Progress on electron microscopy diagnosis on Banff classification for renal allograft pathology / 器官移植

With the development of organ transplantation in clinical practice, allograft pathology has been constantly developing and advancing. The convening of Banff conference on allograft pathology and the establishment of Banff classification on allograft pathology (Banff classification) are pivotal milestones in the development of international allograft pathology. Since then, Banff classification on pathological diagnosis of various transplant organs have been continually updated and improved. Ultrastructural pathological observation by electron microscope plays an irreplaceable role in the early diagnosis of antibody-mediated rejection, recurrent disease and de novo disease of renal allograft. Early detection and rational treatment help to maintain the long-term survival of renal allograft and reduce the failure of renal allograft. In this article, the basic definition of electron microscope and the ultrastructural pathological diagnosis, the research history and main progress on electron microscope diagnosis on Banff classification for renal allograft pathology were introduced, and typical pathological changes, specific terminology and diagnostic criteria of electron microscope diagnosis on renal allograft biopsy were summarized, aiming to provide reference for clinical and basic research of organ transplantation.

Clinical and pathological analysis of rejection cases after kidney transplantation / Шинэ санаа Шинэ нээлт

Kidney transplantation is the best alternative treatment for end-stage renal disease and health-related quality of life and survival of the patients are improved compared with dialysis. Worldwide, more than 1.4 million patients with CKD receive renal replacement therapy with incidence growing by approximately 8% annually.1 Unfortunately, despite significant improvement in graft function, kidney transplants can still fail due to acute rejection and chronic allograft nephropathy.2 Kidney biopsy after transplantation, which has evaluated by Banff 09 classification is usefull method for diagnose of transplanted kidney disease.3,4Kidney graft rejection was diagnosed in 10 renal allograft biopsy specimens (bs) obtained from transplant patients followed up at our institute between 2015 and 2016. All specimens were evaluated as satisfactory which show more than 8 glomerulus under the light microscopy. Each renal cortical tissue was divided into two tips: one piece for routine H&E stain and special stains, including Masson’s trichrome, and PAS stain; another piece for immunofluorescence by frozen section, which were stained with IgA, IgM, IgG and complement component (C3, C4, C1q, C4d). All the renal biopsies were examined by the same pathologist.Out of 117 transplantations, 10 episodes of rejection selected. Among the 10 patients, 30% had an acute T cell rejection and 70% had a chronic allograft nephropathy. Interstitial inflammation (i1-7) was present in 7 bs (70%), tubulitis (t1-4,t2-2) in 6 bs (60%), transplant glomerulitis (g1-1, g2-2, g3-1) in 4 bs (40%), transplant interstitial fibrosis (ci1-2, ci2-2, ci3-2) in 6 bs (60%), tubular atrophy (ct1-6, ct2-2, ct3-1) in 9 bs (90%), mesangial matrix increase (mm1-5) in 5 bs (50%), vascular fibrosis intimal thickeness (cv1-3) in 3 bs (30%), arteriolar hyaline thickening (ah1-5) in 5 bs (50%), tubulitis (ti1-6, ti2-3, ti3-1) in 10 bs (100%) and peritubular capillaritis (ptc1-1, ptc2-2, ptc3-1) in 4 bs (40%). C4d deposition was present very mild in wall of the vessels and peritubular capillaries. Because of not good working Methenamin silver stain, we couldn’t demostrate glomerular basement membrane changes (cg) fully.We suggest that histopathological changes of transplant glomerulopathy might be accompanied by inflammation of the microvasculature, such as transplant glomerulitis and peritubular capillaritis. C4d deposition in the wall of the vessels and peritubular capillaritis is not always present in biopsy specimens of transplant glomerulopathy.

Glomerular damage as a predictor of renal allograft loss

Interstitial fibrosis and tubular atrophy (IF/TA) are the most common cause of renal graft failure. Chronic transplant glomerulopathy (CTG) is present in approximately 1.5-3.0 percent of all renal grafts. We retrospectively studied the contribution of CTG and recurrent post-transplant glomerulopathies (RGN) to graft loss. We analyzed 123 patients with chronic renal allograft dysfunction and divided them into three groups: CTG (N = 37), RGN (N = 21), and IF/TA (N = 65). Demographic data were analyzed and the variables related to graft function identified by statistical methods. CTG had a significantly lower allograft survival than IF/TA. In a multivariate analysis, protective factors for allograft outcomes were: use of angiotensin-converting enzyme inhibitor (ACEI; hazard ratio (HR) = 0.12, P = 0.001), mycophenolate mofetil (MMF; HR = 0.17, P = 0.026), hepatitis C virus (HR = 7.29, P = 0.003), delayed graft function (HR = 5.32, P = 0.016), serum creatinine ≥1.5 mg/dL at the 1st year post-transplant (HR = 0.20, P = 0.011), and proteinuria ≥0.5 g/24 h at the 1st year post-transplant (HR = 0.14, P = 0.004). The presence of glomerular damage is a risk factor for allograft loss (HR = 4.55, P = 0.015). The presence of some degree of chronic glomerular damage in addition to the diagnosis of IF/TA was the most important risk factor associated with allograft loss since it could indicate chronic active antibody-mediated rejection. ACEI and MMF were associated with better outcomes, indicating that they might improve graft survival.

Glomerulopatias após o transplante renal: uma primeira abordagem / Post transplant glomerulopathies: an initial approach

Introdução: As glomerulopatias são uma importante causa de insuficiência renal crônica terminal em grande parte dos pacientes que irão receber umtransplante renal. Já a glomerulopatia após o transplante renal é incomum e dados clínico-epidemiológicos sobre esta condição são escassos. Pacientese Métodos: Foi realizado levantamento retrospectivo de todas as biópsias renais oriundas do Departamento de Patologia da Escola Paulista de Medicinae do Serviço de Patologia do Hospital do Rim e Hipertensão, de agosto de 1998 até dezembro de 2002, num total de 1.015 laudos revisados de biópsiasdo enxerto renal. Resultados: Vinte e seis biópsias (2,5%) preenchiam critérios histológicos para glomerulopatia. Apenas 17 pacientes fizeram acompanhamento no Centro e foram submetidos à análise no presente estudo. Sete pacientes tiveram diagnóstico de glomerulosclerose segmentar e focal(41,1%); 3, de nefropatia membranosa (17,6%); 3, de glomerulonefrite (GN) membranoproliferativa (17,6%); 2, de nefropatia por IgA (11,7%); 1, de GNproliferativa difusa (5,8%) e 1 de GN por anticorpo anti-membrana basal glomerular. As primeiras alterações urinárias foram em sua maioria nos primeiros6 meses de transplante (4 no 1º mês, 9 nos 4 primeiros meses e 4 após 1 ano de transplante). Em 10 pacientes, as biópsias renais foram realizadas nosprimeiros 6 meses após aparecimento das alterações urinárias, 3 deles no 1º mês. O uso de drogas inibidoras da enzima conversora de angiotensinaisoladamente foi o tratamento mais utilizado. Quatorze pacientes (82,3%) não apresentaram melhora das alterações urinárias e da creatinina sérica duranteo seguimento. Apenas três pacientes (17,6%) obtiveram resposta terapêutica. Oito pacientes (47%) apresentaram perda dos seus respectivos aloenxertos.O menor tempo de perda do enxerto correspondeu a 3 meses de transplante e o maior, a 40 meses. Conclusões: Continua-se falhando na detecção precoce...

Introduction: Glomerulopathies are an important cause of end-stage renal disease in an expressive number of patients that will receive a renal allograft. However, post transplant glomerulopathy is uncommon and clinical and epidemiological information about this condition is scarce. Methodos: A retrospective study of all renal biopsies from the Pathology Service of Escola Paulista de Medicina (UNIFESP, Sao Paulo, Brazil) since August 1998 toDecember 2002 was performed totalizing 1.015 revised biopsy results of renal grafts. Results: Twenty-six out of all renal biopsies (2.5%) corresponded to glomerulopathies based on histological data. Only 17 patients were followed in our center and their data were analyzed in this study. Seven had focal segmental glomerulosclerosis (41.1%); 3, membranous nephropathy (17.6%); 3, membranoproliferative GN (17.6%); 2, IgA nephropathy (11.7%); 1, diffuse proliferative GN (5.8%) and 1, anti glomerular basement membrane GN. The onset of urinary changes were observed mostly in the initial 6 months (mo) post transplant (4 in the 1st mo, 9 in the 1st 4 mo and 4 after the 1st year). Renal biopsies were performed in the first 6 mo after the detection of urinary changes in 10 cases, 3 of them in the 1st month. Angiotensin converting enzyme inhibitor was the most utilized treatment. Fourteen patients (82.3%) showed no recovery of urinary or serum creatinine changes during the follow-up. Only three (17.6%) responded to therapy. Eight patients (47%) lost their allografts. The time elapsed from the transplant until the loss of the allograft ranged from 3 to 40 months...

A Case of Transplant Glomerulopathy Complicated by Crescent Formation / 대한이식학회지

Transplant glomerulopathy (TGP) is specified as thickening of capillary wall of glomerulus and clinically presented with proteinuria and progressive graft dysfunction. In contrast, crescent formation represents an extracapillary proliferative glomerular change and is clinically presented with rapidly progressive renal failure. Previously, in transplant kidneys, crescent formation was reported only in anti-GBM disease and ANCA- associated vasculitis. Here we report a case with a very unusual combination of transplant glomerulopathy and crescent formation. Ten years after the renal transplantation the patient was admitted due to proteinuria and progressive azotemia. Although his underlying renal disease was IgA nephropathy, the transplant kidney biopsy revealed typical findings of transplant glomerulopathy without specific immune deposits, but with extensive cellular crescents. Methylprednisolone pulse therapy was not successful, and he was switched to maintenance hemodialysis.

Relationship of Proteinuria and Graft Survival According to the Degree of Transplant Glomerulopathy / 대한이식학회지

Transplant glomerulopathy (TG) is a special form of glomerular injury in renal allografts. It affects varying proportions of glomeruli, which may have an influence on the amount of proteinuria or graft survival. We reviewed 32 cases of TG to evaluate histologic changes and graft outcome. The severity of TG as well as acute and chronic changes of the glomerular, tubulointerstitial and vascular compartment were scored according to Banff classification. There were 17 cases of cg1, 3 cases of cg2 and 12 cases of cg3. There was no significant difference in age, duration of transplant at time of biopsy and duration of follow-up between groups. Serum creatinine level and the degree of proteinuria were higher in cg3 and statistically significant. However, there was no difference in the degree of glomerulosclerosis, interstitial inflammation, fibrosis, tubular atrophy or vascular wall thickening between groups. Graft failure was present in 13 cases, mostly due to chronic rejection including sepsis and CMV infection in one case each. Five-year graft survival was 84.1% and was not significantly different from cases without TG. In conclusion, the severity of TG indicates profuse proteinuria, but does not affect graft outcome, which indicates tubulointerstitial and vascular pathology as being a more important prognosticator.