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ObjectiveTo characterize the incidence, type, and risk factors of severe infections (SI) in patients with autoimmune kidney diseases treated with rituximab (RTX).MethodsWe conducted a multicenter retrospective cohort study of adult patients with immune-related kidney diseases treated with at least one course of RTX between 2015 and 2019. As a part of the ABCDE Registry, detailed data on RTX application and SI were collected. SI were defined by Common Terminology Criteria for Adverse Events v5.0 as infectious complications grade 3 and above. Patients were dichotomized between “nephrotic” and “nephritic” indications. The primary outcome was the incidence of SI within 12 months after the first RTX application.ResultsA total of 144 patients were included. Twenty-five patients (17.4%) presented with SI, mostly within the first 3 months after RTX administration. Most patients in the nephritic group had ANCA-associated vasculitis, while membranous nephropathy was the leading entity in the nephrotic group. Respiratory infections were the leading SI (n= 10, 40%), followed by urinary tract (n=3, 12%) and gastrointestinal infections (n=2, 8%). On multivariable analysis, body mass index (BMI, 24.6 kg/m2versus 26.9 kg/m2, HR: 0.88; 95%CI: 0.79-0.99; p=0.039) and baseline creatinine (HR: 1.25; 95%CI: 1.04-1.49; p=0.017) were significantly associated with SI. All patients in the nephritic group (n=19; 100%) who experienced a SI received oral glucocorticoid (GC) treatment at the time of infection. Hypogammaglobulinemia was frequent (58.5%) but not associated with SI.ConclusionsAfter RTX administration, impaired kidney function and lower BMI are independent risk factors for SI. Patients with nephritic glomerular diseases having concomitant GC treatment might be at higher risk of developing SI.

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Introduction: Magnesium (Mg2+) deficiency is a common finding in the early phase after kidney transplantation (KT) and has been linked to immune dysfunction and infections. Data on the association of hypomagnesemia and the rate of infections in kidney transplant recipients (KTRs) are sparse. Methods: We conducted a single-center retrospective cohort study of KTRs transplanted between 2005 and 2015. Laboratory data, including serum Mg2+ (median time of the Mg2+ measurement from KT: 29 days), rate of infections including mainly urinary tract infections (UTI), and common transplant-related viral infections (CMV, polyoma, EBV) in the early phase after KT were recorded. The primary outcome was the incidence of infections within one year after KT, while secondary outcomes were hospitalization due to infection, incidence rates of long-term (up to two years) infections, and all-cause mortality. Results: We enrolled 376 KTRs of whom 229 patients (60.9%) suffered from Mg2+ deficiency defined as a serum Mg2+ < 0.7 mmol/L. A significantly higher incidence rate of UTIs and viral infections was observed in patients with versus without Mg2+ deficiency during the first year after KT (58.5% vs. 47.6%, p = 0.039 and 69.9% vs. 51.7%, p < 0.001). After adjustment for potential confounders, serum Mg2+ deficiency remained an independent predictor of both UTIs and viral infections (odds ratio (OR): 1.73, 95% CI: 1.04–2.86, p = 0.035 and OR: 2.05, 95% CI: 1.23–3.41, p = 0.006). No group differences according to Mg2+ status in hospitalizations due to infections and infection incidence rates in the 12–24 months post-transplant were observed. In the Cox regression analysis, Mg2+ deficiency was not significantly associated with all-cause mortality (HR: 1.15, 95% CI: 0.70–1.89, p = 0.577). Conclusions: KTRs suffering from Mg2+ deficiency are at increased risk of UTIs and viral infections in the first year after KT. Interventional studies investigating the effect of Mg2+ supplementation on Mg2+ deficiency and viral infections in KTRs are needed.

BACKGROUND AND AIMS Plasma cells (PC) are the most differentiated antibody and cytokine-producing B lineage cells and are thought to contribute to the perpetuation of inflammation in patients with ANCA-associated vasculitis (AAV). Agents targeting PCs are of interest in AAV, however, little is known about the role of interstitial CD138 + PCs in these patients. In this study, we aim to demonstrate the impact of this cell population in the prediction of renal outcomes in patients with AAV. METHOD Forty AAV patients with glomerulonephritis, diagnosed between 2014 and 2018 at the Division of Nephrology of the Medical University of Graz were included and followed for 36 months. Histological assessments using the kidney allograft Banff classification were performed to describe the tubulointerstitial (TI) damages. Immunohistochemistry analysis was performed in 29 patients to assess the renal interstitial CD138 + cell expression. More than ten CD138 + cells per high power field were stated as high expression (excluding CD138 staining of renal tubular epithelial cells). Changes in kidney function, the incidence of renal relapses (RR), and end-stage renal disease (ESRD) were analyzed. RESULTS In the kidney biopsies, N = 21 (72%) patients had a high expression of CD138 + plasma cells. No significant difference was observed in PR3 and MPO serotypes in the group of patients with high CD138 + cell expression (43% versus 57%, P = .793). In addition, no significant difference was seen in the changes in kidney function and the incidence of RR or ESRD between the groups with high and low expression of CD138 + cells during the follow-up period. However, patients with more severe TI damage had more severe proteinuria {urinary albumin/creatinine ratio: 51 [interquartile range (IQR) 42–123] versus 360 (IQR 202–1112) mg/g Creatinine; P = .016} at 3-year follow-up, and tended to have a higher rate of RR and ESRD [i0/i1: N = 2/18 (11%) versus i2/i3: N = 6/22 (27%), P = .258 and i0/i1: N = 2/18 (11%) versus i2/i3: N = 6/22 (27%), P = .258, respectively]. CONCLUSION Our data indicate a significant proportion of CD138 + PCs in kidney specimens of patients with AAV. Despite the lack of association between this cell population and our cohort’s renal outcome, these results provide additional insights on the renal B-cell clusters in patients with AAV. In addition, our findings go along with already existing data on the association between extended TI damage and worse renal outcome.