Renal fibrosis is the central pathogenic process in progression of chronic 
kidney disease (CKD). Collagen type VI (COL VI) is upregulated in renal 
fibrosis. Endotrophin is released from COL VI and promotes pleiotropic 
pro-fibrotic effects. Kidney disease severity varies considerably and accurate 
information regarding CKD progression may improve clinical decisions. We tested 
the hypothesis that urinary endotrophin derived during COL VI deposition in 
fibrotic human kidneys is a marker for progression of CKD in the Renal 
Impairment in Secondary Care (RIISC) cohort, a prospective observational study 
of 499 CKD patients. Endotrophin localised to areas of increased COL VI 
deposition in fibrotic kidneys but was not present in histologically normal 
kidneys. The third and fourth quartiles of urinary endotrophin:creatinine ratio 
(ECR) were independently associated with one-year disease progression after 
adjustment for traditional risk factors (OR (95%CI) 3.68 (1.06-12.83) and 8.65 
(2.46-30.49), respectively). Addition of ECR quartiles to the model for disease 
progression increased prediction as seen by an increase in category-free net 
reclassification improvement (0.45, 95% CI 0.16-0.74, p = 0.002) and integrated 
discrimination improvement (0.04, 95% CI 0.02-0.06, p < 0.001). ECR was 
associated with development of end-stage renal disease (ESRD). It is concluded 
that ECR predicts disease progression of CKD patients.