Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status

Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN.

Dysregulation of the CD163-Haptoglobin Axis in the Airways of COPD Patients

Pulmonary iron levels are increased in chronic obstructive pulmonary disease (COPD) patients. Iron causes oxidative stress and is a nutrient for pathogenic bacteria. Iron may therefore play an important role in the pathophysiology of COPD. The CD163-haptglobin axis plays a central role in the regulation of iron bioavailability. The aim of this study was to examine dysregulation of the CD163-haptglobin axis in COPD. We measured soluble CD163 (sCD163) and haptoglobin levels in sputum supernatants by enzyme-linked immunosorbent assay (ELISA) and sputum macrophage CD163 and haptoglobin expression by flow cytometry in COPD patients and controls. SCD163 levels were lower in COPD patients compared to controls (p = 0.02), with a significant correlation to forced expiratory volume in 1 s (FEV1)% predicted (rho = 0.5, p = 0.0007). Sputum macrophage CD163 expression was similar between COPD patients and controls. SCD163 levels and macrophage CD163 expression were lower in COPD current smokers compared to COPD ex-smokers. Haptoglobin levels were not altered in COPD patients but were regulated by genotype. Macrophage CD163 and haptolgobin expression were significantly correlated, supporting the role of CD163 in the cellular uptake of haptoglobin. Our data implicates a dysfunctional CD163-haptoglobin axis in COPD, which may contribute to disease pathophysiology, presumably due to reduced clearance of extracellular iron.

Circulating Soluble CD163: A Potential Predictor for the Functional Outcome of Acute Ischemic Stroke

Background: CD163 is a transmembrane glycoprotein receptor expressed on innate immune cells that sheds from the cell membrane and circulates as a soluble form (sCD163). This study aimed to investigate the circulating levels and clinical relevance of soluble CD163 (sCD163) in acute ischemic stroke (AIS).Methods: This study recruited 300 patients with AIS and 78 healthy controls. The patients were followed up for 1 month to observe the functional outcomes. The neurological functions of the patients were assessed using the NIH Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). The plasma concentrations of sCD163 at the baseline (patient admission) were determined by ELISA.Results: We found that patients with AIS had significantly higher plasma sCD163 concentrations than the healthy control. Patients with high sCD163 concentrations had better functional outcomes than patients with low sCD163 concentrations. The plasma sCD163 concentrations were positively associated with the NIHSS scores and infarction volume at the baseline. The plasma sCD163 was positively associated with the improvement of the NIHSS scores but was negatively associated with the risk of poor functional outcomes during follow-up.Conclusions: These findings indicate that circulating sCD163 is a potential biomarker that is associated with disease severity and the functional outcome of AIS.

The Clinical Application of Urine Soluble CD163 in ANCA-Associated Vasculitis

Background Up to 70% of patients with ANCA-associated vasculitis (AAV) develop glomerulonephritis, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (sCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. Methods We assessed a diagnostic-grade urinary sCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and 10 controls. Results We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, urinary sCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic acute kidney injury. Urinary sCD163's specificity declined in AAV patients with nephrotic-range proteinuria and in primary podocytopathy, with 62% of nephrotic patients displaying a "positive" urinary sCD163. In AAV patients with significant proteinuria, urinary sCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis. Conclusions Urinary sCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates urinary sCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.

Soluble CD163 and small dense LDL cholesterol levels in type 2 diabetes patients

Introduction: The sdLDL cholesterol proportion is a better marker for the prediction of cardiovascular diseases (CVDs). Macrophages play a crucial role in both the initiation and progression of atherosclerosis, the underlying mechanism of CVDs. This study investigated the correlation between soluble CD163 as a biomarker macrophage activation and sdLDL cholesterol in type 2 diabetes mellitus (T2DM) subjects for the first time.

Soluble CD163 for Prediction of High-Risk Esophageal Varices and Variceal Hemorrhage in Patients with Liver Cirrhosis

<b><i>Introduction:</i></b> Activation of hepatic macrophages in liver disease is pathogenically related to portal hypertension (PH). Soluble CD163 (sCD163) is shed in blood by activated macrophages and may predict PH progression noninvasively. This study was designed to investigate the relation of serum sCD163 to the grade and bleeding risk of esophageal varices (EV) and its role for prediction of variceal hemorrhage (VH). <b><i>Methods:</i></b> The study included cirrhotic patients divided into 3 groups: patients who presented with acute upper gastrointestinal bleeding (UGIB) proved to originate from EV on endoscopy, patients without any history of UGIB but who revealed EV on surveillance endoscopy, and patients without endoscopic evidence of varices. Variceal grade and risk signs and bleeding stigmata were noted simultaneously with measurement of serum sCD163 concentration. <b><i>Results:</i></b> Serum sCD163 concentration showed a significant increase in cirrhotic patients compared to healthy subjects (<i>p</i> &#x3c; 0.001) with a stepwise increase among the group without varices, nonbleeder group, and bleeder group sequentially. Serum sCD163 levels correlated positively with the variceal grade and risk signs in both the bleeder and nonbleeder groups (<i>p</i> = 0.002, <i>p</i> &#x3c; 0.001 and <i>p</i> = 0.004, <i>p</i> &#x3c; 0.001, respectively). Serum sCD163 at a cutoff value of 3.6 mg/L performed significantly for prediction of EV presence (AUC = 0.888). Serum sCD163 at a cutoff value &#x3e;4 mg/L significantly predicted large-size and high-risk EV (AUC = 0.910 and AUC = 0.939, respectively) and the index bleed risk (AUC = 0.977). Serum sCD163 at a cutoff value &#x3e;4.05 mg/L modestly discriminated bleeding EV from those that had never bled (AUC = 0.811). <b><i>Conclusions:</i></b> Serum sCD163 levels accurately predicted high-grade and high-risk EV and could help plan for primary prophylaxis. However, it modestly identified VH occurrence, and endoscopy would be required to make a definitive diagnosis.