Planned conversion from tacrolimus to sirolimus was evaluated in de novo kidney transplant recipients. In this multicenter, randomized, open-label study, 297 patients were initially treated with tacrolimus, mycophenolate sodium and prednisone. Of the 283 patients reaching 3 months, 97 were converted to sirolimus (SRL), 107 were maintained on tacrolimus (TAC) and 79 were patients receiving TAC without criteria to undergo intervention at month 3 (TACex). The primary objective was to show superior estimated glomerular filtration rate (eGFR) in the SRL group at month 24. Of the 258 patients who completed 24 months, 91 (94%) were in the SRL group, 101 (94%) in the TAC group and 66 (84%) in the TACex group. In the intention-to-treat population there were no differences in eGFR (66.2 AE 25.3 vs. 70.7 AE 25.1, p ¼ 0.817) or in the severity of chronic sclerosing lesions scores in 24-month protocol biopsies. Higher mean urinary protein-tocreatinine ratio (0.36 AE 0.69 vs. 0.15 AE 0.53, p ¼ 0.03) and higher incidence of treated acute rejection between months 3-24 (13.4% vs. 4.7%, p ¼ 0.047) were observed in SRL compared to TAC group. In this population planned conversion from TAC to SRL 3 months after kidney transplantation was not associated with improved renal function at 24 months.

Background Kidney transplant (KT) recipients are considered a high-risk group for unfavorable outcomes in the course of coronavirus disease 2019 (COVID-19). Aim To describe the clinical aspects and outcomes of COVID-19 among KT recipients. Methods 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. Results 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. Conclusion 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.

Summary Despite repeated campaigns promoting transplantation, the high donation refusal rate remains unchanged. We targeted a well‐educated population to assess the impact of our current transplantation promoting programs and personal feelings toward new approaches to organ donation. A questionnaire was proposed in five universities to students and university staffs that would have been likely to benefit from previous information campaigns in two South American and three European countries. All of the 2321 people interviewed replied to at least one question. Organ shortage was considered as a serious public health issue. However, there was a widespread ignorance of religious precepts concerning transplantation that contributed to the low acceptance rate of organ sharing after death. Financial rewards for donors or their families remain controversial. There was a general agreement for early educational programs in schools. Most people still consider organ donation as a gift, but many would now agree to readily share body parts after death. This biased population of well‐educated people has still little knowledge of organ donation. The negative impact of ignorance surrounding religious precepts and the high acceptance rate of educational programs in schools, justify supporting an intensive international effort in education that should also include Church leaders.

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Renal disease is a major issue for global public health. Despite some progress in supportive care, the mortality rates among patients with this condition remain alarmingly high. Studies in pursuit of innovative strategies to treat renal diseases, especially stimulating kidney regeneration, have been developed. In this field, stem cell-based therapy has been a promising area. Induced pluripotent stem cell-derived renal cells (iPSC-RCs) represent an interesting source of cells for treating kidney diseases. Advances in regenerative medicine using iPSC-RCs and their application to the kidney are discussed in this review. Furthermore, the way differentiation protocols of induced pluripotent stem cells into renal cells may also be applied for the generation of kidney organoids is also described, contributing to studies in renal development, kidney diseases, and drug toxicity tests. The translation of the differentiation methodologies into animal model studies and the safety and feasibility of renal differentiated cells as a treatment for kidney injury are also highlighted. Although only few studies were published in this field, the results seem promising and support the use of iPSC-RCs as a potential therapy in the future.

Spleen cells from Nippostrongylus brasiliensis-infected mice produce large amounts of histamine in response to adult worm antigen. This phenomenon results from the production of HCSF (histamine-producing cell-stimulating factor, probably related to IL3) by sensitized lymphocytes. This factor acts on its target cells (presumably mast cell precursors) by inducing a rapid increase in histamine synthesis. Similarly, parasite infection generates enhanced histamine production by spleen cells in response to concanavalin A (Con A). This results from increases in both HCSF production and the HCSF sensitivity of its target cells. In all cases, maximal histamine and HCSF productions are obtained on day 8 after infection and coincide with parasite rejection. Methyl prednisolone suppresses HCSF production by infected mouse spleen cells in response to worm antigen or Con A. HCSF activity is found in vivo on day 8 in the sera of infected mice, 4 h after they are challenged with an i.v. injection of adult worm antigen. No activity is detected in the sera of normal mice with or without antigen injection. Sera from infected mice that did not receive the antigen exhibit a slight HCSF activity on day 8. Our data bring the first evidence of the existence of an in vivo production of HCSF.

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Background Metabolic syndrome (MS) has been frequently associated to gout and, in fact, hyperinsulinemia enhances proximal tubular sodium reabsorption, leading to decreased renal uric acid excretion and hyperuricemia.No data regarding the prevalence of MS in gout subsets according to gout-associated clinical characteristics has been published to date. Objectives To determine the prevalence of MS in a large cohort of patients with gout followed at a single tertiary center, searching for related risk factors including metabolic profile, nephrolithiasis, reduced urate excretion and the presence of tophus. Methods This was a cross-sectional study of 158 patients with gout diagnosed according to the ACR criteria. MS was definedaccording to the National Cholesterol Education Program ATP III (NCEP-ATP III) and the International Diabetes Federation (IDF) criteria.Demographic, anthropometric (body mass index - BMI) and clinical data were collected. Fasting serum levels of uric acid, glucose, triglycerides and cholesterol fractions were analyzed by usual laboratory tests.Nephrolithiasis was demonstrated by routine ultrasonography and urate underexcretion was defined as a uric acid clearance lower than 7.5 ml/min. Fisher’s exact, chi-square, student’s T and Spearman’s test were used for statistical analysis and P≤0.05 was considered significant. Results Mean age of patients was 62.7±12.2 yrs (33 – 90 yrs), and 90.5% were males. Mean BMI was 29.13±5.70 kg/m2 (19.0 – 55.1 kg/m2). Hypertension was observed in 84.5% of patients, current alcohol consumption in 22.8%, coronary artery disease in 21% and diabetes mellitus in 19%. Mean serum uric acid, fasting glucose, triglycerides, LDL, HDL levels were 6.84 mg/dL, 107.2 mg/dL, 198.7 mg/dL, 116.7 mg/dL, 47.2 mg/dL respectively. Of note, 31% had nephrolithiasis and 52.5% had tophi. Estimated creatinine clearance was 73.15±29.35 ml/min and 86.1% patients manifested urate underexcretion.Remarkably, more than 70% of gout patients had MS (73% and 71% according to NCEP ATPIII and IDF criteria respectively). This increased prevalence of MS was alike in patients with tophaceous and non tophaceous gout, and regardless of uric acid excretionstatus (p>0,05). In contrast, the prevalence of MS was significantly higher in patients with nephrolithiasis compared to those without this complication (84.7% vs. 65.2%; p=0.026). Conclusions The elevated prevalence of MS in Brazilian gout patients (almost ¾) is higher than previously reported overall rates of MS in gout worldwide (62.8%) and in control populations (25.4%), suggesting possible interference of, dietary, geographical and/or genetic background. Our demonstration, for the first time, of increasedMS prevalence in gout unrelated to the occurrence of tophus, but associated to nephrolithiasis may suggest shared underlying physiopathologic mechanisms, such as the effect of hyperinsulinemia on the kidneys.Further studies are urged to clarify this relationship and therefore allow improvement of multiprofessional management of gout patients, in ...