Urinary type IV collagen excretion is involved in the decline in estimated glomerular filtration rate in the Japanese general population without diabetes: A 5-year observational study

Abstract

Urinary type IV collagen (U-Col4) and albumin excretion is evaluated to monitor the development of diabetic kidney disease. However, U-Col4 excretion in the general population without diabetes has not yet been fully elucidated. In this study, 1067 participants without diabetes and with urinary albumin-creatinine ratio <300 mg/gCr (normo- or microalbuminuria) who underwent an annual health examination in 2004 were enrolled and observed for 5 years. They were divided according to the amount of U-Col4 or urinary albumin excreted. The decline in estimated glomerular filtration rate (eGFR) was calculated. In participants with eGFR ≥80 mL/min, abnormal U-Col4 excretion was indicated as a significant independent risk factor for 10% eGFR change per year, which is one of the prognostic factors for the development of end-stage kidney disease. Moreover, in contrast to urinary albumin excretion, U-Col4 excretion was not related to age or kidney function, suggesting that some individuals with abnormal U-Col4 excretion can have an independent hidden risk for the development of kidney dysfunction. In conclusion, it is important to measure U-Col4 excretion in the general population without diabetes to determine changes in renal features in every individual and help detect future complications such as diabetic kidney disease. If U-Col4 excretion is abnormal, kidney manifestation should be carefully followed up, even if the kidney function and urinalysis findings are normal.

Extracellular Matrix in Kidney Fibrosis: More Than Just a Scaffold

“…176 In a Japanese non-diabetic population, a high urinary collagen IV to creatinine ratio was associated with an increased risk of 10% decline of eGFR per year. 177 Although collagen IV is increased in renal fibrosis, urinary and circulating collagen IV did not correlate with fibrosis in kidney biopsies in a cohort of patients with different diseases, that is, membranous glomerulonephritis, mesangioproliferative glomerulonephritis, tubulointerstitial nephritis, and ESRD. 55 However, high serum amounts of a fragment of collagen IV termed P4NP_7S were shown to be associated with worse survival in hemodialysis patients.…”

Urinary Markers of Tubular Injury and Renal Fibrosis in Patients with Type 2 Diabetes and Different Phenotypes of Chronic Kidney Disease

“…At the same time, we found no association between the excretion of Col4 and eGFR. The lack of association between urinary Col4 and eGFR was also noted in a cross-sectional study involving1554 individuals with diabetes [ 47 ] and in a prospective study with 1067 participants without diabetes in Japan [ 48 ]. However, high urinary excretion of Col4 was recognized as a risk factor for progressive renal function decline in the non-diabetic population [ 48 ].…”

Unifferentiated Connective Tissue Dysplasia as a Potential Predictor of Arterial Hypertension Development in Patients With Type 2 Diabetes Mellitus

“…All patients have undergone a complex general clinical, laboratory and instrumental examination in accordance to the Order of the Diagnosis of UCTD was carried out through a comprehensive examination and evaluation of the presence of internal (visceral) and external (skeletal, skin, articular) signs according to T. I. Kadurina (2009) [15].…”

“…One of the mechanisms of the pathological effect of hyperglycemia is also thought to be the increase in the activity of prophylactic factors, in particular, TGF-β, which is a modulator of proteoglycan synthesis in the extracellular matrix [12][13]. is The increase in excretion of type IV collagen in patients with diabetes, with diabetic nephropathy and nephropathy of another genesis serves as an evidence of connective tissue metabolic abnormalities role in the extracellular matrix [14][15].…”