Chronic Active Antibody-mediated Rejection Research Articles

P8.049: Treatment of Chronic Active Antibody-Mediated Kidney Transplant Rejection With Intravenous Immunoglobulin

Background and Aims: Chronic active antibody-mediated rejection (cAAMR) is one of the main causes of late allograft failure after kidney transplantation. Data on the management of chronic active antibody-mediated rejection after kidney transplantation are limited. Intravenous immunoglobulin (IVIg) is one of the treatment options known to have powerful and multiple immunomodulatory effects. High-dose IVIg delivers a lasting immunomodulatory effect on T cells and especially B cells, resulting in changes in the induction of B cell apoptosis and downstream modulation of B cell signaling. Methods: This was a single-center study of kidney transplant recipients (n=10) treated with high-dose intravenous immunoglobulin for biopsy-confirmed cAAMR. IVIg infusions (1 g/kg) were performed every 4 weeks for 6 months. All patients were followed for at least 12 months clinically and by laboratory tests for graft and patient outcomes. Results: Mean age of recruited patients was 47.3 ±12.74 years. Most of them had first kidney transplant. Glomerulonephritis represented the most common cause of end-stage kidney disease. The time frame for cAAMR development was 32 [7;60] month. 2 patients died from coronavirus COVID-19 and 4 (40%) patients started dialysis during the follow-up period. 4 (40%) kidney transplant recipients with functioning grafts had no significant changes in serum creatinine, glomerular filtration rate and proteinuria after treatment. Conclusion: Monotherapy with intravenous immunoglobulin seems not to be an effective treatment strategy for chronic active antibody-mediated rejection of kidney transplant. New therapeutic approaches are needed to improve the outcome of cAAMR.

Tocilizumab in the treatment of active chronic humoral rejection resistant to standard therapy

IntroductionThere is no consensus on the most appropriate treatment for chronic active antibody-mediated rejection (cAMR). Recent studies suggest that treatment with tocilizumab (TCZ) may stabilize graft function, decrease the intensity of donor-specific HLA antibodies (DSAs) and reduce inflammation of microcirculation. Patients and methodsObservational study with renal allograft recipients diagnosed with cAMR (n = 5) who had not submitted a response to traditional treatment based on the combination of plasma replacements, immunoglobulins, and rituximab. Patients were told to be treated with TCZ as compassionate use in six doses per month (8 mg/kg/month). Renal function, proteinuria, and the intensity of DSAs were monitored during follow-up. ResultsFive patients, average age 60 ± 13 years, three male and two retrasplants (cPRA average 55%) with preformed DSAs. Treatment with TCZ was initiated within 47 ± 52 days of biopsy. In two cases treatment was discontinued after the first dose, by severe bicitopenia with cytomegalovirus viremia and by graft failure, respectively. In the three patients who completed treatment, no stability of renal function (serum creatinine from 1.73 ± 0.70 to 2.04 ± 0.52 mg/dL, e-FGR 4 6 ± 15 to 36 ± 16 mL/min), showed increased proteinuria (3.2 ± 4.0 to 6.9 ± 11.0 g/g) and the intensity of DSAs maintain stable. No changes were observed in the degree of inflammation of microcirculation (g+pt 4.2 ± 0.8 vs. 4.3 ± 1.0) or in the degree of transplant glomerulopathy (cg 1.2 ± 0.4 vs. 1.8 ± 1.0). ConclusionsTCZ therapy does not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection, does not improve the degree of inflammation of microcirculation and does not reduces the intensity of DSAs.

Chronic Active Antibody-mediated Rejection in Kidney Transplant Recipients: Treatment Response Rates and Value of Early Surveillance Biopsies.

Background.There is limited information on the value of short-term invasive and noninvasive monitoring in kidney transplant recipients (KTR) undergoing therapy for chronic active antibody-mediated rejection (cAMR).Methods.We describe response rates in patients with cAMR receiving pulse steroids/IVIG ± rituximab 3-mo after index biopsy.Results.The study included 82 consecutive KTR. Mean time from transplant to cAMR was 10 y. Mean peritubular capillaritis (ptc), glomerulitis (g), microvascular inflammation (MVI), C4d, and cg Banff scores were 1.1, 2.1, 3.2, 0.2, and 2, respectively. Mean estimated glomerular filtration rate (eGFR) and urine protein creatinine (UPC) ratio were 38 mL/min and 1.6 g/g, respectively. Thirty (37%) patients lost their allograft during the mean follow-up of 2.4 y. In patients treated with pulse steroids/IVIG (n = 41), response rates for eGFR, UPC, donor-specific antibodies (DSAs), and MVI were 27%, 49%, 7%, and 19%, respectively. In the pulse steroids/IVIG/rituximab group, response rates were 66%, 61%, 20%, and 69%, respectively. Univariate analysis identified response in eGFR (HR = 0.03; P = 0.001; 95% CI, 0.004-0.26), UPC (HR = 0.38; P = 0.01; 95% CI, 0.18-0.82), and DSA (HR = 0.11; P = 0.004; 95% CI, 0.02-0.49) as predictors of graft survival. Multivariate analysis only retained eGFR response (HR = 0.12; P = 0.01; 95% CI, 0.02-0.64).Conclusions.In cAMR, short-term response to treatment for kidney function and DSA was associated with graft survival, but the role of early surveillance biopsies needs further evaluation.

To improve long-term graft survival rate by comprehensive management in the whole process of kidney transplantation

Chronic active antibody-mediated rejection (caAMR) caused by de novo donor-specific antibodies (dnDSA) is the main risk factor of late allograft loss in kidney transplantation. The treatment remains difficult due to the lack of effective methods. Through comprehensive management pre and post kidney transplantation, which starts from the prevention of dnDSA generation, periodical monitoring of dnDSA, to timely implement of pathological diagnosis and early initiation of synthetical treatment, it will be beneficial to the prevention and treatment of caAMR and ultimately improve the long-term survival of the renal graft.

Poor Outcomes in Patients With Transplant Glomerulopathy Independent of Banff Categorization or Therapeutic Interventions.

BackgroundTransplant glomerulopathy (TG) may indicate different disease entities including chronic AMR (antibody-mediated rejection). However, AMR criteria have been frequently changed, and long-term outcomes of allografts with AMR and TG according to Banff 2017 have rarely been investigated.Methods282 kidney allograft recipients with biopsy-proven TG were retrospectively investigated and diagnosed according to Banff'17 criteria: chronic AMR (cAMR, n = 72), chronic active AMR (cAAMR, n = 76) and isolated TG (iTG, n = 134). Of which 25/72 (34.7%) patients of cAMR group and 46/76 (60.5%) of cAAMR group were treated with antihumoral therapy (AHT).ResultsUp to 5 years after indication biopsy, no statistically significant differences were detected among iTG, cAMR and cAAMR groups in annual eGFR decline (−3.0 vs. −2.0 vs. −2.8 ml/min/1.73 m2 per year), 5-year median eGFR (21.5 vs. 16.0 vs. 20.0 ml/min/1.73 m2), 5-year graft survival rates (34.1 vs. 40.6 vs. 31.8%) as well as urinary protein excretion during follow-up. In addition, cAMR and cAAMR patients treated with AHT had similar graft and patient survival rates in comparison with those free of AHT, and similar comparing with iTG group. The TG scores were not associated with 5-year postbiopsy graft failure; whereas the patients with higher scores of chronic allograft scarring (by mm-, ci- and ct-lesions) had significantly lower graft survival rates than those with mild scores. The logistic-regression analysis demonstrated that Banff mm-, ah-, t-, ci-, ct-lesions and the eGFR level at biopsy were associated with 5-year graft failure.ConclusionsThe occurrence of TG is closely associated with graft failure independent of disease categories and TG score, and the long-term clinical outcomes were not influenced by AHT. The Banff lesions indicating progressive scarring might be better suited to predict an unfavorable outcome.

Histologic and Molecular Patterns in Responders and Non-responders With Chronic-Active Antibody-Mediated Rejection in Kidney Transplants.

IntroductionThere is no proven therapy for chronic-active antibody-mediated rejection (caABMR), the major cause of late kidney allograft failure. Histological and molecular patterns associated with possible therapy responsiveness are not known.MethodsBased on rigorous selection criteria this single center, retrospective study identified 16 out of 1027 consecutive kidney transplant biopsies taken between 2008 and 2016 with pure, unquestionable caABMR, without other pathologic features. The change in estimated GFR pre- and post-biopsy/treatment were utilized to differentiate subjects into responders and non-responders. Gene sets reflecting active immune processes of caABMR were defined a priori, including endothelial, inflammatory, cellular, interferon gamma (IFNg) and calcineurin inhibitor (CNI) related-genes based on the literature. Transcript measurements were performed in RNA extracted from stored, formalin-fixed, paraffin-embedded (FFPE) samples using NanoString™ technology. Histology and gene expression patterns of responders and non-responders were compared.ResultsA reductionist approach applying very tight criteria to identify caABMR and treatment response excluded the vast majority of clinical ABMR cases. Only 16 out of 139 cases with a written diagnosis of chronic rejection fulfilled the caABMR criteria. Histological associations with therapy response included a lower peritubular capillaritis score (p = 0.028) along with less glomerulitis. In contrast, no single gene discriminated responders from non-responders. Activated genes associated with NK cells and endothelial cells suggested lack of treatment response.ConclusionIn caABMR active microvascular injury, in particular peritubular capillaritis, differentiates treatment responders from non-responders. Transcriptome changes in NK cell and endothelial cell associated genes may further help to identify treatment response. Future prospective studies will be needed which include more subjects, who receive standardized treatment protocols to identify biomarkers for treatment response.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT03430414].

The Proteome of Antibody-Mediated Rejection: From Glomerulitis to Transplant Glomerulopathy.

Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Its histological hallmark is represented by lesions of glomerulitis i.e., inflammatory cells within glomeruli. Current therapies for ABMR fail to prevent chronic allograft damage i.e., transplant glomerulopathy, leading to allograft loss. We used laser microdissection of glomeruli from formalin-fixed allograft biopsies combined with mass spectrometry-based proteomics to describe the proteome modification of 11 active and 10 chronic active ABMR cases compared to 8 stable graft controls. Of 1335 detected proteins, 77 were deregulated in glomerulitis compared to stable grafts, particularly involved in cellular stress mediated by interferons type I and II, leukocyte activation and microcirculation remodeling. Three proteins extracted from this protein profile, TYMP, WARS1 and GBP1, showed a consistent overexpression by immunohistochemistry in glomerular endothelial cells that may represent relevant markers of endothelial stress during active ABMR. In transplant glomerulopathy, 137 proteins were deregulated, which favor a complement-mediated mechanism, wound healing processes through coagulation activation and ultimately a remodeling of the glomerular extracellular matrix, as observed by light microscopy. This study brings novel information on glomerular proteomics of ABMR in kidney transplantation, and highlights potential targets of diagnostic and therapeutic interest.

Evaluation of Clazakizumab (Anti–Interleukin-6) in Patients With Treatment-Resistant Chronic Active Antibody-Mediated Rejection of Kidney Allografts

IntroductionInterleukin-6 (IL-6) is an important mediator of inflammation and activation of T cells, B cells, and plasma cells. Excessive IL-6 production is linked to human diseases characterized by unregulated antibody production, including alloimmunity, where persistence of donor-specific antibodies (DSAs), chronic active antibody-mediated rejection (cAMR), and graft loss are noted. Here, we report our experience investigating clazakizumab, a novel IL-6 inhibitor, in treating human leukocyte antigen (HLA)-sensitized patients with cAMR.MethodsBetween February 2018 and January 2019, 10 adults with biopsy-proven cAMR were enrolled in a phase 2, single-center, open-label study. Patients received clazakizumab 25 mg subcutaneously (s.c.) monthly for 12 months, with a 6-month protocol biopsy. Primary end points included patient survival, graft survival, estimated glomerular filtration rate (eGFR), and safety. Secondary end points assessed immune markers (DSAs, IgG, T-regulatory [Treg] cells). At 12 months, stable patients entered a long-term extension (LTE).ResultsLTE patients received clazakizumab for >2.5 years. Mean eGFRs showed significant declines from −24 months to study initiation (0 months) (52.8 ± 14.6 to 38.11 ± 12.23 ml/min per 1.73 m2, P = 0.03). However, after initiation of clazakizumab, eGFR stabilized at (41.6 ± 14.2 and 38.1 ± 20.3 ml/min per 1.73 m2, at 12 and 24 months, respectively). Banff 2017 analysis of pre- and post-treatment biopsies showed reductions in g+ptc and C4d scores. DSA reductions were seen in most patients. Adverse events (AEs) were minimal, and 2 graft losses occurred, both in patients who discontinued clazakizumab therapy at 6 months and 12 months after study initiation.ConclusionIn this small cohort of patients with cAMR, clazakizumab treatment showed a trend toward stabilization of eGFR and reductions in DSA and graft inflammation. No significant safety issues were observed. A randomized, placebo-controlled clinical trial (IMAGINE) of clazakizumab in cAMR treatment is underway (NCT03744910).

POS-798 HISTOLOGIC AND MOLECULAR PATTERNS IN TREATMENT RESPONDERS AND NON-RESPONDERS WITH CHRONIC ACTIVE ANTIBODY-MEDIATED REJECTION

Chronic active antibody-mediated rejection (caABMR) is the major cause of late kidney allograft failure. So far no effective treatment is available. The identification of histological and/or molecular patterns associated with therapy response would be a major step forward.

Role of Early Serial Renal Transplant Allograft Protocol Biopsies in Living Kidney Transplantations

This study aimed to analyze the incidence of subclinical rejection (SCR) in kidney transplantation patients and risk factors associated with SCR. We assessed 80 protocol biopsies taken within 2 years postoperatively in 41 adult patients who underwent living donor kidney transplantation between 2017 and 2020. All patients were on immunosuppressant therapy that included tacrolimus, mycophenolate mofetil, and steroids. The prevalence of Banff Borderline classification at 3, 6, and 12 months after transplantation was 4%, 5%, and 8 %, respectively, whereas none of the biopsies met the Banff criteria for acute T cell-mediated rejection throughout the study period. Active antibody-mediated rejection (ABMR) was only present in 8% of patients at 3 months after transplantation and chronic active ABMR at 6, 12, and 24 months after transplantation was detected in 10%, 13%, and 11% of the patients, respectively. Subgroup analysis revealed that 50% of the 6 patients with preformed anti-donor specific antibodies (DSAs) developed clinical or subclinical active ABMR within 3 months after transplantation, followed by chronic active ABMR according to serial histologic assessment. Conversely, only a small proportion of patients (3%) without preformed DSAs exhibited clinically active ABMR. SCR occurs too infrequently in patients with low immunologic risk and strong contemporary immunosuppression therapy to justify the diagnostic effort of serial protocol biopsies. However, protocol biopsies remain an indispensable tool in renal transplant monitoring and may be especially important in immunologically high-risk patients with pre-existing DSAs.

Incisional Hernia Repaired Using Thigh Muscle Fascia After Kidney Transplantation: A Case Report

Although monofilament mesh-based repair is a safe and effective procedure for incisional hernia (IH) in organ transplant patients, there is no definite evidence of IH treatment for patients with graft rejection and enhanced immunosuppressive therapy. We report a successful case of large IH repair using an autologous thigh muscle fascia sheet in a kidney transplant patient. A 69-year-old man had IH from the incision of kidney transplantation, which was performed 6 years ago. He had a large right lower abdominal distension hanging down to the inguinal portion. A computed tomography scan revealed a large IH with a maximum abdominal defect diameter of 15 cm. The hernia sac contained the intestine, colon, and transplanted kidney, which had pulled out along with the retroperitoneum and protruded into the abdominal wall. He had chronic active acute antibody-mediated rejection, which required frequent steroid pulse therapy and additional or adjusted immunosuppressive drugs. After total circumferential exposure of the hernia sac and abdominal fascia, the abdominal wall defect was closed using a horizontal mattress suture. The sutured line was covered with a thigh muscle fascia sheet harvested from the patient's right femur and attached to the closed fascia. He was discharged on postoperative day 13 without any complications, and no IH recurrence was observed 10 months after surgery. Hernia repair using autologous tissue could be a treatment option for post-transplant IH with a higher risk of infection.

Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants.

The advances in acute phase care have firmly established the practice of organ transplantation in the last several decades. Then, the next issues that loom large in the field of transplantation include antibody-mediated rejection (ABMR) and recurrent primary disease. Acute ABMR is a daunting hurdle in the performance of organ transplantation. The recent progress in desensitization and preoperative monitoring of donor-specific antibodies enables us to increase positive outcomes. However, chronic active ABMR is one of the most significant problems we currently face. On the other hand, recurrent primary disease is problematic for many recipients. Notably, some recipients, unfortunately, lost their vital organs due to this recurrence. Although some progress has been achieved in these two areas, many other factors remain largely obscure. In this review, these two topics will be discussed in light of recent discoveries.

Glomerular Size in Transplanted Kidneys: Does Size Matter?

Glomerular Size in Transplanted Kidneys: Does Size Matter?

Histopathologic Features of Antibody Mediated Rejection: The Banff Classification and Beyond.

Antibody mediated rejection (ABMR) in the kidney can show a wide range of clinical presentations and histopathologic patterns. The Banff 2019 classification currently recognizes four diagnostic categories: 1. Active ABMR, 2. Chronic active ABMR, 3. Chronic (inactive) ABMR, and 4. C4d staining without evidence of rejection. This categorization is limited in that it does not adequately represent the spectrum of antibody associated injury in allograft, it is based on biopsy findings without incorporating clinical features (e.g., time post-transplant, de novo versus preformed DSA, protocol versus indication biopsy, complement inhibitor drugs), the scoring is not adequately reproducible, and the terminology is confusing. These limitations are particularly relevant in patients undergoing desensitization or positive crossmatch kidney transplantation. In this article, I discuss Banff criteria for these ABMR categories, with a focus on patients with pre-transplant DSA, and offer a framework for considering the continuum of allograft injury associated with donor specific antibody in these patients.

Tocilizumab en el tratamiento del rechazo humoral crónico activo resistente a terapia estándar

IntroductionThere is no consensus on the most appropriate treatment for chronic active antibody-mediated rejection (cAMR). Recent studies suggest that treatment with tocilizumab (TCZ) may stabilize graft function, decrease the intensity of donor-specific HLA antibodies (DSAs) and reduce inflammation of microcirculation. Patients and methodsObservational study with renal allograft recipients diagnosed with cAMR (n = 5) who had not submitted a response to traditional treatment based on the combination of plasma replacements, immunoglobulins, and rituximab. Patients were told to be treated with TCZ as compassionate use in six doses per month (8 mg/kg/month). Renal function, proteinuria, and the intensity of DSAs were monitored during follow-up. ResultsFive patients, average age 60 ± 13 years, three male and two retrasplants (cPRA average 55%) with preformed DSAs. Treatment with TCZ was initiated within 47 ± 52 days of biopsy. In two cases treatment was discontinued after the first dose, by severe bicitopenia with cytomegalovirus viremia and by graft failure, respectively. In the three patients who completed treatment, no stability of renal function (serum creatinine from 1.73 ± 0.70 to 2.04 ± 0.52 mg/dL, e-FGR 4 6 ± 15 to 36 ± 16 mL/min), showed increased proteinuria (3.2 ± 4.0 to 6.9 ± 11.0 g/g) and the intensity of DSAs maintain stable. No changes were observed in the degree of inflammation of microcirculation (g + pt 4.2 ± 0.8 vs. 4.3 ± 1.0) or in the degree of transplant glomerulopathy (cg 1.2 ± 0.4 vs. 1.8 ± 1.0). ConclusionsTCZ therapy does not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection, does not improve the degree of inflammation of microcirculation and does not reduces the intensity of DSAs.

Tocilizumab in a patient affected by chronic active antibody mediated rejection; histological improvement, reduction of proteinuria and renal function stabilization

Introduction: Chronic active antibody-mediated rejection (cAMR) is a significant and rapid destructive form of allograft rejection and it is related to donor specific antibodies (DSA). Interleukin 6 (IL-6) plays an important role in mediating the allograft rejection by promoting CD4+ T cells differentiation to Th17 phenotype while inhibiting Treg. Tocilizumab is a humanized monoclonal antibody directed to IL-6 receptor (IL6-R). The aim of the study is to demonstrate the efficacy of tocilizumab as rescue therapy for cAMR. Case Presentation: A 50-year-old man with Alport syndrome and with positive DSA against B7 e B55 underwent a second kidney transplant (HLA 2 mismatch). He received thymoglobulin and three plasma exchanges as induction therapy. Proteinuria (1-1.3 g/24 h) and decline in kidney function (serum creatinine; 1.5 mg/dL) appeared at 9 months. Kidney biopsy showed endocapillary proliferation, mononuclear cells infiltration, glomerular basal membrane duplication and tubulitis suggestive of cAMR. The patient has been treated with tocilizumab (6 mg/kg/mon) for six months. Reduction of proteinuria (0.6 g/24 h) and mild improvement of kidney function (serum creatinine; 1.3 mg/dL) were observed after tocilizumab treatment. A second biopsy revealed a significant decrease of glomerulitis and peritubular capillaritis. A significant reduction in DSA was detected. Conclusion: Inhibition of the IL-6 receptor by tocilizumab may represent a novel and cheering approach to treat cAMR.

Renal allograft DARCness in subclinical acute and chronic active ABMR.

SummaryGene expression profiling of renal allograft biopsies revealed the Duffy antigen receptor for chemokines (DARC) as being strikingly upregulated in antibody‐mediated rejection (ABMR). DARC has previously been shown to be associated with endothelial injury. This study aimed at assessing the value of DARC immunohistochemistry as diagnostic marker in ABMR. The study was performed on 82 prospectively collected biopsies of a clinically well‐defined population (BORTEJECT trial, NCT01873157) of DSA‐positive patients with gene expression data available for all biopsies. Diagnostic histologic assessment of biopsies was performed according to the Banff diagnostic scheme. DARC expression was focally accentuated, on peritubular capillaries (PTC) mostly in areas of interstitial fibrosis and/or inflammation. DARC positivity was associated with diagnosis of ABMR and correlated with DARC gene expression levels detected by microarray analysis. Still, as previously described, a substantial number of biopsies without signs of rejection showed DARC‐positive PTC. We did not observe significantly reduced graft survival in cases showing histologic signs of ABMR and being DARC‐positive, as compared to DARC‐negative ABMR. In summary, the upregulation of DARC, detected by immunohistochemistry, is associated with but not specific for ABMR. We did not observe reduced graft survival in DARC‐positive patients.

B-cell Deficiency Attenuates Transplant Glomerulopathy in a Rat Model of Chronic Active Antibody-mediated Rejection.

Transplant glomerulopathy (TG) is a pathological feature of chronic active antibody-mediated rejection (cAMR) and is associated with renal allograft failure. The specific role of B cells in the pathogenesis of TG is unclear. We used a minor mismatched rat kidney transplant model with B cell-deficient recipients, generated by clustered regularly interspaced short palindromic repeats/Cas9 technology, to investigate the impact of B-cell depletion on the pathogenesis of TG. We hypothesized that B-cell deficiency would prevent TG in the rat kidney transplant model of cAMR. Treatment groups included syngeneic, allogeneic, sensitized allogeneic, and B cell-deficient allogeneic transplant recipients. B cell-deficient recipients demonstrated reduced TG lesions, decreased microvascular inflammation, reduced allograft infiltrating macrophages, and reduced interferon gamma transcripts within the allograft. Allograft transcript levels of interferon gamma, monocyte chemoattractant protein-1, and interleukin-1β correlated with numbers of intragraft macrophages. B cell-deficient recipients lacked circulating donor-specific antibodies and had an increased splenic regulatory T-cell population. In this model of cAMR, B-cell depletion attenuated the development of TG with effects on T cell and innate immunity.

Recovery of kidney function after AKI because of COVID-19 in kidney transplant recipients.

SummaryEvidence on the evolution of graft function in kidney transplant recipients recovering from coronavirus disease‐2019 (COVID‐19) is lacking. This multicenter observational study evaluated the short‐term clinical outcomes in recipients with acute kidney injury (AKI) secondary to COVID‐19. Out of 452 recipients following up at five centers, 50 had AKI secondary to COVID‐19. 42 recipients with at least 3‐month follow‐up were included. Median follow‐up was 5.23 months [IQR 4.09–6.99]. Severe COVID‐19 was seen in 21 (50%), and 12 (28.6%) had KDIGO stage 3 AKI. Complete recovery of graft function at 3 months was seen in 17 (40.5%) patients. Worsening of proteinuria was seen in 15 (37.5%) patients, and 4 (9.5%) patients had new onset proteinuria. Graft failure was seen in 6 (14.3%) patients. Kidney biopsy revealed acute tubular injury (9/11 patients), thrombotic microangiopathy (2/11), acute cellular rejection (2/11), and chronic active antibody‐mediated rejection (3/11). Patients with incomplete recovery were likely to have lower eGFR and proteinuria at baseline, historical allograft rejection, higher admission SOFA score, orthostatic hypotension, and KDIGO stage 3 AKI. Baseline proteinuria and the presence of orthostatic hypotension independently predicted incomplete graft recovery. This shows that graft recovery may remain incomplete after AKI secondary to COVID‐19.

MO963GRAFT- AND PATIENT-SURVIVAL AFTER FIRST KIDNEY TRANSPLANT BIOPSY

Abstract Background and Aims Kidney transplantation is frequently used as a treatment in uremic patients. However, long term function is not easily predicted. The aim of this study was to investigate to what extent histological diagnosis in the first registered transplant kidney biopsy is related to clinical outcome. Method Included were data of 1463 patients (36.6 % women, 63.4 % men) that were merged from a kidney transplantation register and a biopsy register. These patients obtained their first registered transplant biopsy during the period January 1, 2007 until July 30, 2017. Fisher’s exact test and χ-2 analyses were used for cross-tabulation of data. Graft- and patient-survival analysis was performed by Kaplan-Meier analysis with log-rank tests comparing different groups and in next step age and gender adjusted analysis were performed by multivariate Cox-regression-analysis. Data are presented as Hazard Ratio (HR) and 95% Confidence Intervals (CI). A two-sided p-value of <0.05 was considered as statistically significant. Results The graft-survival was shorter for patients with biopsy-proven glomerular diseases (HR 8.1, CI 3.1-20.7) and rejections (HR 4.3, CI 1.7 -10.5) compared to normal biopsy findings. Further, there was a shorter graft-survival for those with chronic damages (HR 3.2, CI 1.3-8.0), acute tubular injuries (HR 3.0, CI 1.2-7.8), and borderline changes (HR 2.9, CI 1.1-7.6). The patient-survival was reduced for patients with biopsy-proven hematological diseases (HR 9.6, CI 2.1-44.0). Sub analysis of all types of rejections showed shorter graft-survival for chronic T-cell-mediated rejection (TCMR) (HR 4.8, CI 2.1-11.7), active antibody-mediated rejection (ABMR) (HR 4.4, CI 2.1-9.3), chronic ABMR (HR 3.8, CI 2.2-6.7), combined chronic ABMR and TCMR (HR 4.0, CI 2.4-6.9) and other rejections (HR 3.3, CI 1.1-9.6) compared to acute TCMR. Patients with TCMR Banff grade II rejection had a better graft-survival (HR 0.35, CI 0.20-0.63) compared to other rejections as well as patients with TCMR Banff grade I (HR 0.52, CI 0.29-0.93). 265 patients had graft-loss and 42 of those patients died afterwards (15.8%). Of the 42 who died after graft-loss 9 patients died within 30 days after transplant failure (21.4%). Conclusion A shorter graft-survival was found in kidneys with glomerular diseases, rejections, acute tubular injuries, borderline changes and chronic damages. A shorter patient-survival was noted for patients with transplant kidney biopsies with hematological diseases. Patients with Banff grade II rejection had a better graft-survival compared to all other diagnosis and other rejections. Further, awareness should be given to patients the first month after graft-loss.