Lymphopenia and neutropenia are associated with subsequent incident proteinuria in Danish patients with systemic lupus erythematosus

Abstract

Objective: The aim of this study was to investigate whether incident proteinuria in patients with systemic lupus erythematosus (SLE) was preceded by changes in blood lymphocytes and neutrophil counts and/or neutrophil–lymphocyte ratio (NLR).

Method: SLE patients with no proteinuria before or at the time of classification were included. Longitudinal data on SLE manifestations, vital status, and SLE-associated medications were collected during clinical visits and chart review. Laboratory data were collected through a nationwide database. Lymphopenia, severe lymphopenia, and neutropenia were defined as values below 0.8 × 10⁹, 0.5 × 10⁹, and 2.0 × 10⁹ cells/L, respectively. High NLR was defined as values above the median. Proteinuria was defined by at least two measurements of elevated urine protein excretion (> 0.5 g/day). Hazard ratios (HRs) were calculated by Cox modelling using time-dependent continuous and binary covariates based on multiple laboratory measurements adjusted for use of immunosuppressants.

Results: In total, 260 SLE patients were available for the analysis, of whom 30 (12%) developed incident proteinuria following the diagnosis of SLE. Median follow-up time was 73.5 months. Lymphocyte and neutrophil counts, but not NLR, were associated with incident proteinuria. HRs for incident proteinuria were 2.71 for lymphopenia [95% confidence interval (CI) 1.20–6.11], 4.73 for severe lymphopenia (95% CI 1.93–11.59), and 2.54 for neutropenia (95% CI 1.14–5.65).

Conclusion: Lymphopenia and neutropenia predicted the risk of first-time proteinuria independently of immunosuppressants.

Acknowledgements

This study was a joint venture between the Centre for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, the Centre of Excellence for Personalized Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE), Rigshospitalet, Copenhagen, and the Danish national rheumatological registry, DANBIO. The authors wish to thank the staff associated with DANBIO and PERSIMUNE for their help throughout this work. This work was supported by the Danish Rheumatism Association (A3865), the Research Foundation at Rigshospitalet (E-23390-01), and the Danish National Research Foundation (grant number DNRF126). The funders only supported the project financially and had no influence on the study or reporting of its results.

Disclosure statement

No potential conflict of interest was reported by the authors.