Marker for kidney fibrosis is associated with inflammation and deterioration of kidney function in people with type 2 diabetes and microalbuminuria
by Christina Gjerlev Poulsen, Daniel G. K. Rasmussen, Federica Genovese, Tine W. Hansen, Signe Holm Nielsen, Henrik Reinhard, Bernt Johan von Scholten, Peter K. Jacobsen, Hans-Henrik Parving, Morten Asser Karsdal, Peter Rossing, Marie Frimodt-Møller
BackgroundDiabetic kidney disease is a major cause of morbidity and mortality. Dysregulated turnover of collagen type III is associated with development of kidney fibrosis. We investigated whether a degradation product of collagen type III (C3M) was a risk marker for progression of chronic kidney disease (CKD), occurrence of cardiovascular disease (CVD), and mortality during follow up in people with type 2 diabetes (T2D) and microalbuminuria. Moreover, we investigated whether C3M was correlated with markers of inflammation and endothelial dysfunction at baseline.
MethodsC3M was measured in serum (sC3M) and urine (uC3M) in 200 participants with T2D and microalbuminuria included in an observational, prospective study at Steno Diabetes Center Copenhagen in Denmark from 2007–2008. Baseline measurements included 12 markers of inflammation and endothelial dysfunction. The endpoints were CVD, mortality, and CKD progression (>30% decline in eGFR).
ResultsMean (SD) age was 59 (9) years, eGFR 90 (17) ml/min/1.73m2 and median (IQR) urine albumin excretion rate 102 (39–229) mg/24-h. At baseline all markers for inflammation were positively correlated with sC3M (p≤0.034). Some, but not all, markers for endothelial dysfunction were correlated with C3M. Median follow-up ranged from 4.9 to 6.3 years. Higher sC3M was associated with CKD progression (with mortality as competing risk) with a hazard ratio (per doubling) of 2.98 (95% CI: 1.41–6.26; p = 0.004) adjusted for traditional risk factors. uC3M was not associated with CKD progression. Neither sC3M or uC3M were associated with risk of CVD or mortality.
ConclusionsHigher sC3M was a risk factor for chronic kidney disease progression and was correlated with markers of inflammation.