Role of antidiabetic agents in type 2 diabetes patients with chronic kidney disease.

Insulin resistance is a condition in which the target tissues have a decreased response to insulin signaling, resulting in glucose uptake defect, and an increased blood sugar level. Pancreatic beta cells thus enhance insulin production to compensate. This situation may cause further beta cell dysfunction and failure, which can lead diabetes mellitus (DM). Insulin resistance is thus an important cause of the development of type 2 DM. Insulin resistance has also been found to have a strong relationship with cardiovascular disease and is common in chronic kidney disease (CKD) patients. The mechanisms of insulin resistance in CKD are complex and multifactorial. They include physical inactivity, inflammation and oxidative stress, metabolic acidosis, vitamin D deficiency, adipose tissue dysfunction, uremic toxins, and renin-angiotensin-aldosterone system activation. Currently, available anti-diabetic agents, such as biguanides, sulfonylureas, thiazolidinediones, alfa-glucosidase inhibitors, glucagon-like peptide-1-based agents, and sodium-glucose co-transporter-2 inhibitors, have different effects on insulin resistance. In this short review, we describe the potential mechanisms of insulin resistance in CKD patients. We also review the interaction of currently available anti-diabetic medications with insulin resistance.

Trajectory of Humoral Responses to Two Doses of ChAdOx1 nCoV-19 Vaccination in Patients Receiving Maintenance Hemodialysis.

The ChAdOx1 nCoV-19 (AZD1222) vaccine is one of the most commonly delivered SARS-CoV-2 vaccines worldwide; however, few clinical studies have investigated its immunogenicity in dialysis patients. We prospectively enrolled 123 patients on maintenance hemodialysis at a medical center in Taiwan. All patients were infection-naive, had received two doses of the AZD1222 vaccine, and were monitored for 7 months. The primary outcomes were anti-SARS-CoV-2 receptor-binding domain (RBD) antibody concentrations before and after each dose and 5 months after the second dose and neutralization capacity against ancestral SARS-CoV-2, delta, and omicron variants. The anti-SARS-CoV-2 RBD antibody titers significantly increased with time following vaccination, with a peak at 1 month after the second dose (median titer, 498.8 U/mL; interquartile range, 162.5 to 1,050 U/mL), and a 4.7-fold decrease at 5 months. At 1 month after the second dose, 84.6, 83.7, and 1.6% of the participants had neutralizing antibodies against the ancestral virus, delta variant, and omicron variant, respectively, measured by a commercial surrogate neutralization assay. The geometric mean 50% pseudovirus neutralization titers for the ancestral virus, delta variant, and omicron variant were 639.1, 264.2, and 24.7, respectively. The anti-RBD antibody titers correlated well with neutralization capacity against the ancestral virus and delta variant. Transferrin saturation and C-reactive protein were associated with neutralization against the ancestral virus and delta variant. Although two doses of the AZD1222 vaccine initially elicited high anti-RBD antibody titers and neutralization against the ancestral virus and delta variant in hemodialysis patients, neutralizing antibodies against omicron variant were rarely detected, and the anti-RBD and neutralization antibodies waned over time. Additional/booster vaccinations are warranted in this population. IMPORTANCE Patients with kidney failure have worse immune response following vaccination compared to general population, but few clinical studies have investigated immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccination in hemodialysis patients. Here, we showed two doses of AZD1222 vaccines lead to high seroconversion rate of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies, and more than 80% patients acquired neutralizing antibodies against ancestral virus and delta variant. However, seldom did they obtain neutralizing antibodies against the omicron variant. The geometric mean 50% pseudovirus neutralization titer against the ancestral virus was 25.9-fold higher than that against the omicron variant. Also, there was a substantial decay in anti-RBD titers with time. Our findings provided evidence supporting that more protective measures, including additional/booster vaccinations, is warranted in these patients during the current COVID-19 pandemic.

Effect of dialysis modalities on risk of hospitalization for gastrointestinal bleeding.

Dialysis patients are at risk of both thromboembolic and bleeding events, while thromboembolism prevention and treatment may confer a risk of major bleeding. Gastrointestinal (GI) bleeding is a great concern which can result in high subsequent mortality rates. Our object was to clarify whether hemodialysis (HD) and peritoneal dialysis (PD) confer different incidence of GI bleeding, and further assist individualized decision-making on dialysis modalities. We conducted a population-based retrospective cohort study which included all incident dialysis patients above 18 years old derived from the National Health Insurance database from 1998 to 2013 in Taiwan. 6296 matched pairs of HD and PD patients were identified. A propensity score matching method was used to minimize the selection bias. The adjusted hazard ratio for GI bleeding was 1.13 times higher in the HD group than in the PD group, and data from the unmatched cohort and the stratified analysis led to similar results. Among subgroup analysis, we found that the use of anticoagulants will induce a much higher incidence of GI bleeding in HD patients as compared to in PD patients. We concluded that PD is associated with a lower GI bleeding risk than HD, and is especially preferred when anticoagulation is needed.

Development and validation of the dialysis dementia risk score: A retrospective, population-based, nested case-control study.

BACKGROUND: Dementia is prevalent and underdiagnosed in the dialysis population. We aimed to develop and validate a simple dialysis dementia scoring system to facilitate identification of individuals who are at high risk for dementia. METHODS: We applied a retrospective, nested case-control study design using a national dialysis cohort derived from the National Health Insurance Research Database in Taiwan. Patients aged between 40 and 80 years were included and 2940 patients with incident dementia were matched to 29,248 non-dementia controls. All subjects were randomly divided into the derivation and validation sets with a ratio of 4:1. Conditional logistic regression models were used to identify factors contributing to the risk score. The cutoff value of the risk score was determined by Youden's J statistic and the graphic method. RESULTS: The dialysis dementia risk score (DDRS) finally included age and 10 comorbidities as risk predictors. The C-statistic of the model was 0.71 (95% confidence interval [CI] 0.70-0.72). Calibration revealed a strong linear relationship between predicted and observed dementia risk (R2  = 0.99). At a cutoff value of 50 points, the high-risk patients had an approximately three-fold increased risk of having dementia compared to those with low risk (odds ratio [OR] 3.03, 95% CI 2.78-3.31). The DDRS performance, including discrimination (C-statistic 0.71, 95% CI 0.69-0.73) and calibration (p value of Hosmer-Lemeshow test for goodness of fit = 0.18), was acceptable during validation. The OR value (2.82, 95% CI 2.37-3.35) was similar to those in the derivation set. CONCLUSION: The DDRS system has the potential to serve as an easily accessible screening tool to determine the high-risk groups who deserve subsequent neurological evaluation in daily clinical practice.

Comparison of Immunogenicity and Safety between a Single Dose and One Booster Trivalent Inactivated Influenza Vaccination in Patients with Chronic Kidney Disease: A 20-Week, Open-Label Trial.

BACKGROUND: Non-dialysis-dependent chronic kidney disease (CKD-ND) patients are recommended to receive a one-dose influenza vaccination annually. However, studies investigating vaccine efficacy in the CKD-ND population are still lacking. In this study, we aimed to evaluate vaccine efficacy between the one-dose and two-dose regimen and among patients with different stages of CKD throughout a 20-week follow-up period. METHODS: We conducted a single-center, non-randomized, open-label, controlled trial among patients with all stages of CKD-ND. Subjects were classified as unvaccinated, one-dose, and two-dose groups (4 weeks apart) after enrollment. Serial changes in immunological parameters (0, 4, 8, and 20 weeks after enrollment), including seroprotection, geometric mean titer (GMT), GMT fold-increase, seroconversion, and seroresponse, were applied to evaluate vaccine efficacy. RESULTS: There were 43, 84, and 71 patients in the unvaccinated, one-dose, and two-dose vaccination groups, respectively. At 4-8 weeks after vaccination, seroprotection rates in the one- and two-dose group for H1N1, H3N2, and B ranged from 82.6-95.8%, 97.4-100%, and 73.9-100%, respectively. The concomitant seroconversion and GMT fold-increases nearly met the suggested criteria for vaccine efficacy for the elderly population. Although the seroprotection rates for all of the groups were adequate, the seroconversion and GMT fold-increase at 20 weeks after vaccination did not meet the criteria for vaccine efficacy. The two-dose regimen had a higher probability of achieving seroprotection for B strains (Odds ratio: 3.5, 95% confidence interval (1.30-9.40)). No significant differences in vaccine efficacy were found between early (stage 1-3) and late (stage 4-5) stage CKD. CONCLUSIONS: The standard one-dose vaccination can elicit sufficient protective antibodies. The two-dose regimen induced a better immune response when the baseline serum antibody titer was low. Monitoring change in antibody titers for a longer duration is warranted to further determine the current vaccine strategy in CKD-ND population.