Graft Loss In Kidney Transplant Recipients Research Articles

C4d, rather than C3d and C5b-9, is associated with graft loss in recurrent IgA deposition after kidney transplantation.

Recurrent IgA deposition is common after kidney transplantation. However, it is difficult to define whether IgA deposition is innocuous or contributes to organ damage. Next, although complement is known to be involved in the pathogenesis of IgA nephropathy (IgAN), its involvement has not been studied systematically in kidney transplant recipients (KTR). KTR with biopsy-proven native IgAN who underwent kidney biopsy after transplantation between 1995 and 2020 were included. Recurrent IgA deposition was defined as IgA deposit in the glomerulus. Staining of complement factors C4d, C3d, and C5b-9 were quantitatively evaluated using ImageScope. Sixty-seven KTR (85% male, 46±13 years old, 12 [6-24] months after transplantation, 58% with indication biopsy) were included in the analyses. Of them, 25 (37%) had recurrent IgA deposition. There were no clinical differences between KTR with and without recurrent IgA deposition. C3d and C5b-9 were always present in biopsies with IgA deposition, while C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTR developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition (Hazard ratio = 2.55, 95% confidence interval = 1.07-6.03, p = 0.034). Recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN.

#1474 COVID-19-infection in kidney transplant recipients during the omicron surge, a sigh of relief

Abstract Background and Aims The COVID-19 pandemic had a profound impact on global health, particularly affecting high-risk individuals such as solid organ transplant recipients (SOTRs). SOTRs have an elevated risk of severe COVID-19 disease and increased mortality. Kidney transplant recipients (KTRs) vaccinated with mRNA-based vaccines exhibit a lower response rate and shorter half-time of the serologic conversion. However, the percentage of serologic response improves with increasing number of vaccine doses. Studies also indicate that KTRs with prior COVID-19 infection demonstrate a more robust immune response post-immunization compared to COVID-19 naïve patients. Factors such as age, immunosuppressive regimen, eGFR, time since transplantation also impact vaccination response. This study aims to investigate COVID-19 infection outcome and vaccination response among KTRs during the Omicron surge. Method This study is a retrospective single-center cohort study at the Department of Nephrology and Transplantation at Skåne University Hospital in Malmö, Sweden. KTRs infected with COVID-19 during the Omicron surge were included (January 2022 until August 2023). Results 97 KTRs diagnosed with COVID-19 were included of whom 91 were vaccinated. In average, three doses of COVID-19-vaccine had been given to the patients. 67 KTRs showed seroconversion, 28 remained seronegative and the status of the remaining 2 KTRs was unknown. There was a significant association between lack of antibody production and mycophenolic acid (MPA) treatment (P = 0.019, Chi2 test), however the significance was not retained in a multivariate logistic regression analysis. Among the seroconverted (n = 67), 61 experienced mild infection, 5 moderate infection and 1 severe infection, according to the WHO clinical progression scale. In the seronegative group (n = 28), 25 had mild infection while the remaining three had moderate infection. The median time for viral clearance was examined in 79 KTRs and was 23 days (IQR 18-31). Immunosuppression was adjusted in 34% (n = 33) of cases. 2.1% (n = 2) of KTRs experienced graft rejection post infection. Conclusion While most patients experienced a mild infection, unlike during the first surges of the pandemic, the observed subsequent graft rejections emphasize the complexity of COVID-19´s potentially immunologic triggering effect and risk of graft loss in KTRs. The correlation between MPA treatment and a lower degree of serologic conversion after vaccination underscores the need for personalized immunologic follow up and treatment regimen in KTRs.

Association between acute graft pyelonephritis and kidney graft survival: A single-center observational study

The association between acute graft pyelonephritis (AGPN) and graft failure in kidney transplant recipients (KTR) remains controversial. In this single-center observational study, we aimed to assess the incidence of AGPN as a time-dependent posttransplantation event. We also examined the association between the diagnosis of AGPN and graft outcomes. In total, we evaluated 1480 patients who underwent kidney transplantation between January 2007 and December 2017. During a median follow-up of 5.04years, we observed 297 AGPN episodes that occurred in 158 KTR. To evaluate the association between AGPN and clinical outcomes, we performed Cox proportional hazards regression analyses in which AGPN was entered as a time-dependent covariate. AGPN was independently associated with an increased risk of graft loss (hazard ratio=1.66; 95% confidence interval [CI]: 1.05-2.64, p<.03) and a persistently decreased eGFR (fixed effect on intercept: -2.29ml/min/1.73m2 ; 95% CI: from -3.23 to -1.35, p<.01). However, neither mortality nor biopsy-proven acute rejection was found to correlate with AGPN. Moreover, recurrent AGPN episodes did not appear to have an additive detrimental impact on graft loss. These data represent a promising step in understanding whether AGPN prevention may decrease the risk of graft loss in KTR.

1706. Association between Cytomegalovirus Infection/Disease and Morbidity and Mortality in Kidney Transplantation: A Systematic Literature Review of Observational Studies

Background Cytomegalovirus (CMV) is a common pathogen in kidney transplant recipients (KTRs). KTRs may develop CMV viremia that is asymptomatic (‘CMV infection’) or associated with clinical and laboratory findings (‘CMV disease’) such as fever, leukopenia/neutropenia, and malaise (‘CMV syndrome’), and/or evidence of specific organ(s) involvement (‘CMV end-organ disease’). The extent to which CMV affects morbidity such as acute rejection (AR), graft loss (GL), other opportunistic infections (OI), or mortality in KTRs has not been systematically evaluated recently. Therefore, we examined the association between CMV infection/disease and morbidity and mortality in KTRs using a systematic review of observational studies from the last decade.MethodsMEDLINE and Embase were searched to identify observational studies published between January 2008 and November 2018 reporting outcomes of interest by CMV status. Meta-analysis was used to derive pooled odds ratio (pOR) with 95% confidence intervals(CIs) using the random-effects models and I2 statistics to estimate heterogeneity between studies using R version 3.5.1.ResultsOf 1,860 retrieved citations, 23 studies with a total of 6,994 KTRs met inclusion criteria. The majority of studies were conducted in Europe (N=14) and included participants regardless of donor/recipient CMV serostatus (N=14). Included studies reported outcomes by different clinical manifestations of CMV. Overall, CMV infection/disease was associated with an increased odd of AR, with significant heterogeneity. CMV infection/disease was also associated with an increase in the odds of GL and mortality compared to no CMV infection/disease without heterogeneity (Figure 1). A higher rate of all-cause hospital readmission and a greater mean number of OI episodes were reported with CMV infection/disease in a single study.Pooled Estimates on the Association between Outcomes and CMV Infection/Disease among Individuals undergoing Kidney Transplant ConclusionCMV infection/disease was associated with increased mortality and GL in adults with KT. The association between CMV and AR remained similar in direction with high heterogeneity limiting the robustness of the conclusion. Nonetheless, our analysis underscores the importance of interventions to reduce the incidence of CMV infection/disease to reduce mortality and GL in KTRs even in the current era.DisclosuresAmit D. Raval, PhD, Merck and Co., Inc (Employee) Kristin Kistler, PhD, Evidera, Inc. (Employee, Evidera, Inc. received the funding to conduct this study.) Yuexin Tang, PhD, Merck and Co., Inc. (Employee) Yoshihiko Murata, MD, PhD, Merck and Co., Inc. (Employee) David R. Snydman, MD, Merck (Consultant)Merck (Advisor or Review Panel member)Pfizer (Consultant)Reviral, Anthrax Vaccine, Influenza Vaccine (Other Financial or Material Support, Data Safety Monitoring Board)Takeda/Shire (Advisor or Review Panel member)

Endostatin Is an Independent Risk Factor of Graft Loss after Kidney Transplant

Background: Endostatin is a 20-kDa C-terminal fragment of collagen XVIII, known for its ability to inhibit the proliferation of capillary endothelial cells. Previous studies suggested that circulating endostatin independently predicts incident chronic kidney disease. However, the impact of endostatin on graft loss level in kidney transplant recipients (KTRs) remains unknown. Methods: We conducted a prospective observational cohort study in 574 maintenance KTRs. Patients were followed for kidney graft loss and all-cause mortality during a median follow-up of 48 months. Serum-, and urine-samples and clinical data were collected at baseline. Serum Endostatin concentration was analyzed by an ELISA. Results: Among 574 patients, 37 patients had graft loss and 62 patients died. For graft loss, the optimal cut-off value based on receiver operating characteristics analysis (area under the curve 0.79, 95% CI 0.71–0.86, p < 0.001) of endostatin was 147.3 pmol/L. Kaplan-Meier curves revealed that higher serum endostatin concentrations positively correlated with graft loss (p < 0.001). Multivariable Cox regression analyses showed that baseline endostatin concentrations were significantly associated with graft loss after adjusting for graft loss risk factors (adjusted hazard ratio [HR] 8.34; 95% CI 2.19–31.72; p = 0.002). The adjusted HRs for classical graft loss risk factors such as baseline estimated glomerular filtration rate and urinary protein excretion were lower (1.91 and 5.44, respectively). In contrast to graft loss, baseline endostatin concentrations were not associated with all-cause mortality. Conclusion: Increased serum endostatin at baseline is independently associated with the risk of graft loss in KTRs.