Transplant glomerulopathy

Filippone, Edward J.; McCue, Peter A.; Farber, John L.

doi:10.1038/modpathol.2017.123

Cited by 40 publications

(63 citation statements)

References 152 publications

(171 reference statements)

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“…The result of the present study underscored that severe baseline interstitial chronic changes (ci + ct) and cg at biopsy were predictors of unfavorable allograft prognosis in TG patients even after taking into consideration clinical characteristics. TG is not a specific diagnosis but rather a pattern of endothelial injury with at least 3 well-documented overlapping etiologies that included AMR, thrombotic microangiopathy, and chronic HCV infection-associated glomerular lesions [6,13,14]. In line with previous reports [13], the current study also demonstrated the striking prevalence of HCV infection in recipients with TG (21.1%), which was significantly higher than the prevalence seen in the non-TG patients (7.0%) [15].…”

Section: Discussionsupporting

confidence: 71%

“…It has been demonstrated that impaired allograft function (decreased estimated glomerular filtration rate [eGFR]) and increased proteinuria at the time of allograft biopsy served as clinically important predictors of adverse outcomes [5,6]. Nevertheless, studies focusing on histologic features' impact on TG survival are scarce and it remains unknown whether histologic alterations observed in TG provide additional prognostic value in addition to clinical parameters.…”

Section: Introductionmentioning

confidence: 99%

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Histopathologic Features that Predict Transplant Glomerulopathy Progression in a Chinese Cohort

Chen

Dai

et al. 2019

Am J Nephrol

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Background: Transplant glomerulopathy (TG) represents a major cause of long-term allograft failure and is the leading cause of overall post-transplant proteinuria. The extent to which histopathologic features predicts prognostication is uncertain. Methods: A single-center retrospective cohort with biopsy-proven TG was investigated. Renal biopsies were scored according to Banff 2017. The primary outcome was death-censored graft failure defined as return to dialysis or estimated glomerular filtration rate (eGFR) decreased to <15 mL/min/1.73 m². The prognostic significance of clinical and histopathologic parameters was determined using Cox proportional hazards models. Results: Data from 180 cases were available for analysis with a median follow-up of 5.0 (2.6–8.2) years. In multivariable models, ci + ct score (HR 3.1; 95% CI 2.0–4.9), cg score (HR 1.7; 95% CI 1.1–2.8), eGFR (HR 2.1; 95% CI 1.4–3.2) and proteinuria (HR 2.4; 95% CI 1.6–3.7) were independent predictors of the primary outcome. Mesangial Immunoglobulin A deposition did not significantly affect allograft survival. The only significant pathologic factors for the severity of proteinuria were cg and g + ptc (adjusted R² = 0.46) as determined by multivariable stepwise linear regression analysis. Conclusions: Severe ci + ct and cg at biopsy were predictors of unfavorable allograft prognosis in TG patients even after taking into consideration clinical characteristics. Histologic severity of cg and g + ptc was significantly associated with clinical proteinuria.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Histopathologic Features that Predict Transplant Glomerulopathy Progression in a Chinese Cohort

Chen

Dai

et al. 2019

Am J Nephrol

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“…The presence of glomerular capillary remodeling alone is not pathognomonic in TG. Duplication of GBMs is also observed in recurrent membranoproliferative glomerulonephritis, hepatitis C virus infection, and thrombotic microangiopathy in renal allografts (4,9). cells of glomerular capillaries and PTCs are important as pathological changes of early-stage ABMR (3,6,21).…”

Section: Abmr Group -Other Ultrastructural Changesmentioning

confidence: 99%

Low-vacuum scanning electron microscopy may allow early diagnosis of human renal transplant antibody-mediated rejection

et al. 2020

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Antibody-mediated rejection (ABMR) is an important cause of both short-and long-term injury to renal allografts. Transplant glomerulopathy (TG) is strongly associated with ABMR and reduced graft survival. Ultrastructural changes in early-stage ABMR include TG as a duplication of the glomerular basement membrane (GBM), which can be observed only by transmission electron microscopy (TEM). Low-vacuum scanning electron microscopy (LVSEM) is a new technique that allows comparatively inexpensive, rapid, and convenient observations with high magnification. We analyzed human renal transplants using LVSEM and evaluated the ultrastructural changes representing TG in ABMR. GBM duplication was more clearly visible in the LVSEM images than in the light microscopy (LM) images. In the ABMR group, the cg score of the Banff classification was higher in 54% (7/13) of specimens for LVSEM images than for LM images. And 4 specimens exhibited duplication of the GBM analyzed by LVSEM, but not by LM. In addition, three-dimensional ultrastructural changes, such as coarse meshwork structures of GBM, were observed in ABMR specimens. The ABMR group also exhibited ultrastructural changes in the peritubular capillary basement membranes. In conclusion, analyses of renal transplant tissues using LVSEM allows the identification of GBM duplication and ultrastructural changes of basement membranes at the electron microscopic level, and is useful for early-stage diagnosis of ABMR.

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“…It is sometimes difficult if not impossible to ascertain the exact etiology for TG in an individual case. Regardless of the underlying etiology, endothelial cell injury and subsequent remodeling has been demonstrated to be the essential pathophysiology for the formation of double contours in TG [1].…”

Section: Introductionmentioning

confidence: 99%

“…Transplant glomerulopathy (TG), which is histologically characterized by double contours of the glomerular basement membrane (GBM) without concomitant immuno-complex deposition, is a histomorphologic pattern frequently seen in patients presented with late allograft dysfunction several years or decades after kidney transplantation [1,2]. Although it has been elucidated that chronic antibody-mediated rejection accounts for the majority of cases with a morphologic diagnosis of TG, other pathoetiologies such as hepatitis C virus (HCV) infection and thrombotic microangiopathy (TMA) could also incur allograft chronic injury with a morphologic manifestation of TG [3].…”

Section: Introductionmentioning

confidence: 99%

Proteinuria, Estimated Glomerular Filtration Rate and Urinary Retinol-Binding Protein as Clinical Predictors of Long-Term Allograft Outcomes in Transplant Glomerulopathy

Chen

Cheng

et al. 2018

Kidney Blood Press Res

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Background/Aims: We aimed to explore the associations between clinical parameters and long-term allograft outcomes in transplant glomerulopathy (TG) in a large retrospective cohort with long follow-up. Methods: Clinical and laboratory data at biopsy from 180 cases of TG with an estimated glomerular filtration rate (eGFR)> 15ml/min/1.73m² from January 2004 to December 2016 at our center were retrospectively analyzed. The main outcome of this study was initiation of replacement therapy or an eGFR declined to < 15 ml/min/1.73m². Results: During a median follow-up of 5 years (interquartile range 2.6-8.2 years), 117 cases (65.0%) achieved the combined event. Kaplan-Meier method yielded the 1-year and 5-year cumulative renal allograft survival rates after a histopathologic diagnosis of TG were 84% (95% confidence interval [CI] 81-87%) and 33% (95% CI 27–39%) respectively. In univariate analysis, allograft outcome differed significantly by eGFR, proteinuria, blood hemoglobin level, urinary retinol-binding protein (urRBP) and urinary N-acetyl-β-D-glucosaminidase (urNAG) level at the time of biopsy. Multivariate Cox analysis revealed that a higher level of eGFR was the most powerful predictor of allograft survival. Compared with those with eGFR≥60, the hazard ratio (HR) increased from 4.50 (95% CI: 1.03-19.71, p=0.0462) for patients with eGFR between 30 and 59 ml/min/1.73m² to 9.14 (95% CI 1.97-42.45, P=0.0047) when eGFR decreased to 15 to 29 ml/min/1.73m². Additionally, proteinuria and higher urRBP values (≥2.85mg/dl) were found to confer much worse survival rates for TG patients in multivariate Cox analysis. Male sex (HR 0.48, P=0.02) and HCV infection (HR 1.78, P=0.0499) were also found to be independent risk factors for worse allograft survival. Conclusion: Five clinical features—impaired renal function, higher proteinuria, higher urRBP level, male sex and HCV infection—are independent predictors of an unfavorable renal allograft outcome. urRBP is a simple and useful parameter that can add invaluable information for the clinical follow-up of patients with TG.

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Transplant glomerulopathy

Cited by 40 publications

References 152 publications

Histopathologic Features that Predict Transplant Glomerulopathy Progression in a Chinese Cohort

Histopathologic Features that Predict Transplant Glomerulopathy Progression in a Chinese Cohort

Low-vacuum scanning electron microscopy may allow early diagnosis of human renal transplant antibody-mediated rejection

Proteinuria, Estimated Glomerular Filtration Rate and Urinary Retinol-Binding Protein as Clinical Predictors of Long-Term Allograft Outcomes in Transplant Glomerulopathy

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