Thomas Welte

Background Diabetes mellitus is a major risk factor for the development of chronic kidney disease (CKD). There is limited data addressing the value of glycated hemoglobin (HbA1c) to predict renal outcomes independent of diabetes status. Methods This single‐center retrospective observational study presents data of 19,285 subjects, irrespective of initial CKD or diabetes status. The primary endpoint was defined as the time to manifestation of moderate CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m 2 ) in subjects with eGFR ≥60 mL/min/1.73 m 2 at baseline. The secondary endpoint was defined as time to progression of CKD (eGFR <30 mL/min/1.73 m 2 ) in subjects with eGFR 30–60 mL/min/1.73 m 2 . Multivariate time‐to‐event and logistic regression models were applied to estimate the influences of HbA1c, sex, age, eGFR, triglycerides, and cholesterol on both endpoints. Results Lowest baseline HbA1c levels were associated with the slowest decline of kidney function (median time to manifestation of moderate CKD for HbA1c <5.7%: 15.9 years [95% confidence interval (CI): 15.2–16.7]; for HbA1c 5.7%–6.5%: 14.5 years [95% CI: 14.0–15.1]; for HbA1c 6.5%–8.5%: 11.1 years [95% CI: 10.4–11.7]; for HbA1c >8.5%: 8.3 years [95% CI: 7.8–9.2]; p < 0.001). Similar results were observed for the secondary endpoint. Covariate‐adjusted time‐to‐event analysis demonstrated an almost linear correlation between continuous baseline HbA1c levels and the probabilities of reaching both endpoints. Conclusions HbA1c levels are a strong predictor for eGFR decline, irrespective of diabetes status or CKD stage, demonstrating a tight concentration‐dependent relationship. This association becomes apparent in the prediabetic HbA1c range and remains constant over the entire HbA1c spectrum.

Objective B‐cell depletion using the anti‐CD20 monoclonal antibody rituximab is a cornerstone in the therapeutic concept of multiple autoimmune diseases. B‐cell depletion is associated with a higher risk for severe infections, and the time span of B‐cell repopulation differs greatly between individuals. Data on factors influencing B‐cell repopulation kinetics are limited. This study aims to identify patient‐specific and therapy‐associated covariates that modulate B‐cell repopulation. Methods This single‐center retrospective observational study presents data of 839 subjects receiving 2,017 courses of rituximab for autoimmune diseases. Assessed covariates are patient‐specific factors (sex, age, kidney function, and underlying disease) and co‐immunosuppression with common agents (azathioprine, cyclosporine A, cyclophosphamide, hydroxychloroquine, methotrexate, mycophenolate mofetil, tacrolimus, and corticosteroids). The primary end point is the time to B‐cell repopulation (≥5/μl). The secondary end point is the time to B‐cell reconstitution (≥50/μl). Multivariate time‐to‐event analysis and logistic regression models were applied to estimate the influence of covariates. Results Age over 60 years (hazard ratio [HR] 0.71 for repopulation, P = 0.008), impaired kidney function (HR 0.72, P = 0.001), antineutrophil cytoplasmic antibody‐associated vasculitis (HR 0.61, P < 0.001), solid organ transplantation (HR 0.4, P < 0.001), and co‐immunosuppression with corticosteroids (HR 0.64, P < 0.001) or azathioprine (HR 0.49, P < 0.001) were associated with impaired B‐cell repopulation and reconstitution. Effects of corticosteroids ( P = 0.043) and azathioprine ( P = 0.025) were dose dependent. Conclusion Prolonged rituximab dosing intervals may be effective to achieve B‐cell depletion and reduce risk of infection in advanced age or patients with impaired kidney function. Co‐medication with corticosteroids or azathioprine prolongs B‐cell recovery, which may increase therapeutic effects but also the rate of adverse events. image