Long-Term Mortality and SGLT2 Inhibitors in Type 2 Diabetes with and without Renal Impairment: An Observational Cohort Study.

AIM: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a vital part of management of type 2 diabetes, as they have been shown to have both cardiovascular and renal benefits along with an improved survival rate in several randomized clinical trials. We designed a retrospective cohort study to investigate the impact of SGLT2 inhibitors on mortality among type 2 diabetes patients. METHODS: Patients with type 2 diabetes who presented to the Dasman Diabetes Institute in Kuwait were followed from January 1st, 2015, until January 20th, 2023. To control for non-random allocation of SGLT2 inhibitors and measured confounders, we performed one-to-one propensity score matching and evaluated outcomes in the matched cohorts using a Cox proportional hazards model. The primary treatment variable was SGLT2 inhibitor use; time to mortality from any cause was used as the outcome of interest. RESULTS: 1,551 patients were taking SGLT2 inhibitors, and 1,687 patients were not. After propensity score matching, 845 patients were on SGLT2 inhibitors, and 845 patients were not. In post-matching analysis, all-cause mortality was higher among patients who did not take SGLT2 inhibitors compared to patients taking SGLT2 inhibitors (5.2 vs. 2.1%, p = 0.0012). The hazard ratio of all-cause mortality in patients taking SGLT2 inhibitors was 0.42 (95% confidence interval [95% CI], 0.24-0.72). Additional adjustment of matching factors did not change the results. CONCLUSION: This observational study demonstrated substantial long-term reduction in mortality risk among patients with type 2 diabetes treated with SGLT2 inhibitors. This is irrespective of the stage of their renal diseases or GLP1 agonist.

Response to and outcomes of the Pfizer BNT162B2 vaccine in hemodialysis patients-A prospective observational study.

INTRODUCTION: COVID-19 infection is associated with high mortality among hemodialysis patients. Standard vaccine response is generally lower among these patients. The adequate antibody titer response and the outcome of COVID-19 vaccine responders versus non-responders are unknown. METHODS: Hemodialysis patients on maintenance hemodialysis who have received two doses of Pfizer BNT162B2 vaccine were studied. Antibody response was tested after 14 days of the second dose. LIAISON SARS-CoV2 S1/S2 IgG test by DiaSorin (Italy) was used to assess antibody response. Patients were followed between 3 and 7 months after vaccination for COVID-19 infection, hospitalization and death related to COVID-19. FINDINGS: A total of 138 patients received two doses of Pfizer BNT162B2 vaccine. One hundred and twenty-seven patients had adequate response to the vaccine with IgG level ≥ 15 AU/ml versus 11 patients had poor response with IgG level ≤ 15 AU/ml. The response was 92% (127/138). Patient with history of prior COVID-19 infection had higher antibody titer mean of 339 ± 113 versus 157 ± 140 for patient with no prior history of COVID-19. Seven patients in both groups had COVID-19 infection post vaccine. Among the responders, five patients had COIVD-19 infection and two were hospitalized. These two patients had lower antibody titer of 23.9 and 75.2 AU/ml. In comparison, three patients who were not hospitalized had higher antibody titer 96.3, 118, and 319 AU/ml, respectively. In the non-responders one patient was hospitalized and one death occurred with rate of infection of 18%. DISCUSSION: Seropositive patients with low antibody titer might be associated with worse outcome among responders. The ideal antibody titer level among dialysis patient is not known. Also, prior COVID-19 infection is associated with higher response to vaccine with higher antibody titer. All non-responders did not have prior COVID-19 infection. More research is required to further evaluated protective antibody titer.

Use of Rituximab as an Off-Label Medication in Glomerular Diseases: Clinical Perspective.

OBJECTIVES: The aim of this study was to review the use rituximab (RTX) and outcomes in immune-mediated glomerular diseases (glomerulonephritis [GN]) and to compare it to the established literature. METHODS: Adult GN patients who received RTX between January 2014 and January 2018 in three public hospitals were reviewed. Membranous nephropathy (MN) and minimal change disease (MCD) were considered diseases with the literature supporting RTX use. Lupus nephritis (LN), primary focal segmental glomerulosclerosis (1o FSGS), IgA nephropathy, IgG4-related disease (IgG4-RD), and C3GN had insufficient literature support for RTX use. Clinical remission was assessed 6 months after receiving RTX. RESULTS: A total of 61 cases were analyzed. RTX was an add-on therapy in 87%. The remission rate was 95% in the MCD and MN versus 56% in the off-label group (p = 0.002). LN patients had a mean initial estimated glomerular filtration rate (eGFR) of 69 mL/min. All class III LN achieved remission, and 11 of 21 class IV achieved remission. The mean initial eGFR for 1o FSGS was 33 mL/min, and it did not improve, and only 2 of 5 had partial resolution of proteinuria. Proteinuria improved in 3 of 5 IgG4-RD cases with eGFR stabilization but failed to improve in C3GN cases with eGFR deterioration. Vasculitis cases (6 ANCA-associated vasculitis and 2 IgA vasculitis) were analyzed separately. Remission was achieved in only 2 ANCA-associated vasculitis cases, and none in IgA vasculitis cases. CONCLUSIONS: Our data support the use of RTX in resistant MCD and MN. RTX showed success in LN and IgG4-RD but not FSGS or C3GN. The small number of cases of vasculitis does not allow drawing a conclusion on RTX effectiveness.