Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy

Tam, Frederick W.K.; Riser, Bruce L.; Meeran, Karim; Rambow, Joann; Pusey, Charles D.; Frankel, Andrew

doi:10.1016/j.cyto.2009.04.001

Cited by 101 publications

(89 citation statements)

References 26 publications

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“…FG-3019 was previously evaluated in an open-label, dose-escalation trial in subjects with moderately severe idiopathic pulmonary fibrosis, and the single-dose pharmacokinetic data were similar (45). Although there are varying reports regarding association of urinary CTGF with DKD (32,46), the results reported here show that diabetic subjects with microalbuminuria did not have elevated urinary CTGF values. Plasma levels of CTGF-whole were low in these subjects, and changes could not be measured.…”

Section: Discussionsupporting

confidence: 38%

Phase 1 Study of Anti-CTGF Monoclonal Antibody in Patients with Diabetes and Microalbuminuria

Adler¹,

Schwartz²,

Williams³

et al. 2010

Clinical Journal of the American Society of Nephrology

185

103

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Background and objectives: This report summarizes the first phase 1 trial treating patients with microalbuminuric diabetic kidney disease (DKD) using FG-3019, a human monoclonal antibody to connective tissue growth factor (CTGF). CTGF is critically involved in processes of progressive fibrosis, including DKD. This phase 1, open-label, dose-escalation trial evaluated safety, pharmacokinetics, and possible therapeutic effects of FG-3019 on albuminuria, proteinuria, and tubular proteins.Design, setting, participants, and measurements: Microalbuminuric subjects (n ‫؍‬ 24) with type 2 (79%) or type 1 (21%) diabetes received 3 or 10 mg/kg FG-3019 dosed intravenously every 14 days for four doses. Albuminuria and safety follow-up were to days 62 and 365, respectively.Results: No infusion was interrupted for symptoms, although 5 of 24 subjects had mild infusion-day adverse events thought to be possibly drug-related. No subject developed anti-FG-3019 antibodies. FG-3019 clearance was lower at 10 mg/kg than at 3 mg/kg, suggesting a saturable elimination pathway. Although this study was not designed for efficacy testing, it was notable that urinary albumin/creatinine ratio (ACR) decreased significantly from mean pretreatment ACR of 48 mg/g to mean post-treatment (day 56) ACR of 20 mg/g (P ‫؍‬ 0.027) without evidence for a dose-response relationship.Conclusions: Treatment of microalbuminuric DKD subjects using FG-3019 was well tolerated and associated with a decrease in albuminuria. The data demonstrate a saturable pathway for drug elimination, minimal infusion adverse events, and no significant drug-attributable adverse effects over the year of follow-up. Changes in albuminuria were promising but require validation in a prospective, randomized, blinded study.

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Section: Discussionsupporting

confidence: 38%

Phase 1 Study of Anti-CTGF Monoclonal Antibody in Patients with Diabetes and Microalbuminuria

Adler¹,

Schwartz²,

Williams³

et al. 2010

Clinical Journal of the American Society of Nephrology

185

103

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“…Another report observed a strong association between MCP-1, IL-6 and IL-8 in patients with vitreoretinal diseases (including proliferative diabetic retinopathy and macular oedema), implying a common inflammatory pathway [24]. Interestingly, our study describing urinary MCP-1's prognostic role in progression of diabetic nephropathy also reported a fourfold increase in urinary MCP-1/creatinine ratio in patients who had diabetic retinopathy [20]. Therefore, urinary MCP-1 levels may predict the advent of diabetic retinopathy.…”

Section: Mcp-1 In Diabetic Retinopathysupporting

confidence: 58%

“…Urinary MCP-1 was initially highlighted as a potential prognostic marker for progression of diabetic renal disease in a prospective observational study where 40 patients were followed over 6 years [20]. It had the most predictive merit in patients with macroalbuminuria, and levels at time zero foretold the rate of decline in eGFR better than the conventionally used urine protein/creatinine ratio.…”

Section: Mcp-1 In Diabetic Nephropathymentioning

confidence: 99%

Review Article - MCP-1: A Potential Target for Diabetic Microvascular Complications?

Yap¹

2017

UNOAJ

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MCP-1 is a potent chemokine with the ability to mobilize and stimulate leucocytes, especially monocytes and macrophages. It is increasingly recognized as an important player in the inflammatory process that is diabetic nephropathy. In this article, we describe its role in inducing renal injury by outlining key studies in animal models and clinical studies of diabetic nephropathy, its association with diabetic retinopathy, as well as its potential use as a prognostic biomarker and as a therapeutic target in the clinical setting. IntroductionMonocyte Chemoattractant Protein-1 (MCP-1) was first identified as a chemoattractant cytokine by Matsushima in 1989 [1], using conditioned media from a human myelomonocytic cell line. DNA cloning and sequencing of MCP-1 was completed that

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“…Several independent studies have evaluated CCN2 levels in the urine and/or serum in several chronic kidney diseases. Some groups have found elevated levels of the full-length CCN2, 5,6 or the N-terminal, 6,7 or the C-terminal [8][9][10] CCN2 fragments determined by ELISA, using antibodies that recognized each part of the molecule. Based on these data, CCN2 has been proposed as a risk biomarker of human diabetic nephropathy and other forms of chronic kidney disease, 2,5-10 and for cardiac dysfunction in patients exhibiting myocardial fibrosis and chronic heart failure.…”

mentioning

confidence: 99%

The C-terminal module IV of connective tissue growth factor is a novel immune modulator of the Th17 response

Rodrigues‐Díez

Rodrigues-Díez

Rayego‐Mateos

et al. 2013

Laboratory Investigation

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Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy

Cited by 101 publications

References 26 publications

Phase 1 Study of Anti-CTGF Monoclonal Antibody in Patients with Diabetes and Microalbuminuria

Phase 1 Study of Anti-CTGF Monoclonal Antibody in Patients with Diabetes and Microalbuminuria

Review Article - MCP-1: A Potential Target for Diabetic Microvascular Complications?

The C-terminal module IV of connective tissue growth factor is a novel immune modulator of the Th17 response

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