Search Results (6)

Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to address these challenges and revolutionize RT patient care. Our review synthesizes the existing scientific literature to highlight promising biomarkers, their biological characteristics, and their potential roles in enhancing clinical decision-making and patient outcomes. Emerging non-invasive biomarkers seemingly provide valuable insights into the immunopathology of nephron injury and allograft rejection. Moreover, we analyzed biomarkers with intra-nephron specificities, i.e., glomerular vs. tubular (proximal vs. distal), which can localize an injury in different nephron areas. Additionally, this paper provides a comprehensive analysis of the potential clinical applications of biomarkers in the prediction, detection, differential diagnosis and assessment of post-RT non-surgical allograft complications. Lastly, we focus on the pursuit of immune tolerance biomarkers, which aims to reclassify transplant recipients based on immune risk thresholds, guide personalized immunosuppression strategies, and ultimately identify patients for whom immunosuppression may safely be reduced. Further research, validation, standardization, and prospective studies are necessary to fully harness the clinical utility of RT biomarkers and guide the development of targeted therapies. Full article

Chronic kidney disease (CKD) is a slow-developing, progressive deterioration of renal function. The final common pathway in the pathophysiology of CKD involves glomerular sclerosis, tubular atrophy and interstitial fibrosis. Transforming growth factor-beta (TGF-β) stimulates the differentiation of fibroblasts towards myofibroblasts and the production of extracellular matrix (ECM) molecules, and thereby interstitial fibrosis. It has been shown that endoglin (ENG, CD105), primarily expressed in endothelial cells and fibroblasts, can function as a co-receptor of TGF signaling. In several human organs, endoglin tends to be upregulated when chronic damage and fibrosis is present. We hypothesize that endoglin is upregulated in renal interstitial fibrosis and plays a role in the progression of CKD. We first measured renal endoglin expression in biopsy samples obtained from patients with different types of CKD, i.e., IgA nephropathy, focal segmental glomerulosclerosis (FSGS), diabetic nephropathy (DN) and patients with chronic allograft dysfunction (CAD). We showed that endoglin is upregulated in CAD patients (p < 0.001) and patients with DN (p < 0.05), compared to control kidneys. Furthermore, the amount of interstitial endoglin expression correlated with eGFR (p < 0.001) and the amount of interstitial fibrosis (p < 0.001), independent of the diagnosis of the biopsies. Finally, we investigated in vitro the effect of endoglin overexpression in TGF-β stimulated human kidney fibroblasts. Overexpression of endoglin resulted in an enhanced ACTA2, CCN2 and SERPINE1 mRNA response (p < 0.05). It also increased the mRNA and protein upregulation of the ECM components collagen type I (COL1A1) and fibronectin (FN1) (p < 0.05). Our results suggest that endoglin is an important mediator in the final common pathway of CKD and could be used as a possible new therapeutic target to counteract the progression towards end-stage renal disease (ESRD). Full article

Chronic allograft dysfunction (CAD) is a major condition affecting long-term kidney graft survival. Serum microRNA (miRNA) has been reported as a biomarker for various conditions of allograft injuries. The upregulation of miR-21 is the best-known miRNA change in graft tissue, urine and plasma. However, the correlation of plasma miR-21 with the severity of CAD remains unclear. In our study, 40 kidney transplantation recipients with late graft survival for more than 10 years were enrolled. The CAD group (n = 20) had either an eGFR between 15 to 60 mL/min or a biopsy-proved chronic allograft nephropathy or rejection. The control group (n = 20) had an eGFR ≥ 60 mL/min without proteinuria and hematuria for a consecutive 3 months before the study. We performed RNA sequencing to profile the miRNAs expression. There were six differentially expressed miRNAs in the CAD group. Among them, miR-21-5p and miR-101-3p were decreased, and miR-20a-5p was increased. We found that miR-21-5p, miR-20a-5p and miR-101-3p all participated in the TGF-beta pathway. We demonstrated that decreased miR-21-5p and miR-101-3p, and increased miR-20a-5p were the novel CAD-associated miRNAs in the TGF-beta pathway. These findings may pave the way for developing early prediction miRNAs biomarkers for CAD, and possibly developing therapeutic tools in the field of kidney transplantation. Full article

The purpose of this study was to evaluate the feasibility of the combination of point-shear wave elastography (p-SWE) and estimated glomerular filtration rate (eGFR) for assessing different stages of interstitial fibrosis and tubular atrophy (IF/TA) in patients with chronic renal allograft dysfunction (CAD). From September 2020 to August 2021, 47 patients who underwent renal biopsy and p-SWE examinations were consecutively enrolled in this study. The areas under the receiver operating characteristic curves (AUCs) were calculated to evaluate overall accuracy and to identify the optimal cutoff values for different IF/TA stages. A total of 43 patients were enrolled in this study. The renal cortical stiffness and eGFR showed a significant difference between IF/TA Grade 0–1 and Grade 2–3 (p < 0.001). Additionally, renal stiffness and eGFR were independent predictors for moderate-to-severe IF/TA (Grade ≥ 2) according to multiple logistic regression analysis. The combination of p-SWE and eGFR, with an optimal cutoff value of −1.63, was superior to eGFR alone in assessing moderate-to-severe interstitial fibrosis (AUC, 0.86 vs. 0.72, p = 0.02) or tubular atrophy (AUC, 0.88 vs. 0.74, p = 0.02). There was no difference between p-SWE and eGFR in assessing moderate-to-severe IF/TA (AUC, 0.85 vs. 0.79, p = 0.61). Therefore, combining p-SWE and eGFR is worthy of clinical popularization and application. Full article

New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management. Full article

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. Full article