Serum Propeptides of Type I and III Procollagens in Renal Transplant Recipients

Abstract

Chronic cyclosporine nephrotoxicity is characterized morphologically by cortical interstitial fibrosis. The most important collagens involved in renal fibrosis are collagen types I and III. In order to estimate the synthesis of type III and type I collagens, we analyzed serum levels of the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP) in 11 renal transplant recipients receiving cyclosporine (group CY) and a comparable group of 16 renal transplant recipients treated with azathioprine (group AZ). In addition, 27 healthy subjects and 15 patients with chronic renal disease and reduced renal function (group CRD) were examined. The cyclosporine-treated patients had serum PIIINP and PICP similar to the azathioprine-treated patients. Both groups of renal transplant recipients had significantly increased serum PIIINP compared to healthy controls (2p < 0.01) and serum PIIINP levels similar to group CRD in which serum PIIINP was also elevated compared to healthy controls (2p < 0.01). Mean serum PIIINP levels were: group CY 0.81 U/l (n = 11); group AZ 0.98 U/l (n = 16); controls 0.62 U/l (n = 27); and group CRD 1.06 U/l (n = 15). The renal graft recipients – both cyclosporine- and azathioprine-treated patients – had significantly increased PICP serum levels compared to healthy controls, but the patients with chronic renal disease had serum PICP levels which did not differ from that of healthy controls. Mean serum PICP levels were: group CY 174 μg/l; group AZ 151 μg/l; controls 106 μg/l; and group CRD 119 μg/l. A significant positive correlation was seen between serum creatinine and serum PIIINP in the renal graft recipients (r = 0.51, p < 0.01), but not in the patients with chronic renal disease (r =-0.009, p = 0.49). The data point to an increased synthesis of type I and III collagens in renal transplant recipients. The graft is most likely the source of the increased serum PIIINP and PICP levels. It is suggested that the increased serum levels of propeptides derived from collagen metabolism may reflect continuous immunological destruction of renal tissue causing inflammation and fibrosis.

Integrative Urinary Peptidomics in Renal Transplantation Identifies Biomarkers for Acute Rejection

“…Recent MS analyses 50 proved that C-terminal cleavage of the precursor, which has 640 amino acids, occurred after phenylalanine residue 587. Because part of the C-terminal peptide cleaved from the UMOD precursor, the UMOD peptide biomarker cluster (colored in red) discovered in this study spans from serine residue 589, following arginine residue 588, and to lysine residue 607. and later decrease in the collagen-derived urinary naturally occurring peptides during collagen catabolism suggest that increased turnover of renal collagens [23][24][25][26] may be valuable biomarkers for noninvasive diagnosis of the rejection process in the kidney. The upregulation of extracellular matrix regulators (MMP-7, SERPING1, and TIMP1) also supports the hypothesis of tissue remodeling at the time of AR.…”

Changes in Serum Type I and III Procollagen Levels in Children with Chronic Renal Failure

“…In our study, PIIIN P in the patients with end-stage renal disease (ESRD) was significantly higher than in the patients with C R F and the healthy controls. Glomerular mesangial cells have been shown to produce collagen type III [28], It is known that types I and III are the most important collagens involved in renal fibrosis [29], The serum concentrations o f PIIIN P reflect the degradation as well as the synthesis o f type III collagen, whereas serum PICP reflects only the synthesis of type I collagen [20].…”

Noninvasive assessment of liver fibrosis and its clinical significance in nonalcoholic fatty liver disease

“…Therefore, etiology‐specific thresholds of M2BPGi are needed. Type III collagen is found in not only in liver but also other organs 65,66 . Therefore, type III collagen level increases in other fibrotic disease such as lung disease and kidney disease and the diagnostic accuracy of ELF or PRO‐C3 is influenced by these diseases.…”