Comparing Survival Outcomes between Hemodialysis and Hemodiafiltration Using Real-World Data from Brazil.

The CONVINCE trial demonstrates that high-dose hemodiafiltration offers a survival advantage for patients in the high-flux hemodiafiltration group compared to hemodialysis. We compared the outcomes of hemodialysis and hemodiafiltration using real-world data. We conducted an analysis on a cohort of patients who underwent hemodiafiltration therapy (HDF) at a single center, NefroStar Clinics. The results obtained were then compared with data from patients receiving hemodialysis (HD) therapy within the Brazilian Public Health System (SUS). The primary outcome was mortality from any cause. Results: A total of 85 patients undergoing hemodiafiltration were compared with 149,372 patients receiving hemodialysis through the Brazilian Public Health System (SUS). Using a 2:1 propensity score, we compared the 170 best-match HD patients with 85 HDF patients. In the Cox analysis, HDF therapy showed a reduced risk of mortality with an HR of 0.29 [0.11-0.77]. The propensity score analysis showed a HR of 0.32 [95% CI: 0.11-0.91]. This analysis was adjusted for age, type of access, KT/v, hemoglobin, and phosphorus. The Kaplan-Meier analysis showed respective survival rates for HDF and HD at the end of one year, 92.1% and 79.9%, p < 0.001. These results suggest high-flux hemodiafiltration has survival advantages over hemodialysis in a real-world scenario.

Oxygen Requirement in Overweight/Obese Kidney Transplant Recipients with COVID-19: An Observational Cohort Study.

INTRODUCTION: Obesity is one of the components of the cardiometabolic syndrome that contributes to COVID-19 progression and mortality. Immunosuppressed individuals are at greater risk of the COVID-19 burden. Therefore, we sought to investigate the impact of the combination of overweight/obesity and kidney transplant on oxygen (O2) requirements in the COVID-19 setting. METHODS: Retrospective analysis of 284 kidney transplant recipients (KTRs) from March/2020 to August/2020 in a single center. We investigated the risk factors associated with O2 requirements in overweight/obese KTRs. RESULTS: Overall, 65.1% had a BMI (body mass index) ≥ 25 kg/m2, 52.4% were male, the mean age was 53.3 ± 11 years old, 78.4% had hypertension, and 41.1% had diabetes mellitus. BMI was an independent risk factor for O2 requirements (OR = 1.07, p = 0.02) alongside age, lymphopenia, and hyponatremia. When overweight/obese KTRs were older, smokers, they presented higher levels of lactate dehydrogenase (LDH), and lower levels of estimated glomerular filtration rate (eGFR), lymphocytes, and sodium at admission, and they needed O2 more often. CONCLUSION: Being overweight/obese is associated with greater O2 requirements in KTRs, in particular in older people and smokers, with worse kidney allograft functions, more inflammation, and lower sodium levels. Therefore, the early identification of factors that predict a worse outcome in overweight/obese KTRs affected by COVID-19 contributes to risk stratification and therapeutic decisions.

A Machine Learning Prediction Model for Immediate Graft Function After Deceased Donor Kidney Transplantation.

BACKGROUND: After kidney transplantation (KTx), the graft can evolve from excellent immediate graft function (IGF) to total absence of function requiring dialysis. Recipients with IGF do not seem to benefit from using machine perfusion, an expensive procedure, in the long term when compared with cold storage. This study proposes to develop a prediction model for IGF in KTx deceased donor patients using machine learning algorithms. METHODS: Unsensitized recipients who received their first KTx deceased donor between January 1, 2010, and December 31, 2019, were classified according to the conduct of renal function after transplantation. Variables related to the donor, recipient, kidney preservation, and immunology were used. The patients were randomly divided into 2 groups: 70% were assigned to the training and 30% to the test group. Popular machine learning algorithms were used: eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine, Gradient Boosting classifier, Logistic Regression, CatBoost classifier, AdaBoost classifier, and Random Forest classifier. Comparative performance analysis on the test dataset was performed using the results of the AUC values, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score. RESULTS: Of the 859 patients, 21.7% (n = 186) had IGF. The best predictive performance resulted from the eXtreme Gradient Boosting model (AUC, 0.78; 95% CI, 0.71-0.84; sensitivity, 0.64; specificity, 0.78). Five variables with the highest predictive value were identified. CONCLUSIONS: Our results indicated the possibility of creating a model for the prediction of IGF, enhancing the selection of patients who would benefit from an expensive treatment, as in the case of machine perfusion preservation.

The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19.

BACKGROUND: The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19-associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes. METHODS: This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed. RESULTS: Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA. CONCLUSIONS: This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.

Eculizumab in low-middle income countries: how much does a life cost?

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease and eculizumab was approved as first line therapy in 2011 by the Food and Drug Administration. Access to eculizumab in low-middle income countries is challenging. We discuss access to eculizumab in Brazil that was made possible by judicialization or compassionate use. We showed a nationwide cohort of unplanned eculizumab interruptions resulted in higher rates of aHUS relapse. Similar to the French cohort, the use of eculizumab after transplantation showed superior graft survival compared to conventional treatment. We speculate a possible solution to the higher cost of eculizumab in which the government negotiates with the manufacturers. In this process, the government should compromise to ensure validated protocols of drug use, and the pharmaceutical companies, on the other hand, should reduce prices, especially in low-income countries. We also suggest a price adjustment based on gross domestic product.

Temporal Reduction in COVID-19-Associated Fatality Among Kidney Transplant Recipients: The Brazilian COVID-19 Registry Cohort Study.

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) (pfor-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, pfor-trend = 0.062), and better baseline renal function (43.6-47.7 ml/min/1.73 m2, pfor-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea (pfor-trend = 0.001) and hypoxemia (pfor-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced (pfor-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.

Development and validation of a simple web-based tool for early prediction of COVID-19-associated death in kidney transplant recipients.

This analysis, using data from the Brazilian kidney transplant (KT) COVID-19 study, seeks to develop a prediction score to assist in COVID-19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28-day fatality after the COVID-19 diagnosis, assessed by the area under the ROC curve (AUC-ROC), was confirmed in a validation cohort. The better calibration values were used to build the applicable ImAgeS score. The 28-day fatality rate was 17% (n = 235), which was associated with increasing age, hypertension and cardiovascular disease, higher body mass index, dyspnea, and use of mycophenolate acid or azathioprine. Higher kidney graft function, longer time of symptoms until COVID-19 diagnosis, presence of anosmia or coryza, and use of mTOR inhibitor were associated with reduced risk of death. The coefficients of the best model were used to build the predictive score, which achieved an AUC-ROC of 0.767 (95% CI 0.698-0.834) in the validation cohort. In conclusion, the easily applicable predictive model could assist health care practitioners in identifying non-hospitalized kidney transplant patients that may require more intensive monitoring. Trial registration: ClinicalTrials.gov NCT04494776.

Association between vitamin D levels and mortality in hemodialysis patients: a cohort study.

Introduction: Low vitamin D levels are associated with mortality in hemodialysis (HD) patients; however, the serum vitamin D thresholds are unclear. This study aimed to identify the vitamin D level below which mortality increases in HD patients.Methods: A cohort of HD patients enrolled from January 2014 to January 2017 was evaluated. The variables were analyzed according to the season, namely, summer, winter, and annual average, mortality was the primary outcome. The patients were assigned to vitamin D quintiles, and multivariate Cox regression analysis adjusted for age, ethnicity, gender, body mass index (BMI), inhibitors of the renin-angiotensin system, statin, calcitriol, and antiplatelet drugs use, hemodialysis vintage, hypertension, diabetes mellitus, atherosclerotic disease, and C-reactive protein was performed.Results: There were studied 306 patients. Vitamin D levels of 18.0-23.6 ng/mL (hazard ratio [HR] = 4.30; 95% confidence interval [CI] 1.60-11.54, p = 0.004) and <18.0 ng/mL (HR = 3.83; 95% CI: 1.42-10.35, p = 0.008) in summer and vitamin D levels of 21.5-27.1 ng/mL (HR = 3.70; 95% CI: 1.50-9.11, p = 0.004) and ≤17.5 ng/mL (HR = 2.84; 95% CI: 1.13-7.13, p = 0.026) in winter were associated with mortality. The average annual values of vitamin D associated with all-cause mortality were <17.7 ng/dL (adjusted HR = 4.25, 95% CI: 1.57-11.48, p = 0.004), and between >17.7 ng/dL and ≤23.1 ng/dL (adjusted HR = 3.91, 95% CI: 1.47-10.42, p = 0.006).Conclusions: Annual average vitamin D levels <23.1 ng/mL were associated with higher all-cause mortality, regardless of the confounding variables evaluated.

Frailty predicts surgical complications after kidney transplantation. A propensity score matched study.

BACKGROUND AND OBJECTIVE: Surgical complications after kidney transplantation can lead to catastrophic outcomes. Frailty has been associated with important kidney transplantation outcomes; however, there are no studies assessing this measure of physiological reserve as a specific predictor of surgical complications in this population. Such an assessment was, therefore, the objective of the present study. METHODS: A total of 87 individuals aged ≥ 18 years who underwent kidney transplantation between March 2017 and March 2018 were included. At the time of admission for kidney transplantation, demographic, clinical, and kidney transplantation data were collected, and the frailty score was calculated according to Fried et al., which comprises five components: shrinking, weakness, exhaustion, low activity, and slowed walking speed. Urological, vascular, and general surgical complications were assessed three months later, or until graft loss or death. The propensity score was used to achieve a better homogeneity of the sample, and new analyses were performed in this new, balanced sample. RESULTS: Of the 87 individuals included, 30 (34.5%) had surgical complications. After propensity score matching, the risk of surgical complications was significantly higher among the frail individuals (RR 2.14; 95% CI 1.01-4.54; p = 0.035); specifically, the risk of noninfectious surgical complications was significantly higher among these individuals (RR 2.50; 95% CI 1.11-5.62; p = 0.017). CONCLUSION: The results showed that individuals with some degree of frailty before kidney transplantation were more subject to surgical complications. The calculation of the frailty score for transplant candidates and the implementations of measures to increase the physiological reserve of these patients at the time of kidney transplantation may possibly reduce the occurrence of surgical complications.

Impact of adjusted kidney volume measured in the bench surgery on one-year renal function in kidney transplantation.

BACKGROUND: Kidney transplantation is the treatment of choice in patient with end stage chronic kidney disease, offering the best long term survival and greater Quality of Life in this group of patients. Graft volume was correlated with improved renal function in living donor transplantations. The primary aim of this study was to correlate renal volume adjusted to body surface area with renal function one year (estimated glomerular filtration rate; eGFR) after kidney transplantation. METHODS: This single-center, prospective cohort study included 256 patients who underwent kidney transplantation from January 2011 through December 2015 at Hospital das Clínicas de Botucatu-UNESP. We evaluated three kidney measurements during the bench surgery; the final graft volume was calculated using the ellipsoid formula and adjusted to body surface area. RESULTS: In the living donors there was positive correlation between adjusted graft volume and eGFR (r = 0.311, p = 0.008). Multivariate analysis revealed that low rejection rate and increased adjusted graft volume were independent factors correlated with eGFR. In deceased donors, there was no correlation between adjusted kidney volume and eGFR (r = 0.08, p = 0.279) in univariate analysis, but a multivariate analysis indicated that lower kidney donor profile index (KDPI), absence of rejection and high adjusted kidney volume were independent factors for better eGFR. CONCLUSION: Adjusted kidney volume was positively correlated with a satisfactory eGFR at one year after living donor and deceased donor transplantations.

Nephrectomy Versus Embolization of Non-Functioning Renal Graft: A Systematic Review with a Proportional Meta-Analysis.

There is no standardization on the timing of the best approach to treat a non-functioning renal graft. We reviewed the literature and performed a proportional meta-analysis of case series of transplantectomy and embolization for a non-functioning renal graft. The groups were compared for mortality and morbidity outcomes. A total of 2421 patients were included in this review. Of these, 2232 patients underwent transplantectomy and 189 underwent percutaneous embolization. The mortality rate in the nephrectomy group was 4% [95% confidence interval [CI], 2-7%; I²=87%] as compared with 0.1% [95% CI, 0.1-0.5%; I²=0%] in the embolization group. The rates of common morbidities were 18% [95% CI, 13-26%, I²=79.7%] for nephrectomy compared with 1.2% [95% CI, 0.7-2.1%, I²=26.4%] for embolization. The incidence of post-embolization syndrome was 68%, and 20% of patients needed post-embolization nephrectomy. Percutaneous embolization was associated with lower mortality and morbidity rates but also with a high rate of post-embolization syndrome. However, in most cases this complication had easily manageable symptoms. Embolization is a new and attractive technique that can be considered in treating non-functioning renal grafts.

Randomized Trial of Machine Perfusion Versus Cold Storage in Recipients of Deceased Donor Kidney Transplants With High Incidence of Delayed Graft Function.

BACKGROUND: This study compared the use of static cold storage versus continuous hypothermic machine perfusion in a cohort of kidney transplant recipients at high risk for delayed graft function (DGF). METHODS: In this national, multicenter, and controlled trial, 80 pairs of kidneys recovered from brain-dead deceased donors were randomized to cold storage or machine perfusion, transplanted, and followed up for 12 months. The primary endpoint was the incidence of DGF. Secondary endpoints included the duration of DGF, hospital stay, primary nonfunction, estimated glomerular filtration rate, acute rejection, and allograft and patient survivals. RESULTS: Mean cold ischemia time was high but not different between the 2 groups (25.6 ± 6.6 hours vs 25.05 ± 6.3 hours, 0.937). The incidence of DGF was lower in the machine perfusion compared with cold storage group (61% vs. 45%, P = 0.031). Machine perfusion was independently associated with a reduced risk of DGF (odds ratio, 0.49; 95% confidence interval, 0.26-0.95). Mean estimated glomerular filtration rate tended to be higher at day 28 (40.6 ± 19.9 mL/min per 1.73 m2 vs 49.0 ± 26.9 mL/min per 1.73 m2; P = 0.262) and 1 year (48.3 ± 19.8 mL/min per 1.73 m2 vs 54.4 ± 28.6 mL/min per 1.73 m2; P = 0.201) in the machine perfusion group. No differences in the incidence of acute rejection, primary nonfunction (0% vs 2.5%), graft loss (7.5% vs 10%), or death (8.8% vs 6.3%) were observed. CONCLUSIONS: In this cohort of recipients of deceased donor kidneys with high mean cold ischemia time and high incidence of DGF, the use of continuous machine perfusion was associated with a reduced risk of DGF compared with the traditional cold storage preservation method.

Treatment of adriamycin-induced nephropathy with erythropoietin and G-CSF.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) and Erythropoietin (EPO) are known to stimulate the growth and differentiation of progenitor cells to prevent acute renal injury. This study aimed to assess the use of growth factors to mobilize stem cell in a mouse model of adriamycin-induced chronic kidney disease. METHODS: All animals were injected with adriamycin for kidney injury and allocated into three treatment groups (G-CSF, EPO and G-CSF + EPO), and a control group (adriamycin alone). RESULTS: Number of atrophic sites, glomerulosclerosis rate and interstitial fibrosis severity score were assessed in all groups. In all treatment groups, histologic parameters did not significantly differ, but were lower than in the control group (P<.001). Scal and CD34 expressions among treatment groups showed no statistically significant difference, but were higher than in the control group (P<.0001). CD105 expression was higher in EPO and G+EPO as compared to G-CSF and the control group (P<.0001), with no statistically significant difference between the latter two groups (P = NS). CONCLUSION: G-CSF and EPO had a histologic protective effect, while treatment with EPO + G-CSF had no additive effects in a model of adriamycin-induced chronic kidney disease.