Search

Aim: This study presents the causes of death-censored graft loss among kidney transplant recipients. Materials and Methods: Medical records of the patients, who had undergone kidney transplantation at a tertiary center between November 2010 and December 2018, were retrospectively reviewed. Death-censored graft loss was described as an irreversible graft failure signified by return to long-term dialysis (or re-transplantation). Inclusion criteria were: patients who had undergone kidney transplantation, and subsequently lost their first graft, and a follow-up of more than one year after kidney transplantation. Results: Of 269 kidney transplant recipients, 33 recipients with a mean age of 33.54 ± 15.37 years (17 male and 16 female) were included in the study. The rate of death-censored graft loss was 12.26%. Of graft failures, 3.03% occurred in the hyperacute phase, 18.18% in the acute phase, and 78.78% in the chronic phase. Chronic allograft nephropathy was the leading cause of graft failure (48.48%). Other causes were medical problems (18.18), immunological problems (18.18%) and surgical complications (15.15%). Conclusion: Identification of the true causes of graft failure described under the heading chronic allograft nephropathy is noteworthy. Comprehensive biochemical, physiological, pathological, immunological, and genetic research should be implemented to remove the obstacles in kidney transplantations. [ABSTRACT FROM AUTHOR]

Background: Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. Purpose: To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). Study Type: Prospective. Subjects: Seventy‐seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well‐functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). Field Strength/Sequence: 1.5 T/T2‐weighted imaging and DTI. Assessment: The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. Statistical Test: One‐way analysis of variance; correlation analysis; independent‐sample t‐test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P‐value <0.05. Results: The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 μmol/L vs. 82.3 ± 20.9 μmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. Data Conclusion: DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. Evidence Level: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Rates of late allograft loss have improved slowly in the last decades. Well described traditional risk factors that influence allograft survival include cardiovascular events, rejection, infections and post-transplant neoplasia. Here, we critically evaluate the influence of several non-immunological, non-traditional risk factors and describe their impact on allograft survival and cardiovascular health of kidney transplant recipients. We assessed the following risk factors: arterial stiffness, persistent arteriovenous access, mineral bone disease, immunosuppressive drugs residual levels variability, hypomagnesemia, glomerular pathological alterations not included in Banff criteria, persistent inflammation and metabolic acidosis. [ABSTRACT FROM AUTHOR]

Introduction: Kidney transplantation (KT) has surpassed dialysis as the optimal therapy for end-stage kidney disease. Yet, most patients could suffer from a slow but continuous deterioration of kidney function leading to graft loss mostly due to chronic allograft nephropathy (CAN) after KT. The dysregulated gene expression for CAN is still poorly understood. Methods: To explore the pathogenesis of genomics in CAN, we analyzed the differentially expressed genes (DEGs) of kidney transcriptome between CAN and nonrejecting patients by downloading gene expression microarrays from the Gene Expression Omnibus database. Then, we used weighted gene coexpression network analysis (WGCNA) to analyze the coexpression of DEGs to explore key modules, hub genes, and transcription factors in CAN. Functional enrichment analysis of key modules was performed to explore pathogenesis. ROC curve analysis was used to validate hub genes. Results: As a result, 3 key modules and 15 hub genes were identified by WGCNA analysis. Three key modules had 21 mutual Gene Ontology term enrichment functions. Extracellular structure organization, extracellular matrix organization, and extracellular region were identified as significant functions in CAN. Furthermore, transcription factor 12 was identified as the key transcription factor regulating key modules. All 15 hub genes, Yip1 interacting factor homolog B, membrane trafficking protein, toll like receptor 8, neutrophil cytosolic factor 4, glutathione peroxidase 8, mesenteric estrogen dependent adipogenesis, decorin, serpin family F member 1, integrin subunit beta like 1, SRY-box transcription factor 15, trophinin associated protein, SRY-box transcription factor 1, metallothionein 3, lysosomal protein transmembrane, FERM domain containing kindlin 3, and cathepsin S, had a great diagnostic performance (AUC > 0.7). Conclusion: This study updates information and provides a new perspective for understanding the pathogenesis of CAN by bioinformatics means. More research is needed to validate and explore the results we have found to reveal the mechanisms underlying CAN. [ABSTRACT FROM AUTHOR]

Background Reliable diagnosis of the cause of renal allograft dysfunction is of clinical importance. The aim of this study is to develop a hybrid deep-learning approach for determining acute rejection (AR), chronic allograft nephropathy (CAN) and renal function in kidney-allografted patients by multimodality integration. Methods Clinical and magnetic resonance imaging (MRI) data of 252 kidney-allografted patients who underwent post-transplantation MRI between December 2014 and November 2019 were retrospectively collected. An end-to-end convolutional neural network, namely RtNet , was designed to discriminate between AR, CAN and stable renal allograft recipient (SR), and secondarily, to predict the impaired renal graft function [estimated glomerular filtration rate (eGFR) ≤50 mL/min/1.73 m2]. Specially, clinical variables and MRI radiomics features were integrated into the RtNet , resulting in a hybrid network (RtNet+). The performance of the conventional radiomics model RtRad, RtNet and RtNet+ was compared to test the effect of multimodality interaction. Results Out of 252 patients, AR, CAN and SR was diagnosed in 20/252 (7.9%), 92/252 (36.5%) and 140/252 (55.6%) patients, respectively. Of all MRI sequences, T2-weighted imaging and diffusion-weighted imaging with stretched exponential analysis showed better performance than other sequences. On pairwise comparison of resulting prediction models, RtNet+ produced significantly higher macro-area-under-curve (macro-AUC) (0.733 versus 0.745; P = 0.047) than RtNet in discriminating between AR, CAN and SR. RtNet+ performed similarly to the RtNet (macro-AUC, 0.762 versus 0.756; P > 0.05) in discriminating between eGFR ≤50 mL/min/1.73 m2 and >50 mL/min/1.73 m2. With decision curve analysis, adding RtRad and RtNet to clinical variables resulted in more net benefits in diagnostic performance. Conclusions Our study revealed that the proposed RtNet+ model owned a stable performance in revealing the cause of renal allograft dysfunction, and thus might offer important references for individualized diagnostics and treatment strategy. [ABSTRACT FROM AUTHOR]

Background: The principal cause of renal graft loss after the first year is chronic allograft nephropathy which is represented histologically by tubulo-interstitial fibrosis. Its early diagnosis and treatment are crucial to prevent late graft failure. Ultrasound is unequivocally the first-line imaging modality for the evaluation of renal transplants in the immediate postoperative period and for long-term follow-up. Ultrasound shear wave elastography is an imaging technique based on estimation of the elastic properties of tissues. Elastography is performed in the same clinical setting with conventional B-mode ultrasonography. Tissue elasticity is displayed as an absolute number and color-coded real-time estimation. So, it can be used in screening and diagnosing chronic allograft nephropathy. However, the accurate diagnosis and prognosis of renal parenchymal complications still relies on tissue biopsy. Many studies have proved the high specificity of ultrasound elastography in decreasing the number of unnecessary biopsies. Results: In our study, we included 36 patients with biopsy-proven chronic allograft nephropathy. All patients had a B-mode ultrasound examination and followed by ultrasound shear wave elastography in the same session. The results were compared to the histopathological results. Time since transplantation was directly correlated with mean renal stiffness, revealing that with longer time of transplantation renal stiffness and interstitial fibrosis and tubular atrophy (IF/TA) percentage increased with r = 0.72, 0.90 and p value < 0.001. Antero-posterior (AP) diameter of the renal graft was significantly correlated with mean renal stiffness as the larger the AP diameter, the higher the mean kidney stiffness with r = 0.47, 0.73 and p value 0.001. Sensitivity analysis showed that US shear wave elastography through mean kidney stiffness can significantly predict moderate Banff score of renal fibrosis using cutoff value 28.67 kPa with sensitivity 87.5%, specificity 90%, AUC 0.91 and p value < 0.001. Conclusion: Shear wave elastography (SWE) may be useful for the prediction of fibrosis in renal transplant patients, especially in the case of moderate Banff score, where the accuracy reached 87.5% using a cutoff value 28.67 kPa. We conclude that US SWE can be of great help during the regular follow-up of renal transplant patients. It can act as a screening tool to identify patients with stiffness values that suggest moderate tubulo-interstitial fibrosis, so eventually helping in the early diagnosis, management and help in selecting patients who are candidate for biopsy and in avoiding the repeated unnecessary biopsies for others. [ABSTRACT FROM AUTHOR]

Abstract Background The principal cause of renal graft loss after the first year is chronic allograft nephropathy which is represented histologically by tubulo-interstitial fibrosis. Its early diagnosis and treatment are crucial to prevent late graft failure. Ultrasound is unequivocally the first-line imaging modality for the evaluation of renal transplants in the immediate postoperative period and for long-term follow-up. Ultrasound shear wave elastography is an imaging technique based on estimation of the elastic properties of tissues. Elastography is performed in the same clinical setting with conventional B-mode ultrasonography. Tissue elasticity is displayed as an absolute number and color-coded real-time estimation. So, it can be used in screening and diagnosing chronic allograft nephropathy. However, the accurate diagnosis and prognosis of renal parenchymal complications still relies on tissue biopsy. Many studies have proved the high specificity of ultrasound elastography in decreasing the number of unnecessary biopsies. Results In our study, we included 36 patients with biopsy-proven chronic allograft nephropathy. All patients had a B-mode ultrasound examination and followed by ultrasound shear wave elastography in the same session. The results were compared to the histopathological results. Time since transplantation was directly correlated with mean renal stiffness, revealing that with longer time of transplantation renal stiffness and interstitial fibrosis and tubular atrophy (IF/TA) percentage increased with r = 0.72, 0.90 and p value

Background Mesenchymal stem cells (MSCs)-based therapy has shown promising results for renal injury. In this study, the efficacy and safety of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating nonspecific interstitial fibrosis and tubular atrophy (IFTA) were evaluated. Methods From March 2011 to January 2013, 11 renal transplanted patients with IFTA were recruited. At baseline, patients were given one intra-arterial infusion of BM-MSCs; 7 days and 1 month later, another two intravenous infusions of cells were followed. Serum creatinine, creatinine clearance rate, and serum cystatin-C at baseline and 7 days, 1 month, 3 months, 6 months, and 12 months after the intra-arterial infusion of BM-MSCs were used to assess renal function. At baseline and 6 months, histological examination based on hematoxylin-eosin, Masson’s trichrome and periodic acid-Schiff staining and immunohistochemistry for transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) was performed. Adverse events were recorded to evaluate the safety of BM-MSCs treatment. Results At 12 months, the renal function of 6 patients (54.5%) was improved, 3 (27.3%) were stable and 2 (18.2%) were worsened. At 6 months, the mean IFTA scores of all participators were similar with the baseline (1.73 ± 0.41 vs.1.50 ± 0.0.77, p = 0.242); however, it was significantly decreased when only 6 patients with improved renal function were analyzed (1.67 ± 0.41 vs. 1.08 ± 0.20, p = 0.013). Besides, decreased expression of TGF-β1 and CTGF were also observed at 6 months. During 1 year follow-up period, only two minor complications including infection and allergy were observed. Conclusion Our results demonstrated that autologous BM-MSCs are safe and beneficial for IFTA patients. Abbreviations: MSCs: mesenchymal stem cells; BM-MSCs: marrow-derived mesenchymal stem cells; IFTA: interstitial fibrosis and tubular atrophy; CAN: chronic allograft nephropathy; CNIs: calcineurin inhibitors; Scr: serum creatinine; CCr: creatinine clearance rate; Cys-C: cystatin-C; TGF-β1: transforming growth factor β1; CTGF: connective tissue growth factor

Mesenchymal stem cells (MSCs)-based therapy has shown promising results for renal injury. In this study, the efficacy and safety of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating nonspecific interstitial fibrosis and tubular atrophy (IFTA) were evaluated. From March 2011 to January 2013, 11 renal transplanted patients with IFTA were recruited. At baseline, patients were given one intra-arterial infusion of BM-MSCs; 7 days and 1 month later, another two intravenous infusions of cells were followed. Serum creatinine, creatinine clearance rate, and serum cystatin-C at baseline and 7 days, 1 month, 3 months, 6 months, and 12 months after the intra-arterial infusion of BM-MSCs were used to assess renal function. At baseline and 6 months, histological examination based on hematoxylin-eosin, Masson's trichrome and periodic acid-Schiff staining and immunohistochemistry for transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) was performed. Adverse events were recorded to evaluate the safety of BM-MSCs treatment. At 12 months, the renal function of 6 patients (54.5%) was improved, 3 (27.3%) were stable and 2 (18.2%) were worsened. At 6 months, the mean IFTA scores of all participators were similar with the baseline (1.73 ± 0.41 vs.1.50 ± 0.0.77, p = 0.242); however, it was significantly decreased when only 6 patients with improved renal function were analyzed (1.67 ± 0.41 vs. 1.08 ± 0.20, p = 0.013). Besides, decreased expression of TGF-β1 and CTGF were also observed at 6 months. During 1 year follow-up period, only two minor complications including infection and allergy were observed. Our results demonstrated that autologous BM-MSCs are safe and beneficial for IFTA patients. Abbreviations: MSCs: mesenchymal stem cells; BM-MSCs: marrow-derived mesenchymal stem cells; IFTA: interstitial fibrosis and tubular atrophy; CAN: chronic allograft nephropathy; CNIs: calcineurin inhibitors; Scr: serum creatinine; CCr: creatinine clearance rate; Cys-C: cystatin-C; TGF-β1: transforming growth factor β1; CTGF: connective tissue growth factor [ABSTRACT FROM AUTHOR]

Although kidney transplantation is the best treatment option for end stage kidney disease, it is still associated with long-term graft failure. One of the greater challenges for transplant professionals is the ability to identify grafts with a high risk of failure before initial decline of eGFR with irreversible graft changes. Transplantation medicine is facing an emerging need for novel disease end point-specific biomarkers, with practical application in preventive screening, early diagnostic, and improved prognostic and therapeutic utility. The aim of our review was to evaluate the clinical application of urinary proteomics in kidney transplant recipients at risk for any type of future graft failure. [ABSTRACT FROM AUTHOR]

Background: Currently, allograft renal biopsy is the only reliable tool available to detect fibrosis in the transplanted kidney. However, it is an invasive procedure and is associated with complications. Therefore, a noninvasive tool to detect renal allograft fibrosis is needed. Aims: The aim of the study was to evaluate the usefulness of real-time sonoelastography (RTS) in the diagnosis of renal allograft fibrosis. Subjects and Methods: We studied 15 renal allograft recipients who had chronic allograft nephropathy. RTS was performed by an experienced radiologist to semi-quantitatively determine cortical and medullary stain ratio. These parameters were compared with the degree of fibrosis as assessed by allograft renal biopsy. For comparison, patients were divided into two groups based on the degree of fibrosis: those with mild fibrosis (interstitial fibrosis and tubular atrophy [IFTA] 25%). A receiver operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of cortical strain ratio to discriminate between patients with mild fibrosis versus patients with moderate-to-severe fibrosis. Results: The mean cortical strain ratio was significantly higher in those who had mild fibrosis as compared to those who had moderate-to-severe fibrosis (2.46 ± 0.55 vs. 1.78 ± 0.15, P = 0.01), while the medullary strain ratio was comparable between the two groups. The diagnostic accuracy of cortical strain ratio, as evaluated by area under the curve of ROC analysis, was 0.96. Conclusion: RTS can differentiate between mild fibrosis and moderate-to-severe fibrosis with high accuracy.

In clinical kidney transplantation, the marginal kidney donors are known to develop chronic allograft rejection more frequently than living kidney donors. In our previous study, we have reported that the hydrogen gas-containing organ preservation solution prevented the development of acute injuries in the kidney of the donor after cardiac death by using preclinical miniature pig model. In the present study, we verified the impact of hydrogen gas treatment in transplantation with the optimal immunosuppressive protocol based on human clinical setting by using the miniature pig model. Marginal kidney processed by hydrogen gas-containing preservation solution has been engrafted for long-term (longer than 100 days). A few cases showed chronic rejection reaction; however, most were found to be free of chronic rejection such as graft tissue fibrosis or renal vasculitis. We concluded that marginal kidney graft from donor after cardiac death is an acceptable model for chronic rejection and that if the transplantation is carried out using a strict immunosuppressive protocol, chronic rejection may be alleviated even with the marginal kidney.

In clinical kidney transplantation, the marginal kidney donors are known to develop chronic allograft rejection more frequently than living kidney donors. In our previous study, we have reported that the hydrogen gas-containing organ preservation solution prevented the development of acute injuries in the kidney of the donor after cardiac death by using preclinical miniature pig model. In the present study, we verified the impact of hydrogen gas treatment in transplantation with the optimal immunosuppressive protocol based on human clinical setting by using the miniature pig model. Marginal kidney processed by hydrogen gas-containing preservation solution has been engrafted for long-term (longer than 100 days). A few cases showed chronic rejection reaction; however, most were found to be free of chronic rejection such as graft tissue fibrosis or renal vasculitis. We concluded that marginal kidney graft from donor after cardiac death is an acceptable model for chronic rejection and that if the transplantation is carried out using a strict immunosuppressive protocol, chronic rejection may be alleviated even with the marginal kidney. [ABSTRACT FROM AUTHOR]

Steroid avoidance is safe and effective in children receiving kidney transplants in terms of graft function and survival, but the effects on allograft histology are unknown. In this multicenter trial, 130 pediatric renal transplant recipients were randomized to steroid-free (SF; n = 60) or steroid-based (SB; n = 70) immunosuppression, and underwent renal allograft biopsies at the time of graft dysfunction and per protocol at implantation and 6, 12 and 24 months after transplantation. Clinical follow-up was 3 years posttransplant. Subclinical acute rejection was present in 10.6% SF versus 11.3% SB biopsies at 6 months (p = 0.91), 0% SF versus 4.3% SB biopsies at 1 year (p = 0.21) and 0% versus 4.8% at 2 years (p = 0.20). Clinical acute rejection was present in 13.3% SF and 11.4% SB patients by 1 year (p = 0.74) and in 16.7% SF and 17.1% SB patients by 3 years (p = 0.94) after transplantation. The cumulative incidence of antibody-mediated rejection was 6.7% in SF and 2.9% in SB by 3 years after transplantation (p = 0.30). There was a significant increase in chronic histological damage over time (p < 0.001), without difference between SF and SB patients. Smaller recipient size and higher donor age were the main risk factors for chronic histological injury in posttransplant biopsies.

Matrix metalloproteinase (MMP) is a large class of proteases which can cut or reshape extracellular matrix (ECM) and cell surface proteins. The activity of MMP is regulated by a variety of cytokines, including tissue inhibitor of metalloprotease (TIMP), signal transduction molecules and cell adhesion molecules. The latest research shows that MMP has a role in the pathophysiology process of many acute and chronic kidney diseases. In this article, the classification, expression and distribution in the kidney of MMP and its role in injury related renal transplantation was reviewed. [ABSTRACT FROM AUTHOR]

Background: Currently, allograft renal biopsy is the only reliable tool available to detect fibrosis in the transplanted kidney. However, it is an invasive procedure and is associated with complications. Therefore, a noninvasive tool to detect renal allograft fibrosis is needed. Aims: The aim of the study was to evaluate the usefulness of real-time sonoelastography (RTS) in the diagnosis of renal allograft fibrosis. Subjects and Methods: We studied 15 renal allograft recipients who had chronic allograft nephropathy. RTS was performed by an experienced radiologist to semi-quantitatively determine cortical and medullary stain ratio. These parameters were compared with the degree of fibrosis as assessed by allograft renal biopsy. For comparison, patients were divided into two groups based on the degree of fibrosis: those with mild fibrosis (interstitial fibrosis and tubular atrophy [IFTA] <25%) and those with moderate-to-severe fibrosis (IFTA >25%). A receiver operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of cortical strain ratio to discriminate between patients with mild fibrosis versus patients with moderate-to-severe fibrosis. Results: The mean cortical strain ratio was significantly higher in those who had mild fibrosis as compared to those who had moderate-to-severe fibrosis (2.46 ± 0.55 vs. 1.78 ± 0.15, P = 0.01), while the medullary strain ratio was comparable between the two groups. The diagnostic accuracy of cortical strain ratio, as evaluated by area under the curve of ROC analysis, was 0.96. Conclusion: RTS can differentiate between mild fibrosis and moderate-to-severe fibrosis with high accuracy. [ABSTRACT FROM AUTHOR]

Non-HLA antibodies are recognized as a potential source of antibody mediated rejection following transplantation. The epitopes which lead to production of these antibodies are a result of tissue disruption, specifically endothelium, secondary to inflammation and injury. Vimentin is a cytoskeletal protein involved in many aspects of cellular organization, signaling, and proliferation. Recently, antivimentin antibodies have been shown to be important not only for rheumatological autoimmune diseases, but also cardiac and renal transplant dysfunction. In cardiac transplant recipients, antivimentin antibodies are associated with coronary artery vasculopathy and chronic graft loss. In renal transplantation, antivimentin antibodies are detected prior to transplantation and are also correlated with chronic graft dysfunction. In renal transplant recipients, antivimentin antibodies seen prior to transplantation are thought to be secondary to chronic endothelial injury during hemodialysis and therefore more prevalent prior to renal transplant than cardiac transplantation. In this review, we will examine the generation and pathogenesis of antivimentin antibodies. Given that these antibodies appear to be associated with both post-cardiac and -renal transplant dysfunction, developing standard detection paradigms may be important for risk stratification prior to transplantation. Finally, understanding the pathogenesis of antivimentin antibodies may lead to the development potential therapies in order to improve long-term survival. [ABSTRACT FROM AUTHOR]

Immunosuppression is an obligate necessity in kidney transplant. However, the standard immunosuppression causes chronic deterioration of allograft function over long term use. Mammalian target of rapamycin (mTOR) inhibitors provide an alternative in such scenario. The mTOR inhibitors engage FKBP12 to create complexes that engage and inhibit the target of rapamycin. Inhibition of the TOR blocks signal 3 by preventing cytokine receptors from activating the cell cycle. mTOR inhibitors are associated with less viral infection and disease in kidney transplants and also beneficial in post-transplant malignancy. There are various strategies of using mTOR inhibitors either as upfront de novo therapy or later on as switch over therapy. They can also be used in cases of complications arising from standard immunosuppression. mTOR inhibitors also have adverse effects which can be managed by dose reduction but may require stoppage in case of serious complications. Surgical issues need to be kept in mind in view of delayed wound healing. mTOR inhibitors add on to the armamentarium of the available immunosuppression and can give excellent results with judicious use. The present review aims to provide updated information regarding the use of these drugs in post-renal transplantation setting.

Background and Objectives: Renal allograft biopsy is the gold standard for diagnosing chronic allograft nephropathy, but noninvasive methods are needed to avoid unnecessary biopsies. Doppler ultrasonography, particularly the resistive index (RI), correlates with renal allograft dysfunction. This study aims to assess the relationship between renal sonographic parameters and biochemical parameters in diagnosing graft interstitial fibrosis., Methods: The study evaluated 60 renal allograft recipients for sonographic renal morphological features and Doppler indices. The estimated glomerular filtration rate (eGFR) was calculated, and cortical fibrosis after the biopsy was determined using the Banff score. Continuous variables like mean and SD were calculated, and categorical variables were reported using frequencies and proportions. Associations were examined using independent sample t -tests, χ 2 tests, and multivariate regression analysis., Results: The mean eGFR was 75.23±25.45 ml/min/1.73 m 2 . A significant correlation of eGFR with RI ( r =0.341, P =0.008) was seen. A significant difference in mean RI (F=10.167; df=2,57; P <0.001) was seen among the histological grades of fibrosis. Among the histological grades of fibrosis, significant differences in RI among mild and moderate (S.E. 0.033, P =0.043), mild and severe (S.E. 0.026, P =0.001) as well as moderate and severe (S.E. 0.036, P =0.029) was seen., Conclusion: Doppler was able to noninvasively predict allograft fibrosis and could be used as a complementary imaging tool during the follow-up of renal allograft patients. Future research is needed to improve evidence, diagnostic criteria, guidelines, and long-term impact., Competing Interests: Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Chronic kidney allograft damage is characterized by IFTA and GS. We sought to identify urinary metabolite signatures associated with severity of IFTA and GS in pediatric kidney transplant recipients. Urine samples (n = 396) from 60 pediatric transplant recipients were obtained at the time of kidney biopsy and assayed for 133 metabolites by mass spectrometry. Metabolite profiles were quantified via PLS‐DA. We used mixed‐effects regression to identify laboratory and clinical predictors of histopathology. Urine samples (n = 174) without rejection or AKI were divided into training/validation sets (75:25%). Metabolite classifiers trained on IFTA severity and %GS showed strong statistical correlation (r = .73, P < .001 and r = .72; P < .001, respectively) and remained significant on the validation sets. Regression analysis identified additional clinical features that improved prediction: months post‐transplant (GS, IFTA); and proteinuria, GFR, and age (GS only). Addition of clinical variables improved performance of the %GS classifier (AUC = 0.9; 95% CI = 0.85‐0.96) but not for IFTA (AUC = 0.82; 95% CI = 0.71‐0.92). Despite the presence of potentially confounding phenotypes, these findings were further validated in samples withheld for rejection or AKI. We identify urine metabolite classifiers for IFTA and GS, which may prove useful for non‐invasive assessment of histopathological damage. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis. Methods: Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification. Results: A total of 40 elastography scans were carried out (median creatinine 172.5 μmol/L [interquartile range 133.8–281.8 μmol/L]). Median tissue stiffness at the cortex (22.6 kPa [interquartile range 18.8–25.7 kPa] vs 22.3 kPa [interquartile range 19.0–26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7–18.0 kPa] vs 15.6 kPa [interquartile range 14.4–18.2 kPa]) showed no significant differences between the two observers. Interobserver agreement was satisfactory (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70–0.92 and intraclass correlation coefficient of the medulla 0.88, 95% CI 0.78–0.94). The areas under the receiver operating characteristic curves for detection of tubulointerstitial fibrosis were estimated to be 0.75 (95% CI 0.61–0.89), 0.85 (95% CI 0.75–0.95) and 0.65 (95% CI 0.53–0.78) for cortical, medullary tissue stiffness and serum creatinine, respectively. Conclusions: Shear wave elastography can be used as a non‐invasive tool to evaluate kidney allograft fibrosis with reasonable interobserver agreement and superior test performance to serum creatinine in detecting early tubulointerstitial fibrosis. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the association between high mobility group protein B1 (HMGB1), transforming growth factor-β1 (TGF-β1), nuclear factor-κB (NF-κB) and chronic allograft nephropathy (CAN) and to identify the clinical significance of HMGB1, TGF-β1, NF-κB on patients with CAN. Between September 2012 and November 2014, 27 patients with CAN diagnosed by biopsy were enrolled in the present study and a further 30 patients that underwent nephrectomy following trauma were selected as the control group. Immunohistochemical staining with HMGB1, TGF-β1 and NF-κB expression in the renal tissues, and western blot analysis were used to measure the relative expression of HMGB1, TGF-β1 and NF-κB. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to estimate the relative expression of HMGB1, TGF-β1 and NF-κB mRNA. Statistical analysis was used to calculate the association between HMGB1, TGF-β1 and NF-κB expression and CAN grade. Immunohistochemical staining demonstrated that HMGB1, TGF-β1 and NF-κB had markedly positive expression rates in renal tubular epithelial cell cytoplasm and membranes in CAN renal tissues, and the positive rates of HMGB1, TGF-β1 and NF-κB increased with the aggravation of CAN pathological grade (I, II and III). The results of western blot analysis indicated that the expression levels of HMGB1, TGF-β1 and NF-κB were significantly higher in the CAN group, compared with the normal group (P<0.05), and the expression levels increased with the progression of CAN grade. A positive association among HMGB1, TGF-β1 and NF-κB expression was identified. RT-qPCR analysis demonstrated that the expression of HMGB1, TGF-β1 and NF-κB mRNA in the CAN group was significantly higher than in the normal group (P<0.05), and the relative expression level of HMGB1, TGF-β1 and NF-κB mRNA not only increased with the aggravation of CAN grade, but was also positively associated with the expression of HMGB1, TGF-β1 and NF-κB, respectively. The abnormal expression of HMGB1, TGF-β1 and NF-κB is therefore, an important manifestation of CAN and the expression of HMGB1, TGF-β1 and NF-κB mRNA in the renal tissues are significantly associated with CAN pathological progression. HMGB1, TGF-β1 and NF-κB may form a signaling pathway that leads to the occurrence of CAN, which induces renal interstitial fibrosis. [ABSTRACT FROM AUTHOR]

Since the mid-1980s magnetic resonance imaging (MRI) has been investigated as a non- or minimally invasive tool to probe kidney allograft function. Despite this long-standing interest, MRI still plays a subordinate role in daily practice of transplantation nephrology. With the introduction of new functional MRI techniques, administration of exogenous gadolinium-based contrast agents has often become unnecessary and true non-invasive assessment of allograft function has become possible. This raises the question why application of MRI in the follow-up of kidney transplantation remains restricted, despite promising results. Current literature on kidney allograft MRI is mainly focused on assessment of (sub) acute kidney injury after transplantation. The aim of this review is to survey whether MRI can provide valuable diagnostic information beyond 1 year after kidney transplantation from a mechanistic point of view. The driving force behind chronic allograft nephropathy is believed to be chronic hypoxia. Based on this, techniques that visualize kidney perfusion and oxygenation, scarring, and parenchymal inflammation deserve special interest. We propose that functional MRI mechanistically provides tools for diagnostic work-up in long-term follow-up of kidney allografts.

Since the mid-1980s magnetic resonance imaging (MRI) has been investigated as a non- or minimally invasive tool to probe kidney allograft function. Despite this long-standing interest, MRI still plays a subordinate role in daily practice of transplantation nephrology. With the introduction of new functional MRI techniques, administration of exogenous gadolinium-based contrast agents has often become unnecessary and true non-invasive assessment of allograft function has become possible. This raises the question why application of MRI in the follow-up of kidney transplantation remains restricted, despite promising results. Current literature on kidney allograft MRI is mainly focused on assessment of (sub) acute kidney injury after transplantation. The aim of this review is to survey whether MRI can provide valuable diagnostic information beyond 1 year after kidney transplantation from a mechanistic point of view. The driving force behind chronic allograft nephropathy is believed to be chronic hypoxia. Based on this, techniques that visualize kidney perfusion and oxygenation, scarring, and parenchymal inflammation deserve special interest. We propose that functional MRI mechanistically provides tools for diagnostic work-up in long-term follow-up of kidney allografts. [ABSTRACT FROM AUTHOR]

This review focuses on the role of OMICs technologies, concentrating in particular on proteomics, in biomarker discovery in chronic allograft injury (CAI). CAI is the second most prevalent cause of allograft dysfunction and loss in the first decade post-transplantation, after death with functioning graft (DWFG). The term CAI, sometimes referred to as chronic allograft nephropathy (CAN), describes the deterioration of renal allograft function and structure as a result of immunological processes (chronic antibody-mediated rejection), and other non-immunological factors such as calcineurin inhibitor (CNI) induced nephrotoxicity, hypertension and infection. Current methods for assessing allograft function are costly, insensitive and invasive; traditional kidney function measurements such as serum creatinine and glomerular filtration rate (GFR) display poor predictive abilities, while the current “gold-standard” involving histological diagnosis with a renal biopsy presents its own inherent risks to the overall health of the allograft. As early as two years post-transplantation, protocol biopsies have shown more than 50% of allograft recipients have mild CAN; ten years post-transplantation more than 50% of the allograft recipients have progressed to severe CAN which is associated with diminishing graft function. Thus, there is a growing medical requirement for minimally invasive biomarkers capable of identifying the early stages of the disease which would allow for timely intervention. Proteomics involves the study of the expression, localization, function and interaction of the proteome. Proteomic technologies may be powerful tools used to identify novel biomarkers which would predict CAI in susceptible individuals. In this paper we will review the use of proteomics in the elucidation of novel predictive biomarkers of CAI in clinical, animal and in vitro studies.