Estimation of kidney injury molecule-1 (Kim-1) in patients with lupus nephritis

Nozaki, Yuji; Kinoshita, Koji; Yano, Tomohiro; Shiga, Toshihiko; Hino, Shoichi; Niki, Kaoru; Kishimoto, Kazuya; Funauchi, Masanori; Matsumura, Itaru

doi:10.1177/0961203314526292

Cited by 34 publications

(50 citation statements)

References 29 publications

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“…This rapid effect on kidney function was accompanied by upregulation in expression of lipocalin-2 and kidney injury molecule 1 (kim-1) ( Fig. 3K, L), markers of tubular kidney damage, also observed in lupus nephritis [40][41][42] . Despite the transient nature of proteinuria, expression of these kidney injury markers persisted up to day 6 ( Fig.…”

Section: Skin Exposure To Uv Light Causes Rapid But Reversible Kidneymentioning

confidence: 74%

Neutrophils Mediate Kidney Inflammation Following Acute Skin Exposure to UVB Light

Skopelja-Gardner

Tai

Sun

et al. 2020

Preprint

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Photosensitivity to ultraviolet (UV) light affects up to ~80% of lupus patients and can exacerbate local skin disease as well as systemic disease, including lupus nephritis. While neutrophils have been implicated in local tissue injury in lupus in response to immune complex deposition, whether and how they play a role in photosensitivity induced systemic disease is unknown. Here, we show that following skin exposure to UV light, neutrophils migrate not only to the skin, but also to the kidney, in an IL-17A-dependent manner. Kidney infiltrating neutrophils produced reactive oxygen species and their presence was associated with upregulation of endothelial adhesion molecules and inflammatory cytokines as well as the induction of kidney injury markers, including transient proteinuria. Neutrophils were responsible for inflammation and renal injury as demonstrated by experiments that inhibited neutrophil mobilization. Exploiting a mouse model containing photoactivatable immune cells, we observed that a subset of neutrophils found in the kidney had transited through UV light-exposed skin suggesting reverse transmigration. These findings demonstrate that neutrophils mediate transient kidney injury following skin exposure to UV light and, coupled with observations identifying similar neutrophil phenotypes in human lupus, could provide a mechanistic link to explain sun-induced systemic lupus flares.

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Section: Skin Exposure To Uv Light Causes Rapid But Reversible Kidneymentioning

confidence: 74%

Neutrophils Mediate Kidney Inflammation Following Acute Skin Exposure to UVB Light

Skopelja-Gardner

Tai

Sun

et al. 2020

Preprint

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“…Previous studies focused mostly on the diagnostic value of KIM-1, particularly the diagnostic value of urinary KIM-1, in AKI. A few studies detected KIM-1 expression and suggested that it may be related to individual chronic kidney diseases, such as IgA nephropathy, lupus nephritis, or limited cases of type-1 diabetes [19, 20, 16]. Our cross-sectional study recruited patients with kidney diseases of various aetiologies, indicating that both plasma and urinary KIM-1 levels were significantly elevated in both AKI and CKD patients, thereby revealing that KIM-1 expression was also closely associated with chronic kidney injury.…”

Section: Discussionmentioning

confidence: 99%

Kidney Injury Molecule-1 is Elevated in Nephropathy and Mediates Macrophage Activation via the Mapk Signalling Pathway

Tian¹,

Shao²,

Xie³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Kidney injury molecule-1 (KIM-1) is highly expressed in renal tubular cells after injury and is usually regarded as an early biomarker of acute kidney injury(AKI). The aim of this study was to determine the role of KIM-1 in the development of renal tubular injury Methods: Clinical samples, three different animal models and in vitro experiments were utilized to determine the possible mechanism underlying the involvement of KIM-1 in kidney injury. Results: Both plasma and urinary KIM-1 expression levels were significantly higher in AKI and chronic kidney disease (CKD) patients than in healthy volunteers, and urinary KIM-1 expression was significantly higher in CKD patients than in AKI patients. According to the results of our research involving three different mouse models, KIM-1 expression was significantly increased during the early stage of kidney injury and was persistently elevated in renal fibrosis. Our immunofluorescence staining results indicated that KIM-1-positive tubules were surrounded by macrophage infiltrates in regions of kidney injury. Moreover, our transwell, western blotting and real-time PCR data showed that macrophage migration and phenotype transitions were mediated by KIM-1 through the mitogen-activated protein kinase (MAPK) pathway. MAPK pathway inhibition could significantly reverse the effects of KIM-1 with respect to these macrophage phenotype changes and migration. Conclusions: KIM-1 expression was markedly elevated in both acute and chronic kidney injury and may play a pivotal role in macrophage activation via the MAPK pathway in kidney disease.

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“…Clinical studies showed similar data in biopsies of patients with acute tubular necrosis and demonstrated that increased concentration of KIM‐1 can also be detected in the urine with a high specificity for acute proximal tubular necrosis as soon as 24 h after the insult . Additionally, KIM‐1 is increased in patients with chronic kidney disease and active lupus nephritis . The monocyte chemoattractant protein‐1 (MCP‐1) is a key regulator of the immune system as a potent chemotactic factor for monocytes/macrophages .…”

Section: Introductionmentioning

confidence: 83%

Effect of a single intravenous zoledronic acid administration on biomarkers of acute kidney injury (AKI) in patients with osteoporosis: a pilot study

Cipriani

Pepe

Clementelli

et al. 2017

Brit J Clinical Pharma

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Estimation of kidney injury molecule-1 (Kim-1) in patients with lupus nephritis

Abstract: These data suggest the potential use of the u-Kim-1 levels to screen for active LN and for the estimation of t-Kim-1 expression in renal biopsies to predict renal damage, ongoing glomerular nephritis and tubulointerstitial inflammation, and tubular atrophy.

Cited by 34 publications

References 29 publications

Neutrophils Mediate Kidney Inflammation Following Acute Skin Exposure to UVB Light

Neutrophils Mediate Kidney Inflammation Following Acute Skin Exposure to UVB Light

Kidney Injury Molecule-1 is Elevated in Nephropathy and Mediates Macrophage Activation via the Mapk Signalling Pathway

Effect of a single intravenous zoledronic acid administration on biomarkers of acute kidney injury (AKI) in patients with osteoporosis: a pilot study

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