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Transplant glomerulopathy

Sandesh Parajuli, Didier A Mandelbrot, Brenda Muth, Maha Mohamed, Neetika Garg, Fahad Aziz, Robert R Redfield, Weixiong Zhong, Brad C Astor, Arjang Djamali
Background: There is limited information on treatment strategies and monitoring strategies for late antibody-mediated rejection (ABMR) after kidney transplantation. Methods: In this observational and nonrandomized study, we compared 78 patients diagnosed with late ABMR (>3 months after transplant) who were treated with standard of care steroids/IVIG (n = 38) ± rituximab (n = 40) at our center between March 1, 2013 and December 31, 2016. All patients had follow-up biopsy and donor-specific antibodies (DSA) monitoring within 3 to 12 weeks...
December 2017: Transplantation Direct
P S Malhotra, T Jorna, S Bhandari
Immunoglobulin A nephropathy (IgAN) is the most commonly occurring glomerulonephritis. Recurrence of disease in the transplanted kidney can significantly reduce allograft survival rates. Currently, there is no definitive management plan for IgAN recurrence in a transplant that reduces the rate of decline of allograft function and prolongs time to dialysis or re-transplantation. Herein we present a 48-year-old man who had received a renal transplantation in 2006 following his diagnosis of IgAN. In 2015, the patient was noted to have an elevated blood pressure and proteinuria (urinary protein:creatinine ratio [uPCR] 170 mg/mmol)...
January 2018: Transplantation Proceedings
Essa Hariri, Anthony Mansour, Andrew El Alam, Yazan Daaboul, Serge Korjian, Sola Aoun Bahous
Sickle cell nephropathy is a major complication of sickle cell disease. It manifests in different forms, including glomerulopathy, proteinuria, hematuria, and tubular defects, and frequently results in end-stage renal disease (ESRD). Different pathophysiologic mechanisms have been proposed to explain the development of nephropathy in SCD, where hemolysis and vascular occlusion are the main contributors in the manifestations of this disease. Markers of renal injury, such as proteinuria and tubular dysfunction, have been associated with outcomes among patients with sickle cell nephropathy and provide means for early detection of nephropathy and screening prior to progression to renal failure...
January 30, 2018: International Urology and Nephrology
Michael Kaabak, Nadeen Babenko, Ron Shapiro, Allan Zokoyev, Olga Dymova, Edward Kim
Ischemia-reperfusion injury has multiple effects on a transplanted allograft, including delayed or impaired graft function, compromised long-term survival, and an association with an increased incidence of rejection. Eculizumab, a monoclonal antibody blocking terminal complement activation, has been postulated to be an effective agent in the prevention or amelioration of IRI. We performed a single-center prospective, randomized controlled trial involving 57 pediatric kidney transplant recipients between 2012 and 2016...
January 29, 2018: Pediatric Transplantation
Neetika Garg, Yuzhou Zhang, Anne Nicholson-Weller, Eliyahu V Khankin, Nicolò Ghiringhelli Borsa, Nicole C Meyer, Susan McDermott, Isaac E Stillman, Helmut G Rennke, Richard J Smith, Martha Pavlakis
Background: C3 glomerulonephritis (C3GN) is caused by alternate complement pathway over-activation. It frequently progresses to end-stage renal disease, recurs in two-thirds of transplants and in half of these cases progresses to allograft loss. There is currently no proven treatment for C3GN. Case Presentation: We describe a family segregating pathogenic alleles of complement factor H and I (CFH and CFI). The only member carrying both mutations developed C3GN. Prolonged delayed graft function after deceased donor transplantation, heavy proteinuria and isolated C3 hypocomplementemia prompted an allograft biopsy confirming diagnosis of recurrent C3GN...
January 23, 2018: Nephrology, Dialysis, Transplantation
Omer Shahab, Pegah Golabi, Zobair M Younossi
Hepatitis C virus (HCV) infection affects many organs in the body, including the liver, kidneys, skin, joints and others. Although the hepatic manifestation of HCV has been widely studied, the extrahepatic manifestaions of HCV have not been fully appreciated. Studies have shown that patients with HCV have a higher risk of chronic kidney disease and end-stage renal disease, as well as poorer outcomes after kidney transplantation. Given these findings, it is important to screen HCV patients for presence of renal impairement in a timely manner...
January 10, 2018: Minerva Gastroenterologica e Dietologica
Harald Seeger, Maja T Lindenmeyer, Clemens D Cohen, Carsten Jaeckel, Peter J Nelson, Jin Chen, Ilka Edenhofer, Nicolas Kozakowski, Heinz Regele, Georg Boehmig, Simone Brandt, Rudolf P Wuethrich, Mathias Heikenwalder, Thomas Fehr, Stephan Segerer
The kidney is the most frequently transplanted solid organ. Recruitment of inflammatory cells, ranging from diffuse to nodular accumulations with defined microarchitecture, is a hallmark of acute and chronic renal allograft injury. Lymphotoxins (LTs) mediate the communication of lymphocytes and stromal cells and play a pivotal role in chronic inflammation and formation of lymphoid tissue. The aim of this study was to assess the expression of members of the LT system in acute rejection (AR) and chronic renal allograft injury such as transplant glomerulopathy (TG) and interstitial fibrosis/tubular atrophy (IFTA)...
2018: PloS One
Mark Haas
PURPOSE OF REVIEW: To review changes in the Banff schema for antibody-mediated renal allograft rejection over the past decade, including key revisions agreed upon during and immediately subsequent to the 2017 Banff Conference on Allograft Pathology. RECENT FINDINGS: The original Banff schema for diagnosis of acute and chronic active antibody-mediated rejection (ABMR) in renal allografts was formulated at the 2001 and 2007 Banff Conferences, and required histologic (primarily microvascular inflammation and transplant glomerulopathy), immunohistologic (C4d in peritubular capillaries), and serologic [circulating donor-specific antibodies (DSA)] evidence for a definitive diagnosis of ABMR...
January 2, 2018: Current Opinion in Nephrology and Hypertension
Bogdan Obrişcă, Adriana Roxana JurubiŢă, Andreea Gabriella Andronesi, Mihaela Gherghiceanu, Gener Ismail, George Mitroi, Mihai Cristian Hârza
Nephrotic syndrome (NS) is a rare complication of hematopoietic cell transplantation (HCT) and is thought to represent a renal manifestation of chronic graft-versus-host disease (cGVHD). Glomerulopathies occur less often in recipients of autologous as compared to allogeneic HCT and, in this setting, renal pathology is less well characterized. This case report describes a 54-year-old man admitted for the evaluation of a nephrotic-range proteinuria. His past medical history included a ? light-chain secreting multiple myeloma (MM) for which he underwent autologous HCT...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
Nicola Lepori, Wisit Cheungpasitporn, Sanjeev Sethi, David Murray, Shaji Kumar, Nelson Leung, Karthik V Giridhar, Fernando C Fervenza
There is currently no standard treatment for monoclonal immunoglobulin (MIg)-associated C3 glomerulopathy, and treatment is often dictated by the extent of the monoclonal gammopathy. Although chemotherapy treatment for MIg-associated C3 glomerulopathy may stabilize renal function, the overall renal prognosis of MIg-associated C3 glomerulopathy is still poor with frequent progression to end-stage renal disease. We present a case of a 55-year-old man with IgG-κ gammopathy-associated C3 glomerulonephritis (C3GN) with bone marrow biopsy demonstrating 5 - 10 κ-restricted plasma cells...
December 18, 2017: Clinical Nephrology
Vasishta S Tatapudi, Robert A Montgomery
Purpose of Review: Over the past two decades, significant strides made in our understanding of the etiology of antibody-mediated rejection (AMR) in transplantation have put the complement system in the spotlight. Here, we review recent progress made in the field of pharmacologic complement inhibition in clinical transplantation and aim to understand the impact of this therapeutic approach on outcomes in transplant recipients. Recent Findings: Encouraged by the success of agents targeting the complement cascade in disorders of unrestrained complement activation like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), investigators are testing the safety and efficacy of pharmacologic complement blockade in mitigating allograft injury in conditions ranging from AMR to recurrent post-transplant aHUS, C3 glomerulopathies and antiphospholipid anti-body syndrome (APS)...
2017: Current Transplantation Reports
Prateek Sanghera, Mythili Ghanta, Fatih Ozay, Venkatesh K Ariyamuthu, Bekir Tanriover
Atypical hemolytic uremic syndrome and C3 glomerulopathy (dense deposit disease and C3 glomerulonephritis) are characterized as inappropriate activation of the alternative complement pathway. Genetic mutations affecting the alternative complement pathway regulating proteins (complement factor H, I, membrane cofactor protein and complement factor H-related proteins) and triggers (such as infection, surgery, pregnancy and autoimmune disease flares) result in the clinical manifestation of these diseases. A decade ago, prognosis of these disease states was quite poor, with most patients developing end-stage renal disease...
December 2017: American Journal of the Medical Sciences
Brian J Nankivell, Meena Shingde, Karen L Keung, Caroline L-S Fung, Richard J Borrows, Philip J O'Connell, Jeremy R Chapman
Inflammation within areas of interstitial fibrosis and tubular atrophy (i-IFTA) is associated with adverse outcomes in kidney transplantation. We evaluated i-IFTA in 429 indication- and 2052 protocol-driven biopsy samples from a longitudinal cohort of 362 kidney-pancreas recipients to determine its prevalence, time course, and relationships with T cell-mediated rejection (TCMR), immunosuppression, and outcome. Sequential histology demonstrated that i-IFTA was preceded by cellular interstitial inflammation and followed by IF/TA...
February 2018: American Journal of Transplantation
A L Croci Chiocchini, C Sportoletti, G Comai, S Brocchi, I Capelli, O Baraldi, P Bruno, F Conti, C Serra, M Meola, M Zompatori, G La Manna
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...
December 2017: Progress in Transplantation
Elodie Bailly, Dany Anglicheau, Gilles Blancho, Philippe Gatault, Vincent Vuiblet, Valérie Chatelet, Emmanuel Morelon, Paolo Malvezzi, Anne Parissiadis, Jérôme Tourret, Gwendaline Guidicelli, Johnny Sayegh, Christiane Mousson, Philippe Grimbert, Isabelle Top, Moglie Le Quintrec, Raj Purgus, Pierre François Westeel, Barbara Proust, Valérie Chabot, Yvon Lebranchu, Frédéric Dehaut, Matthias Büchler
BACKGROUND: The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs help better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown. METHODS: We included patients from the French multicenter RITUX ERAH study diagnosed with acute antibody-mediated rejection (ABMR) within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange)...
November 13, 2017: Transplantation
Macaulay Amechi Onuigbo, Nneoma Agbasi
INTRODUCTION: We first described the syndrome of rapid onset end stage renal disease (SORO-ESRD), acute yet irreversible renal failure, in 2010. OBJECTIVE: The impact of SORO-ESRD renal allograft survival remains speculative and we plan to study this question. METHODS: A retrospective analysis of individual adult patient-level serum creatinine trajectories of ESRD patients on maintenance hemodialysis for >90 days at Mayo Clinic, Rochester, 2001-2013...
October 2017: Hemodialysis International
Anja K Büscher, Nora Celebi, Peter F Hoyer, Hanns-Georg Klein, Stefanie Weber, Julia Hoefele
BACKGROUND: In 2010, INF2 mutations were associated with autosomal-dominant focal segmental glomerulosclerosis (FSGS), clinically presenting with moderate proteinuria in adolescence. However, in the meantime, cases with more severe clinical courses have been described, including progression to end-stage renal disease (ESRD) during childhood. INF2 mutations in patients with isolated FSGS are clustered in exons 2 to 4, encoding the diaphanous inhibitory domain, involved in the regulation of the podocyte actin cytoskeleton...
October 6, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Edward J Filippone, Peter A McCue, John L Farber
In the renal allograft, transplant glomerulopathy represents a morphologic lesion and not a specific diagnosis. The hallmark pathologic feature is glomerular basement membrane reduplication by light microscopy or electron microscopy in the absence of immune complex deposits. Transplant glomerulopathy results from chronic, recurring endothelial cell injury that can be mediated by HLA alloantibodies (donor-specific antibodies), various autoantibodies, cell-mediated immune injury, thrombotic microangiopathy, or chronic hepatitis C...
February 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Irene Capizzi, Luigi Teta, Federica Neve Vigotti, Giuliana Tognarelli, Valentina Consiglio, Stefania Scognamiglio, Giorgina Barbara Piccoli
In advanced chronic kidney disease, obesity may bring a survival advantage, but many transplant centres demand weight loss before wait-listing for kidney graft. The case here described regards a 71-year-old man, with obesity-related glomerulopathy; referral data were: weight 110 kg, Body Mass Index (BMI) 37 kg/m², serum creatinine (sCr) 5 mg/dL, estimated glomerular filtration rate (eGFR) 23 mL/min, blood urea nitrogen (BUN) 75 mg/dL, proteinuria 2.3 g/day. A moderately restricted, low-protein diet allowed reduction in BUN (45-55 mg/dL) and good metabolic and kidney function stability, with a weight increase of 6 kg...
October 11, 2017: Nutrients
Sabiha M Hussain, Kalathil K Sureshkumar
BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a newly described and rare entity that can develop in native and very rarely in transplanted kidneys. We present a patient who developed de novo PGNMID in the kidney allograft along with a review of the literature. CASE PRESENTATION: A 38-year old female with type 1 diabetes who underwent successful simultaneous pancreas-kidney (SPK) transplantation 6 years earlier presented with rising serum creatinine, nephrotic range proteinuria and microhematuria...
July 2017: Journal of Nephropathology
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