Chronic kidney diseases are characterized by alterations in connective tissue turnover resulting in fibrosis. We measured circulating peptides related to type VI collagen and undulin in serum and urine of 125 patients with various kidney diseases, on chronic hemodialysis and after kidney transplantation. Using a double-armed ELISA technique (median, 95% CI), normal serum concentrations for type VI collagen were 50 ng/ml [46-63] with no type VI collagen detectable in urine. Normal values for undulin were 215 ng/ml [207-241] in serum and 240 micrograms/d [223-284] in urine. The serum concentrations of undulin were most significantly (477 ng/mg [358-737]) increased in 18 hemodialysis patients. A significant increase (330 ng/ml [306-368]) was also observed in patients with various kidney diseases not requiring dialysis. No differences were found between the various forms of glomerulonephritis, interstitial nephritis and other kidney diagnoses. Although very low in normals (1.16 ml/min [1.05-1.27]) renal undulin clearance was even significantly lower in patients with kidney diseases (0.5 ml/min [0.4-0.6]). Serum concentrations for undulin were in the normal range in the direct postoperative phase after kidney transplantation (207 ng/ml [167-306]), whereas in kidney transplant out-patient levels were elevated to 425 ng/ml [357-563]. There was a slight but significant correlation between serum undulin and creatinine values and between renal undulin clearance and creatinine clearance. Values of serum type VI collagen increased in analogy to those of undulin. We conclude, that type VI collagen and undulin are novel serum parameters of renal extracellular matrix turnover that merit further exploration in patients with chronic kidney diseases.