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Proteinuria changes over time and association with allograft survival. (a) Changes of urine protein level based on the level at the time of biopsy (n = 156, 149, 147, 156, 138, 121, respectively). (b) ROC curves of association between proteinuria and graft loss at 5 years after TG. AUC was shown and the corresponding P value < 0.001. (c) TG patients were stratified into groups with different levels of proteinuria, the higher level of proteinuria corresponded to a higher risk of graft loss (P = 0.001). AUC, area under the ROC curve; PU, proteinuria; SEM, standard error of the mean.
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Proteinuria and transplant glomerulopathy (TG) are common in kidney transplantation. To date, there is limited knowledge regarding proteinuria in different types of TG and its relationship to allograft survival. A retrospective cohort analysis of TG patients from indication biopsies was performed to investigate the relationship of proteinuria, hist...
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... 0.327, 0.533, 0.398, respectively). Significant differences were also detected between the two groups in Transplant International 2020;proteinuria change at six and twelve months before biopsy (Mann-Whitney U-test Z = À2.14, À2.84; P = 0.032, 0.005, respectively) other than three months before biopsy (Z = À1.31, P = 0.191 by Mann-Whitney U-test; Fig. 2a). The utility of proteinuria at the time of biopsy for differentiating those TG patients with graft loss was evaluated by ROC analysis. Proteinuria at the time of biopsy yielded an area under the ROC curve (AUC) of 0.64 (95% CI 0.56-0.72, P < 0.001; Fig. 2b). The optimal cutoff point for proteinuria according to the maximum Youden ...
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... other than three months before biopsy (Z = À1.31, P = 0.191 by Mann-Whitney U-test; Fig. 2a). The utility of proteinuria at the time of biopsy for differentiating those TG patients with graft loss was evaluated by ROC analysis. Proteinuria at the time of biopsy yielded an area under the ROC curve (AUC) of 0.64 (95% CI 0.56-0.72, P < 0.001; Fig. 2b). The optimal cutoff point for proteinuria according to the maximum Youden index (0.26) was 0.92 g/24 h with a sensitivity of 59.8% (95% CI 50.3-68.6%) and specificity of 65.8% (95% CI 54.9-75.3%). KaplanMeier survival analysis results showed a significantly inferior allograft survival in TG patients with higher level of proteinuria (P ...
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... The optimal cutoff point for proteinuria according to the maximum Youden index (0.26) was 0.92 g/24 h with a sensitivity of 59.8% (95% CI 50.3-68.6%) and specificity of 65.8% (95% CI 54.9-75.3%). KaplanMeier survival analysis results showed a significantly inferior allograft survival in TG patients with higher level of proteinuria (P = 0.001; Fig. 2c). Patients with proteinuria ≥0.92 g/24 h had higher peak panel reactive antibody (pPRA) level (Z = À2.11, P = 0.035 by Mann-Whitney U-test). Incidence of hypertension (69.2% vs. 44.2%, P < 0.001) and delayed graft function proportion (39.6% vs. 23.2%, P = 0.040) were also higher in patients with proteinuria ≥0.92 g/ 24 h. No ...
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... as a continuous variable, proteinuria increased 5-year graft loss after diagnosis of TG (unadjusted HR 1.25 for every 1 g/24 h increase in proteinuria, 95% CI 1.11-1.41, P < 0.001; Table 3). TG patients with normal proteinuria <0.3 g/24 h at time of biopsy had the lowest risk for graft loss at 5 years after diagnosis (42.1%, 16/38 patients; Fig. 2c), while TG patients with proteinuria ≥1 g/24 h had an unadjusted 2.35-fold higher risk for graft loss (95% CI 1.33-4.17, P = 0.003) with 70.1% 5-year graft loss (61/87 patients). The effect of proteinuria on graft loss was highest in TG patients with nephrotic range proteinuria (≥3 g/24 h; unadjusted HR 2.96, 95% CI 1.49-5.89, P = ...
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Methods:
In...
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Citations
... Therefore, individualized treatment strategies and close follow-up monitoring should Am J Nephrol DOI: 10.1159/000519648 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. ...
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.
... TG is an independent risk factor for graft loss; meanwhile, other factors (serum creatinine, proteinuria, C4d positivity) can also affect the prognosis of TG patients (5)(6)(7). Graft survival of TG patients with a higher level of proteinuria was much worse compared to those with less proteinuria (6,8). ...
Background: Transplant glomerulopathy (TG) is one of the main causes of post-transplant proteinuria (PU). The features and possible risk factors for proteinuria in TG patients are uncertain.
Methods: We investigated all patients who had biopsy-proven TG from 2000 to 2018 in our center. The clinical and histological data were compared between two groups with or without PU (cut-off = 0.3 g/day). Spearman correlation analysis was used to evaluate the relationship between PU and pathological changes. The risk factors for PU in TG patients were determined by multivariable logistic regression analysis.
Results: One hundred and twenty-five (75.76%) of all enrolled 165 TG patients had proteinuria ≥0.3 g/day at the time of biopsy. TG patients' PU level was significantly correlated with Banff lesion score cg (ρ = 0.247, P = 0.003), and mm (ρ = 0.257, P = 0.012). Systolic blood pressure ≥140 mmHg (OR 2.72, 95% CI 1.04–7.10, P = 0.041), diastolic blood pressure ≥90 mmHg (OR 4.84, 95% CI 1.39–16.82, P = 0.013), peak PRA ≥5% (OR 6.47, 95% CI 1.67–25.01, P = 0.007), positive C4d staining (OR 4.55, 95% CI 1.29–16.11, 0.019), tacrolimus-based regimen (OR 3.5, 95% CI 1.28–9.54, P = 0.014), and calcium channel blocker usage (OR 4.38, 95% CI 1.59–12.09, P = 0.004) were independent risk factors for PU.
Conclusions: Proteinuria is common in TG patients. systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, peak PRA ≥5%, positive C4d staining, tacrolimus-based regimen, and calcium channel blocker usage are associated with proteinuria in TG patients.
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.
TBase is an electronic health record (EHR) for kidney transplant recipients (KTR) combining automated data entry of key clinical data (e.g., laboratory values, medical reports, radiology and pathology data) via standardized interfaces with manual data entry during routine treatment (e.g., clinical notes, medication list, and transplantation data). By this means, a comprehensive database for KTR is created with benefits for routine clinical care and research. It enables both easy everyday clinical use and quick access for research questions with highest data quality. This is achieved by the concept of data validation in clinical routine in which clinical users and patients have to rely on correct data for treatment and medication plans and thereby validate and correct the clinical data in their daily practice. This EHR is tailored for the needs of transplant outpatient care and proved its clinical utility for more than 20 years at Charité - Universitätsmedizin Berlin. It facilitates efficient routine work with well-structured, comprehensive long-term data and allows their easy use for clinical research. To this point, its functionality covers automated transmission of routine data via standardized interfaces from different hospital information systems, availability of transplant-specific data, a medication list with an integrated check for drug-drug interactions, and semi-automated generation of medical reports among others. Key elements of the latest reengineering are a robust privacy-by-design concept, modularity, and hence portability into other clinical contexts as well as usability and platform independence enabled by HTML5 (Hypertext Markup Language) based responsive web design. This allows fast and easy scalability into other disease areas and other university hospitals. The comprehensive long-term datasets are the basis for the investigation of Machine Learning algorithms, and the modular structure allows to rapidly implement these into clinical care. Patient reported data and telemedicine services are integrated into TBase in order to meet future needs of the patients. These novel features aim to improve clinical care as well as to create new research options and therapeutic interventions.
