Urinary soluble CD163 level reflects glomerular inflammation in human lupus nephritis

Endo, Nobuhide; Tsuboi, Naotake; Furuhashi, Kazuhiro; Shi, Yiqin; Du, Qiuna; Abe, Tomoko; Hori, Mayuko; Imaizumi, Tsutomu; Kim, Hangsoo; Kuriyama, Takayuki; Ozaki, Tomoya; Kosugi, Tomoki; Matsuo, Seiichi; Maruyama, Shoichi

doi:10.1093/ndt/gfw214

Cited by 67 publications

(64 citation statements)

References 48 publications

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“…Thus, the observed elevation in urine sCD163 in active LN and proliferative LN could not be attributed to medications. Indeed, it has been reported that urine sCD163 levels were comparable between glucocorticoid treated and untreated patients with LN IV, and was not related to the dosage of glucocorticoids (23).…”

Section: Discussionmentioning

confidence: 89%

“…While tubulointerstitial CD163 + macrophages significantly correlated with serum creatinine, serum urea and creatinine clearance, glomerular CD163 + macrophages negatively correlated with plasma C3 and C4 (22,23). Additionally, CD163 was found mainly expressed in active crescentic glomerulonephritis, proliferative glomerular lesions and areas of tubulointerstitial injury (21)(22)(23)(24). In another study including patients with pauci-immune necrotizing glomerulitis, CD68 + and CD163 + macrophages predominated at sites of fibrinoid necrosis (25).…”

Section: Discussionmentioning

confidence: 96%

“…CD163 + M2c-like macrophages were significantly elevated in LN III and LN IV when compared with LN V, and correlated with AI of renal pathology (22). While tubulointerstitial CD163 + macrophages significantly correlated with serum creatinine, serum urea and creatinine clearance, glomerular CD163 + macrophages negatively correlated with plasma C3 and C4 (22,23). Additionally, CD163 was found mainly expressed in active crescentic glomerulonephritis, proliferative glomerular lesions and areas of tubulointerstitial injury (21)(22)(23)(24).…”

Section: Discussionmentioning

confidence: 98%

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Association of Urine sCD163 With Proliferative Lupus Nephritis, Fibrinoid Necrosis, Cellular Crescents and Intrarenal M2 Macrophages

et al. 2020

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CD163 is a marker for alternatively activated macrophages, which have been implicated in the pathogenesis of lupus nephritis (LN). In our preliminary screening of urine proteins in LN, urine soluble CD163 (sCD163) was significantly elevated in patients with active LN. To evaluate the potential of sCD163 as a biomarker in LN, urine sCD163 was assayed in patients with active LN, active non-renal lupus patients (ANR), inactive SLE and healthy controls (HC), using ELISA and normalized to urine creatinine. The correlation of urine sCD163 with clinical parameters and renal pathological attributes was further investigated in LN patients with concurrent renal biopsies. A total of 228 SLE patients and 56 HC were included from three cohorts. Results demonstrated that urine sCD163 was significantly elevated in active LN when compared with HC, inactive SLE, or ANR in African-American, Caucasian and Asian subjects (all P < 0.001). In LN patients with concurrent renal biopsies, urine sCD163 was significantly increased in patients with proliferative LN when compared with non-proliferative LN (P < 0.001). Urine sCD163 strongly correlated with SLEDAI, rSLEDAI, activity index (AI) of renal pathology, fibrinoid necrosis, cellular crescents, and interstitial inflammation on biopsies (all P < 0.01). Macrophages, particularly M2 macrophages, the predominant cells expressing CD163 within LN kidneys, represented a potential source of elevated urine sCD163, based on single-cell RNA sequencing analysis. To conclude, urine sCD163 discriminated patients with active LN from other SLE patients and was significantly elevated in proliferative LN. It strongly correlated with concurrent AI and several specific pathological attributes, demonstrating its potential in predicting renal pathology.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 98%

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Association of Urine sCD163 With Proliferative Lupus Nephritis, Fibrinoid Necrosis, Cellular Crescents and Intrarenal M2 Macrophages

et al. 2020

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“…5). FSP1 levels in U-EVs correlated positively with urinary sCD163 levels, which are already an established biomarker of active renal vasculitis [18,36] and LN [35] ( Fig. 6).…”

Section: Discussionmentioning

confidence: 93%

“…Urinary sCD163 levels were measured using a commercial ELISA kit according to the manufacturer's instructions (DY1607 Duo Set, R&D Systems, Minneapolis, MN, USA) [18,35,36]. Stored urine samples were diluted 1: 4 or 1: 10 as described previously [18].…”

Section: Sandwich Elisa For Urinary Scd163mentioning

confidence: 99%

Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis

Morikawa

Takahashi

Kamiyama

et al. 2018

Nephron

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Background/Aims: Extracellular vesicles (EVs), including exosomes, are present in various bodily fluids, including urine. We and others previously reported that cells expressing fibroblast-specific protein 1 (FSP1) accumulate within damaged glomeruli, and that urinary FSP1, as well as urinary soluble CD163, could potentially serve as a biomarker of ongoing glomerular injury. Methods: To test that idea, we collected urine samples from 37 patients with glomerular disease; purified the urinary EVs; characterized them using Nanosight, western blotting, and immunoelectron microscopy; and determined FSP1 and soluble CD163 levels using enzyme-linked immunosorbent assays. Results: Deemed to be mainly exosomes based on their size distribution, the EVs in urine contained FSP1, and a portion of the FSP1-positive vesicles was also positive for podocalyxin. FSP1 levels in urinary EVs were (1) positively correlated with rates of biopsy-proven cellular crescent formation (r = 0.562, p < 0.001) and total crescent formation (r = 0.448, p = 0.005) among total glomeruli; (2) significantly higher in patients with cellular crescents affecting 20% or more of their glomeruli than in those with fewer affected glomeruli (p = 0.003); and (3) significantly decreased after glucocorticoid and immunosuppressant therapy (p < 0.05). A positive correlation between FSP1 levels in urinary EVs and urinary soluble CD163 levels was confirmed (r = 0.367, p < 0.05). Conclusion: These data suggest that a portion of urinary FSP1 is secreted as EVs originating from podocytes, and that FSP1 levels reflect active and ongoing glomerular injury and disease activity, such as cellular crescent formation.

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M2 macrophages and their role in rheumatic diseases

Bhattacharya

Aggarwal

2018

Rheumatol Int

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As a component of the innate immune system, macrophages play a crucial role in host defense against a variety of microbes. Conventionally, macrophages have been classified as M1 and M2 depending on their phenotype and role in immune regulation. M1 macrophages are generally pro-inflammatory, while M2 (also known as alternatively activated macrophages) are anti-inflammatory. M1 macrophages release pro-inflammatory cytokines, reactive nitrogen, and oxygen intermediates, and kill pathogens, whereas their M2 counterparts participate in the resolution of inflammation, remodeling of tissue, angiogenesis, and tissue repair. Macrophages are also crucial in the pathogenesis of immune-inflammatory disorders, such as, arthritis. In this review, we discuss the markers of human M2 macrophages, the role played by them in inflammation or progression of rheumatic diseases, their potential to act as biomarkers, and, finally, therapeutic strategies aiming at altering/enhancing the macrophage phenotype.

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Urinary soluble CD163 level reflects glomerular inflammation in human lupus nephritis

Abstract: Glomerular CD163 macrophages are the predominant phenotype in the kidneys of lupus patients. These findings indicate that the u-sCD163 level can serve as a biomarker for macrophage-dependent glomerular inflammation in human LN.

Cited by 67 publications

References 48 publications

Association of Urine sCD163 With Proliferative Lupus Nephritis, Fibrinoid Necrosis, Cellular Crescents and Intrarenal M2 Macrophages

Association of Urine sCD163 With Proliferative Lupus Nephritis, Fibrinoid Necrosis, Cellular Crescents and Intrarenal M2 Macrophages

Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis

M2 macrophages and their role in rheumatic diseases

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