Significance of urinary type IV collagen in patients with diabetic nephropathy using a highly sensitive one-step sandwich enzyme immunoassay

Yagame, Mitsunori; Suzuki, Daisuke; Jinde, Kiichiro; Saotome, Noboru; Sato, Haru–Tada; Noguchi, M.; Sakai, Hideto; Kuramoto, Takao; Sekizuka, Keiko; Iwamoto, Toshihiko; Suzuki, Shigenobu; Tomino, Yasuhiko

doi:10.1002/(sici)1098-2825(1997)11:2<110::aid-jcla7>3.0.co;2-f

Cited by 28 publications

(9 citation statements)

References 27 publications

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“…In this study, the median level of urinary type IV collagen was higher in diabetic patients with microalbuminuria than in those with normoalbuminuria, in agreement with previous studies (9–14). Several cross-sectional studies reported that a substantial number of diabetic patients with normoalbuminuria had high levels of urinary type IV collagen (10,14).…”

Section: Discussionsupporting

confidence: 93%

“…We and others reported previously that the production of type IV collagen is enhanced in glomerular mesangial cells (4,5), podocytes (6), and proximal tubular cells (7,8) cultured under a high-glucose condition. Cross-sectional studies reported a stepwise increase in urinary type IV collagen excretion in diabetic patients, in parallel with increased levels of urinary albumin (9–14). Thus, a high level of urinary type IV collagen has been proposed as a marker of development and progression of early diabetic kidney disease.…”

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confidence: 99%

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Association Between Urinary Type IV Collagen Level and Deterioration of Renal Function in Type 2 Diabetic Patients Without Overt Proteinuria

et al. 2010

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OBJECTIVECross-sectional studies have reported increased levels of urinary type IV collagen in diabetic patients with progression of diabetic nephropathy. The aim of this study was to determine the role of urinary type IV collagen in predicting development and progression of early diabetic nephropathy and deterioration of renal function in a longitudinal study.RESEARCH DESIGN AND METHODSJapanese patients with type 2 diabetes (n = 254, 185 with normoalbuminuria and 69 with microalbuminuria) were enrolled in an observational follow-up study. The associations of urinary type IV collagen with progression of nephropathy and annual decline in estimated glomerular filtration rate (eGFR) were evaluated.RESULTSAt baseline, urinary type IV collagen levels were higher in patients with microalbuminuria than in those with normoalbuminuria and correlated with urinary β2-microglobulin (β = 0.57, P < 0.001), diastolic blood pressure (β = 0.15, P < 0.01), eGFR (β = 0.15, P < 0.01), and urinary albumin excretion rate (β = 0.13, P = 0.01) as determined by multivariate regression analysis. In the follow-up study (median duration 8 years), urinary type IV collagen level at baseline was not associated with progression to a higher stage of diabetic nephropathy. However, the level of urinary type IV collagen inversely correlated with the annual decline in eGFR (γ = −0.34, P < 0.001). Multivariate regression analysis identified urinary type IV collagen, eGFR at baseline, and hypertension as factors associated with the annual decline in eGFR.CONCLUSIONSOur results indicate that high urinary excretion of type IV collagen is associated with deterioration of renal function in type 2 diabetic patients without overt proteinuria.

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Section: Discussionsupporting

confidence: 93%

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confidence: 99%

Association Between Urinary Type IV Collagen Level and Deterioration of Renal Function in Type 2 Diabetic Patients Without Overt Proteinuria

et al. 2010

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“…16 Type IV collagen is the principal component of the glomerular and tubular basement membrane as well as the mesangial matrix. An increased level of type IV collagen fragments in urine may reflect increase turnover of matrix in diabetic nephropathy, 17 whereas a decrease, on the other hand, may represent a state of low turnover. In a study from Thailand in 30 subjects with type 2 DM and proteinuria, Katavetin et al reported a modest but statistically significant inverse correlation between urinary excretion of type IV collagen and GFR (r=−0.39, P=0.04); 18 in other words, the higher the urinary collagen IV levels, the more rapid the decline in renal function.…”

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Urinary biomarkers of diabetic nephropathy

Mehta¹,

Cabrera²,

Upputalla³

et al. 2013

CBF

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Abstract:The fervent search for an early biomarker for diabetic nephropathy is continuing because this entity has become the leading cause of end-stage renal disease in many countries. Novel biomarkers are being described in a high-speed manner. Using urine as a biological source is especially appealing given its ease of collection and its ability to serve as a direct conduit to the site of injury. We begin by briefly discussing the merits and pitfalls of our gold standard of microalbuminuria, and shift quickly to several promising nontraditional protein and messenger (m)RNA biomarkers. The quality of the evidence for using urinary podocyte as a marker will be described. Exploring entire sets of protein in humans in terms of proteomics has been a favorite approach in the last decade because the technology of protein separation and mass spectrometry allows for the unbiased search for new biomarkers. Isolating urinary microRNA may become yet another preferred method because these small, noncoding mRNA that regulate gene expression are particularly stable and apt for biomarker studies. Finally, the latest development is perhaps the study of exosomes, which are nanometer particles derived from the fusion of internal vesicles to the plasma membrane. These particles harbor protein, mRNA, and microRNA that may be isolated for further study. With the advent of newer technologic approaches, we hope that these newly discovered biomarkers will be rigorously tested in large, prospective, clinical trials so they can be implemented in clinical practice.

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“…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).…”

mentioning

confidence: 99%

“…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). The reasons for this discordancy are unknown but may relate to various immunoassay constructs and/or various populations.…”

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confidence: 99%

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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Significance of urinary type IV collagen in patients with diabetic nephropathy using a highly sensitive one-step sandwich enzyme immunoassay

Cited by 28 publications

References 27 publications

Association Between Urinary Type IV Collagen Level and Deterioration of Renal Function in Type 2 Diabetic Patients Without Overt Proteinuria

Association Between Urinary Type IV Collagen Level and Deterioration of Renal Function in Type 2 Diabetic Patients Without Overt Proteinuria

Urinary biomarkers of diabetic nephropathy

Serum Type IV Collagen in Diabetic Patients at Risk for Nephropathy

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