chronic allograft renal dysfunction

Antibody-mediated rejection (ABMR) is a major cause of late renal allograft dysfunction and graft loss. Risks and benefits of treatment of late ABMR have not been evaluated in randomized clinical trials. We report on a 35-year-old patient with deterioration in renal function and progressive proteinuria 15 years after transplantation. Recurrent infections after a splenectomy following traumatic splenic rupture 3 years earlier had led to reduction of immunosuppression. Renal transplant biopsy showed glomerular double contours, 40% fibrosis/tubular atrophy, peritubular capillaritis, and positive C4d staining indicating chronic-active ABMR...

BACKGROUND Correction of hypovitaminosis D is simple, but it is unclear whether it is associated with an accelerated decline of renal allograft function in pediatric renal transplantation patients. This retrospective single center cohort study aimed at analyzing the effect of vitamin D and covariates on the slope of 1/creatinine after the first year. MATERIAL AND METHODS After ethics committee approval, 37 (14 male) pediatric renal transplant recipients on mycophenolate mofetil, who were followed between 2006 and 2014, were included in this study...

BACKGROUND: The progression from acute to chronic antibody-mediated rejection in kidney transplant recipients is usually not prevented by current therapeutic options. Here, we investigated whether the use of tofacinitib, a Janus kinase 3 inhibitor, was capable of preventing the progression of allograft dysfunction in a Fisher-to-Lewis rat model of kidney transplantation. METHODS: Rats were treated from the third week after transplantation in order to allow the development of rejection...

Chronic renal allograft dysfunction (CRAD) is the primary factor affecting the long-term survival of patients who have undergone renal transplantation. Oxidative stress and inflammation serve an important role in the pathological damage caused by CRAD in the early post-transplantation phase. Previous studies have demonstrated that sirtuin 3 (sirt3) protects cells from oxidative stress and inflammation. A model of renal orthotopic transplantation was established in the current study and kidney samples were harvested from the rats 12 weeks following surgery...

Renal rejection clinically represents a major cause of graft dysfunction and sadly the loss of the renal transplant. This is despite the considerable progress in immunosuppressive therapy. It is strongly believed that the complex immunologic network underlying the response against major histocompatibility molecules (MHC) is responsible for rejection, an unresolved issue that is, in part, not inhibited by the current prophylactic and therapeutic strategies. Extracorporeal photopheresis (ECP) is an effective cell therapy approach that was successfully used in immunomodulating heart rejection, acute and chronic GvHD, lung rejection and some selected autoimmune diseases...

BACKGROUND/AIMS: Chronic renal allograft dysfunction (CRAD) is a leading cause of long-term renal allograft loss. Oxidative stress may account for the nonspecific interstitial fibrosis and tubular atrophy that occur in CRAD. An antioxidant intervention via Nrf2 signaling pathway activation might be a promising therapy for some kidney diseases. The present paper investigates whether there is an association between oxidative stress alleviation via sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation and CRAD improvement...

OBJECTIVE: To investigate the expression and significance of Sirt1 in renal allografts at the early stage of chronic renal allograft dysfunction (CRAD). METHODS: CRAD rat models were established using classical orthotopic F344-Lewis kidney transplantation. F344 and Lewis uninephrectomized rats were used as controls. Twelve weeks after the operation, the rats were sacrificed for renal function, histological, immunohistochemistry and molecular biological analyses...

Background: Since introduction of the MELD score in the liver allograft allocation system, renal insufficiency has emerged as an increasing problem. Here we evaluated the course of kidney function in patients with advanced renal insufficiency prior to liver transplantation (LT). Methods: A total of 254 patients undergoing LT at the University Medical Centre Hamburg-Eppendorf (2011-2015) were screened for renal impairment (GFR < 30 ml/min) prior to LT in this observational study...

Ischemia-reperfusion injury (IRI) during renal transplantation often initiates non-specific inflammatory responses that can result in the loss of kidney graft viability. However, the long-term consequence of IRI on renal grafts survival is uncertain. Here we review clinical evidence and laboratory studies, and elucidate the association between early IRI and later graft loss. Our critical analysis of previous publications indicates that early IRI does contribute to later graft loss through reduction of renal functional mass, graft vascular injury, and chronic hypoxia, as well as subsequent fibrosis...

Although Tacrolimus is an immunosuppressive drug widely used in renal transplantation, its chronic use paradoxically induces nephrotoxic effects, in particular renal fibrosis, which is responsible for chronic allograft dysfunction and represents a major prognostic factor of allograft survival. As molecular pathways and mechanisms involved in Tacrolimus-induced fibrogenic response are poorly elucidated, we assessed whether miRNAs are involved in the nephrotoxic effects mediated by Tacrolimus. Treatment of CD-1 mice with Tacrolimus (1 mg/kg/d for 28 days) resulted in kidney injury and was associated with alteration of a gene expression signature associated with cellular stress, fibrosis and inflammation...

Renal allograft loss is most often a chronic process, irrespective of the mechanism at stake. In this prospective study, we studied the expression of epithelial to mesenchymal transition (EMT) markers vimentin and β-catenin by immunohistochemistry in the surveillance biopsy and measured the mRNA encoding vimentin (VIM), CD45, GAPDH and uroplakin 1a (UPK) by quantitative PCR in urinary cells in 75 renal transplant patients. The aim is to establish a simple screening test for chronic renal allograft dysfunction...

Background Monitoring of renal allograft function is essential for early identification of dysfunction and improvement of kidney transplant (KTX) outcome. Purpose To non-invasively assess renal stiffness in KTX recipients using ultrasound shear wave elastography (USE) in correlation with multifrequency magnetic resonance elastography (MRE), renal allograft function, and renal microvascular flow determined using a novel ultrasound microvascular imaging technique. Material and Methods This prospective study investigated 25 KTXs (functional KTX [FCT], n = 14; chronic KTX insufficiency [DYS], n = 11) in 20 KTX recipients (mean age = 43 ± 14 years)...

Over a period of two years thirty five renal allograft recipients & donors were evaluated to find out the aetiology of early renal allograft dysfunction, in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from March 2010 to February 2012. A comparison was made between dysfunction & functioning graft group. Mean age of recipients were (36.4±9.4) years, mean age of donors were (41.7±8.3) years, with a male and female ratio of 3:1. Fifty percent recipients showed one heliotype match, ninety percent recipients were anti CMV antibody IgG positive, few were anti CMV antibody IgM positive...

BACKGROUND: With increasing graft survival, post-transplant immunoglobulin A nephropathy (IgAN) has emerged as an important cause of chronic graft dysfunction in renal allograft recipients. We studied the clinico-pathological features of post-transplant IgAN regardless of the primary disease. The aim was to study the usefulness of the Oxford classification in predicting survival. METHODS: Indication graft biopsy specimens (n = 915) were received during a 10-year period; 27 biopsy specimens from 22 patients were diagnosed as IgAN...

INTRODUCTION: Renal allograft biopsy is the gold standard for the detection of histological lesions of chronic allograft dysfunction. The identification of a noninvasive routine test would be desirable. Elastosonography is used to assess tissue stiffness according to viscosity, and no data are available on the use of point quantification shear-wave elastography (ElastPQ) for the evaluation of renal chronic lesions. RESEARCH QUESTION: To evaluate the feasibility of ElastPQ to assess cortical allograft stiffness and to determine the correlation of clinical, biological, and pathological factors with the diagnostic accuracy of kidney stiffness values in patients with histological lesions...

BACKGROUND: Chronic allograft dysfunction (CAD) is characterized by allograft kidney interstitial fibrosis, the underlying mechanism of which is unclear. Our aim was to elucidate the role and mechanism of TNF-α-induced epithelial-to-mesenchymal transition (EMT) in transplant kidney tubular interstitial fibrosis. METHODS: Human kidney tissues from normal volunteers and CAD patients were assessed using periodic acid-Schiff, Masson trichrome and immunohistochemical staining...

Despite potent immunosuppression, clinical and biopsy confirmed acute renal allograft rejection (AR) still occurs in 10-15% of recipients, ~30% of patients demonstrate subclinical rejection on biopsy, and ~50% of them can show molecular inflammation, all which increase the risk of chronic dysfunction and worsened allograft outcomes. Mitochondria represent intracellular endogenous triggers of inflammation, which can regulate immune cell differentiation, and expansion and cause antigen-independent graft injury, potentially enhancing the development of acute rejection...

Cardiac transplantation remains the gold standard in the treatment of advanced heart failure. With advances in immunosuppression, long-term outcomes continue to improve despite older and higher risk recipients. The median survival of the adult after heart transplantation is currently 10.7 years. While early graft failure and multiorgan system dysfunction are the most important causes of early mortality, malignancy, rejection, infection, and cardiac allograft vasculopathy contribute to late mortality. Chronic renal dysfunction is common after heart transplantation and occurs in up to 68% of patients by year 10, with 6...

OBJECTIVE: Early allograft dysfunction may be caused by several technical factors including vascular complications such as thrombosis, kinking, or extrinsic compression. Renal allograft compartment syndrome (RACS) is an unrecognized cause of early allograft dysfunction. This complication is characterized by increased pressure of the iliac fossa that reduces the blood supply to the graft with a potentially devastating consequence. The main objective when recognizing this condition is to create a tension-free muscle closure...

Renal transplantation is the best treatment of choice for patient with chronic renal insufficiency because it provides better quality of life and longer survival. Survival rates for grafts and patients have improved over the recent decades because of significant evolution of surgical techniques and immunosuppressive treatment. However, renal transplantation is still associated with several complications, which may result in poor outcome. Cause of allograft dysfunction, which occurs in the early or late post-transplantation period, should be recognized immediately, so that it can be managed correctly...