The Prevalence of Immunologic Injury in Renal Allograft Recipients with De Novo Proteinuria

Post-transplant proteinuria is a common complication after renal transplantation; it is associated with reduced graft and recipient survival. However, the prevalence of histological causes has been reported with considerable variation. A clinico-pathological re-evaluation of post-transplant proteinuria is necessary, especially after dismissal of the term “chronic allograft nephropathy,” which had been considered to be an important cause of proteinuria. Moreover, urinary protein can promote interstitial inflammation in native kidney, whether this occurs in renal allograft remains unknown. Factors that affect the graft outcome in patients with proteinuria also remain unclear. Here we collected 98 cases of renal allograft recipients who developed proteinuria after transplant, histological features were characterized using Banff scoring system. Cox proportional hazard regression models were used for graft survival predictors. We found that transplant glomerulopathy was the leading (40.8%) cause of post-transplant proteinuria. Immunological causes, including transplant glomerulopathy, acute rejection, and chronic rejection accounted for the majority of all pathological causes of proteinuria. Nevertheless, almost all patients that developed proteinuria had immunological lesions in the graft, especially for interstitial inflammation. Intraglomerular C3 deposition was unexpectedly correlated with the severity of proteinuria. Moreover, the severity of interstitial inflammation was an independent risk factor for graft loss, while high level of hemoglobin was a protective factor for graft survival. This study revealed a predominance of immunological parameters in renal allografts with post-transplant proteinuria. These parameters not only correlate with the severity of proteinuria, but also with the outcome of the graft

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Molecular analysis of rejection and injury in liver transplant biopsies: The INTERLIVER STUDY

Background. Distinguishing T cell-mediated rejection (TCMR) from other sources of inflammation in liver transplant biopsies by histology has been challenging. Recent progress in molecular assessment of kidney, heart, and lung transplants suggests that microarray biopsy phenotyping would provide novel insights for liver transplantation. Method. We prospectively studied 102 liver transplant biopsies (90% for indications) from USA, Canada, Europe, and Australia with gene expression microarrays (INTERLIVER ClinicalTrials.gov NCT03193151). We used 453 kidney-derived rejection-associated transcripts (RATs) in unsupervised archetypal (AA) and principal component analyses (PCA). Results. Every liver biopsy yielded abundant high quality RNA for microarray analysis. In PCA, principal component 1 correlated with transcripts associated with inflammation (e.g. PTPRC/CD45), TCMR (e.g. Granzyme A) and interferon-gamma effects (e.g. GBP5), and with histologic portal triaditis; PC2 correlated with injury-induced transcripts (e.g. SERPINB8). AA identified 3 archetypes (A1, A2, and A3) and scored every biopsy for similarity to each: S1normal, S2TCMR, and S3injury (Figure 1, with biopsies colored by highest score). Biopsy groups were studied for expression of previously annotated transcript sets (Table 1). S1normal biopsies lacked rejection, inflammation, and injury. S2TCMR biopsies had high expression of rejection- and IFNG-inducible transcripts. S3injury biopsies had increased transcripts reflecting injury and cellular damage (e.g. DAMPs), and were early post-transplant i.e. had donation-implantation injury. Additional 5-archetype analyses suggested a small subclass of late biopsies with plasma cells and mast cell transcripts, which in other organs are associated with fibrosis. No biopsies manifested molecular changes suggesting ABMR. Conclusion. Molecular phenotyping classifies liver transplant biopsies as normal, TCMR, and early injury. The incidence of biopsies with TCMR-like changes (25%) was higher than in other organ transplants which raises the possibility that immunoregulatory mechanisms such as T cell exhaustion may be operating