Exploring Acute Pancreatitis in Kidney Transplant Recipients: A Multicentre Retrospective Cohort Analysis of Incidence, Causes, and Clinical Outcomes.

Background: The aim of this multicentre retrospective study is to determine the incidence, etiology, clinical characteristics, and outcomes of kidney transplant recipients diagnosed and treated for acute pancreatitis. Methods: We analyzed data from kidney transplant recipients who received kidney allografts between October 1973 and December 2023 and were diagnosed and treated for acute pancreatitis. Results: Of 2482 patients who received kidney allografts, 10 (0.4%) (5 male) were diagnosed with acute pancreatitis, with a mean age of 48.6 years. Patients were diagnosed with acute pancreatitis between 3 weeks and 24 years after the transplantation. Possible etiologies included cholecystolithiasis, COVID-19, hypercalcemia, postprocedural, use of cannabis, trimetoprim-sulphometoxasole, statins, sirolimus, tacrolimus and obesity. There was no suspected etiology in two patients. Patients were treated with aggressive hydration, pain alleviation and antibiotics if indicated. Four patients developed complications. Local complications included peripancreatic collections, pseudocyst, and abscesses formation, while systemic complications occurred in the form of Cytomegalovirus (CMV) reactivation and urinary tract infection. All patients survived with preserved kidney allograft function. Conclusions: Acute pancreatitis in kidney transplant recipients is rare. However, it may be linked to significant morbidity and mortality. While symptoms may be nonspecific and brought on by a variety of viral and non-infectious illnesses, as well as adverse effects from immunosuppressive medications, a high degree of awareness is required.

JC Virus in Kidney Transplant Population: Are We Cautious Enough?

The John Cunningham virus (JCV) is a polyomavirus that usually infects people at a young age and does not cause any symptoms in immunocompetent individuals. However, in immunocompromised individuals, such as kidney transplant recipients, JCV can cause severe and potentially fatal disease. Unfortunately, JCV has not been researched as extensively as the BK virus and is not mentioned in relevant kidney transplant guidelines. This lack of attention to JCV can lead to less consideration in kidney transplant patients' care. Surveillance using locally available diagnostic methods is of the utmost importance. The presence of JCV can be diagnosed with urine decoy cells, viruria, or viremia verified by the PCR method. A low threshold for considering JCV as a possible cause of any neurological or renal dysfunction in kidney transplant recipients must be maintained. In such cases, kidney and brain biopsy are indicated. Maintaining the appropriate immunosuppression while avoiding over-immunosuppression to prevent JCV disease is crucial, and the approach should be individual, according to overall immunological risk. We hypothesize that the presence of the JCV can indicate overt immunosuppression and identify kidney transplant recipients more prone to opportunistic infections and diseases, including some malignancies. To explore that, future observational studies are needed.

Immunomodulatory Effect of COVID-19 on HLA-Antibody Profile in Renal Transplant Recipients.

Background/Objectives: The novel coronavirus disease 2019 (COVID-19) has led to significant morbidity and mortality among kidney transplant recipients. SARS-CoV-2 has been hypothesized to cause an unusual immunological dysregulation triggering alloimmunity and leading to graft rejection. Methods: This prospective observational cohort study assessed 321 kidney transplant recipients who had COVID-19 infection. After the infection, patients' sera were tested for the presence of anti-HLA de novo DSA and non-DSA specificities. Logistic regression analysis and a stepwise multivariable logistic regression analysis were used to analyze the independent risk factors associated with the development of antibodies, adjusting for known confounders. The variables evaluated were acute COVID-19 characteristics (i.e., presentation, and need for hospitalization), demographic characteristics (i.e., age, gender, and primary renal disease), clinical characteristics (i.e., various comorbidities), and post-COVID-19 sequelae. Results: Anti-HLA de novo DSA developed in 18.7% of patients, while anti-HLA class I and class II non-DSA antibodies developed de novo in 84 (26.3%) and 83 (25.9%) patients, respectively. The development of DSA, HLA-DQ, and HLA-DR antibodies was predicted by the history of graft rejection. Obesity appeared to be protective against the emergence of de novo DSA. De novo DSA and HLA-DR antibody formation was positively linked with intravenous immunoglobulin use, CMV-hyperimmune globulin use, and decreased doses of immunosuppression during acute infection. Better allograft function during the acute disease was a protective factor against the formation of HLA-DQ and HLA-DR antibodies. Positive predictors of de novo DSA development were graft biopsy and the reactivation of EBV after infection. Conclusions: These findings suggest that the SARS-CoV-2 virus has an immunomodulatory effect and may be associated with an increased mortality in this population.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients.

BACKGROUND: Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019 (COVID-19) but its full correlation with COVID-19 infection remains unknown. AIM: To identify acute pancreatitis' occurrence, clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19. METHODS: A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19. Data were obtained from hospital electronic medical records. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab. RESULTS: Four hundred and eight out of 1432 (28.49%) patients who received a renal allograft developed COVID-19 disease. The analyzed cohort included 321 patients (57% males). One hundred and fifty patients (46.7%) received at least one dose of the anti-SARS-CoV-2 vaccine before the infection. One hundred twenty-five (39.1%) patients required hospitalization, 141 (44.1%) developed pneumonia and four patients (1.3%) required mechanical ventilation. Treatment included immunosuppression modification in 233 patients (77.1%) and remdesivir in 53 patients (16.6%), besides the other supportive measures. In the study cohort, only one transplant recipient (0.3%) developed acute pancreatitis during acute COVID-19, presenting with abdominal pain and significantly elevated pancreatic enzymes. She survived without complications with a stable kidney allograft function. CONCLUSION: Although rare, acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients. The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

A Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients.

In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation.

Histopathological Features of Time-Zero Kidney Biopsy Are Predictive Factors for Posttransplant Anemia.

INTRODUCTION: Posttransplant anemia (PTA) is a common complication of kidney transplantation, associated with reduced graft survival and higher mortality. We aimed to determine the association of PTA with histopathological characteristics of time-zero allograft biopsy and donor clinical characteristics. METHODS: We conducted a retrospective, observational cohort study that included 587 patients who underwent kidney transplantation in our center. Hemoglobin levels were assessed at 6 and 12 months after transplantation, and anemia was defined according to World Health Organization criteria. The kidney allograft time-zero biopsy has been done in all investigated cases. The evaluated histopathological parameters of the kidney allografts included glomerulosclerosis, arteriolar hyalinosis (AH), vascular fibrous intimal thickening (CV), interstitial fibrosis, tubular atrophy, and interstitial fibrosis and tubular atrophy. The Banff Classification of Allograft Pathology criteria were followed to assess the allograft histopathological changes. RESULTS: The prevalence of anemia was 31.3% at 6 months after transplantation and 23.5% at 12 months. There was an association between 20-50% glomerulosclerosis and PTA in both time points, independently from estimated glomerular filtration rate. AH and interstitial fibrosis were identified as independent risk factors for anemia 6 months after transplantation. CONCLUSION: Histopathological features of time-zero kidney biopsy may be predictors of PTA. Among them, our study recognized 20-50% degree of glomerulosclerosis, AH, and CV as the most significant risk factors for PTA.

Autoantibodies in COVID-19, a possible role in the pathogenesis of the disease.

OBJECTIVES: In this study, we investigated whether SARS-CoV-2 stimulates autoantibody production. METHODS: The study included 91 patients hospitalized due to COVID 19, with no previous history of immunological diseases. Immunofluorescence assays were performed to detect antinuclear antibodies (ANAs) and antineutrophil cytoplasmic antibodies (ANCAs), along with tests for specific autoantibodies. RESULTS: The median age (57% male) was 74 years (range 38-95 years). Autoantibodies were positive in 67 (74%), ANA in 65 (71%), and ANCA in 11 (12%) patients. Female gender (p = 0.01), age (p = 0.005), and Charlson comorbidity index (p = 0.004) were significant predictors for the development of ANA/ANCA antibodies (p = 0.004). Nuclear mitotic apparatus (NuMA)-like, positivity was the strongest predictor of acute kidney injury (AKI), together with noninvasive ventilation and eGFR (χ2 = 49.01, P < 0.001). CONCLUSION: Positive autoantibodies in a large proportion of patients suggest a role of autoimmunity in the pathophysiology of acute COVID-19 disease. NuMA was the strongest predictor of AKI.

Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study.

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients. DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials). PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021. MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys. TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.

Cardiovascular Outcomes in De Novo Kidney Transplant Recipients Receiving Everolimus and Reduced Calcineurin Inhibitor or Standard Triple Therapy: 24-month Post Hoc Analysis From TRANSFORM Study.

BACKGROUND: The comparative impact of everolimus (EVR)-based regimens versus standard of care (mycophenolic acid+standard calcineurin inhibitor [MPA+sCNI]) on cardiovascular outcomes in de novo kidney transplant recipients (KTRs) is poorly understood. The incidence of major adverse cardiac events (MACEs) in KTRs receiving EVR+reduced CNI (rCNI) or MPA+sCNI from the TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen study was evaluated. METHODS: The incidence of MACE was determined for all randomized patients receiving at least 1 dose of the study drug. Factors associated with MACEs were determined by logistic regression. Risk of MACE out to 3 y post-study was calculated using the Patient Outcome in Renal Transplantation equation. RESULTS: MACE occurred in 81 of 1014 (8.0%; EVR+rCNI) versus 89 of 1012 (8.8%; MPA+sCNI) KTRs (risk ratio, 0.91 [95% confidence interval [CI], 0.68-1.21]). The incidence of circulatory death, myocardial infarction, revascularization, or angina was similar between the arms. Incidence of MACE was similar between EVR+rCNI and MPA+sCNI arms with a higher incidence in prespecified risk groups: older age, pretransplant diabetes (15.1% versus 15.9%), statin use (8.5% versus 10.8%), and low estimated glomerular filtration rate (Month 2 estimated glomerular filtration rate <30 versus >60 mL/min/1.73 m 2 ; odds ratio, 2.23 [95% CI, 1.02-4.86]; P = 0.044), respectively. Predicted risk of MACE within 3 y of follow-up did not differ between the treatment arms. CONCLUSIONS: Cardiovascular morbidity and mortality were similar between de novo KTRs receiving EVR+rCNI and MPA+sCNI. EVR+rCNI is a viable alternative to the current standard of care in KTRs.

Collapsing Focal Segmental Glomerulosclerosis After Kidney Transplantation: Is It a Consequence of Viral Infections?

BACKGROUND: The aim of this case study was to explore the possible link between viral infections and collapsing focal segmental glomerulosclerosis (cFSGS) in patients who underwent kidney transplantation. METHODS: This case study included 3 case reports of patients who underwent kidney transplantation. The case reports were presented clinically and pathohistologically with cFsGS as a possible consequence of viral infections. RESULTS: The first patient developed cFSGS after polymerase chain reaction for SARS-CoV2 was positive twice. He gradually developed terminal stage chronic kidney disease. The second patient developed cFSGS with high range proteinuria after cytomegalovirus infection, which has been treated with 3 lines of antiviral medicaments. The third patient developed cFSGS as a possible consequence of hepatitis B virus infection. CONCLUSIONS: This case study highlighted the importance of viral etiology in the pathway of cFSGS. Pathogenic links between viral infections and concomitant glomerulopathies are challenging, especially in immunocompromised transplanted patients.

MANAGEMENT OF PROSTATE CANCER IN KIDNEY TRANSPLANT RECIPIENTS.

Kidney transplantation is the treatment of choice in eligible patients with end-stage kidney disease. Prostate cancer (PC) is the second most common cancer in men worldwide. The prevalence of chronic kidney disease worldwide is 13.4%. The management of localized PC in these patients is challenging due to immunosuppressive therapy and pelvic graft localization. High graft and recipient survival rates have resulted in higher numbers of these patients in our everyday practice. A retrospective analysis of male patients who had undergone kidney transplantation at our center between 2002 and 2022 and were diagnosed and treated for PC was performed. We analyzed the incidence, treatment methods, and follow-up of PC patients in this population. A total of 1079 male patients were transplanted. PC was diagnosed in 12 patients (8 after and 4 before transplantation). The incidence of PC was 1.11%. Radical prostatectomy was performed in 11 patients, and one patient was treated with radical radiotherapy. Eleven patients had stable graft function; 1 graftectomy was performed, unrelated to PC. Three patients were indicated for salvage radiotherapy, one is in process for prostate-specific membrane antigen positron emission tomography (PSMA PET CT), and 7 patients are in follow-up and without recurrence. Radical prostatectomy is a safe treatment method for localized PC in kidney transplant recipients, which does not impair graft function and survival.

Kidney Transplantation in Patients With the History of SARS-CoV-2 Infection.

BACKGROUND: The aim of this study is to present the experience and results of kidney transplantation in patients with the history of SARS-CoV-2 infection. METHODS: We retrospectively analyzed waitlisted patients who had a history of SARS-CoV-2 infection and offered a kidney transplant between March 2020 and December 2021. RESULTS: Of the 97 waitlisted potential kidney transplant recipients who were offered a kidney, 13 (13.4%) had a history of SARS-CoV-2 infection. All patients were tested negative for SARS-CoV-2 at the time of the kidney offer. Successful transplantation was performed in 9 patients (5 male; average age was 40.8 years), with the average time between SARS-CoV-2 infection and transplantation of 8 months. Four of 13 patients with a history of SARS-CoV-2 infection were finally not transplanted, with 2 patients not eligible for transplantation due to significant post-COVID findings in routine pretransplant chest CT scans, and 2 patients were not transplanted because of poor donor organ quality. CONCLUSIONS: Kidney transplantation after SARS-CoV-2 infection is possible in a setting of full recovery from acute infection, negative PCR test, and no pneumonic infiltrates on chest CT scan. A growing number of waitlisted patients with a history of SARS-CoV-2 infection imposes the need for decision-making tools and guidelines for risk/benefit assessment in these patients.

Successful Kidney Transplantation From A Donor With Inherited Thrombophilia: A Case Report.

Inherited thrombophilia is a blood clotting disorder caused by genetic mutations of specific coagulation plasma factors. It is a well-established predisposing factor for venous as well as arterial thromboembolism. Thromboembolic events with renal involvement in patients with inherited thrombophilia are possible but relatively rare. On the other hand, vascular complications, including renal artery and vein thrombosis, are the main causes of early graft loss after kidney transplantation. Furthermore, there is evidence that inherited thrombophilia has a role in chronic kidney disease development. Although there are data on kidney transplantation of recipients with inherited thrombophilia, to the best of our knowledge there are no reports on kidney donation from patients with thrombophilia in the English literature. We present 2 cases of successful kidney transplantation from the same donor with inherited thrombophilia.