Sara Querido

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.

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.

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.

Introduction: 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.Material and Methods: The 114 adult KT recipients enrolled in this prospective single‐center cohort study received two doses of SARS‐CoV‐2 mRNA BNT162b2 vaccine. Serum samples were collected immediately before vaccination at the days when patients received both the first (T0) and the second dose (T1) and 16–45 days after the second dose (T2). Primary endpoint was the development of anti‐spike total antibodies after vaccination. Demographic, clinical, and laboratorial parameters were compared between patients with and without detectable SARS‐CoV‐2 antibodies at T2.Results: Ninety‐nine patients (86.8%) were naïve for SARS‐CoV‐2 before vaccination. Fifty‐six (56.6%) patients developed anti‐spike total antibodies at T2. The use of mTOR inhibitors was associated with a favorable response (p = .005); conversely, mycophenolic acid (MPA) was associated with a negative response (p = .006). In a multivariable model, the presence of TTV at T0 ≥ 3.36 log₁₀ cp/ml was associated with unfavorable vaccine response (OR: 5.40; 95% CI: 1.47–19.80; p = .011), after adjusting for age and eGFR at T0.Conclusions: Higher TTV viral loads before vaccination are associated with reduced anti‐spike total antibody response in SARS‐CoV‐2 mRNA BNT162b2 vaccinated KT patients. The association between TTV viral load and vaccine response may be an added‐value in the optimization of vaccination regimens in KT.

Introduction: Few studies have investigated pre-donation factors that could affect renal recovery after living kidney donation (LKD). We retrospectively investigated the role of John Cunningham virus (JCV) infection and other pre-donation factors on the magnitude of kidney function decline after LKD. Methods: Urine JCV viral loads, glomerular filtration rate, and blood pressure were evaluated in 60 consecutive LK donors before donation. Suboptimal compensatory hypertrophy was defined as an eGFR <60% of the pre-donation eGFR. Results: LKD (40% JCV infected) were followed for 3.2±1.6 years. No association was found between age, gender, and baseline hypertension with 1st, 2nd, 3rd, and 4th years post-donation eGFR <60% of the pre-donation eGFR. Mean eGFR recovery at the 3rd year after donation was lower in JCV infected donors vs non-infected donors (61.8% vs 71.0%, p=0.006). Conclusion: We hypothesized that JCV could shift glomeruli into a hyperfiltration state before nephrectomy, modulating the magnitude of compensatory hypertrophy after donation. Conversely, JCV might curtail the ability of the remaining kidney to promote hyperfiltration. Longer follow up is needed to determine whether JCV viruria ultimately leads to lower eGFR over time or if it is a protective factor for the remaining kidney.

Thrombotic microangiopathy (TMA) is a rare disease that presents with haemolysis and organ damage. The kidney is one of the main affected organs, and TMA is associated with serious complications and increased mortality. In transplanted patients, TMA is even less common and has a variety of possible causes, including thrombotic thrombocytopenic purpura (TTP) and haemolytic-uremic syndrome (HUS), infections, drugs, autoimmune disease, tumours, and malignant hypertension. Transplant-related causes, such as antibody-mediated rejection, calcineurin inhibitors, and viral infections, need to be considered as well. The authors report a rare case of TMA in a kidney transplant recipient, whose investigation revealed malignant hypertension secondary to primary hyperaldosteronism.