Asian multicenter trials on urinary type IV collagen in patients with diabetic nephropathy

Tomino, Yasuhiko; Suzuki, Shigenobu; Azushima, Chieko; Shou, Ichiyu; Iwamoto, Toshihiko; Yagame, Mitsunori; Wang, Li Ning; Chen, Hung‐Chun; Lai, K. C.; Tan, Si Yen; Kim, Myung Jae

doi:10.1002/jcla.1026

Cited by 38 publications

(40 citation statements)

References 12 publications

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“…Therefore, we measured type IV collagen in the urine as a possible sensitive marker of early kidney damage. The baseline value in our diabetic patients was about 6.0 µg/g cr, which was higher than that reported in nondiabetic controls (3.44 0.11 µg/g cr, mean SEM) (21). Unlike albumin and transferrin, urinary type IV collagen excretion was not increased in the control group during the study.…”

Section: Discussioncontrasting

confidence: 65%

Low-Dose Candesartan Cilexetil Prevents Early Kidney Damage in Type 2 Diabetic Patients with Mildly Elevated Blood Pressure.

et al. 2003

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To determine the effect of a low-dose angiotensin receptor blocker, candesartan, on early kidney damage associated with diabetes. Fifty-two patients with type 2 diabetes with normo-and microalbuminuria participated in this study. Nineteen patients with high-normal and mildly high blood pressure received low-dose candesartan cilexetil at 4 mg daily (candesartan group), and 33 patients did not receive candesartan (control group). Blood pressure, urinary excretion of albumin, transferrin, and type IV collagen (expressed as urinary creatinine index) and plasma parameters were determined at baseline and at 2, 6, 12 and 18 months after the start of candesartan therapy. Baseline urinary albumin, transferrin, and type IV collagen excretions was similar in the control and candesartan groups. The higher baseline systolic blood pressure was decreased by candesartan treatment to a level similar to that in the control group, such that blood pressure was comparable between the control and candesartan groups during the run-in period. In the control group, urinary albumin excretion was significantly increased at 18 months when compared with baseline, while urinary albumin excretion did not increase in the candesartan group throughout the study. Urinary transferrin excretion was significantly increased at 6, 12, and 18 months when compared with baseline in the control group, while it did not increase in the candesartan group during the study. In both groups, urinary type IV collagen excretion did not change significantly during the study. Hemoglobin A1c, serum urea nitrogen, creatinine, albumin, and lipids were comparable between the two groups throughout the study.

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Section: Discussioncontrasting

confidence: 65%

Low-Dose Candesartan Cilexetil Prevents Early Kidney Damage in Type 2 Diabetic Patients with Mildly Elevated Blood Pressure.

et al. 2003

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“…Type IV collagen is a major structural component of basement membrane and mesangial matrix; and thus an increase in urinary type IV collagen is considered to reflect acceleration of fibrosis in the kidney. It has been reported that the more diabetic nephropathy progresses, the higher the concentration of urinary type IV collagen becomes (48)(49)(50). Moreover, increase in urinary type IV collagen has been shown to be ameliorated by an ACE-I, indicating that ACE-Is have an antifibrotic effect (51).…”

Section: Discussionmentioning

confidence: 99%

Effect of Renin-Angiotensin-Aldosterone System Triple Blockade on Non-Diabetic Renal Disease: Addition of an Aldosterone Blocker, Spironolactone, to Combination Treatment with an Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker

et al. 2008

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“…In clinical situations, serum levels of type IV collagen in liver fibrosis and urine levels of type IV collagen in diabetic nephropathy reportedly correlate with the degree of liver and kidney fibrosis, respectively. 13,14 The serum concentrations of type IV collagen also increased in patients with IPF. 15 However, little is known of the expression and role of type IV collagen, especially in early fibrotic lesions of IIPs.…”

mentioning

confidence: 99%

Role of α1 and α2 chains of type IV collagen in early fibrotic lesions of idiopathic interstitial pneumonias and migration of lung fibroblasts

Urushiyama

Terasaki

Nagasaka

et al. 2015

Laboratory Investigation

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Early fibrotic lesions are thought to be the initial findings of fibrogenesis in idiopathic interstitial pneumonias, but little is known about their properties. Type IV collagen comprises six gene products, α1-α6, and although it is known as a major basement membrane component, its abnormal deposition is seen in fibrotic lesions of certain organs. We studied the expression of type I and III collagen and all α chains of type IV collagen in lung specimens from patients with usual interstitial pneumonia (UIP) or organizing pneumonia (OP) via immunohistochemistry. With cultured lung fibroblasts, we analyzed the expression and function of all α chains of type IV collagen via immunohistochemistry, western blotting, realtime quantitative PCR, and a Boyden chamber migration assay after the knockdown of α1 and α2 chains. Although we observed type I and III collagens in early fibrotic lesions of both UIP and OP, we found type IV collagen, especially α1 and α2 chains, in early fibrotic lesions of UIP but not OP. Fibroblasts enhanced the expression of α1 and α2 chains of type IV collagen after transforming growth factor-β1 stimulation. Small interfering RNA against α1 and α2 chains increased fibroblast migration, with upregulated phosphorylation of focal adhesion kinase (FAK), and adding medium containing fibroblast-produced α1 and α2 chains reduced the increased levels of fibroblast migration and phosphorylation of FAK. Fibroblasts in OP were positive for phosphorylated FAK but fibroblasts in UIP were not. These results suggest that fibroblasts in UIP with type IV collagen deposition, especially α1 and α2 chains, have less ability to migrate from early fibrotic lesions than fibroblasts in OP without type IV collagen deposition. Thus, type IV collagen deposition in early fibrotic lesions of UIP may be implicated in refractory pathophysiology including migration of lesion fibroblasts via a FAK pathway.

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Asian multicenter trials on urinary type IV collagen in patients with diabetic nephropathy

Cited by 38 publications

References 12 publications

Low-Dose Candesartan Cilexetil Prevents Early Kidney Damage in Type 2 Diabetic Patients with Mildly Elevated Blood Pressure.

Low-Dose Candesartan Cilexetil Prevents Early Kidney Damage in Type 2 Diabetic Patients with Mildly Elevated Blood Pressure.

Effect of Renin-Angiotensin-Aldosterone System Triple Blockade on Non-Diabetic Renal Disease: Addition of an Aldosterone Blocker, Spironolactone, to Combination Treatment with an Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker

Role of α1 and α2 chains of type IV collagen in early fibrotic lesions of idiopathic interstitial pneumonias and migration of lung fibroblasts

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