The relationship between proteinuria and allograft survival in patients with transplant glomerulopathy: a retrospective single‐center cohort study

Zhou, Qiang; Rudolph, Birgit; Choi, Mira; Bachmann, Friederike; Schmidt, Danilo; Duerr, Michael; Naik, Marcel; Duettmann, Wiebke; Schrezenmeier, Eva; Mayrdorfer, Manuel; Halleck, Fabian; Wu, Kaiyin; Budde, Klemens

doi:10.1111/tri.13787

Cited by 4 publications

(5 citation statements)

References 38 publications

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“…Regarding the etiology of mm, our data showed that 39% of mm-positive lesions had ABMR ( Figure 3 ). Similarly, a recent study stated that transplant glomerulopathy affects approximately half of the patients with chronic active ABMR, and the Banff mm score reflects poor graft survival [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, four of five mm-positive patients with transplant glomerulopathy and proteinuria experienced graft loss ( Figure 6 ). A recent study of transplant glomerulopathy showed that the level of proteinuria and the presence of mm ≥ 1 affect the graft survival [ 15 ]. Electron microscopy reveals endothelial injury in glomeruli in ABMR leading to transplant glomerulopathy [ 19 ], and we also recently reported that the electron microscopic findings of glomerular endothelial injury are detected in patients with low-level proteinuria with ABMR [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

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Prognostic value of the 7-year protocol biopsy of adult kidney allografts: impact of mesangiosclerosis and proteinuria

Itabashi

Oguchi

Mikami³

et al. 2023

Renal Failure

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Aim The aim of the present study was to clarify the relationship between the Banff score of the 7-year protocol biopsy and the allograft outcome. Methods One-hundred-and-eighty-four patients received kidney transplantation from 2002 to 2008. We excluded patients aged <20 years at transplantation ( n = 24), those who did not undergo a 7-year protocol biopsy ( n = 66), and those who underwent for-cause biopsy ( n = 5). Consequently, 89 patients who underwent a 7-year protocol biopsy were enrolled. We analyzed the relationship between the clinicopathological findings 7 years after transplantation and the estimated glomerular filtration rate (eGFR) change per year and allograft survival. Histological evaluation was performed using the Banff 2015 classification. Results Among the clinicopathological findings, each Banff mesangial matrix increase (mm) score ≥1 and proteinuria ≥1+ was independently associated with the eGFR decline per year during a median follow-up of 73 months. Furthermore, in the model of the clinicopathological findings including the presence of mm with proteinuria, mm ≥1 alone and mm ≥1 with proteinuria were each independently associated with the eGFR decline. The graft survival was significantly worse for those with mm ≥1 with proteinuria than those with mm ≥1 without proteinuria. Conclusion Among the 7-year protocol biopsy findings, the presence of mm alone and mm with proteinuria were each significant predictors of eGFR decline. The presence of both proteinuria and mm had a negative impact on graft survival. These results underscore the significance of the Banff mm score and proteinuria at the time of the 7-year protocol biopsy to predict the allograft outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prognostic value of the 7-year protocol biopsy of adult kidney allografts: impact of mesangiosclerosis and proteinuria

Itabashi

Oguchi

Mikami³

et al. 2023

Renal Failure

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“…Therefore, individualized treatment strategies and close follow-up monitoring should be adopted for patients with FSGS to improve allograft outcomes. Previous studies [14, 28, 29] have indicated that proteinuria and impaired renal graft function at biopsy were independent risk factors for allograft loss in TG. Relative histopathological risk factors including interstitial fibrosis [21, 30], chronic score [15, 28], cg [22], and glomerular C3 deposition [15] have also been reported but are not seen in our study, probably due to the limited sample size and to the differences in follow-up time.…”

Section: Discussionmentioning

confidence: 99%

Focal Segmental Glomerulosclerosis Superimposed on Transplant Glomerulopathy: Implications for Graft Survival

Zhu

Fan

et al. 2021

Am J Nephrol

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Introduction: Transplant glomerulopathy (TG) is a morphological lesion resulting from chronic glomerular endothelium injury, and it is strongly associated with poor graft survival. TG coexisting with focal segmental glomerulosclerosis (FSGS) can be found in renal allograft biopsies, but few related studies are available. Methods: Consecutive kidney transplant recipients with biopsy-proven TG were studied retrospectively. Patients concomitant with FSGS were identified and compared with those without FSGS. The influence of FSGS on allograft outcomes was assessed using univariate and multivariate Cox regression models. Results: Of the 66 patients with TG, 40 (60.6%) had concomitant FSGS. TG patients with FSGS had higher proteinuria (median, 2.6 vs. 0.8 g/24 h, p < 0.001) and serum creatinine levels (median, 2.5 vs. 2.1 mg/dL, p = 0.04), lower serum albumin levels, higher chronic glomerulopathy (cg) score, larger glomerular tuft area, lower number of podocytes, and higher incidences of podocyte hyperplasia, pseudotubule formation, and diffuse foot process effacement than those without FSGS (all p < 0.05). The kidney allograft loss rate of patients with FSGS was higher than that of patients without FSGS (65.7% vs. 37.5%, p = 0.03). The presence of FSGS was independently associated with allograft loss in TG (hazard ratio (HR) = 3.42, 95% confidence interval (CI): 1.30–8.98, p = 0.01). Other independent predictors were proteinuria (HR = 1.18, 95% CI: 1.02–1.37, p = 0.02), estimated glomerular filtration rate (HR = 0.94, 95% CI: 0.91–0.97, p < 0.001), and panel reactive antibody (HR = 3.99, 95% CI: 1.14–13.99, p = 0.03). Moreover, FSGS (odds ratio (OR) = 4.39, 95% CI: 1.29–14.92, p = 0.02) and cg (OR = 5.36, 95% CI: 1.56–18.40, p = 0.01) were independent risk factors for proteinuria. Conclusion: In this cohort of patients with TG, the presence of FSGS was strongly associated with more severe clinicopathological features and worse allograft survival.

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“…Another retrospective analysis of TG in 954 kidney transplant recipients (3744 biopsies) found that TG occurred in >75% of the patients in the absence of HLA-DSA, independent of HLA molecular mismatches; it represented a different phenotype that had lower levels of concomitant inflammation and graft loss compared with HLA-DSA+ TG ( 56 ). An additional recent retrospective study found that proteinuria, C4d presence, and mesangial matrix expansion were important for outcome, while other histological markers (e.g., Banff Lesion Score cg) were not ( 57 ).…”

Section: Banff Classification: Amr Subcategories As Endpointsmentioning

confidence: 99%

Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation

Roufosse

Becker

Rabant³

et al. 2022

Transpl Int

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Antibody-mediated rejection (AMR) is caused by antibodies that recognize donor human leukocyte antigen (HLA) or other targets. As knowledge of AMR pathophysiology has increased, a combination of factors is necessary to confirm the diagnosis and phenotype. However, frequent modifications to the AMR definition have made it difficult to compare data and evaluate associations between AMR and graft outcome. The present paper was developed following a Broad Scientific Advice request from the European Society for Organ Transplantation (ESOT) to the European Medicines Agency (EMA), which explored whether updating guidelines on clinical trial endpoints would encourage innovations in kidney transplantation research. ESOT considers that an AMR diagnosis must be based on a combination of histopathological factors and presence of donor-specific HLA antibodies in the recipient. Evidence for associations between individual features of AMR and impaired graft outcome is noted for microvascular inflammation scores ≥2 and glomerular basement membrane splitting of >10% of the entire tuft in the most severely affected glomerulus. Together, these should form the basis for AMR-related endpoints in clinical trials of kidney transplantation, although modifications and restrictions to the Banff diagnostic definition of AMR are proposed for this purpose. The EMA provided recommendations based on this Broad Scientific Advice request in December 2020; further discussion, and consensus on the restricted definition of the AMR endpoint, is required.

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The relationship between proteinuria and allograft survival in patients with transplant glomerulopathy: a retrospective single‐center cohort study

Cited by 4 publications

References 38 publications

Prognostic value of the 7-year protocol biopsy of adult kidney allografts: impact of mesangiosclerosis and proteinuria

Prognostic value of the 7-year protocol biopsy of adult kidney allografts: impact of mesangiosclerosis and proteinuria

Focal Segmental Glomerulosclerosis Superimposed on Transplant Glomerulopathy: Implications for Graft Survival

Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation

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