Protocol biopsy of kidney allograft enables early detection of BK virus nephropathy to preserve kidney allograft function.

BACKGROUND: The Banff Working Group has updated the histological classification of BK virus nephropathy (BKVN), highlighting the importance of early detection. However, an early detection strategy for BKVN using biopsy has not yet been established. Our investigation aimed to assess the efficacy of protocol biopsy for the diagnosis of BKVN. METHODS: We performed a retrospective cohort study of 314 patients who had undergone kidney transplantation between 2006 and 2021. Kidney allograft biopsies were performed as part of a protocol biopsy at 3 months and 1 year post-transplantation. Following the diagnosis of BKVN, the immunosuppressant dose was reduced. RESULTS: Twelve patients (3.8%) were diagnosed with BKVN by biopsy. Most diagnoses are established during the early stages of BKVN (polyomavirus nephropathy class 1 in six, class 2 in five, and class 3 in one). Following the reduction in immunosuppressant dose, kidney allograft function did not deteriorate in any patients. Additionally, test for BK virus DNA in the blood was negative. All but one patient demonstrated histological resolution of BKVN, and the other had a very slight positivity for the simian virus 40 large T antigen. The median follow-up time after BKVN diagnosis was 6 years. One patient developed de novo donor-specific antibody and subclinical acute antibody-mediated rejection that was successfully cured. CONCLUSIONS: Our analysis indicates that protocol biopsy may enable the early detection of BKVN, resulting in the preservation of kidney function.

Exploring kidney allograft rejection: A proof-of-concept study using spatial transcriptomics.

In this proof-of-concept study, spatial transcriptomics combined with public single-cell ribonucleic acid-sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathologic states by examining biopsies classified across nonrejection, T cell-mediated acute rejection, interstitial fibrosis, and tubular atrophy. Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology.

Banff 2022 Liver Group Meeting report: Monitoring long-term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists, and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimization, and long-term structural changes. Potential revision of the rejection classification scheme to better accommodate and communicate late T cell-mediated rejection patterns and related structural changes, such as nodular regenerative hyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression to match the heterogeneity of patient settings will be central to improving long-term patient survival. Such personalized therapeutics are in turn contingent on a better understanding and monitoring of allograft status within a rational decision-making approach, likely to be facilitated in implementation with emerging decision-support tools. Proposed revisions to rejection classification emerging from the meeting include the incorporation of interface hepatitis and fibrosis staging. These will be opened to online testing, modified accordingly, and subject to consensus discussion leading up to the next Banff conference.

New Insights into Pediatric Kidney Transplant Rejection Biomarkers: Tissue, Plasma and Urine MicroRNAs Compared to Protocol Biopsy Histology.

The early identification of a subclinical rejection (SCR) can improve the long-term outcome of the transplanted kidney through intensified immunosuppression. However, the only approved diagnostic method is the protocol biopsy, which remains an invasive method and not without minor and/or major complications. The protocol biopsy is defined as the sampling of allograft tissue at pre-established times even in the absence of an impaired renal function; however, it does not avoid histological damage. Therefore, the discovery of new possible biomarkers useful in the prevention of SCR has gained great interest. Among all the possible candidates, there are microRNAs (miRNAs), which are short, noncoding RNA sequences, that are involved in mediating numerous post-transcriptional pathways. They can be found not only in tissues, but also in different biological fluids, both as free particles and contained in extracellular vesicles (EVs) released by different cell types. In this study, we firstly performed a retrospective miRNA screening analysis on biopsies and serum EV samples of 20 pediatric transplanted patients, followed by a second screening on another 10 pediatric transplanted patients' urine samples at one year post-transplant. In both cohorts, we divided the patients into two groups: patients with histological SCR and patients without histological SCR at one year post-transplantation. The isolated miRNAs were analyzed in an NGS platform to identify different expressions in the two allograft states. Although no statistical data were found in sera, in the tissue and urinary EVs, we highlighted signatures of miRNAs associated with the histological SCR state.

The role of hyperleptinaemia and low values of interleukin 10 in de novo DSA production after kidney transplantation.

BACKGROUND: White adipose tissue secretes a number of peptide hormones. The aim of this paper was to determine the role of leptin, adiponectin and interleukin-10 and interleukin-6 on the development of graft rejection in protocol biopsy after kidney transplantation. METHODS: In a prospective analysis (n = 104), we monitored the values of leptin, adiponectin, IL-6, and IL-10 prior to the transplantation and in the 3rd month after the transplantation. The protocol biopsy of the graft was performed in the 3rd month after the transplantation. The group was divided into the following according to the biopsy result: negative result, IFTA 1, borderline, and DSA positive. RESULTS: After adjusting for the differences in the baseline recipient and donor characteristics, we identified the hyperleptinaemia baseline (HR = 2.0444, P = 0.0341) and month 3 (HR = 49.8043, P < 0.0001) as independent risk factors for borderline changes in the protocol biopsy. The hyperleptinaemia baseline (HR = 7.4979, P = 0.0071) and month 3 (HR = 9.7432, P = 0.0057) are independent risk factors for de novo DSA positivity. A low value of IL-10 month 3 is a risk factor for de novo DSA positivity (HR = 3.0746, P = 0.0388). CONCLUSIONS: Higher leptin levels and low values of IL-10 might play a role in rejection and de novo DSA production.

Urinary tract infection in the context of mini-invasive procedures after kidney transplantation.

INTRODUCTION: The use of antibiotic prophylaxis in invasive procedures is generally accepted and highly recommended. The question is the need to apply antibiotic prophylaxis even in the case of mini-invasive procedures in the post-transplantation period. The aim of the study was to dermine the occurrence of infectious complications during mini-invasive procedures (pig-tail extraction, protocol biopsy) withou the use of antibiotic (ATB) prophylaxis. The secondary aim was to identify risk factors for a positive urine culture finding at the time of mini-invasive procedures. MATERIAL: This is a prospective monocentric study in which pacients after kidney transplantation at Transplantation centrum in Martin were included (n = 68). We investigated the incidence of positive urine findings at the time of pig-tail extraction (6 weeks after transplantation) and at the time of protocol biopsy (3 months after transplantation) with comparison within the group with and without ATB prophylaxis. RESULTS: Patients in group without ATB prophylaxis had a significantly higher tacrolimus value at the time of pig-tail extraction (p = 0.0274) and a significantly higher dose of mycophenolic acid at the time of protocol biopsy (p = 0.0429). We did not confirm significant difference in occcurence of positive urine findings at the time of pig-tail extraction or at the time of protocol biopsy. We completed a univariate logistic regression in order to identify a potential risk predictor for positive urine findings at the time of pig-tail extraction and protocol biopsy. None of the monitored parameters, including ATB prophylaxis, was confirmed as risk or protective factor. CONCLUSION: The use of antibiotic prophylaxis during mini-invasive procedures (pig-tail extraction, protocol biopsy) in the posttransplantation period had no effect on positive culture findings at our department. Based on our analysis, we therefore do not use antibiotic prophylaxis in the case of these procedures at our centre (Tab. 3, Fig. 6, Ref. 23).

Vesicoureteral Reflux Causes Interstitial Inflammation in Pediatric Kidney Allograft: A Clinicopathological Analysis of 1-Year Protocol Biopsies.

INTRODUCTION: At present, there is limited evidence of the histological impact of vesicoureteral reflux (VUR) on pediatric kidney allografts. In this study, we aimed to investigate the relationship between VUR diagnosed by voiding cystourethrography (VCUG) and 1-year protocol biopsy results. METHODS: One hundred thirty-eight pediatric kidney transplantations were performed in Toho University Omori Medical Center between 2009 and 2019. We included 87 pediatric transplant recipients who were evaluated for VUR by VCUG prior to or at the time of the 1-year protocol biopsy and underwent a 1-year protocol biopsy after transplantation. We evaluated the clinicopathological findings of the VUR and non-VUR groups, and histological scores were evaluated using the Banff score. Tamm-Horsfall protein (THP) within the interstitium was identified by light microscopy. RESULTS: Of the 87 transplant recipients, 18 cases (20.7%) were diagnosed with VUR by VCUG. The clinical background and findings were not significantly different between the VUR and non-VUR groups. The pathological findings revealed a significantly higher Banff total interstitial inflammation (ti) score in the VUR group than in the non-VUR group. Multivariate analysis indicated a significant relationship between the Banff ti score and THP within the interstitium, and VUR. The 3-year protocol biopsy results (n = 68) revealed a significantly higher Banff interstitial fibrosis (ci) score in the VUR group than in the non-VUR group. CONCLUSION: VUR caused interstitial fibrosis in the 1-year pediatric protocol biopsies, and interstitial inflammation at the 1-year protocol biopsy may affect interstitial fibrosis at the 3-year protocol biopsy.

Progress in Pathological Diagnosis after Kidney Transplantation: Current Trend and Future Perspective.

Advances in immunosuppressive therapy; posttransplant management of allograft rejection; and measures against infectious diseases, cardiovascular diseases, and malignancy dramatically improved graft and patient survival after kidney transplantation (KT). Among them, kidney allograft biopsy is an important tool and the gold standard for the diagnosis of various kidney allograft injuries, including allograft rejection, virus-induced nephropathy, calcineurin inhibitor toxicity, and posttransplant glomerular diseases. The Banff Conference on Allograft Pathology has contributed to establishing the diagnostic criteria for kidney allograft rejection and polyomavirus-associated nephropathy that are used as a common standard worldwide. In addition to the for-cause biopsy, many transplant centers perform protocol biopsies in the early and late posttransplant periods to detect and treat allograft injury earlier. Preimplantation biopsy in deceased-donor KT has also been performed, especially in the marginal donor, and attempts have been made to predict the prognosis in combination with clinical information and the renal resistance of hypothermic machine perfusion. Regarding the preimplantation biopsy from a living kidney donor, it can provide useful information on aging and/or early changes in lifestyle diseases, such as glomerulosclerosis, tubulointerstitial changes, and arterial and arteriolar sclerosis, and be used as a reference for the subsequent management of living donors. In this review, morphologic features of important kidney allograft pathology, such as allograft rejection and polyomavirus-associated nephropathy, according to the latest Banff classification and additional information derived from protocol biopsy, and future perspectives with recently developed technologies are discussed.

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

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.

Protocol Biopsy After Kidney Transplant: Clinical Application and Efficacy to Detect Allograft Rejection.

Background Kidney transplant rejection is a major cause of graft dysfunction and failure. In recent years, there has been increased interest in renal allograft protocol biopsies to allow earlier detection of acute or chronic graft dysfunction or rejection to improve long-term graft survival and reduce graft failure. This study aimed to determine if renal allograft protocol biopsies performed within the first 12 months after transplantation help detect subclinical graft dysfunction or rejection. Methods We performed a retrospective analysis utilizing SUNY Upstate University Hospital data from January 2016 to March 2022 to assess transplant outcomes and biopsies. The study population was divided into two subgroups: non-protocol biopsies and protocol biopsies within the 12 months post-transplant. Results A total of 332 patients met our inclusion criteria and were included in the study. Patients were divided into two subgroups: 135 patients (40.6%) in the protocol biopsy group and 197 patients (59.4%) with non-protocol indication biopsies during the first year after the transplant. The overall number of rejection episodes reported was eight episodes (4.6%) in the protocol biopsy group and 56 episodes (18.3%) in the non-protocol indication biopsy group, which was significantly higher in the non-protocol biopsy group (P=0.001). Antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR) diagnoses were significantly higher in the non-protocol biopsy group (P=0.03 and P=0.03, respectively). We also mentioned a trend in terms of mixed antibody-mediated rejection and T-cell-mediated rejection diagnosis (P=0.07). One year after the rejection, the mean glomerular filtration rate (GFR) was 56.78 mL/min/1.73m2 in the protocol biopsy group and 49.14 mL/min/1.73m2 in the non-protocol indication biopsy group, and there was no significant difference anymore (P=0.11). The patient survival rate was not significantly higher in the protocol biopsy group compared to the non-protocol indication biopsy group (P=0.42). Conclusion This study suggests that performing protocol biopsies does not significantly benefit rejection rates, graft survival, or renal function within the first 12 months post-transplant. Given these results and the small but non-zero risk of complications associated with protocol biopsies, they should be reserved for those patients at high risk of rejection. It may be more feasible and beneficial to utilize less invasive tests, such as DSA and dd-cfDNA testing, for early diagnosis of a rejection episode.

Transmission of pancreatic adenocarcinoma by a single multiorgan donor to two kidney transplant recipients: A case report.

We present two cases of transmission of a pancreatic adenocarcinoma from a single donor to two kidney transplant recipients. Autopsy of the donor revealed a pancreatic adenocarcinoma that had already spread locally to the regional lymph nodes and had not been detected at the time of organ procurement. Both recipients were carefully monitored, as neither consented to graft nephrectomy. In one patient, the tumor was discovered on surveillance biopsy of the graft approximately 14 months after transplantation, and in the second patient, ultrasound-guided aspiration needle biopsy of a growing formation in the lower pole of the graft revealed poorly differentiated metastatic adenocarcinoma. Both patients were successfully treated with graft nephrectomy and complete discontinuation of immunosuppression. None of the follow-up imaging showed persistent or recurrent malignancy, and both patients were candidates for re-transplantation. These exceptional cases of donor-derived pancreatic adenocarcinoma suggest that removal of the donor organ and restoration of immunity may lead to complete recovery.

Application progress in classification of puncture biopsy after kidney transplantation / 器官移植

Renal allograft biopsy (biopsy) remains the "gold standard" for the diagnosis of renal dysfunction after kidney transplantation. Puncture biopsy after kidney transplantation could be divided into indicative biopsy and protocol biopsy according to renal function of the patients. Indicative biopsy is mainly applied to diagnose postoperative complications of kidney transplantation, evaluate the severity of disease and guide subsequent treatment. Protocol biopsy is primarily employed to regular monitor renal allograft function of kidney transplant recipients and exclude subclinical rejection and other complications. Due to the willingness of patients and other reasons, protocol biopsy has not been widely applied in China. Currently, indicative biopsy is the main biopsy pattern. At present, the indications of puncture of indicative biopsy, the timing and necessity of puncture of protocol biopsy remain controversial. In this article, the classification of puncture biopsy after kidney transplantation and research progress on tissue biomarkers based on biopsy were reviewed, aiming to assist clinical diagnosis and targeted treatment of complications after kidney transplantation and provide reference for further improving the survival of renal allografts and recipients.

Applications and new understandings of protocol biopsy during kidney transplantation / 中华器官移植杂志

Protocol biopsy (PB) is a planned needle biopsy of transplanted kidney and pathological observation for timely diagnosing the potential complications in transplanted kidney and guiding clinical interventions and adjusting immunosuppression regimen before an onset of dysfunction of transplanted kidney.With accurate information, it may grasp the baseline data of transplanted kidney histopathology.If detected early, timely measures may avert the existence of subclinical rejection or viral infection, avoid inflammation or injury and prevent various complications to ensure a better prognosis of transplanted kidney.At the same time, it is imperative to recognize the disadvantages of procedural biopsy, such as invasiveness, time consuming, greater patient discomfort and medical expenditure.This review focused upon the advantages and disadvantages of PB and its clinical application value.In light of the latest advances of clinical researches, favorable factors of PB are optimized for better long-term functional survival of transplanted kidney.

A Histology-Guided Approach to the Management of Patients with Lupus Nephritis: Are We There Yet?

Renal involvement is a frequent complication of systemic lupus erythematosus (SLE). It occurs in up to two-thirds of patients, often early during the disease course, and is the most important predictor of the morbidity and mortality of SLE patients. Despite tremendous improvements in the approach of the lupus nephritis (LN) therapy, including the recent approval of two new disease-modifying therapies, up to 50% of patients do not obtain a renal response and up to 25% will eventually progress to end-stage renal disease (ESRD) within 10 years of diagnosis. Given the lack of correlation between clinical features and histological lesions, there is an increasing need for a histology-guided approach to the management of patients with LN. Apart from the initial diagnosis of type and severity of renal injury in SLE, the concept of a repeat kidney biopsy (either in a for-cause or a per-protocol scenario) has begun to gain increasing popularity in the nephrology community. Herein, we will provide a comprehensive overview of the most important areas of utility of the kidney biopsy in patients with LN.

Two-Week Protocol Biopsy in Renal Allograft: Feasibility, Safety, and Outcomes.

BACKGROUND: Protocol biopsy in renal allograft helps to early detect subclinical rejection (SCR) in patients who have no abnormal clinical and laboratory findings. Still, there are rare reports about the techniques and outcomes of two-week protocol biopsy. The aim of this study was to assess two-week protocol biopsy regarding the technical feasibility, procedure safety, and clinical outcomes. METHODS: A total of 894 protocol biopsies were performed in adult recipients between 2012 and 2019. Two-week and one-year protocol biopsies were guided with ultrasound in 842 and 399 patients by one of four radiologists with wide range of biopsy experience, respectively. These protocol biopsies were compared in terms of feasibility and safety. Standard references were clinico-laboratory findings and biopsy examinations. RESULTS: The median period of two-week and one-year protocol biopsies were 12 days (10-20 days) and 383 days (302-420 days), respectively. All protocol biopsies were technically successful and there was no difference between radiologists regarding technical success and complications (p = 0.453). Major complication (Clavien-Dindo grading II-IV) rates of two-week and one-year protocol biopsies were 0.3% (3/842) and 0.2% (1/399), respectively (p = 1.000). However, univariate analysis demonstrated that platelet count < 100 K/mL and blood urea nitrogen ≥ 40 mg/dL were associated with major complications in two-week protocol biopsy. The SCRs of these protocol biopsies were 15.4% (130/842) and 33.6% (134/399), respectively (p < 0.001). CONCLUSION: Two-week protocol biopsy is technically feasible and safe. It contributes to early detecting a substantial number of SCRs. Prior to the biopsy, platelet count and blood urea nitrogen should be carefully checked to predict major complications.

Histologic acute graft pyelonephritis after kidney transplantation: Incidence, clinical characteristics, risk factors, and association with graft loss.

BACKGROUND: Histologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known. METHODS: We performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly. RESULTS: HAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%-7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122-755 days). Indications for biopsy were follow-up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss. CONCLUSION: HAGPN is an infrequent, unanticipated, and clinically significant complication of KT.

Donor-derived cell-free DNA and renal allograft rejection in surveillance biopsies and indication biopsies.

To evaluate the role of circulating dd-cfDNA in allograft surveillance in immunologically high-risk patients, a retrospective cross-sectional study of 261 kidney transplant recipients who underwent outpatient allograft biopsy at our center between September 2020 and August 2021 was performed. Of the 236 dd-cfDNA results included, 37 samples were obtained at the time of a surveillance biopsy in sensitized recipients and 199 at the time of a clinically indicated biopsy. The median serum creatinine at the time of the biopsy was 1.3 mg/dl and 2.1 mg/dl for surveillance biopsies and clinically indicated biopsies, respectively (P < .001). Rejection was diagnosed in 27% of surveillance biopsies and 29% of clinically indicated biopsies. Among surveillance biopsies, sensitivity and specificity to detect rejection were 0% and 89%, respectively, and among clinically indicated biopsies they were 28% and 96%, respectively. The sensitivity and specificity to detect antibody-mediated rejection were 0% and 91% among surveillance biopsies and 50% and 94% among clinically indicated biopsies. Nine biopsies without rejection findings had corresponding dd-cfDNA of ≥1%. Our data does not support dd-cfDNA as a biomarker for kidney allograft rejection, even in immunologically high-risk patients in the absence of graft dysfunction.

Posttransplant recurrence of calcium oxalate crystals in patients with primary hyperoxaluria: Incidence, risk factors, and effect on renal allograft function.

Primary hyperoxaluria (PH) is a metabolic defect that results in oxalate overproduction by the liver and leads to kidney failure due to oxalate nephropathy. As oxalate tissue stores are mobilized after transplantation, the transplanted kidney is at risk of recurrent disease. We evaluated surveillance kidney transplant biopsies for recurrent calcium oxalate (CaOx) deposits in 37 kidney transplants (29 simultaneous kidney and liver [K/L] transplants and eight kidney alone [K]) in 36 PH patients and 62 comparison transplants. Median follow-up posttransplant was 9.2 years (IQR: [5.3, 15.1]). The recurrence of CaOx crystals in surveillance biopsies in PH at any time posttransplant was 46% overall (41% in K/L, 62% in K). Higher CaOx crystal index (which accounted for biopsy sample size) was associated with higher plasma and urine oxalate following transplant (p < .01 and p < .02, respectively). There was a trend toward higher graft failure among PH patients with CaOx crystals on surveillance biopsies compared with those without (HR 4.43 [0.88, 22.35], p = .07). CaOx crystal deposition is frequent in kidney transplants in PH patients. The avoidance of high plasma oxalate and reduction of CaOx crystallization may decrease the risk of recurrent oxalate nephropathy following kidney transplantation in patients with PH. This study was approved by the IRB at Mayo Clinic.

Diffuse C4d staining of peritubular capillaries in renal allograft following bamlanivimab therapy.

Neutralizing monoclonal antibodies such as bamlanivimab emerged as promising agents in treating kidney transplant recipients with COVID-19. However, the impact of bamlanivimab on kidney allograft histology remains unknown. We report a case of a kidney transplant recipient who received bamlanivimab for COVID-19 with subsequent histologic findings of diffuse peritubular capillary C4d staining. A 33-year-old man with end-stage kidney disease secondary to hypertension who received an ABO compatible kidney from a living donor, presented for his 4-month protocol visit. He was diagnosed with COVID-19 44 days prior to his visit and had received bamlanivimab with an uneventful recovery. His 4-month surveillance biopsy showed diffuse C4d staining of the peritubular capillaries without other features of antibody-mediated rejection (ABMR). Donor-specific antibodies were negative on repeat evaluations. ABMR gene expression panel was negative. His creatinine was stable at 1.3 mg/dl, without albuminuria. Given the temporal relationship between bamlanivimab and our observations of diffuse C4d staining of the peritubular capillaries, we hypothesize that bamlanivimab might bind to angiotensin-converting enzyme 2, resulting in classical complement pathway and C4d deposition. We elected to closely monitor kidney function which has been stable at 6 months after the biopsy. In conclusion, diffuse C4d may present following bamlanivimab administration without any evidence of ABMR.