Effect of an intensive nutrition intervention of a high protein and low glycemic load diet on weight of kidney transplant recipients: a randomized clinical trial.

PURPOSE: The purpose of this study is to evaluate the effect of a high protein and low glycemic load diet in preventing weight gain after kidney transplantation. METHODS: We designed a prospective, single-center, open-label, randomized controlled study to compare the efficacy of a high protein (1.3-1.4 g/kg/day) and low glycemic load diet versus a conventional diet (0.8-1.0 g/kg/day of protein and no recommendations on glycemic load) in preventing weight gain (ClinicalTrials.gov identifier: NCT02883777). A total of 120 patients were evaluated. Patients were followed for 12 months, and the primary outcome was weight maintenance or weight gain lower than 5%. RESULTS: There were no differences in total energy intake, carbohydrates, and total fats between groups. Intervention group (IG) increased protein intake to 1.38 ± 0.56 g/kg/day and decreased the glycemic load to 87.27 ± 4.54 g/day, while control group (CG) had a dietary protein intake of 1.19 ± 0.43 g/kg/day and a glycemic load of 115.60 ± 7.01 g/day. Total fiber intake was greater and trans-fat was lower in IG. Dietetic cholesterol increased in IG over time and was significantly different between groups. Overall, patients had an increase in body weight over time, with a mean increment of 4.1 ± 5.5 kg (5.75%). The percentage of patients who achieved the primary outcome was 50% of sample size, without differences between groups. The glomerular filtration rate improved over time in both groups. Considering 24-h proteinuria and albuminuria, a similar rise was observed in both groups. CONCLUSION: The present dietary intervention was safe, but had no effect on weight gain in kidney transplant subjects. Our findings suggest that other strategies, including alternative dietary and/or pharmacological and psychological interventions might be tested in randomized control trials in order to improve patients' body weight outcomes after transplant.

Outcomes of kidney transplant recipients exposed to Chagas disease under Benznidazole prophylaxis. A single center 10-year experience.

BACKGROUND: Chagas disease (ChD) is endemic in many parts of the world and can be transmitted through organ transplantation or reactivated by immunosuppression. Organs from infected donors are occasionally used for transplantation, and the best way of managing the recipients remains a subject of debate. METHODS: We present a single-center cohort study describing a 10-year experience of kidney transplantation in patients at risk of donor-derived ChD and or reactivation. Patients received prophylactic treatment with Benznidazole and were monitored for transmission or reactivation. Monitoring included assessing direct parasitemia, serology, and polymerase chain reaction (PCR). RESULTS: Fifty-seven kidney transplant recipients (KTRs) were enrolled in the study. Forty-four patients (77.2%) were at risk of primary ChD infection, nine patients (15.8%) were at risk of disease reactivation, and four patients (7.0%) were at risk of both. All patients received Benznidazole prophylaxis, starting on the first day after transplantation. Parasitemia was assessed in 51 patients (89.5%), serology also in 51 patients (89.5%), and PCR in 40 patients (70.2%). None of the patients exhibited clinically or laboratory-detectable signs of disease. A single patient experienced a significant side effect, a cutaneous rash with intense pruritus. At 1-year post-transplantation, the patient and graft survival rates were 96.5% and 93%, respectively. CONCLUSION: In this study, no donor-derived or reactivation of Trypanosoma cruzi infection occurred in KTRs receiving Benznidazole prophylaxis.

Chronic Kidney Disease in Brazil: Current Status and Recommended Improvements.

Background: Over the last 3 decades, over 700 million individuals worldwide have been diagnosed with chronic kidney disease (CKD). In a 2017 survey in southern Brazil, 11.4% of those surveyed had CKD. Early identification and effective therapy in Brazil may reduce CKD's impact. This panel discusses the early diagnosis and treatment of CKD and the barriers and actions needed to improve the management of CKD in Brazil. A panel of Brazilian nephrologists was provided with relevant questions to address before a multiday conference. During this meeting, each narrative was discussed and edited through several rounds until agreement on the relevant topics and recommendations was achieved. Summary: Panelists highlighted hurdles to early diagnosis and treatment of CKD. These include, but are not limited to, a lack of public and patient education, updated recommendations, multidisciplinary CKD treatment, and a national CKD database. People-centered, physician-centered, and healthcare institution-centered actions can be taken to improve outcomes. Patient empowerment is needed via multiple channels of CKD education and access to health-monitoring wearables and apps. Primary care clinicians and nonspecialists must be trained to screen and manage CKD-causing illnesses, including diabetes and hypertension. The healthcare system may implement a national health data gathering system, more screening tests, automated test result reporting, and telehealth. Key Messages: Increasing access to early diagnosis can provide a path to improving care for patients with CKD. Concerted efforts from all stakeholders are needed to overcome the barriers.

Assessing the impact of positive cultures in preservation fluid on renal transplant outcomes: a scoping review.

BACKGROUND: Infection following kidney transplantation is a significant risk factor for adverse outcomes. While the donor may be a source of infection, microbiological assessment of the preservation fluid (PF) can mitigate potential recipient contamination and help curb unnecessary antibiotic use. This scoping review aimed to describe the available literature on the association between culture-positive preservation fluid, its clinically relevant outcomes, and management. METHODS: Following the Joanna Briggs Institute's scoping review recommendations, a comprehensive search in databases (EMBASE, MEDLINE, and gray literature) was conducted, with data independently extracted by two researchers from selected studies. RESULTS: We analysed 24 articles involving 12,052 samples, predominantly published post-2000, 91% of which retrospective. The prevalence of culture-positive preservation fluid varied from 0.86 to 77.8%. Coagulase-negative staphylococci emerged as the most frequently isolated pathogen in 14 studies. The presence of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), observed in two studies involving 1074 donors, was significantly associated with an increased risk of probable donor-derived infections (p-DDI). Of the reviewed articles, 14 reported on probable donor-derived infections, while 19 addressed the topic of preemptive antibiotic therapy. CONCLUSIONS: Routine culturing of preservation fluid is crucial for the identification of pathogenic organisms, facilitates targeted treatment and prevents probable donor-derived infections. Furthermore, this approach helps avoid the treatment of low-virulence contaminants, thereby reducing unnecessary antimicrobial use and the risk of antibiotic resistance. In cases where ESKAPE or Candida species are detected, preemptive therapy appears to be an important strategy. Given that the current evidence primarily stems from retrospective studies, there is a pressing need for large-scale, prospective trials to corroborate these recommendations. This scoping review currently represents the most thorough compilation of evidence on how contamination of preservation fluids affects kidney transplant management.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study.

BACKGROUND: Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries. METHODS: A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months. RESULTS: Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing. CONCLUSION: Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Early Elbow Flexion Contracture Predicts Shoulder Contracture in Infants with Brachial Plexus Birth Injury.

OBJECTIVE: To determine if children who present with an elbow flexion contracture (EFC) from brachial plexus birth injury (BPBI) are more likely to develop shoulder contracture and undergo surgical treatment. STUDY DESIGN: Retrospective review of children <2 years of age with BPBI who presented to a single children's hospital from 1993 to 2020. Age, elbow and shoulder range of motion (ROM), imaging measurements, and surgical treatment and outcome were analyzed. Patients with an EFC of ≥10° were included in the study sample. Data from 2445 clinical evaluations (1190 patients) were assessed. The final study cohort included 72 EFC cases matched with 230 non-EFC controls. Three patients lacked sufficient follow-up data. RESULTS: There were 299 included patients who showed no differences between study and control groups with respect to age, sex, race, ethnicity, or functional score. Patients with EFC had 12° less shoulder range of motion (95% CI, 5°-20°; P < .001) and had 2.5 times the odds of shoulder contracture (OR, 2.5; 95% CI, 1.3-4.7; P = .006). For each additional 5° of EFC, the odds of shoulder contracture increased by 50% (OR, 1.5; 95% CI, 1.2-1.8; P < .001) and odds of shoulder procedure increased by 62% (OR, 1.62; 95% CI, 1.04-2.53; P = .03). Sensitivity of EFC for predicting shoulder contracture was 49% and specificity was 82%. CONCLUSIONS: In patients with BPBI <2 years of age, presence of EFC can be used as a screening tool in identifying shoulder contractures that may otherwise be difficult to assess. Prompt referral should be arranged for evaluation at a BPBI specialty clinic, because delayed presentation risks worsening shoulder contracture and potentially more complicated surgery.

Single-dose antithymocyte globulin in standard immunological risk kidney transplant recipients: efficacy and kinetics of peripheral blood CD3+ T lymphocyte modulation.

BACKGROUND: Polyclonal anti-T cell antibodies (ATG or thymoglobulin®) are used as induction therapy in kidney transplant recipients. This study evaluates the safety, efficacy, and CD3+ T lymphocyte modulation of two ATG regimens. METHODS: The trial included two cohorts of kidney transplant recipients that were followed for one year. The study group, including standard immunological risk recipients, received one 3 mg/kg dose of ATG. The comparator group, including standard and high immunological risk kidney transplant recipients, received a fractionated dose regimen (up to four 1.5 mg/kg doses). Patient and graft outcomes and the kinetics of CD3+ T lymphocyte modulation in the peripheral blood were evaluated. RESULTS: One hundred kidney transplant recipients were included in each group. The one-year incidence of treated acute rejection, and patient and graft survival did not differ between groups. Bacterial infections were significantly more frequent in fractionated-dose group patients (66% versus 5%; P = 0.0001). At one-year follow-up, there was no difference in the incidence of cytomegalovirus infection (P = 0.152) or malignancies (P = 0.312). CD3+ T lymphocyte immunomodulation in the single-dose group was more effective in the first two days after transplantation. After the third post-transplant day, CD3+ T lymphocyte modulation was more efficient in the fractionated dose group. CONCLUSION: Both regimens resulted in low rejection rates and equivalent survival. The single and reduced dose regimen protects from the occurrence of bacterial infections. CD3+ T lymphocyte modulation occurred with different kinetics, although it did not result in distinct outcomes.

Early retinal neurovascular findings in post-transplant diabetes mellitus patients without clinical signs of diabetic retinopathy.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a specific subtype of diabetes with an uncertain impact on mortality and morbidity in post-transplant patients. Diabetic retinopathy is the most common microvascular complication of diabetes mellitus, but the long-term clinical progression in PTDM is unknown. New technologies are being used to assess pre-clinical signs of retinal changes, such as swept-source optical coherence tomography (OCT) and OCT-angiography. The aim of this study was to detect pre-clinical structural and vascular changes in the retina using swept-source-OCT and OCT-angiography in patients with PTDM. METHODS: In this retrospective cohort study, post-kidney transplant patients were divided into PTDM and non-PTDM (control) groups. Both eyes of eligible PTDM patients and controls were included in this study. Inner retinal layer thickness was measured with swept-source-OCT. Retinal capillary density and the foveal avascular zone were measured with OCT-angiography. RESULTS: In the PTDM group, reduced thickness was found in the inferior ganglion cell layer plus inner plexiform layer (95% CI -8.76 to -0.68; p = 0.022) and the temporal inferior segment (95% CI -10.23 to -0.76; p = 0.024) of the inner retina, as well as in the retinal nerve fiber layer in the temporal (95% CI -34.78 to -9.28 p = 0.001) and temporal inferior segments (95% CI -33.26 to -5.03 p = 0.008). No significant differences were found in the vascular capillary plexus between groups at all depths, segments, or foveal avascular zone (p = 0.088). CONCLUSIONS: According to OCT-angiography, PTDM patients had reduced inner neurosensory retinal layers but no significant change in vascular density, which suggests that early neuroretinal degeneration might occur prior to vascular changes secondary to PTDM. Prospective studies could help elucidate the clinical course of retinal neuropathy and microvascular pathology in PTDM and provide a better understanding of PTDM complications.

The lncRNA MALAT1 is upregulated in urine of type 1 diabetes mellitus patients with diabetic kidney disease.

Long non-coding RNAs (lncRNAs) are RNAs with >200 nucleotides that are unable to encode proteins and are involved in gene expression regulation. LncRNAs have a key role in many physiological and pathological processes and, consequently, they have been associated with several human diseases, including diabetes chronic complications, such as diabetes kidney disease (DKD). In this context, some studies have identified the dysregulation of the lncRNAs MALAT1 and TUG1 in patients with DKD; nevertheless, available data are still contradictory. Thus, the objective of this study was to compare MALAT1 and TUG1 expressions in urine of patients with type 1 diabetes mellitus (T1DM) categorized according to DKD presence. This study comprised 18 T1DM patients with DKD (cases) and 9 long-duration T1DM patients without DKD (controls). MALAT1 and TUG1 were analyzed using qPCR. Bioinformatics analyses were done to identify both lncRNA target genes and the signaling pathways under their regulation. The lncRNA MALAT1 was upregulated in urine of T1DM patients with DKD vs. T1DM controls (P = 0.007). The expression of lncRNA TUG1 did not differ between groups (P = 0.815). Bioinformatics analysis showed these two lncRNAs take part in metabolism-related pathways. The present study shows that the lncRNA MALAT1 is upregulated in T1DM patients presenting DKD.

One-year impact of COVID-19 pandemic on renal replacement therapy and kidney transplantation in a tertiary center in Southern Brazil / Impacto de um ano da Pandemia COVID 19 na terapia renal substitutiva e no transplante renal em centro terciário no Sul do Brasil

ABSTRACT Introduction: Patients on renal replacement therapy (RRT) and kidney transplant recipients (KTR) present multiple factors that may increase the risk of death from coronavirus disease 2019 (COVID-19). This study aimed to evaluate the incidence and impact of COVID-19 in RRT patients and KTRs. Methods: Between March 2020 and February 2021, we monitored the RRT population of thirteen dialysis facilities that refer patients for transplantation to our center, a tertiary hospital in Southern Brazil. In the same period, we also monitor COVID-19 incidence and mortality in our KTR population. Demographical, clinical, and COVID-19-related information were analyzed. Results: We evaluated 1545 patients in the dialysis centers, of which 267 (17.4%) were infected by COVID-19 and 53 (19.9%) died. Among 275 patients on the kidney transplant waiting list, 63 patients (22.9%) were infected and seven (11.1%) died. COVID-19 was the leading cause of death (29.2%) among patients on the waiting list. Within the population of 1360 KTR, 134 (9.85%) were diagnosed with COVID-19 and 20 (14.9%) died. The number of kidney transplants decreased by 56.7% compared with the same period in the previous twelve months. Conclusion: In the study period, patients on RRT and KTRs presented a high incidence of COVID-19 and high COVID-19-related lethality. The impact on the patients on the transplant waiting list was less pronounced. The lethality rate observed in both cohorts seems to be related to age, comorbidities, and disease severity.

Resumo Introdução: Pacientes em terapia renal substitutiva (TRS) e receptores de transplante renal (RTR) apresentam múltiplos fatores que podem aumentar o risco de óbito por doença do coronavírus 2019 (COVID-19). Este estudo teve como objetivo avaliar incidência e impacto da COVID-19 em pacientes em TRS e RTR. Métodos: Entre Março de 2020 e Fevereiro de 2021, monitoramos a população em TRS de treze unidades de diálise que encaminham pacientes para transplante ao nosso centro, um hospital terciário no Sul do Brasil. No mesmo período, também monitoramos a incidência e mortalidade da COVID-19 em nossa população de RTR. Foram analisadas informações demográficas, clínicas e relacionadas à COVID-19. Resultados: Avaliamos 1545 pacientes nos centros de diálise, dos quais 267 (17,4%) foram infectados pela COVID-19 e 53 (19,9%) foram a óbito. Entre 275 pacientes na lista de espera para transplante renal, 63 (22,9%) foram infectados e sete (11,1%) foram a óbito. COVID-19 foi a principal causa de óbito (29,2%) entre pacientes na lista de espera. Dentre a população de 1360 RTR, 134 (9,85%) foram diagnosticados com COVID-19 e 20 (14,9%) foram a óbito. O número de transplantes renais diminuiu em 56,7% comparado ao mesmo período nos doze meses anteriores. Conclusão: No período do estudo, pacientes em TRS e RTR apresentaram alta incidência de COVID-19 e alta letalidade relacionada à COVID-19. O impacto nos pacientes na lista de espera para transplante foi menos pronunciado. A taxa de letalidade observada em ambas as coortes parece estar relacionada à idade, comorbidades e gravidade da doença.

Polymorphisms in TIE2 and ANGPT-1 genes are associated with protection against diabetic retinopathy in a Brazilian population.

Objective: The objective of this study was to investigate the association between SNPs in the TIE2 and ANGPT-1 genes and diabetic retinopathy (DR). Subjects and methods: This study comprised 603 patients with type 2 diabetes mellitus (T2DM) and DR (cases) and 388 patients with T2DM for more than 10 years and without DR (controls). The TIE2 rs639225 (A/G) and rs638203 (A/G) SNPs and the ANGPT-1 rs4324901 (G/T) and rs2507800 (T/A) SNPs were genotyped by real-time PCR using TaqMan MGB probes. Results: The G/G genotype of the rs639225/TIE2, the G/G genotype of the rs638203/ TIE2 and the T allele of the rs4324901/ANGPT-1 SNPs were associated with protection against DR after adjustment for age, glycated hemoglobin, gender, and presence of hypertension (P = 0.042, P = 0.003, and P = 0.028, respectively). No association was found between the rs2507800/ANGPT-1 SNP and DR. Conclusion: We demonstrated, for the first time, the association of TIE2 rs638203 and rsrs939225 SNPs and ANGPT-1 rs4324901 SNP with protection against DR in a Brazilian population.

One-year impact of COVID-19 pandemic on renal replacement therapy and kidney transplantation in a tertiary center in Southern Brazil.

INTRODUCTION: Patients on renal replacement therapy (RRT) and kidney transplant recipients (KTR) present multiple factors that may increase the risk of death from coronavirus disease 2019 (COVID-19). This study aimed to evaluate the incidence and impact of COVID-19 in RRT patients and KTRs. METHODS: Between March 2020 and February 2021, we monitored the RRT population of thirteen dialysis facilities that refer patients for transplantation to our center, a tertiary hospital in Southern Brazil. In the same period, we also monitor COVID-19 incidence and mortality in our KTR population. Demographical, clinical, and COVID-19-related information were analyzed. RESULTS: We evaluated 1545 patients in the dialysis centers, of which 267 (17.4%) were infected by COVID-19 and 53 (19.9%) died. Among 275 patients on the kidney transplant waiting list, 63 patients (22.9%) were infected and seven (11.1%) died. COVID-19 was the leading cause of death (29.2%) among patients on the waiting list. Within the population of 1360 KTR, 134 (9.85%) were diagnosed with COVID-19 and 20 (14.9%) died. The number of kidney transplants decreased by 56.7% compared with the same period in the previous twelve months. CONCLUSION: In the study period, patients on RRT and KTRs presented a high incidence of COVID-19 and high COVID-19-related lethality. The impact on the patients on the transplant waiting list was less pronounced. The lethality rate observed in both cohorts seems to be related to age, comorbidities, and disease severity.

Polymorphisms in TIE2 and ANGPT-1 genes are associated with protection against diabetic retinopathy in a Brazilian population

ABSTRACT Objective: The objective of this study was to investigate the association between SNPs in the TIE2 and ANGPT-1 genes and diabetic retinopathy (DR). Subjects and methods: This study comprised 603 patients with type 2 diabetes mellitus (T2DM) and DR (cases) and 388 patients with T2DM for more than 10 years and without DR (controls). The TIE2 rs639225 (A/G) and rs638203 (A/G) SNPs and the ANGPT-1 rs4324901 (G/T) and rs2507800 (T/A) SNPs were genotyped by real-time PCR using TaqMan MGB probes. Results: The G/G genotype of the rs639225/TIE2, the G/G genotype of the rs638203/TIE2 and the T allele of the rs4324901/ANGPT-1 SNPs were associated with protection against DR after adjustment for age, glycated hemoglobin, gender, and presence of hypertension (P = 0.042, P = 0.003, and P = 0.028, respectively). No association was found between the rs2507800/ANGPT-1 SNP and DR. Conclusion: We demonstrated, for the first time, the association of TIE2 rs638203 and rsrs939225 SNPs and ANGPT-1 rs4324901 SNP with protection against DR in a Brazilian population.

The 2021-2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD.

BACKGROUND: Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021-2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. METHODS: The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. RESULTS: The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75-89% of agreement; IIb 50-74% of agreement, and III, when most of the panelist recommends against a defined treatment. CONCLUSIONS: To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin-angiotensin-aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients' survival.

The rs705708 A allele of the ERBB3 gene is associated with lower prevalence of diabetic retinopathy and arterial hypertension and with improved renal function in type 1 diabetic patients.

INTRODUCTION: The Erb-b2 receptor tyrosine kinase 3 (ERBB3) is involved in autoimmune processes related to type 1 diabetes mellitus (T1DM) pathogenesis. Accordingly, some studies have suggested that single nucleotide polymorphisms (SNPs) in the ERBB3 gene confer risk for T1DM. Proliferation-associated protein 2G4 (PA2G4) is another candidate gene for this disease because it regulates cell proliferation and adaptive immunity. Moreover, PA2G4 regulates ERBB3. To date, no study has evaluated the association of PA2G4 SNPs and T1DM. AIM: To evaluate the association of ERBB3 rs705708 (G/A) and PA2G4 rs773120 (C/T) SNPs with T1DM and its clinical and laboratory characteristics. METHODS: This case-control study included 976 white subjects from Southern Brazil, categorized into 501 cases with T1DM and 475 non-diabetic controls. The ERBB3 and PA2G4 SNPs were genotyped by allelic discrimination-real-time PCR. RESULTS: ERBB3 rs705708 and PA2G4 rs773120 SNPs were not associated with T1DM considering different inheritance models and also when controlling for covariables. However, T1DM patients carrying the ERBB3 rs705708 A allele developed T1DM at an earlier age vs. G/G patients. Interestingly, in the T1DM group, the rs705708 A allele was associated with lower prevalence of diabetic retinopathy and arterial hypertension as well as with improved renal function (higher estimated glomerular filtration rate and lower urinary albumin excretion levels) compared to G/G patients. CONCLUSIONS: Although no association was observed between the ERBB3 rs705708 and PA2G4 rs773120 SNPs and T1DM, the rs705708 A allele was associated, for the first time in literature, with lower prevalence of diabetic retinopathy and arterial hypertension. Additionally, this SNP was associated with improved renal function.

Delayed Graft Function Under the Microscope: Surveillance Biopsies in Kidney Transplantation.

Delayed graft function (DGF) is a common complication of kidney transplantation and frequently leads to the necessity of surveillance biopsies. The purpose of this study is to describe the histological findings in surveillance biopsies of deceased donor kidney transplant recipients and evaluate the risk factors for graft outcomes. This is a monocentric, retrospective study including kidney transplant recipients that underwent a graft biopsy during the DGF period between January 2006 and July 2019. 356 biopsies were performed in 335 deceased donor transplant recipients. Biopsies were analyzed according to the Banff classification. The main histological findings were: acute tubular necrosis in 150 biopsies (42.1%), acute rejection in 96 biopsies (26.9%), and borderline findings in 91 biopsies (25.5%). In the multivariate analysis, recipient age (p = 0.028) and DGF duration (p = 0.005) were associated with rejection, antibody-induction with anti-thymocyte globulin (ATG) was protective (p = 0.001). The occurrence of rejection was associated with lower death-censored graft survival (log-rank; p = 0.009). Surveillance biopsies of kidney grafts experiencing DGF remain an essential tool for the care of kidney transplant recipients. The recipient's age and duration of DGF are independent risk factors for acute rejection, while antibody-induction therapy with ATG is associated with protection from its occurrence.

The A allele of the rs759853 single nucleotide polymorphism in the AKR1B1 gene confers risk for diabetic kidney disease in patients with type 2 diabetes from a Brazilian population

ABSTRACT Objective: The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. Materials and methods: The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years' duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Results: Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Conclusion: Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.

The A allele of the rs759853 single nucleotide polymorphism in the AKR1B1 gene confers risk for diabetic kidney disease in patients with type 2 diabetes from a Brazilian population.

OBJECTIVE: The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. METHODS: The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years' duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. RESULTS: Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. CONCLUSION: Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.

Benefits of water intake on kidney function in older adults: protocol for a randomized controlled trial / Benefícios da ingestão de água na função renal de idosos: protocolo para um estudo clínico randomizado controlado

Objective: The goal of this study is to evaluate the benefits of an increase in water intake guided by a mathematical formula (per kg of body weight) on kidney function in older adults. Methods: Older adults (≥ 65 years old) cared for at the Internal Medicine Unit of a tertiary hospital will be randomized to receive or not guidance on water intake (30 mL/kg per day) after initial assessment of kidney function. After 14 days, participants will be reevaluated through clinical and laboratory examinations. Patients with uncompensated disease will be excluded. The main outcomes will be glomerular filtration rate and laboratory measures such as serum and urinary osmolality, sodium, urea, 24-h urine volume and serum creatinine, uric acid, and copeptin. The Mini Nutritional Assessment (MNA) questionnaire will be applied to participants at each visit. Categorical variables will be described as numbers of cases (%) and compared using the χ2 test whereas continuous variables will be analyzed with Student's t-test in relation to baseline measures. The Generalized Estimating Equations (GEE) method will be performed to assess differences over time and between groups. This study was approved by the Institution's Research Ethics Committee (grant number 16-0153) and is in accordance with the Declaration of Helsinki. Expected Results:By increasing water intake (ml/Kg) we expect to provide an improvement in kidney function in older population assessed by serum creatinine and cystatin-c applied to eGFR formulas. Relevance:Many conditions, both organic and behavioral, can contribute to chronic dehydration states in older adults. To mention, decreased ability to concentrate urine, reduced kidney mass, blood flow, and glomerular filtration rate (GFR) along with changes in sensitivity to hormones such as renin, vasopressin and natriuretic peptide can generate water imbalance, leading to dehydration. For being simple and inexpensive, this strategy may be broadly used and bring several health benefits to older adults.

Objetivo: O objetivo deste estudo é avaliar os benefícios de um aumento da ingestão de água guiado por uma fórmula matemática (por kg de massa corporal) na função renal de idosos. Metodologia:Idosos (≥ 65 anos) atendidos pelo Serviço de Clínica Médica de um hospital terciário foram randomizados para receber ou não orientação sobre o consumo de água (30 mL/kg por dia) após uma avaliação inicial da função renal. Após 14 dias, os participantes serão reavaliados através de exames clínicos e laboratoriais. Pacientes com doença descompensada serão excluídos. Os desfechos principais são a taxa de filtração glomerular e medidas laboratoriais como osmolaridade, sódio e ureia séricos e urinários, volume de urina de 24 horas e creatinina, ácido úrico e copeptina séricos. A Mini Avaliação Nutricional (MNA) será aplicada aos participantes a cada consulta. Variáveis categóricas serão descritas como números de casos (%) e comparadas usando o teste χ2 , enquanto variáveis contínuas serão analisadas com o teste t de Student em relação às medidas iniciais. O método de Equações de Estimativas Generalizadas (GEE) será usado para avaliar diferenças ao longo do tempo e entre grupos. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa da nossa Instituição (processo número 16-0153) e está de acordo com a Declaração de Helsinki. Resultados esperados:Ao aumentar a ingestão de água (ml/Kg) esperamos proporcionar uma melhora na função renal na população idosa avaliada pela creatinina sérica e cistatina-c aplicada às fórmulas de eGFR. Relevância:Muitas condições, tanto orgânicas quanto comportamentais, podem contribuir para estados de desidratação crônica em idosos. Vale mencionar que a diminuição da capacidade de concentração da urina, redução da massa renal, fluxo sanguíneo e taxa de filtração glomerular (TFG) juntamente com alterações na sensibilidade a hormônios como renina, vasopressina e peptídeo natriurético podem gerar desequilíbrio hídrico, levando à desidratação. Por ser simples e de baixo custo, essa estratégia pode ser amplamente utilizada e trazer diversos benefícios à saúde dos idosos.

Chronic urticaria patients are interested in apps to monitor their disease activity and control: A UCARE CURICT analysis.

BACKGROUND: Information/communication technologies such as mobile phone applications (apps) would enable chronic urticaria (CU) patients to self-evaluate their disease activity and control. Yet, recently Antó et al (2021) reported a global paucity of such apps for patients with CU. In this analysis, we assessed patient interest in using apps to monitor CU disease activity and control using questions from the chronic urticaria information and communication technologies (CURICT) study. METHODS: The methodology for CURICT has been reported. Briefly, a 23-item questionnaire was completed by 1841 CU patients from 17 UCAREs across 17 countries. Here, we analyzed patient responses to the CURICT questions on the use of apps for urticaria-related purposes. RESULTS: As previously published, the majority of respondents had chronic spontaneous urticaria (CSU; 63%; 18% chronic inducible urticaria (CIndU) [CIndu]; 19% with both), were female (70%) and in urban areas (75%). Over half of patients were very/extremely interested in an app to monitor disease activity (51%) and control (53%), while only ∼1/10 were not. Patients with both urticaria types versus those with CSU only (odds ratio [OR], 1.36 [1.03-1.79]) and females versus males (OR [95% CI], 1.47 [1.17-1.85]) were more likely to be very to extremely interested in an app to assess disease control. CONCLUSIONS: Overall, half of the patients with CU were very to extremely interested in using an app to assess their disease activity and control. Development of well-designed apps, specific to disease types (CSU, CIndU, CSU + CIndU, etc), validated by experts across platforms would help improve the management and possibly outcomes of CU treatment while providing important patient information to be used in future research.