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Renal lymphatic vessels correlate with disease activity and progression of IgA nephropathy: a retrospective cohort
Xin Xu1, Guangchang Pei1, Zheng Wang1
1Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Rationale & Objective:
The progression of IgA nephropathy (IgAN) involves complement activation and inflammatory infiltration. Lymphatics is reported to connect tissue injury with immunoregulation effect. This study aimed to quantify renal lymphatic vessel (LV) density in a Chinese IgAN cohort, assess its correlation with complement and inflammation, and evaluate its long-term prognostic significance.
Study Design:
Retrospective cohort study.
Setting & Participants:
We enrolled 127 IgAN patients from Tongji Hospital (Wuhan, China) who were treatment-naïve at renal biopsy (no glucocorticoids or immunosuppressants) and had complete, valid follow-up data.
Exposure:
Renal LVs and inflammatory cells were assessed by histological staining; urinary galactose-deficient IgA1 (Gd-IgA1), complement components, and cytokines were measured by ELISA (Enzyme-Linked Immunosorbent Assay).
Outcomes:
Two independent primary endpoints were defined: (1) Serum creatinine (Scr) doubling and (2) end-stage renal disease (ESRD).
Analytical Approach:
Cox proportional hazards regression.
Result:
In patients with IgAN, renal LVs density was significantly elevated compared to controls (P = .004). This increase was positively correlated with urinary levels of Gd-IgA1, (r = 0.41), IL-6 (r = 0.37), C5b-9 (r = 0.34), complement factor H (CFH, r = 0.50), mannose-binding lectin (MBL, r = 0.40), and C4d (r = 0.26). Inflammatory cell infiltration (CD68+, DC-SIGN+, CD1c+, CD4+, CD8+, CD20+) around LVs also was correlated with LVs density. Patients then were stratified by LVs density into LV1-LV3 groups. Those in the LV3 group showed significantly higher proteinuria, Scr, and pathological scores. Over a median follow-up of 93 months, the LV3 group had a significantly increased risk of Scr doubling (HR = 3.67) and progression to ESRD (HR = 19.81) compared to the lower-density groups.
Limitations:
Single-center retrospective design; sample size.
Conclusion:
Renal LVs density exhibits a significant correlation with urinary Gd-IgA1 levels, complement activation, inflammatory cell infiltration and renal lesions. Furthermore, a higher renal LVs density is closely associated with poorer renal outcomes.
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