scholarly journals Clinical and Pathological Analyses of Borderline Changes Cases after Kidney Transplantation

Nephron ◽  
2020 ◽  
pp. 1-6
Author(s):  
Tomokazu Shimizu
Keyword(s):  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Graft Function ◽  
Renal Transplant Recipients ◽  
Tubular Atrophy ◽  
Renal Graft ◽  
Interstitial Inflammation ◽  
Biopsy Specimens ◽  
Allograft Biopsy

<b><i>Aim:</i></b> We aimed to perform a clinicopathological analysis of cases presenting with borderline changes (BC) after renal transplantation and discuss whether BC might be clinically or pathologically important. <b><i>Materials and Methods:</i></b> BC was diagnosed in 22 renal allograft biopsy specimens obtained from 20 renal transplant recipients between April 2010 and March 2019 after follow-up at the Department of Transplant Surgery, Kidney Center, Toda Chuo General Hospital. <b><i>Results:</i></b> BC was diagnosed at a median of 500 days following transplantation. Among the 22 renal allograft biopsy specimens showing evidence of BC, tubulitis was observed in all specimens. Interstitial inflammation was present in 18 specimens (82%), peritubular capillaritis in 14 (64%), interstitial fibrosis (ci) and tubular atrophy (ct) in 4 (18%), and C4d deposition in the peritubular capillary was present in 6 specimens (27%). Glomerulitis and intimal arteritis were not observed. There was no renal graft loss during the observation period, but deterioration of renal allograft function after biopsy occurred in 9 patients (45%). <b><i>Conclusions:</i></b> In BC, tubulitis and interstitial inflammation were the main constituents. Because glomerulitis was not observed in our study, we suspect that BC contributes to acute T-cell-mediated rejection. Although BC did not lead to renal graft loss, renal graft function deterioration was seen in nearly half of the patients after the renal graft biopsy. We conclude that BC is important clinically and pathologically and needs to be monitored and treated appropriately.

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 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 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 Expression of VWF and Interferon γ in renal allograft biopsies and correlation with inflammatory cells; Single center experience

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Alaa Abbas Ali ◽  
Kais Hassan Abd ◽  
Zana Sidiq Saleem
Keyword(s):  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Inflammatory Cells ◽  
Molecular Study ◽  
Interferon Γ ◽  
Tubular Atrophy ◽  
Fresh Tissue ◽  
Antibody Mediated Rejection ◽  
Allograft Biopsy ◽  
Significant Difference

Objective: Gene expression profiling by microarrays or RT PCR had been studied in certain western centers to enhance the diagnostic accuracy of allograft biopsy, however, such sophisticated tests are difficult to apply in developing countries. This study was conducted to evaluate the expression of von Willebrand factor (VWF) and Interferon-gamma (IFNγ) as an end PCR product in renal allograft biopsy with different pathological categories. Methods: Forty-nine indicated renal allograft biopsies were analyzed histologically by the Banff 2017 classification, inflammatory cell infiltration was analyzed by immunohistochemistry study for CD4, CD8, CD16, and CD68 markers, and a fresh tissue used for molecular study.  Results: The biopsy findings were acute T-cell mediated rejection (A- TCMR) 30.6%, interstitial fibrosis and tubular atrophy  (IF/TA) 22.4%, C4d-Transplant glomerulopathy (TG) 12.2%, calcineurin inhibitor toxicity (CNI) 10.2%, C4d+antibody mediated rejection (AMR) 10.2% and normal histology 14.3%. The only significant difference in VWF expression was between acute TCMR and normal, P=0.01, Spearman's correlation also showed a significant relationship between VWF and acute TCMR (r=0.53, P=0.01), and VWF was found to correlate with the numbers of interstitial CD4+ (r=0.29, P=0.03) and CD68+ (r=0.37, P=0.007) cells. IFNγ expression  was significant in acute TCMR versus normal, P=0.009. Spearman's pair-wise testing showed  that INFγ correlated with CD8 in both the glomerular (r=0.38, P=0.006) and interstitial (r=0.30, P=0.04) compartments and with CD16+ interstitial cells (r=0.36, P=0.01). Conclusion: our molecular and IHC data distinguish acute TCMR from other forms of transplant pathology and mildly dysfunctional kidneys with normal histology.

scholarly journals Glomerular Neovascularization in Nondiabetic Renal Allograft Is Associated with Calcineurin Inhibitor Toxicity

Nephron ◽  
2020 ◽  
pp. 1-6
Author(s):  
Anri Sawada ◽  
Masayoshi Okumi ◽  
Shigeru Horita ◽  
Kohei Unagami ◽  
Sekiko Taneda ◽  
...  
Keyword(s):  
Diabetic Kidney Disease ◽  
Renal Allograft ◽  
Calcineurin Inhibitor ◽  
Clinical Information ◽  
Renal Allografts ◽  
Biopsy Specimens ◽  
Allograft Biopsy ◽  
Time Periods ◽  
Medical University ◽  
Trough Levels

<b><i>Introduction:</i></b> Extra efferent arterioles, also known as polar vasculosis (PV), are often observed in the glomerular vascular pole and are associated with glomerular hypertrophy, indicating early recurrent diabetic kidney disease (DKD) in renal allografts. However, its significance in patients without diabetes remains uncertain. <b><i>Methods:</i></b> A total of 9,004 renal allograft biopsy specimens obtained between January 2007 and December 2017 at Tokyo Women’s Medical University were retrospectively analyzed to examine the clinical and pathological significance of PV in renal allografts. PV was identified in 186 biopsy specimens obtained from 165 patients. The PV group comprised 46 patients; 35 patients without DKD and 11 patients with DKD as the initial cause of ESRD, whose clinical information was available and treated with the calcineurin inhibitor (CNI) tacrolimus. The non-PV group comprising patients with renal allografts matched for age and postoperative day included 93 patients without DKD and 16 patients with DKD as the initial cause of ESRD. <b><i>Results:</i></b> In patients with nondiabetic renal allografts, systolic blood pressure was significantly higher in the PV group than in the non-PV group. The trough tacrolimus levels during the overall study period and at 2 weeks, 1 month, and 2 years after transplantation were significantly higher in the PV group compared with the non-PV group. Glomerulomegaly was significantly more common. Moreover, ah and aah scores in Banff score were significantly higher in the PV group than in the non-PV group. In those with diabetic renal allografts, although the clinical parameters and tacrolimus trough levels in all time periods were not significantly different between the PV and non-PV groups, the ah score was significantly higher in the PV group. <b><i>Conclusion:</i></b> PV was associated with CNI toxicity in nondiabetic but not in diabetic renal allografts. The pathogenesis of PV in renal allografts is considered to be multifactorial.

scholarly journals In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes

2021 ◽  
pp. ASN.2020081181 ◽  
Author(s):  
Aishwarya Ravindran ◽  
Marta Casal Moura ◽  
Fernando C. Fervenza ◽  
Samih H. Nasr ◽  
Mariam P. Alexander ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Study Cohort ◽  
Lower Serum ◽  
Tubular Atrophy ◽  
Novel Proteins ◽  
Biopsy Specimens ◽  
Membranous Lupus Nephritis

BackgroundIn patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis.MethodsWe conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared.ResultsOur study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger (P=0.01), had significantly lower serum creatinine levels (P=0.02), were significantly more likely to present with proteinuria ≥3.5 g/24 h (P=0.009), and had significantly less chronicity features (glomerulosclerosis, P=0.001 or interstitial fibrosis and tubular atrophy, P<0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1/EXT2-positive and 96 (60%) were EXT1/EXT2-negative. The proportion of patients with class 3/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1/EXT2-positive and EXT1/EXT2-negative groups (25.0% versus 32.3%; P=0.32). The patients who were EXT1/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1/EXT2-positive patients (18.8% versus 3.1%; P=0.003).ConclusionsThe prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive.

scholarly journals Fenofibrate Improved Interstitial Fibrosis of Renal Allograft through Inhibited Epithelial-Mesenchymal Transition Induced by Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yishu Wang ◽  
Lei Pang ◽  
Yanghe Zhang ◽  
Jiahui Lin ◽  
Honglan Zhou
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Renal Allograft ◽  
Epithelial Mesenchymal Transition ◽  
Interstitial Fibrosis ◽  
Peroxisome Proliferator ◽  
Tubular Atrophy ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
Stage Renal Disease

The best treatment for end-stage renal disease is renal transplantation. However, it is often difficult to maintain a renal allograft healthy for a long time following transplantation. Interstitial fibrosis and tubular atrophy (IF/TA) are significant histopathologic characteristics of a compromised renal allograft. There is no effective therapy to improve renal allograft function once IF/TA sets in. Although there are many underlying factors that can induce IF/TA, the pathogenesis of IF/TA has not been fully elucidated. It has been found that epithelial-mesenchymal transition (EMT) significantly contributes to the development of IF/TA. Oxidative stress is one of the main causes that induce EMT in renal allografts. In this study, we have used H2O2 to induce oxidative stress in renal tubular epithelial cells (NRK-52e) of rats. We also pretreated NRK-52e cells with an antioxidant (N-acetyl L-cysteine (NAC)) 1 h prior to the treatment with H2O2. Furthermore, we used fenofibrate (a peroxisome proliferator-activated receptor α agonist) to treat NRK-52e cells and a renal transplant rat model. Our results reveal that oxidative stress induces EMT in NRK-52e cells, and pretreatment with NAC can suppress EMT in these cells. Moreover, fenofibrate suppresses fibrosis by ameliorating oxidative stress-induced EMT in a rat model. Thus, fenofibrate may effectively prevent the development of fibrosis in renal allograft and improve the outcome.

Intragraft Tubular Vimentin and CD44 Expression Correlate With Long-Term Renal Allograft Function and Interstitial Fibrosis and Tubular Atrophy

2010 ◽  
Vol 90 (5) ◽  
pp. 502-509 ◽  
Author(s):  
Jesper Kers ◽  
Yi-Chun Xu-Dubois ◽  
Eric Rondeau ◽  
Nike Claessen ◽  
Mirza M. Idu ◽  
...  
Keyword(s):  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Cd44 Expression ◽  
Allograft Function
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