Type IV collagen as an early marker for diabetic nephropathy in non-insulin-dependent diabetes mellitus

Kotajima, Nobuo; Kimura, Takao; Kanda, Tsugiyasu; Obata, Kenichi; Kuwabara, Atsushi; Fukumura, Yukihito; Kobayashi, Isao

doi:10.1016/s1056-8727(00)00064-7

Cited by 52 publications

(50 citation statements)

References 22 publications

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“…74 Similar to urinary transferrin and urinary IgG, urinary ceruloplasmin can predict DN earlier than albuminuria in T2DM patients; in fact, the values of the three markers can be elevated concomitantly. 75 Both laminin and type IV collagen are components of glomerular basement membrane, although the latter is also a component of mesangial matrix. Since elevated urinary levels of type IV collagen occur in normoalbuminuric patients with T1DM, the biomarker can also be used as an early predictor of DN, 75 and has actually been considered to be a specific indicator of early DN.…”

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confidence: 99%

“…75 Both laminin and type IV collagen are components of glomerular basement membrane, although the latter is also a component of mesangial matrix. Since elevated urinary levels of type IV collagen occur in normoalbuminuric patients with T1DM, the biomarker can also be used as an early predictor of DN, 75 and has actually been considered to be a specific indicator of early DN. 76 Moreover, some studies indicate that urinary excretion of type IV collagen in T2DM is related to UAE, [77][78][79] while other investigators have shown that T2DM patients with evidence of kidney disease present with a significantly higher type IV collagen/albumin ratio compared to their nondiabetic counterparts with nephropathy.…”

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confidence: 99%

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The role of novel biomarkers in predicting diabetic nephropathy: a review

Uwaezuoke

2017

IJNRD

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Diabetic nephropathy (DN) is one of the microvascular complications of the kidney arising commonly from type 1 diabetes mellitus (T1DM), and occasionally from type 2 diabetes mellitus (T2DM). Microalbuminuria serves as an early indicator of DN risk and a predictor of its progression as well as cardiovascular disease risk in both T1DM and T2DM. Although microalbuminuria remains the gold standard for early detection of DN, it is not a sufficiently accurate predictor of DN risk due to some limitations. Thus, there is a paradigm shift to novel biomarkers which would help to predict DN risk early enough and possibly prevent the occurrence of end-stage kidney disease. These new biomarkers have been broadly classified into glomerular biomarkers, tubular biomarkers, biomarkers of inflammation, biomarkers of oxidative stress, and miscellaneous biomarkers which also include podocyte biomarkers, some of which are also considered as tubular and glomerular biomarkers. Although they are potentially useful for the evaluation of DN, current data still preclude the routine clinical use of majority of them. However, their validation using high-quality and large longitudinal studies is of paramount importance, as well as the subsequent development of a biomarker panel which can reliably predict and evaluate this renal microvascular disease. This paper aims to review the predictive role of these biomarkers in the evaluation of DN.

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The role of novel biomarkers in predicting diabetic nephropathy: a review

Uwaezuoke

2017

IJNRD

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“…Previous studies have reported values ranging from 50 -200 ng/ml in patients with type 1 or type 2 diabetes and in nondiabetic control subjects (11,13,16). The mean Ϯ SEM collagen IV concentration was 219 Ϯ 10 ng/ml in normoalbuminuric diabetic subjects, 209 Ϯ 6 ng/ml in microalbuminuric diabetic patients, 206 Ϯ 7 ng/ml in diabetic patients with proteinuria, and 206 Ϯ 10 ng/ml in 10 nondiabetic normal volunteers with albumin excretion Յ10 g/mg.…”

Section: Results -mentioning

confidence: 99%

“…The association of diabetic glomerulopathy with increased renal production of type IV collagen, a prominent constituent of the thickened basement membrane and expanded mesangium (7-10), has prompted measurement of the concentration of this extracellular matrix protein in biologic fluids in the hope that such measurements might serve as a useful indicator of early diabetic renal disease (11)(12)(13)(14)(15)(16). Indeed, the excretion of collagen IV has been found to be increased in type 1 (13,17) and type 2 (13-16) diabetes, without (15)(16)(17) or with (11,14,17,18) microalbuminuria or overt proteinuria (11,13,17). However, examination of serum levels of collagen IV in diabetic subjects has yielded discordant results; there are reports of a decrease in type 1 and type 2 diabetes (13), no change in type 2 diabetes without or with microalbuminuria (14), and an increase in patients with type 2 diabetes and proteinuria or renal insufficiency (11).…”

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Serum Type IV Collagen in Diabetic Patients at Risk for Nephropathy

2001

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OBJECTIVE -Whereas increased urinary excretion of type IV collagen, which is believed to reflect renal overproduction of this extracellular matrix protein in early diabetic nephropathy, has been confirmed in several studies, examination of serum concentrations of this analyte has yielded conflicting results. We sought to clarify the relationship between early renal dysfunction in diabetes and circulating type IV collagen concentrations.RESEARCH DESIGN AND METHODS -We measured serum (human) collagen IV concentrations by immunoassay in 109 patients with type 1 or type 2 diabetes and various amounts of albuminuria extending from the normo-to the macroalbuminuric range, and we examined its relationship to albumin excretion and to serum creatinine levels.RESULTS -Serum collagen IV concentrations (mean Ϯ SEM) were not significantly different in normoalbuminuric (219 Ϯ 10 ng/ml), microalbuminuric (209 Ϯ 6 ng/ml), or macroalbuminuric (206 Ϯ 7 ng/ml) diabetic subjects or in nondiabetic normal volunteers (206 Ϯ 10 ng/ml). Collagen IV concentrations showed no significant correlation (P Ͼ 0.25) with albumin excretion (r ϭ Ϫ0.001), HbA 1c (r ϭ 0.030), or serum creatinine (r ϭ Ϫ0.161) and were unrelated to urinary excretion of collagen IV in the subset of subjects in whom these data were available.CONCLUSIONS -The results of this cross-sectional analysis discount the utility of measurement of the serum concentration of collagen IV as an indicator of early renal dysfunction in diabetes. Increased urine excretion of collagen IV without a significant change in the serum concentration is consistent with a renal origin of this analyte in early diabetic nephropathy.

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“…Urinary type IV collagen was upregulated in normoalbuminuric and microalbuminuric type 2 diabetic patients compared with healthy controls, and increased urinary type IV collagen was significantly correlated with the amount of albuminuria but not with HbA 1 C( Kado et al 1996, Sthaneshwar andChan 2010). An early study showed that urinary type IV collagen was more sensitive than urinary albumin as a marker for early DN (Kotajima et al 2000), another study showed that urinary type IV collagen excretion increased with microalbuminuria and negatively correlated with creatinine clearance (Tan et al 2002). Another conflicting follow-up study showed that urinary type IV collagen levels were higher in patients with microalbuminuria than in normoalbuminuric patients and correlated with eGFR and urinary albumin excretion rate, but urinary type IV collagen level at baseline was not associated with progression to a higher stage of DN and only suggested renal function deterioration in type 2 diabetic patients without overt proteinuria(Araki et al 2010).…”

Section: Type IV Collagenmentioning

confidence: 99%

Novel Biomarkers for Early Diagnosis and Progression of Diabetic Nephropathy

2015

ARC Journal of Diabetes and Endocrinology

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Type IV collagen as an early marker for diabetic nephropathy in non-insulin-dependent diabetes mellitus

Cited by 52 publications

References 22 publications

The role of novel biomarkers in predicting diabetic nephropathy: a review

The role of novel biomarkers in predicting diabetic nephropathy: a review

Serum Type IV Collagen in Diabetic Patients at Risk for Nephropathy

Novel Biomarkers for Early Diagnosis and Progression of Diabetic Nephropathy

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