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Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. P.F. Halloran holds shares in Transcriptome Sciences Inc., a University of Alberta research company dedicated to developing molecular diagnostics, supported in part by a licensing agreement between Transcriptome Sciences Inc. and Thermo Fisher Scientific, and by a research grant from Natera, Inc. P.F. Halloran is a consultant to Natera, Inc. and Argenx BV. The other authors have declared no conflict of interest exists., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Protocol biopsies are performed to detect subclinical pathologies that may lead to future graft dysfunction. However, they are not routinely performed interventions in every transplant center. There is no established regimen for performing them., Purpose: The study aimed to evaluate if protocol biopsies can improve long-term patient outcomes after detecting early disorders and modifying treatment., Material and Methods: Our observational study included 61 patients who underwent protocol biopsy 12 months after the transplantation. Based on the biopsy results, patients with abnormal histologic material (n = 37) were divided into 3 study groups as follows: patients with mild inflammatory lesions (n = 21), patients with interstitial fibrosis and tubular atrophy (IFTA) grade II to III (n = 12), and patients with BK virus nephropathy (n = 4). The control group (n = 24) included kidney recipients with IFTA 0 to I grade. Outcomes after 5-year follow-up were evaluated., Results: Five years after the biopsy, patients in the control group had stable graft function (5-year change in serum creatinine was -0.09 mg/dL). An increase in serum creatinine levels was observed in patients with IFTA II to III compared with the control group (0.14 mg/dL, P = .04). Immunosuppressive treatment was modified in the group with mild inflammatory changes and in the BKV group after the biopsy result. In the group with mild inflammatory lesions, renal function was stable (change of serum creatinine was -0.01 mg/dL, P = .51). In the BKV nephropathy group, there was a significant reduction in serum creatine levels (-0.48 mg/dL, P = .016). The analysis showed no diagnostic value for serum creatinine concentration (95% CI 0.49-0.78, P = .08)., Conclusions: Protocol biopsies are useful for detecting early pathologies and preventing allograft failure. They greatly benefit patients with detectable pathology that can be treated or in whom therapy modification is possible., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The risk of polyomavirus‑associated nephropathy (PyVAN) currently ranges from 1% to 10%, and the risk of graft loss is 10% to 50% within 2 years post‑diagnosis. There is currently no specific antiviral therapy against BK polyomavirus (BKPyV), and no therapeutic approach has been proven superior. Natural killer cells play a key role in the defense against viral infections., Objectives: A retrospective, single‑center cohort study was performed to investigate the association between the kidney transplant recipients' killer‑cell immunoglobulin‑like receptor (KIR) genotype and PyVAN. We also evaluated other possible risk factors for the occurrence of PyVAN in a population of kidney transplant recipients., Patients and Methods: DNA samples from 134 kidney transplant recipients were identified for the presence or absence of variable KIR genes and their HLA ligands using polymerase chain reaction with sequence‑specific primers., Results: The analysis revealed that the presence of the inhibitory KIR2DL3 (P = 0.03) was a risk factor for posttransplant PyVAN. We also found that the presence of acute rejection before PyVAN (P = 0.02), male sex (P = 0.04), and the lack of antiviral prophylaxis (P = 0.01) were additional risk factors for posttransplant PyVAN., Conclusions: Our findings confirm that the KIR/HLA genotype plays a significant role in the development of PyVAN and suggest the contribution of both environmental and genetic factors to the incidence of BKPyV infection after kidney transplantation.

BACKGROUND COVID-19 disease, caused by the SARS-CoV-2 virus, has been one of the greatest challenges in modern medicine. It is mostly known to affect the pulmonary system, leading to pneumonia and acute respiratory distress syndrome, but there is a growing body of evidence of extrapulmonary manifestations of COVID-19 disease. CASE REPORT This article presents 3 cases of various extrapulmonary symptoms of COVID-19 disease and a literature review of similar clinical cases. Two patients had a medical history of living-donor kidney transplantation, and 1 patient was a kidney donor. We present symptoms, diagnostic processes, laboratory and imaging results, and treatment approach. Patient 1 was 29-year-old woman with new-onset diabetes mellitus due to SARS-CoV-2, which required temporary insulin treatment. Patient 2 was a 34-year-old man with fever, chronic fatigue, back pain, and abdominal pain. Imagining showed acalculous cholecystitis, epiploic appendagitis of the right colic flexure, and inflammation of pericardial fat pad in the left cardiophrenic angle. Coagulopathy due to COVID-19 was the most probable cause of the described processes. Therapeutic doses of low-molecular-weight heparin were administered. Patient 3 was a 68-year-old male kidney donor who had painless, nodular, reddening lesions on both shins, accompanied by itching on both shins and recurrent fever. The diagnosis of erythema nodosum during COVID-19 was made. After treatment with low-molecular-weight heparin, significant decreases of symptoms were observed. CONCLUSIONS We conclude that SARS-CoV-2 infection can have a varied course and can involve other systems and organs. Physicians should be aware of possible extrapulmonary symptoms associated with infection with this virus. Correct diagnosis is a prerequisite for proper treatment and prevention of unexpected complications.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a robust immune response. The development of systemic inflammation leads to a hyperinflammatory state due to cytokine release syndrome during severe COVID-19. The emergence of many new SARS-CoV-2 variants across the world deteriorates the protective antiviral immunity induced after infection or vaccination. The innate immune response to SARS-CoV-2 is crucial for determining the fate of COVID-19 symptomatology. T cell-mediated immunity is the main factor of the antiviral immune response; moreover, SARS-CoV-2 infection initiates a rapid B-cell response. In this paper, we present the current state of knowledge on immunity after COVID-19 infection and vaccination. We discuss the mechanisms of immune response to various types of vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus vaccines and recombinant protein adjuvanted formulations). This includes specific aspects of vaccination in selected patient populations with altered immune activity (the elderly, children, pregnant women, solid organ transplant recipients, patients with systemic rheumatic diseases or malignancies). We also present diagnostic and research tools available to study the anti-SARS-CoV-2 cellular and humoral immune responses.

Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid organ transplant (SOT) recipients are a heterogeneous population with long-lasting immunosuppression as a joining element. Immunocompromised patients are a vulnerable population with a high risk of severe infections and an increased infection-related mortality rate. It was postulated that the hyperinflammatory state due to cytokine release syndrome during severe COVID-19 could be alleviated by immunosuppressive therapy in SOT patients. On the other hand, it was previously established that T cell-mediated immunity, which is significantly weakened in SOT recipients, is the main component of antiviral immune responses. In this paper, we present the current state of science on COVID-19 immunology in relation to solid organ transplantation with prospective therapeutic and vaccination strategies in this population.

Introduction: Early prognostic markers that identify high‑risk kidney transplant recipients may lead to optimization of immunosuppressive therapy and improved long‑term outcomes., Objectives: The aim of this study was to assess whether the measurement of urinary concentrations of CCL2 and CXCL10 chemokines can be a valuable noninvasive tool for identifying ongoing pathological processes in a kidney allograft., Patients and Methods: The study included 40 patients who underwent a protocol biopsy within 1‑year post kidney transplant. The urinary concentrations of CCL2 and CXCL10 with reference to creatinine in urine were assayed in all patients. On the basis of biopsy results, a study group was selected (n = 25), including patients with a diagnosis of interstitial fibrosis and tubular atrophy grades II to III (n = 16), BK virus (BKV) nephropathy (n = 4), or mild inflammatory lesions fulfilling the criteria for mild rejection processes or borderline lesions (n = 11). Patients with normal biopsy results were included in a control group (n = 15)., Results: The ratio of CCL2 to creatinine (CCL2:Cr) was a significant independent predictor of BKV ephropathy (odds ratio, 1.1; 95% CI, 1.0-1.2; P = 0.04). The CXCL10:Cr ratio was not found to be an independent predictor of BKV nephropathy (odds ratio, 1.3; 95% CI, 0.99-1.71; P = 0.06)., Conclusions: The CCL2:Cr and CXCL10:Cr ratios may predict BKV nephropathy. The diagnostic value of CCL2 and CXCL10 in BKV infection should be further evaluated.

Background: Cytomegaly remains one of the most common infectious complications in organ transplant recipients, and the course of the infection may have a negative effect on survival of the transplant and recipient., Case Report: We describe the case of a 32-year-old female patient who received a second kidney transplant from a cadaveric donor in July 2012, treated successfully with ganciclovir for primary CMV infection in August 2012 and then re-treated from November due to re-infection. The viral load at the start of re-treatment was 6 million copies. In view of ganciclovir treatment failure, Sando immunoglobulins were administered. Subsequently, when CMV viral load increased to 18 million copies, a decision was made to use combination treatment with leflunomide and ganciclovir. Immunosuppressive treatment was also modified by administering everolimus in view of its potential antiviral activity. Seizures, pancytopenia, diabetes, diarrhoea, and (probably) drug-induced liver damage and cholangitis were observed in the course of treatment. At 3 months of hospitalization, the patient was discharged home with viral load of 8000 copies. As treatment continuation, she received valganciclovir at the full therapeutic dose in view of very good kidney function (creatinine 0.7 mg/dl). The patient was re-hospitalized after 10 days due to fever and cough. Due to abnormal liver function test results and negative serum markers of viral hepatitis, HCV RNA was tested, with a positive result (above 10^8 copies). Subsequently, decline in clinical status, overhydration, increasing creatinine levels, hepatic failure signs, and renewed CMV DNA increase to 520 000 copies were observed. Despite intensive treatment, the patient died of multi-organ failure., Conclusions: The case described illustrates the difficulties in the treatment of CMV infection and its possible dramatic complications.