Hepatitis E virus (HEV) is a common but often underdiagnosed cause of hepatitis in both the general population and transplant patients. Diagnosis is usually made by detecting IgM anti-HEV antibodies, with immunosuppressed individuals being at higher risk for chronic infection. We present the case of a 56-year-old man who developed asymptomatic liver cytolysis 4 months after a kidney transplant, with no significant physical findings or relevant epidemiological history. Abdominal ultrasound revealed hepatic steatosis. Drug-induced liver injury was suspected, prompting the discontinuation of potential causative agents. However, liver enzymes worsened asymptomatically after 2 weeks, prompting further medication adjustments. Testing for Hepatitis B and C, as well as IgM for Toxoplasma, was negative. Serologies for herpes simplex and varicella zoster were positive for IgG and negative for IgM, and CMV viral load was undetectable. HEV serologies were negative for IgG and IgM. A liver biopsy revealed nonspecific acute hepatitis without fibrosis. The positive HEV plasma viral load was suggestive of Hepatitis E. As the patient was asymptomatic with no further analytical worsening, targeted treatment was not initiated. The patient achieved spontaneous viral clearance in less than 12 weeks, despite his immunocompromised condition. This case report highlights the diagnostic challenges of HEV hepatitis in immunosuppressed patients, as detection may rely solely on viral load testing due to potential serological negativity. This case also highlights that despite the patient's immunosuppressed condition, viral clearance is possible without the need for targeted antiviral therapy.

Background: Torque Teno Virus (TTV) viremia has been proposed as a marker for infection risk in kidney transplant (KT) recipients. This study aimed to evaluate the prognostic value of TTV levels for predicting infections post-KT. Methods: A cohort of 82 KT patients was analyzed. TTV loads were measured before KT and at the time of cutoff analysis (mean time since KT: 20.2 ± 10.3 months). Infections were tracked within six months following the time of cutoff analysis. Univariable analyses and a supervised machine learning approach (logistic regression with leave-one-out cross-validation) were conducted to rigorously assess TTV’s predictive ability for post-transplant infection. Results: Seventy-two patients (87.8%) had detectable TTV before KT. Of these, 30.5% developed infections, predominantly viral. TTV loads increased significantly from 3.35 ± 1.67 log10 cp/mL before KT to 4.53 ± 1.93 log10 cp/mL at the time of cutoff analysis. Infected patients had significantly higher TTV loads (5.39 ± 1.68 log10 vs. 4.16 ± 1.94 log10 cp/mL, p = 0.0057). The optimal TTV threshold for predicting infection at the time of cutoff analysis was 5.16 log10 cp/mL, with 60% sensitivity and 81% specificity. Machine learning models improved performance, with sensitivity and specificity 0.805 and 0.735, respectively. Conclusions: TTV viremia may serve as a biomarker for infection risk, particularly when used with other clinical variables. The identified TTV threshold of 5.16 log10 cp/mL offers a practical tool for clinical decision-making, particularly when integrated with a machine learning model. Further studies with larger cohorts are needed to validate these findings and refine clinical applications.

Kidney transplantation (KT) is a hallmark of modern nephrology, offering improved survival and quality of life to chronic kidney disease (CKD) patients. Despite its success, maintaining optimal graft function on the long term remains a significant challenge, due to complications, including rejection, infections, drug toxicity, and recurrence of primary kidney disease. We aim to present a challenging case of kidney allograft dysfunction. Demographic, clinical, blood analysis and pathology data were obtained from the patient's electronic medical record from our Nephrology and Transplantation Center. We report the case of a 63-year-old caucasian male with medical history of metabolic syndrome (hypertension, dyslipidemia and obesity), chronic HIV-1 infection (Atlanta CDC Stage A3) and CKD of unknown etiology, who began hemodialysis in October 2020. He was submitted to KT from a living related donor in April 2022. Both donor and recipient were AB0 isogroupal. Pre-KT study showed 2 HLA mismatches (1 in A and 1 in DR) and a negative crossmatch for Anti-HLA class I and II alloantibodies (CDC and flow cytometry). However, solid state testing with Luminex technology had previously identified a C1q negative donor-specific antibody (DSA) in DQ07 with a median fluorescence intensity 1189 (zenith 1566). Due to this, immunosuppression protocol included a single dose of Rituximab pre-KT (375 mg/m2), followed by basiliximab and intravenous immunoglobulin 2 g/kg, as well as methylprednisolone (MTP), tacrolimus and mycophenolate mofetil. On the 4th day post-KT, due to acute graft dysfunction (AGD), kidney biopsy (KB) was performed, confirming acute T-cell mediated rejection (TCMR) – Banff category 4 IA, which prompted administration of 4 consecutive MTP 500 mg pulses. On the 14th day post-KT, the patient was discharged with a serum creatinine (sCr) nadir of 1.6 mg/dL. Of note, one-month post-KT, due to AGD (2.5mg/dL sCr), KB was performed, revealing borderline lesions of acute TCMR – Banff category 3, which was treated with 3 consecutive doses of prednisolone 100 mg. Follow-up was maintained, without relevant complications, with a triple immunosuppressive regimen consisting of tacrolimus (through levels ∼7 ng/mL), mycophenolic acid and prednisolone. Graft function remained stable (sCr 1.6 mg/dL), and urinalysis was unremarkable. Two years post-KT, the patient developed new-onset AGD (sCr 2.24 mg/dL), with worsening proteinuria – zenith 1755 mg/g protein-to-creatinine ratio. Graft ultrasound with doppler scan was normal, no DSAs were identified and laboratory values, including C3, C4, serum protein electrophoresis and relevant serum serologies and viral loads (HCV, HIV, HBV, CMV and polyomavirus) were negative. KB was performed, revealing membranoproliferative glomerulonephritis, with no histologic criteria for rejection. Remarkably, immunofluorescence on the frozen section was negative for IgA, IgM, C1q, C3, Kappa and Lambda free light chains, fibrin and albumin. Therefore, ultrastructural evaluation was requested, which showed fibrillar glomerulonephritis (FGN). DNAJB9 testing was unavailable. Other potential secondary causes were excluded, including auto-immune disease and hematological malignancy. Given the diagnosis, an angiotensin receptor II blocker was introduced as an antiproteinuric measure. The approach to AGD in KT patients should include the evaluation for recurring or new-onset glomerular disease, more so in those with CKD of unknown etiology. Glomerular disease due to non-amyloid deposits is a rare diagnosis (1.4% of native KB), with FGN representing up to 90% of cases. Although most cases are considered idiopathic, the strong association with neoplasia, monoclonal gammopathy and auto-immune disease warrants further diagnosis evaluation to exclude potential secondary causes. Use of biomarkers such as DNAJB9 could improve diagnostic accuracy. Evidence based treatment decisions remain scarce, particularly in idiopathic FGN, with experts recommending antiproteinuric measures, and in some cases, rituximab based regimens.

BACKGROUND:Gastrointestinal complications are common in kidney transplant (KT) patients and can be a consequence of the chronic use of immunosuppression. The differential diagnosis of colitis in KT patients includes intolerance to immunosuppressive agents, namely mycophenolate mofetil, de novo inflammatory bowel disease (IBD) and opportunistic infections. Epstein-Barr virus (EBV) infection may cause post-transplant colitis or trigger de novo IBD, although is seldom thought as the causative pathogen. OBJECTIVES:To describe clinical characteristics, endoscopic and histological findings, treatment and outcome of three patients that developed EBV associated colitis following kidney transplantation. METHODS:We retrospectively analyzed three patients with EBV associated colitis; clinical data including transplantation, gastrointestinal symptoms, endoscopy findings, and follow-up data was obtained. RESULTS:We present a case series of three patients with EBV colitis following KT, with an average age at clinical presentation of 59 years and elapsed time since the KT ranging from five to 22 years. Clinical manifestations included bloody diarrhoea, abdominal pain, weight loss and/or fever. Cytomegalovirus colitis, mycophenolate mofetil-related colitis, lymphoproliferative disease and graft versus host disease were excluded. One patient had a prior diagnosis of IBD. Two of the three patients had an unfavourable outcome with death despite reduction and/or switching of immunosuppressants, optimal medical treatment (including antiviral and intravenous immunoglobulin therapies) and salvage surgical therapy. CONCLUSION:A multidisciplinary approach is necessary to allow an expeditious diagnosis of a rare entity such as EBV associated colitis in KT. Long-term surveillance of these patients and the development of effective and safe therapies is essential.

Abstract Background and Aims Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell condition with a reported prevalence of 3 to 4% in population older than 50 years and progression to multiple myeloma in approximately 1% of the cases. The clinical significance of MGUS in patients diagnosed prior to kidney transplantation (KT) has previously been studied, however, the impact on survival and morbidity of newly diagnosed MGUS on the period after KT, remains unclear. The aim of this study was to compare the outcomes between patients with MGUS emerging after KT versus non-MGUS patients. Method This is a retrospective single-center cohort analysis of a population of 793 kidney transplant recipients between 1985 and 2022. Diagnosis of MGUS after KT was based on positive serum protein electrophoresis and confirmed by serum immunofixation. We performed a randomized selection of a matched control group, adjusted for age, gender, and KT duration. Both groups were compared for number of infections (bacterial and viral), acute rejections, neoplastic complications, and for overall patient and graft survival. Results This study included a total of 112 patients, with a mean age of 60 years (±11), of which 86 (77%) were older than 50 years. Median follow-up duration was 149 [IQR 89-207] months. We identified 56 patients (7%) with MGUS after KT. Only 1 (1.7%) patient progressed to multiple myeloma. Induction immunosuppression type was not associated with higher development of MGUS. We found no difference between the MGUS group and the control group in the incidence of infections, acute graft rejections, or solid and hematologic neoplasia (Table 1). There was also no difference between overall patient and graft survival. Conclusion MGUS is a premalignant disease frequently present in KT recipients, with a higher prevalence compared to the general population, although its development after KT does not appear to contribute to a worse prognosis or to a higher progression to multiple myeloma.

Torque teno virus (TTV) was recently identified as a potential biomarker for the degree of immunosuppression, and potentially as a predictor of rejection and infection in solid organ transplant patients. We evaluated TTV viral load in kidney transplant (KT) patients during the first year post-transplant to examine overall kinetics and their relationships with deleterious events, including episodes of infection and the formation of de novo donor-specific antibodies (DSAs). In a single-center, prospective observational cohort study, 81 KT patients were monitored at baseline, week 1, and month 1, 3, 6, 9 and 12, post-KT, and whenever required by clinical events. Kidney function, plasma TTV load, immunoglobulins and lymphocyte subpopulations were assessed at each time point. Twenty-six patients (32.1%) presented a total of 38 infection episodes post-KT. Induction immunosuppression with thymoglobulin, compared to basiliximab, was not associated with more infections (p = 0.8093). Patients with infectious events had lower T-cells (p = 0.0500), CD8+ T-cells (p = 0.0313) and B-cells (p = 0.0009) 1 month post-KT, compared to infection-free patients. Patients with infection also showed higher increases in TTV viral loads between week 1- month 1, post-KT, with TTV viral load variations >2.65 log10 cp/mL predicting the development of infectious events during the 12-month study period (p < 0.0001; sensitivity 99.73%; specificity 83.67%). Patients who developed de novo DSAs had lower TTV DNA viral loads at month 12 after KT, compared to patients who did not develop DSA (3.7 vs. 5.3 log10 cp/mL, p = 0.0023). Briefly, evaluating early TTV viremia is a promising strategy for defining infectious risk in the 1st year post-KT. The availability of standardized commercial real-time PCR assays is crucial to further validate this as an effective tool guiding immunosuppression prescription.

ABSTRACT Background Patients with chronic kidney disease (CKD) present a higher risk of cardiovascular (CV) morbidity and mortality compared with the general population. While there are several well-established traditional CV risk factors, few studies have addressed novel potential risk factors such as α-Klotho, asymmetric dimethylarginine (ADMA) and lean mass. Methods This was an observational, prospective, single-center, cohort study that included prevalent hemodialysis (online hemodiafiltration) adult patients. By univariate logistic regression models, univariate and multivariate Cox proportional hazards models, and Kaplan–Meier analysis, we evaluated the association between the levels of α-Klotho, ADMA and lean mass, with the risk of peripheral vascular disease (PVD), CV events and all-cause mortality in these patients. Results A total of 200 HD patients was included. We found that increased levels of log-α-Klotho were significantly associated with decreased odds of both PVD [odds ratio (OR) 0.521, 95% confidence interval (CI) 0.270–0.954, P = .034] and CV events (OR 0.415, 95% CI 0.203–0.790, P = .01), whereas increased levels of log-ADMA were only significantly associated with increased odds of PVD (OR 13.482, 95% CI 5.055–41.606, P < .001). We also found that the levels of log-α-Klotho (HR 0.357, 95% CI 0.140–0.906, P < .05) and lean mass (HR 0.187, 95% CI 0.042–0.829, P < .05), but not log-ADMA, were significantly associated with the risk of all-cause mortality, even after adjusting for possible confounding variables. Conclusions Novel long-term clinical associations were generated that support α-Klotho and lean mass as novel CV risk factors in hemodialysis patients.

Abstract Background and Aims Infection of the renal allograft by Polyomavirus BK (BKV) causes tubular cell injury and interstitial inflammation, which leads to subsequent interstitial fibrosis and tubular atrophy (IFTA). The presence and degree of inflammation within these areas (i-IFTA) is associated with worse outcomes in kidney transplant (KT) patients. The aim of this study was to investigate the association between BKV viremia and viruria and the presence of IFTA and i-IFTA, decline of renal function, and graft loss. Method We conducted a single-center retrospective case-control study, which included all patients who underwent an allograft biopsy between January 2018 and December 2022. All biopsies were made for-cause (allograft dysfunction with increased serum creatinine). Real-time polymerase chain reaction was used to detect and quantitate BK viral load in serum and urine samples. Patients were included if they had at least 6 months since KT and if they had serial evaluation of BKV viremia and viruria previously to the biopsy. We evaluated, in the graft biopsy, the percentage of IFTA, and also i-IFTA. Estimated glomerular filtration rate (eGFR) was obtained at baseline and 1 year after the biopsy. Graft loss was evaluated at 6 months and 1 year after the biopsy. Results Mean age of the population was 53,5 years and 67% were males. A total of 116 biopsies were performed during the studied period and 72 met the inclusion criteria. Ten percent of patients developed persistent (≥ 3 months) BKV viremia, 24% developed persistent BKV viruria, and 18% developed persistent JCV viruria. Five cases of polyomavirus-associated nephropathy were diagnosed. The other most common diagnoses were T cell-mediated rejection (24%), antibody-mediated rejection (15%), and focal segmental glomerulosclerosis (15%). In patients with persistent BKV viremia, a higher viral load had a strong positive association with the degree of i-IFTA (r=0.954; P = .001). Patients with BKV viremia and/or viruria were more likely to present more severe IFTA (≥ 40%) and i-IFTA (grade ≥2) in allograft biopsy (P = .03). Patients with higher degrees of IFTA and i-IFTA were more likely to experience graft loss 1 year after the biopsy (P = .01). There was no significant association between the presence of BKV viremia and/or viruria and the decline of eGFR, nor with the incidence of graft loss 1 year after the biopsy. In multivariable analysis adjusted for age, eGFR at the time of biopsy, the presence of donor-specific antibodies and the main diagnosis of allograft biopsy, the presence of BK viremia and/or viruria was a significant predictor of more severe IFTA and i-IFTA (P = .04). Conclusion In our population, higher BK viremia loads were associated with more extensive inflammation within areas of IFTA. Patients with BK viremia and/or viruria, independently of the main diagnosis of the biopsy, were more likely to exhibit more severe IFTA and i-IFTA in allograft biopsies, but no association with the incidence of dialysis at 1 year was shown. Longer prospective studies are needed to investigate whether BKV infection treatment/ reduction of immunosuppression can slow down fibrosis progression and minimizes i-IFTA.

The current recommended treatment of patients with heart failure with reduced ejection fraction (HFrEF) is based on four (drug) pillars: angiotensin-converting enzyme inhibitor or angiotensin receptor-neprilysin inhibitor (ARNI – sacubitril/valsartan), beta blockers, mineralocorticoids receptors antagonists and sodium-glucose co-transporter 2 inhibitors. Drugs acting by means of renin-angiotensin aldosterone system inhibition (RAASi) are, however, off-label when used in patients with an estimated glomerular filtration rate less than 20-30 mL/min/1.73 m2. Indeed, most trials in HFrEF excluded patients with end-stage chronic kidney disease (CKD) and those on haemodialysis. Some evidence has suggested a potential benefit of RAASi in similar cases, nonetheless the evidence is limited to a few case reports and observational data, and it is particularly scarce with the most recent drug classes. Safety poses an additional concern, given that adverse events further constrain its use in CKD (namely worsening renal function and/or hyperkalaemia). We report the safety and potential effectiveness of ARNI in a middle-aged man with HFrEF and CKD on haemodialysis. At 2 years follow-up with ARNI treatment, there was clinical improvement and left ventricular ejection fraction has fully normalized. Our case suggests that ARNI might be an option in this subgroup of patients. We hope that these findings may encourage future randomized controlled trials in this population.

Studies analyzing the relationship between BK polyomavirus (BKV) or JC polyomavirus (JCV) infection and kidney transplant (KT) long term clinical outcomes are scarce. Therefore, we evaluated this relationship in a single-center retrospective cohort of 288 KT patients followed for 45.4(27.5; 62.5) months. Detection of BKV viremia in two consecutive analyses led to discontinuation of antimetabolite and initiation of mammalian target of rapamycin inhibitor. Outcome data included de novo BKV and/or JCV viremia and/or viruria after KT, death-censored graft survival and patient survival. BKV viruria and viremia were detected in 42.4% and 22.2% of KT recipients, respectively. BKV viremic patients had higher urinary BKV viral loads at the onset of viruria, when compared to nonviremic patients (7 log10 vs. 4.9 log10  cp/mL, p < 0.001). JCV viruria was identified in 38.5% of KT patients; the 5.9% of KT recipients who developed JCV viremia had higher JCV urinary viral loads at the onset of viruria, when compared to non-viremic patients (5.3 vs. 3.7 log10 cp/mL, p = 0.034). No differences were found in estimated glomerular filtration rate at the end of follow up, when comparing BKV or JCV viruric or viremic patients with nonviremic patients. No association was found between JCV or BKV viruria or viremia and death/graft failure. Therefore, higher BKV urinary viral loads at the onset could serve as an early maker of over immunosuppression. JCV and BKV replication was not associated with inferior clinical outcomes in KT patients with the above-mentioned immunosuppression strategy.

Abstract Background and Aims Patients with end-stage renal disease (ESRD) frequently present serologic evidence of previous contact with hepatitis B virus (HBV). Although uncommon, HBV reactivation after kidney transplantation (KT) may cause serious complications and adverse outcomes in these patients. However, data regarding risk factors for reactivation are still scarce. This study aims to describe a cohort of patients with resolved HBV infection who showed reactivation of the virus after KT. Method Retrospective cohort study including patients with resolved HBV infection who underwent KT between August 2007 and December 2021. Resolved HBV infection was defined as being seronegative to HB surface antigen (HBsAg) and seropositive to HB core antibody (HBcAb), regardless of HB surface antibody (HBsAb) status. HBV reactivation after KT was defined as seropositivity to HBsAg or presence of HBV-DNA in the serum (viraemia). Preemptive prophylactic entecavir was not used. Demographic and clinical data were collected from the electronic records. Results A total of 104 patients (70.2% male) were included with a mean age of 52±10 years. Prior to KT, 93.3% were seropositive to HBsAb. Seropositivity to other viruses was present in 18 patients: human immunodeficiency virus (HIV) alone in 5 patients, hepatitis C virus (HCV) alone in 11 patients and coinfection in 2 patients. Deceased-donor KT was performed in 94.2% and only 9 patients had had a previous KT. Rituximab was used as induction immunosuppressive therapy in 13 patients. Median follow-up time after KT was 75 months (IQR 37-115). HBV reactivation occurred in 6 patients with a median time after KT of 5 months (IQR 3-11.5). At reactivation diagnosis, median HBsAg titer was 83.2 (IQR 34-784.5; reference range < 1) and median viral load was 6.7 × 106 copies/mL (IQR 0.4 × 106-378 × 106). Only one patient presented seropositivity to HBsAg without viraemia. Half of these patients were seropositive to HBsAb prior to KT and became seronegative at reactivation diagnosis. No liver enzyme elevation was registered at reactivation diagnosis. Donor HBcAb status, coinfection with HIV or HCV, Rituximab use and recipient HBsAb status were not associated to HBV reactivation after KT. Two patients with HBV reactivation lost kidney graft function and 2 died during follow-up. Conclusion Hepatitis B virus reactivation is possible after kidney transplantation and may pose major adjustments to the treatment, namely the immunosuppressive therapy. Careful monitoring of hepatitis B virus serology and viraemia could be particularly useful in early diagnosis and prompt approach to its reactivation. Larger and multi-center studies are warranted to identify specific risk factors in this population and prevent reactivation.

Abstract Background and Aims Kidney transplant recipients (KTR) have adverse COVID-19 outcomes due to the immunosuppressed status and multiple comorbidities. Cytomegalovirus (CMV) is one of the most frequent opportunistic infections after kidney transplantation. However, data concerning its reactivation after COVID-19 is scarce. Herein, we present a single-center cohort of KRT presenting with CMV infection after COVID-19 and its clinical outcomes. Method Single-center cross-sectional study including 22 KTR with CMV viraemia detected by quantitative polymerase chain reaction up to 6 months after COVID-19, between 2020 and 2022. Demographic and clinical data were collected from the electronic records. Results A total of 22 KTR (13 male) were included with a mean age of 55.5±15.5 years and a median Charlson score of 4 (IQR 3-6). Median time after transplantation was 65 months (IQR 12.5-174.5; 3 KTR with <6 months) and only one patient had been submitted to living-donor transplantation. Eight patients received induction therapy with antithymocyte globulin (ATG). At transplantation time, CMV serologic status had been: 50% D+/R+, 13.6% D+/R- and 4.5% D-/R+. CMV infection prior to COVID-19 had been documented in 6 patients. Concerning COVID-19, severe or critical disease had been reported in 8 patients. Specific therapy had been used in 4 patients: 2 with remdesivir/baricitinib, one with remdesivir and one with molnupiravir. Moreover, immunosuppressive therapy had been adjusted in 11 patients, namely by withdrawing the antimetabolite and increasing steroids (7 patients). Median maximum steroid dose (expressed as equivalents of prednisone dose) had been 40 mg (IQR 20-40) and mean cumulative steroid dose had been 416±317 mg. CMV disease was documented in 8 patients (4 with gastrointestinal involvement) and the mean time of diagnosis after COVID-19 was 10±6 weeks. Maintenance immunosuppression included tacrolimus, antimetabolite and steroid in 12 patients; 6 patients had supratherapeutic levels of tacrolimus at CMV infection diagnosis. Median initial viraemia was 770 copies/mL (IQR 288-4106). Valganciclovir was used in 14 patients (one was already taking it as prophylaxis), ganciclovir in 4 patients and CMV enriched human intravenous immunoglobulin was used in one patient. Nine patients required hospitalization and 2 were transferred to an intensive care unit; one of these 2 patients died. Induction therapy with ATG, CMV serologic status at transplantation time, previous CMV infection, COVID-19 severity or supratherapeutic immunosuppressive drug levels were not associated with CMV infection severity or hospitalization. However, higher maximum steroid dose during COVID-19 was associated with CMV disease (p = 0.038), higher viraemia at diagnosis (p = 0.032) and hospitalization (p = 0.018). Conclusion CMV infection is a common and clinically relevant complication in KTR. Altered immunologic status after COVID-19 may predispose to this infection. In addition, immunosuppressive therapy adjustments, namely the increase in steroid dosing may be very relevant to favor reactivation of CMV. Larger studies are warranted, but careful monitoring could help identifying risk patients earlier and prophylaxis may be considered when increased corticosteroids are prescribed.

ABSTRACT Introduction: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. Methods: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. Results: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. Conclusion: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

Abstract Background The ISCHEMIA-CKD trial has shown that an initial invasive strategy, as compared to conservative treatment, did not reduce the risk of death and non-fatal myocardial infarction, nor did it improve quality-of-life in patients with advanced chronic kidney disease (CKD) and coronary artery disease (CAD) with moderate-to-severe ischemia. Similar findings were reported in patients with CKD enlisted for kidney transplantation (KT). We aimed to evaluate screening and treatment CAD strategies in patients who ultimately underwent KT at our center. Methods This is a single-center study of consecutive patients who received a KT from 2015 to 2020. Obstructive CAD was defined whenever one of the following criteria was met: lesion with a stenosis >70% (or >50%, if left main disease) or CAD requiring revascularization, as per the Heart Team discussion. CAD evaluation refers to non-invasive or invasive coronary angiography and/or stress testing, irrespective of clinical scenario. Results A total of 324 patients underwent KT [mean age 55±12 years; 65.1% male; CKD most often due to hypertensive or diabetic nephropathy and polycystic kidney disease – 41.8%; median time from renal replacement therapy (RRT) to KT – 60 (40–88) months]. A flow-chart summarizing CAD diagnosis over time is depicted in Figure 1. Overall, 119 (36.7%) patients had CAD evaluation prior to KT, of whom 21 underwent myocardial revascularization – 8, 12 and 1 patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and silent ischaemia, respectively. At a median time of 46 (25–66) months after KT, 36 (11.1%) more patients had CAD evaluation, of whom 8 underwent percutaneous myocardial revascularization – 6 and 2 for ACS and CCS, respectively. Those with obstructive CAD were older (64 vs 54 years-old; p<0.001), with a higher burden of cardiovascular (CV) risk factors (p<0.001) and more likely to have had a CV death (9.5 vs. 1.0%; p=0.025) or CV hospitalization (38.1 vs. 13.4%; p=0.007). CAD status (revascularized vs. non-revascularized) was not associated with improved major outcomes at follow-up. We found no strong predictors of CAD requiring revascularization post-KT, including time from RRT to KT. There were no patients with refractory angina, left main disease or reduced left ventricular ejection fraction (<40%) in need of myocardial revascularization over follow-up. Conclusions Obstructive CAD was uncommon in our cohort of patients who received a KT, most of whom with asymptomatic or mildly (monthly angina) symptomatic CCS or non-fatal ACS. These findings, together with the most recent evidence, may argue against routine CAD screening in all patients being enlisted for KT. Notwithstanding, randomized evidence is eagerly awaited to further guide treatment decisions in the post-ISCHEMIA-CKD era. Funding Acknowledgement Type of funding sources: None.

Kidney transplant patients (KT) are at high risk for severe COVID‐19 and presented attenuated antibody responses to vaccination when compared to immunocompetent individuals. Torquetenovirus (TTV) has recently gained attention as a potential surrogate marker of the net state of immunosuppression. We evaluated the association between pre‐vaccination TTV viral load and anti‐spike total antibody response to SARS‐CoV‐2 vaccination in KT.