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This study evaluated the risk factors for delayed graft function (DGF) in a country where its incidence is high, detailing donor maintenance-related (DMR) variables and using machine learning (ML) methods beyond the traditional regression-based models. A total of 443 brain dead deceased donor kidney transplants (KT) from two Brazilian centers were retrospectively analyzed and the following DMR were evaluated using predictive modeling: arterial blood gas pH, serum sodium, blood glucose, urine output, mean arterial pressure, vasopressors use, and reversed cardiac arrest. Most patients (95.7%) received kidneys from standard criteria donors. The incidence of DGF was 53%. In multivariable logistic regression analysis, DMR variables did not impact on DGF occurrence. In post-hoc analysis including only KT with cold ischemia time<21h (n = 220), urine output in 24h prior to recovery surgery (OR = 0.639, 95%CI 0.444-0.919) and serum sodium (OR = 1.030, 95%CI 1.052-1.379) were risk factors for DGF. Using elastic net regularized regression model and ML analysis (decision tree, neural network and support vector machine), urine output and other DMR variables emerged as DGF predictors: mean arterial pressure, ≥ 1 or high dose vasopressors and blood glucose. Some DMR variables were associated with DGF, suggesting a potential impact of variables reflecting poor clinical and hemodynamic status on the incidence of DGF.

This study evaluated the current practices of selecting cold storage preservation solutions in Brazil and their impact on delayed graft function (DGF) incidence and 1-year outcomes in kidney transplant recipients. A retrospective cohort study was conducted, including 3,134 brain-dead deceased donor kidney transplants performed between 2014 and 2015 in 18 Brazilian centers. The most commonly used preservation solution was Euro-collins (EC, 55.4%), followed by Histidine-tryptophan-ketoglutarate (HTK, 30%) and Institut Georges Lopez (IGL-1, 14.6%). The incidence of DGF was 54.4%, with 11.7% of patients requiring dialysis for more than 14 days, indicating prolonged DGF. Upon adjusting for confounding variables, HTK demonstrated a significantly lower risk of DGF than EC (OR 0.735 0.8250 0.926 ), as did IGL-1 (OR 0.605 0.712 0.837 ). Similar protective effects were observed for prolonged DGF when comparing HTK (OR 0.478 0.599 0.749 ) and IGL-1 (OR 0.478 0.681 0.749 ) against EC. No significant association was found between preservation solutions and 1-year death-censored graft survival. In conclusion, EC was the most frequently used cold storage perfusion solution, demonstrating a higher incidence and duration of DGF compared with HTK and IGL-1, but with no impact on 1-year graft survival.

Background Visceral leishmaniasis (VL) is an important and potentially fatal neglected tropical disease. The aim of this study was to investigate hyponatremia and risk factors for death among VL patients. Methods This is a cross-sectional study with VL patients admitted to a tertiary hospital in Northeast Brazil, from 2002 to 2009. Patients were divided into two groups: non-survivors and survivors. Hyponatremia was defined as serum sodium < 135 mEq/L. A logistic regression model was done to investigate risk factors for death. Results A total of 285 VL patients were included, with mean age 37 ± 15 years, and 74% were males. Thirty-four patients died (11.9%). Non-survivors had a significantly higher prevalence of dyspnea (38.2 vs. 16.7%, p  = 0.003), pulmonary crackles (11.8 vs. 4.0%, p  = 0.049), dehydration (23.5 vs. 10.8%, p  = 0.033), oliguria (8.8 vs. 0.8%, p  = 0.001) and jaundice (47.1 vs. 14.3%, p  < 0.001). They also presented higher prevalence of hyponatremia (41.9 vs. 24.1%, p  = 0.035), thrombocytopenia (91.2 vs. 65.3%, p  = 0.002) and severe hypoalbuminemia (78.3 vs. 35.3%, p  < 0.001). In multivariate analysis, moderate/severe hyponatremia (OR = 2.278, 95% CI = 1.046–4.962), thrombocytopenia (OR = 5.482, 95% CI = 1.629–18.443), jaundice (OR = 5.133, 95% CI = 1.793–14.696) and severe hypoalbuminemia (OR = 6.479, 95% CI = 2.124–19.766) were predictors of death. Conclusion Higher prevalence of dehydration, oliguria, pulmonary symptoms and liver involvement was found in non-survivors VL patients. Hypoalbuminemia and hyponatremia were frequent and significantly associated with mortality.

Data from the general population suggest that fatality rates declined during the course of the pandemic. This analysis, using data extracted from the Brazilian Kidney Transplant COVID-19 Registry, seeks to determine fatality rates over time since the index case on March 3rd, 2020. Data from hospitalized patients with RT-PCR positive SARS-CoV-2 infection from March to August 2020 (35 sites, 878 patients) were compared using trend tests according to quartiles (Q1: <72 days; Q2: 72–104 days; Q3: 105–140 days; Q4: >140 days after the index case). The 28-day fatality decreased from 29.5% (Q1) to 18.8% (Q4) ( p for-trend = 0.004). In multivariable analysis, patients diagnosed in Q4 showed a 35% reduced risk of death. The trend of reducing fatality was associated with a lower number of comorbidities (20.7–10.6%, p for-trend = 0.002), younger age (55–53 years, p for-trend = 0.062), and better baseline renal function (43.6–47.7 ml/min/1.73 m 2 , p for-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea ( p for-trend = 0.001) and hypoxemia ( p for-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced ( p for-trend = 0.038). Despite possible confounding variables and time-dependent sampling differences, we conclude that COVID-19-associated fatality decreased over time. Differences in demographics, clinical presentation, and treatment options might be involved.

Kidney transplant (KT) recipients are considered a high-risk group for unfavorable outcomes in the course of coronavirus disease 2019 (COVID-19). To describe the clinical aspects and outcomes of COVID-19 among KT recipients. This multicenter cohort study enrolled 1,680 KT recipients diagnosed with COVID-19 between March and November 2020, from 35 Brazilian centers. The main outcome was the 90-day cumulative incidence of death, for the entire cohort and according to acute kidney injury (AKI) and renal replacement therapy (RRT) requirement. Fatality rates were analyzed according to hospitalization, intensive care unit (ICU) admission, and mechanical ventilation (MV) requirement. Multivariable analysis was performed by logistic regression for the probability of hospitalization and death. The median age of the recipients was 51.3 years, 60.4% were men and 11.4% were Afro-Brazilian. Comorbidities were reported in 1,489 (88.6%), and the interval between transplantation and infection was 5.9 years. The most frequent symptoms were cough (54%), myalgia (40%), dyspnea (37%), and diarrhea (31%), whereas the clinical signs were fever (61%) and hypoxemia (13%). Hospitalization was required in 65.1%, and immunosuppressive drugs adjustments were made in 74.4% of in-hospital patients. ICU admission was required in 34.6% and MV in 24.9%. In the multivariable modeling, the variables related with the probability of hospitalization were age, hypertension, previous cardiovascular disease, recent use of high dose of steroid, and fever, dyspnea, diarrhea, and nausea or vomiting as COVID-19 symptoms. On the other hand, the variables that reduced the probability of hospitalization were time of COVID-19 symptoms, and nasal congestion, headache, arthralgia and anosmia as COVID-19 symptoms. The overall 90-day cumulative incidence of death was 21.0%. The fatality rates were 31.6%, 58.2%, and 75.5% in those who were hospitalized, admitted to the ICU, and required MV, respectively. At the time of infection, 23.2% had AKI and 23.4% required RRT in the follow-up. The cumulative incidence of death was significantly higher among recipients with AKI (36.0% vs. 19.1%, P < 0.0001) and in those who required RRT (70.8% vs. 10.1%, P < 0.0001). The variables related with the probability of death within 90 days after COVID-19 were age, time after transplantation, presence of hypertension, previous cardiovascular disease, use of tacrolimus and mycophenolate, recent use of high dose of steroids, and dyspnea as COVID-19 symptom. On the other hand, the variables that reduced the risk of death were time of symptoms, and headache and anosmia as COVID-19 symptoms. The patients diagnosed with COVID-19 were long-term KT recipients and most of them had some comorbidities. One in every five patients died, and the rate of death was significantly higher in those with AKI, mainly when RRT was required.

Predicting risk factors for death in leptospirosis is challenging, and identifying high-risk patients is crucial as it might expedite the start of life-saving supportive care. Admission data of 295 leptospirosis patients were enrolled, and a machine-learning approach was used to fit models in a derivation cohort. The comparison of accuracy metrics was performed with two previous models—SPIRO score and quick SOFA score. A Lasso regression analysis was the selected model, demonstrating the best accuracy to predict mortality in leptospirosis [area under the curve (AUC-ROC) = 0.776]. A score-based prediction was carried out with the coefficients of this model and named LeptoScore. Then, to simplify the predictive tool, a new score was built by attributing points to the predictors with importance values higher than 1. The simplified score, named QuickLepto, has five variables (age > 40 years; lethargy; pulmonary symptom; mean arterial pressure < 80 mmHg and hematocrit < 30%) and good predictive accuracy (AUC-ROC = 0.788). LeptoScore and QuickLepto had better accuracy to predict mortality in patients with leptospirosis when compared to SPIRO score (AUC-ROC = 0.500) and quick SOFA score (AUC-ROC = 0.782). The main result is a new scoring system, the QuickLepto, that is a simple and useful tool to predict death in leptospirosis patients at hospital admission.

It is unclear if there is an association between the duration of delayed graft function (DGF) and kidney transplant (KT) outcomes. This study investigated the impact of prolonged DGF on patient and graft survivals, and renal function one year after KT. This single center retrospective analysis included all deceased donor KT performed between Jan/1998 and Dec/2008 (n = 1412). Patients were grouped in quartiles according to duration of DGF (1-5, 6-10, 11-15, and >15 days, designated as prolonged DGF). The overall incidence of DGF was 54.2%. Prolonged DGF was associated with retransplantation (OR 2.110, CI95% 1.064-4.184,p = 0.033) and more than 3 HLA mismatches (OR 1.819, CI95% 1.117-2.962,p = 0.016). The incidence of acute rejection was higher in patients with DGF compared with those without DGF (36.2% vs. 12.2%, p<0.001). Compared to patients without DGF, DGF(1-5), DGF(6-10), and DGF(11-15), patients with prolonged DGF showed inferior one year patient survival (95.2% vs. 95.4% vs. 95.5% vs. 93.4% vs. 88.86%, p = 0.003), graft survival (91% vs. 91.4% vs. 92% vs. 88.7% vs. 70.5%, p<0.001), death-censored graft survival (95.7% vs. 95.4% vs. 96.4% vs. 94% vs. 79.3%, p<0.001), and creatinine clearance (58.0±24.6 vs. 55.8±22.2 vs. 53.8±24.1 vs. 53.0±27.2 vs. 36.8±27.0 mL/min, p<0.001), respectively. Multivariable analysis showed that prolonged DGF was an independent risk factor for graft loss (OR 3.876, CI95% 2.270-6.618, p<0.001), death censored graft loss (OR 4.103, CI95% 2.055-8.193, p<0.001), and death (OR 3.065, CI95% 1.536-6.117, p = 0.001). Prolonged DGF, determined by retransplantation and higher HLA mismatches, was associated with inferior renal function, and patient and graft survivals at one year.

BackgroundThere are only a few reports evaluating the applicability of endothelial-damage markers analysis by immunohistochemistry (IHC) in kidney allograft samples. This study analyzed the expression of Caveolin-1 (Cav), von Willebrand factor (Vwf), and T-cadherin (Cad) in kidney biopsies and their association with antibody-mediated injury.MethodsIn this retrospective study, 114 cases with antibody-mediated changes (Banff, 2020) and 72 with interstitial fibrosis/tubular atrophy were selected. IHC for Cav, Vwf and Cad was performed and evaluated according to their qualitative expression in peritubular capillaries. The cases were grouped according to the presence of microvascular inflammation (MVI), donor-specific antibodies (DSA), C4d positivity and antibody-mediated rejection (AMR). A level of significance < 0.05 was adopted.ResultsVwf expression was associated with MVI (p < 0.001), DSA (p = 0.016), C4d (p < 0.001) and AMR (p < 0.001), and was higher in DSA+/C4d+ cases despite MVI (p < 0.001). The expression of Cad correlated with MVI (p = 0.015), C4d (p = 0.005) and AMR (p = < 0.001). Cad was more expressed in chronic AMR compared with acute/active cases (p = 0.001). Cav expression was associated with MVI (p = 0.029) and AMR (p = 0.016) and was also higher in chronic AMR (p = 0.049). A combined score of Vwf and Cad was higher in AMR when compared with C4d without rejection and IF/TA cases (p < 0.001).ConclusionVwf, Cad and Cav expression shows association with antibody-mediated injury and may be helpful to support AMR diagnosis.

Kidney transplantation significantly improves outcomes in end-stage renal disease, however, long-term graft survival remains suboptimal. Traditional prognostic models often yield limited predictive power. Given the routine use of for-cause biopsies in clinical practice, we aimed to develop and compare ML models to predict graft survival using gene expression profiles from indication biopsies. Data from for-cause renal biopsies were collected from six cohorts in the Gene Expression Omnibus: GSE21374 ( n  = 282), GSE48581 ( n  = 306), GSE36059 ( n  = 411), GSE50058 ( n  = 101), GSE72925 ( n  = 168) and GSE25902 ( n  = 24). Differential expression and Cox regression analysis were applied to identify prognostic genes. These were used to train and validate 117 machine learning models. A total of 11 genes associated with graft loss were identified and used to train ML models. The Gradient Boosting Machine (GBM) achieved the highest C-index (> 0.85) and accurately stratified patients by graft survival. External validation in diagnostic tasks across four independent cohorts confirmed the model’s value of overall rejection (AUCs 0.760-0.826). Patients classified as High-risk showed reduced graft survival, enrichment of pro-inflammatory immune pathways and marked differences in immune cell composition. We developed and validated a transcriptome-based GBM model that accurately predicts graft survival using for-cause biopsy samples. The model demonstrated strong prognostic and diagnostic performance across multiple independent cohorts and reflects key immunological mechanisms of rejection. Its compact gene set offers practicality, supporting its potential integration into routine transplant care.

Everolimus is an immunosuppressive agent used for the prophylaxis of acute rejection after kidney transplantation. Everolimus inhibits the activity of the serine/threonine kinase mammalian target of rapamycin (mTOR), a key enzyme that controls cell growth and metabolism, producing cell cycle arrest from the G1 to S phase. As a consequence, everolimus has antiproliferative and antineoplastic effects. Everolimus is a drug with a narrow therapeutic index. The pharmacokinetics of everolimus indicates a need for twice-daily dosing. Intra- and interindividual variability and drug–drug interactions suggest the need for therapeutic drug monitoring to maximize the efficacy/toxicity ratio. The good correlation between exposure (area under the concentration–time curve) and trough concentration indicates that monitoring of everolimus trough concentrations is an adequate strategy after kidney transplantation. Everolimus is indicated for low- to moderate-risk de novo kidney transplant candidates. There are no conclusive studies thus far indicating that everolimus can be used in high-risk patients, such as sensitized patients, retransplants, and African Americans. In de novo kidney transplant recipients, the recommended initial dose of everolimus is 0.75 mg twice daily, adjusted to maintain blood trough concentrations of 3–8 ng/mL, in combination with progressive reduction in blood trough cyclosporine concentrations to 25–50 ng/mL. In combination with reduced trough blood tacrolimus concentrations of 4–7 ng/mL the recommended initial dose of everolimus is 1.5 mg twice daily, adjusted to maintain trough blood concentrations of 3–8 ng/mL. Everolimus can also be used as a conversion strategy, mainly to preserve renal function and to manage patients with malignancy. There is no definition of the ideal strategy for conversion, ie, abrupt or sequential, initial dose of everolimus, or target therapeutic trough blood concentrations. Intensive monitoring is recommended after conversion, especially for acute rejection and proteinuria. Because mTOR is ubiquitous and central to many intracellular processes, an array of adverse reactions may occur, including delayed tissue regeneration, proteinuria, dyslipidemia, diabetes, myelosuppression, infertility, ovarian cysts, and mouth ulcers. Because long-term benefits are the goal of any immunosuppressive strategy, further investigations aiming to understand, prevent, and manage everolimus-related adverse reactions are necessary to mitigate the risks and improve tolerability, allowing maximization of all the benefits of this drug.