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

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 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.

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.

The rs2442598 polymorphism in the ANGPT-2 gene is associated with risk for diabetic retinopathy in patients with type 1 diabetes mellitus in a Brazilian population

ABSTRACT Objective: As studies have reported the involvement of angiopoietin-2 (ANGPT-2) in the pathogenesis of diabetic retinopathy (DR), the aim of this study was to investigate the association between the ANGPT-2 rs2442598 polymorphism and DR. Materials and methods: This case-control study comprised 107 patients with type 1 diabetes mellitus (T1DM) and DR (cases) and 129 patients with T1DM without DR (controls) and with ≥ 10 years of DM. The ANGPT-2 rs2442598 (G/A) polymorphism was genotyped by real-time PCR using TaqMan MGB probes. Results: Genotype distributions of this polymorphism were consistent with the Hardy-Weinberg equilibrium. The frequency of the rs2442598 A allele was higher in cases compared to controls (p = 0.011). Moreover, the A/A genotype was more frequent in cases than in controls (p = 0.017) and was associated with risk for DR after adjustments for duration of DM, HbA1c, triglycerides, estimated glomerular filtration rate, and hypertension (odds ratio [OR] = 5.19, 95% confidence interval [CI] 1.21-22.27). This association was maintained under recessive (OR = 4.78, 95% CI 1.14-19.99) and additive (OR = 6.861, 95% CI 1.45-32.38) inheritance models. Conclusion: Our data demonstrated, for the first time, an association between the ANGPT-2 rs2442598 A allele and risk for DR in T1DM patients from southern Brazil. Additional studies are necessary to replicate this association in other populations.

Comparison of two techniques for assessing pancreatic islet viability: flow cytometry and fluorescein diacetate/propidium iodine staining

Introduction: The success of islet transplantation for patients with unstable type 1 diabetes mellitus depends, in part, on the number of isolated islets and their quality, which is assessed by functional and viability tests. The test currently employed to evaluate islet viability, used by the Collaborative Islet Transplant Registry to release products for transplantation, is fluorescein diacetate/propidium iodide (FDA/PI) staining. However, the efficacy of this method relies on researcher experience; in this context, a quantitative method may be useful. The aim of this study was to compare islet viability as assessed by flow cytometry and the FDA/PI assay. Methods: Viability was analyzed in islets isolated from 10 male Wistar rats. Upon FDA/PI staining, 50 islets from each animal were analyzed under fluorescence microscopy by two well-trained researchers. For flow cytometry, islets were dispersed and 100 000 single cells were incubated with the 7-amino-actinomycin D (7AAD) fluorophore (dyes necrotic and late apoptotic cells) and the Annexin V-APC antibody (marks early apoptotic cells). Results: A moderate correlation was found between techniques (r = 0.6; p = 0.047). The mean islet viability measured by flow cytometry was higher than that estimated using FDA/PI staining (95.5 ± 1.4% vs 89.5 ± 5.0%; p = 0.002). Conclusions: Although flow cytometry is more expensive and time-consuming than FDA/PI staining, it is a quantitative technique with greater reproducibility that is less subject to inter-observer variability than FDA/PI. Therefore, flow cytometry appears to be the technique of choice when aiming for a more precise determination of islet viability. (AU)