ◽  
Charlotte Laurent ◽  
Anne Soudey ◽  
Xavier Fonrose ◽  
Mouad Hamzaoui ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Kidney Transplant ◽  
Plasma Levels ◽  
Renal Allograft ◽  
Transplant Recipients ◽  
Loss Of Function ◽  
Kidney Transplant Recipients ◽  
Allograft Dysfunction ◽  
Allograft Function ◽  
The Impact

AbstractThis study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia–reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.

scholarly journals Long-Term Outcomes in 831 Kidney Transplant Recipients with 20 Years of Graft Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Varvara Kirchner ◽  
Kristen Gillingham ◽  
Oscar Serrano ◽  
Srinath Chinnakotla ◽  
Ty Dunn ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Graft Function ◽  
Solid Organ ◽  
Kidney Transplant Recipients ◽  
Long Term Outcomes ◽  
Tubular Atrophy

An understanding of long-term outcomes for kidney transplant(KTx) recipients who survive with graft function beyond a specific time posttransplant is the first step in creating protocols to optimize care for current and improve outcomes for future recipients. We studied 831KTx recipients-580 living donor(LD); 251 deceased donor(DD)—with graft survival(GS) >20 years.  For primary LD recipients, 25-year patient survival(PS) was 83%; 35-year, 59%.  Their 25-year death-censored graft survival(DCGS) was 89%; 35-year, 72%.   DD recipients had lower PS(P<0.01), DCGS(P<0.01).   After 20 years, two major causes of graft loss(GL) were death with function(DwF)(58%, LD; 58%, DD) and interstitial fibrosis and tubular atrophy(IFTA)(22%, LD; 23%, DD).  Two major causes of DwF were cancer(31%, LD; 31%, DD) and cardiovascular disease(CVD)(19%, LD;17%, DD).  Per multivariate analysis(MVA), risk factors for GL after 20 years in pre–calcineurin inhibitor(CNI) era were human leukocyte antigen(HLA) mismatches >3 antigens, pretransplant type 1 diabetes mellitus(DM1); in CNI era, a history of rejection, female gender.  New comorbidities after 20 years were common: CVD(13%, non-DM1;18%, DM1), infections(27%, non-DM1;37%, DM1), 20-29 years posttransplant.  Cancer after 20 years included: nonmelanotic skin cancer,22%; solid organ,7%; post-transplant lymphoproliferative disease(PTLD),2%.  To improve long-term outcomes, clinical trials on prevention, recognition, and treatment of new comorbidities are needed.

scholarly journals Urinary vitronectin identifies patients with high levels of fibrosis in kidney grafts

2020 ◽  
Author(s):  
Laura Carreras-Planella ◽  
David Cucchiari ◽  
Laura Cañas ◽  
Javier Juega ◽  
Marcella Franquesa ◽  
...  
Keyword(s):  
Differential Expression ◽  
Kidney Transplant ◽  
Interstitial Fibrosis ◽  
Calcineurin Inhibitors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Tubular Atrophy ◽  
Non Invasive ◽  
Noninvasive Biomarkers

Abstract Background In kidney transplantation, fibrosis represents the final and irreversible consequence of the pathogenic mechanisms that lead to graft failure, and in the late stages it irremediably precedes the loss of renal function. The invasiveness of kidney biopsy prevents this condition from being frequently monitored, while clinical data are rather unspecific. The objective of this study was to find noninvasive biomarkers of kidney rejection. Methods We carried out proteomic analysis of the urinary Extracellular Vesicles (uEVs) from a cohort of kidney transplant recipients (n = 23) classified according to their biopsy-based diagnosis and clinical parameters as interstitial fibrosis and tubular atrophy (IFTA), acute cellular rejection (ACR), calcineurin inhibitors toxicity (CNIT) and normal kidney function (NKF). Results Shotgun mass spectrometry of uEV-proteins identified differential expression of several proteins among these different groups. Up to 23 of these proteins were re-evaluated using targeted proteomics in a new independent cohort of patients (n = 41) classified in the same diagnostic groups. Among other results, we found a differential expression of vitronectin (VTN) in patients displaying chronic interstitial and tubular lesions (ci and ct mean > 2 according to Banff criteria). These results were further confirmed by a pilot study using enzyme-linked immunosorbent assay (ELISA). Conclusion Urinary vitronectin levels are a potential stand-alone biomarker to monitor fibrotic changes in kidney transplant recipients in a non-invasive fashion.

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

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.

scholarly journals Associations of pre-transplant anemia management with post-transplant delayed graft function in kidney transplant recipients

2012 ◽  
Vol 26 (5) ◽  
pp. 782-791 ◽  
Author(s):  
Miklos Z. Molnar ◽  
Csaba P. Kovesdy ◽  
Laszlo Rosivall ◽  
Suphamai Bunnapradist ◽  
Junichi Hoshino ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Anemia Management
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