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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Urinary soluble CD163 is a good biomarker for renal disease activity in lupus nephritis
Ranjan Gupta1,2, Akhilesh Yadav1, Amita Aggarwal3
1Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.
Objectives:
Activated macrophages expressing CD163 (M2) are the most abundant macrophage subtype in renal biopsies from lupus nephritis (LN) patients. We studied the role of proteolytically cleaved soluble CD163 (sCD163) as a biomarker of LN disease activity.
Methods:
SLE patients were classified as active LN (AN), inactive disease (ID), and active non-renal disease (ANR). Urine and plasma samples were collected at baseline from all patients and at 3 monthly follow-up from AN patients. sCD163 was measured by ELISA. Urine values were normalized to urinary creatinine excretion and expressed as pg/mg. Urine samples from 25 healthy controls (HC) and 20 rheumatoid arthritis patients served as disease controls (DC).
Results:
Among the 122 patients studied (114 females, 57 AN, 42 ID, 23 ANR), baseline median urinary sCD163 in the AN group (114.01 pg/mg) was significantly higher (p < 0.001) as compared with ID (10.34 pg/mg), ANR (3.82 pg/mg), HC (0 pg/mg), and DC (7.56 pg/mg) groups and showed modest correlation with renal SLEDAI (r = 0.47; p < 0.001). Urinary sCD163 performed the best on receiver operating characteristics (ROC) analysis (AUC = 0.76) at baseline to differentiate between AN and ANR as compared with plasma sCD163, anti-ds DNA antibodies, and C3 and C4. In follow-up study, urinary sCD163 decreased significantly (p < 0.001) in AN patients at 3 (22.07 pg/mg), 6 (12.7 pg/mg), 9 (11.09 pg/mg), and 12 months (7.2 pg/mg). In 4 patients who had either relapse or developed CKD, urinary sCD163 levels correlated with the changing disease activity.
Conclusions:
Urinary sCD163 is a good biomarker of LN disease activity. Key Points • Urinary sCD163 levels are raised in patients with active lupus nephritis and correlate with renal SLEDAI. • Urinary sCD163 levels fall after treatment and may be helpful in monitoring response to therapy in lupus nephritis.
Insights
Urinary soluble CD163 (sCD163) is elevated in active lupus nephritis (LN) and correlates with disease activity. Levels decrease with treatment, indicating sCD163
Area of Science:
- Nephrology
- Immunology
- Biomarker Discovery
Background:
- Activated M2 macrophages expressing CD163 are abundant in lupus nephritis (LN) renal biopsies.
- Soluble CD163 (sCD163) is a proteolytically cleaved form of the macrophage scavenger receptor.
- The utility of sCD163 as a biomarker for LN disease activity requires investigation.
Purpose of the Study:
- To evaluate the role of urinary and plasma soluble CD163 (sCD163) as a biomarker for lupus nephritis (LN) disease activity.
- To assess the correlation of sCD163 levels with clinical and laboratory markers of LN.
- To determine if sCD163 can monitor treatment response in LN patients.
Main Methods:
- Systemic lupus erythematosus (SLE) patients were categorized into active LN (AN), inactive disease (ID), and active non-renal disease (ANR).
- Urine and plasma samples were collected at baseline and during 3-monthly follow-ups for AN patients.
- Soluble CD163 (sCD163) was quantified using ELISA, with urinary values normalized to creatinine.
Main Results:
- Baseline urinary sCD163 was significantly higher in active LN patients compared to inactive disease, active non-renal disease, healthy controls, and disease controls (p < 0.001).
- Urinary sCD163 demonstrated a modest correlation with renal SLEDAI (r=0.47; p < 0.001) and performed well in ROC analysis for differentiating active vs. non-renal disease (AUC=0.76).
- Urinary sCD163 levels significantly decreased during treatment follow-up and correlated with disease activity fluctuations in patients experiencing relapse or developing chronic kidney disease (CKD).
Conclusions:
- Urinary sCD163 serves as a valuable biomarker for assessing lupus nephritis (LN) disease activity.
- Elevated urinary sCD163 levels in active LN correlate with renal SLEDAI.
- Decreased urinary sCD163 levels post-treatment suggest its potential utility in monitoring therapeutic response in LN.
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