Abstract

Abstract Background and Aims Although absolute risks of infection in patients with lupus nephritis (LN) are believed high, it is not known whether they differ from those of patients with other etiologies of moderate and advanced chronic kidney disease (CKD). The aim of this study was to compare infection outcomes between patients with LN-CKD and other forms of CKD. Method Using data from the Swedish Renal Registry (2006-2021), we compared infection-related outcomes between LN-patients with moderate and advanced, non-dialysis, CKD and patients with 1) diabetic kidney disease (DKD), 2) primary glomerular diseases (PGD, i.e. IgA nephropathy, focal segmental glomerulosclerosis, membranous nephropathy), and 3) autosomal dominant polycystic kidney disease (ADPKD). Cause-specific Cox proportional hazard models were used to estimate the adjusted hazard ratios of death due to infection, first all-cause infection-related hospitalization and first cause-specific infection-related hospitalization (sepsis, pulmonary, gastrointestinal, genitourinary, and other infections). Results We identified 317 patients with LN (61 years, 76% women, median eGFR 30 mL/min per 1.73 m²), 8877 patients with DKD (71 years, 33% women, eGFR 24 mL/min per 1.73 m²), 2296 patients with PGD (57 years, 30% women, eGFR 29 mL/min per 1.73 m²) and 1855 patients with ADPKD (59 years, 45% women, eGFR 26 mL/min per 1.73 m²). Over a median follow-up of 2.8 [1.2; 5.0] years, 667 (5%) deaths due to infection and 4034 (30%), infection-related (first-time) hospitalizations occurred, including 2127 (16%) pulmonary, 1507 (11%) genitourinary, 1130 (8%) gastrointestinal, 615 (5%) other infections, and 450 (3%) sepsis. In multivariable analyses, and when compared to DKD, patients with LN had a similar risk of death due to infection (adjusted HR 1.15 [95% CI: 0.62-2.11]) and sepsis (HR 1.24 [0.64-2.4]), but a higher risk of all infection-related hospitalization (HR 1.31 [1.04-1.65]), the latter being mainly driven by pulmonary, gastrointestinal, and other infections (Figure panel A). The risks of death due to infection (HR LN vs PGD 2.78 [1.62-4.77], HR LN vs ADPKD 2.34 [1.31-4.19]), of infection-related hospitalization (HR 1.87 [1.52-2.31], HR 1.43 [1.16-1.77]), and of cause-specific infection-related hospitalization were higher in LN than in PGD and ADKPD, respectively, except for the risk of sepsis which was similar between LN and ADPKD. The risk of genitourinary infection tended to be lower in LN than in ADPKD, although the 95% CI slightly overlapped (Figure panels B-C). Conclusion LN patients had higher risk of infection-related hospitalization than all other investigated CKD etiologies, and a higher risk of death due to infections than patients with PGD and ADPKD. Our findings highlight the need for improvements in infection prevention in patients with LN. Whether a more tailored immunosuppressive treatment approach could further improve outcomes in this high-risk population remains to be investigated.

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