Urinary Type IV Collagen in Nondiabetic Kidney Disease

Abstract

Background: Type IV collagen is one of the major components of basement membrane. In diabetic nephropathy, it is already known that urinary excretion of type IV collagen increases with the disease progression. However, in nondiabetic kidney disease, urinary type IV collagen (u-IVc) levels have not been extensively investigated. The aim of this study was to evaluate u-IVc levels in various nephropathies except diabetic nephropathy. Methods: u-IVc levels were measured cross-sectionally from 527 biopsy-proven nondiabetic renal disease patients at tertiary care hospitals by one-step sandwich enzyme immunoassay. Results: On simple regression analyses, u-IVc levels had positive correlation with age, blood pressure, urinary protein (u-Prot), urinary β₂ microglobulin, urinary N-acetyl-β-D-glucosaminidase, HbA₁c, and selectivity index (SI), while u-IVc had negative correlation with eGFR and serum albumin. Multiple regression analyses revealed that u-IVc was positively correlated with u-Prot, HbA₁c and SI. Among biopsy-proven nondiabetic nephropathies, elevation of u-IVc was distinctively observed in membranous nephropathy and anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Conclusion: u-IVc levels were elevated with the increase in u-Prot, HbA₁c and SI. In addition, among nondiabetic kidney disease, elevation of u-IVc was observed in patients with membranous nephropathy and ANCA, which might reflect the thickening of basement membrane or severe kidney damage.

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Increased urinary and serum concentrations of procollagen type III N-terminal propeptide (PIIINP) reflecting the expression of collagen type III, a typical scar collagen up-regulated in renal fibrosis, may also reflect fibrogenesis in renal allografts (400-402). Collagen type IV, a major constituent of the renal basement membrane, was shown to be elevated in the urine and to be associated with renal function in diabetic nephropathy and patients with glomerulonephritides (403)(404)(405)(406). Interestingly, although several other collagens and ECM proteins are deposited in renal fibrosis and undergo disease-specific modifications, including crosslinking, this has not yet been widely exploited as a potential source of biomarkers.…”

Non-invasive quantification of collagen turnover in renal transplant recipients

“…It has been demonstrated that serum and urine levels of the collagen type III pro-peptide (surrogate markers for active collagen formation) are increased during renal fibrosis [11–13]. In addition, urinary collagen type IV has been associated with loss of renal function [14–17]. Such non-invasive biomarkers could enable frequent monitoring of renal patients and facilitate clinical trials studying the effect of antifibrotic therapies.…”

The angiotensin II type 1 receptor blocker olmesartan preferentially improves nocturnal hypertension and proteinuria in chronic kidney disease

“…44 The present study included non-diabetic glomerulopathy patients as well as diabetic nephropathy patients. The results of the present study demonstrate that a preferential decrease in nighttime BP levels was accompanied by decreases in urinary protein and albumin excretion and urinary type IV collagen excretion, an important marker of renal injury in diabetic nephropathy and non-diabetic renal disease, 45,46 without any decrease in eGFR resulting from the olmesartan add-on therapy. The results of the ACCOMPLISH study indicated that not only a reduction of albuminuria but also long-term preservation of eGFR are important for the suppression of CKD progression and cardiovascular complications.…”