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.

Abstract 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.

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.

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.

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.

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.

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.

Abstract Autoimmune diseases are characterized by the loss of self-tolerance, leading to immune-mediated tissue destruction and chronic inflammation. Tyrosine kinase 2 (TYK2) protein plays a key role in immunity and apoptosis pathways. Studies have reported associations between single nucleotide polymorphisms (SNPs) in the TYK2 gene and autoimmune diseases; however, results are still inconclusive. Thus, we conducted a systematic review followed by meta-analysis. A literature search was performed to find studies that investigated associations between TYK2 SNPs and autoimmune diseases (multiple sclerosis, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, psoriasis, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease). Pooled odds ratios (OR) with 95 % CI were calculated using random (REM) or fixed (FEM) effects models in the Stata 11.0 Software. Thirty-four articles were eligible for inclusion in the meta-analyses, comprising 9 different SNPs: rs280496, rs280500, rs280523, rs280519, rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800. Meta-analysis results showed the minor alleles of rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800 SNPs were associated with protection against autoimmune diseases. Moreover, the A allele of the rs280519 SNP was associated with risk for systemic lupus erythematosus. Our meta-analyses demonstrated that the rs2304256, rs12720270, rs12720356, rs34536443, rs35018800, and rs280519 SNPs in the TYK2 gene are associated with different autoimmune diseases.

Abstract Uncoupling protein 2 (UCP2) decreases reactive oxygen species (ROS). ROS overproduction is a key contributor to the pathogenesis of diabetic kidney disease (DKD). Thus, UCP2 polymorphisms are candidate risk factors for DKD; however, their associations with this complication are still inconclusive. Here, we describe a case-control study and a meta-analysis conducted to investigate the association between UCP2 -866G/A and Ins/Del polymorphisms and DKD. The case-control study comprised 385 patients with type 1 diabetes mellitus (T1DM): 223 patients without DKD and 162 with DKD. UCP2 -866G/A (rs659366) and Ins/Del polymorphisms were genotyped by real-time PCR and conventional PCR, respectively. For the meta-analysis, a literature search was conducted to identify all studies that investigated associations between UCP2 polymorphisms and DKD in patients with T1DM or type 2 diabetes mellitus. Pooled odds ratios were calculated for different inheritance models. Allele and genotype frequencies of -866G/A and Ins/Del polymorphisms did not differ between T1DM case and control groups. Haplotype frequencies were also similar between groups. Four studies plus the present one were eligible for inclusion in the meta-analysis. In agreement with case-control data, the meta-analysis results showed that the -866G/A and Ins/Del polymorphisms were not associated with DKD. In conclusion, our case-control and meta-analysis studies did not indicate an association between the analyzed UCP2 polymorphisms and DKD.