November 2, 2007
American Society of Nephrology (ASN) Renal Week 2007, San Francisco, CA
Abstract F-PO658

Urinary Connective Tissue Growth Factor (CTGF) Excretion in Patients with Renal Allograft. Peruzzi L¹, Amore A¹, Camilla R¹, Lin X¹, Balegno S¹, Daniela¹, Oliver N², and Coppo R¹.

1 Nephrology, Dialysis and Transplantation Regina Margherita Children's Hospital Torino, Italy and 2 FibroGen, Inc., South San Francisco, CA, USA.

Abstract: Connective tissue growth factor (CTGF) up-regulation has been demonstrated in many fibrotic diseases as well as in experimental chronic allograft rejection. CTGF expression is enhanced by many pathogenic factors and processes that are relevant to chronic allograft nephropathy (CAN) and CTGF is considered the final effector of TGF-beta induced fibrogenesis. In the recent literature, urinary excretion of CTGF has been measured in patients with diabetic nephropathy and was found to be related to renal sclerosis. The aim of this study was evaluation of urinary CTGF excretion and correlation with clinical data in a cohort of kidney transplant recipients who received the graft in pediatric age.

67 fresh morning urine samples were obtained from 48 subjects (19F/29M) transplanted 6.75 ±3.4 years before (0.3-14) at a mean age of 13.3 ±7 years for nephropathies originating in early pediatric age. Mean serum Creatinine was 1.45 ±0.6 (range 0.6-3.5 mg/dL) and mean proteinuria 0.14 ±0.28 g/24h (range 0-2 g/24h). 7 patients received a biopsy for deterioration of renal functional and CAN was diagnosed. Fresh urines were obtained also from 46 healthy, age matched controls. CTGF was assayed by specific ELISA to detect both full length CTGF and N-terminal half fragments which are the predominant form in urine.

Urinary CTGF (uCTGF) was significantly increased in transplanted patients vs controls: median 6.0 ng/mgCr (interquartile range 2.6-4.7 ng/mgCr) in transplanted vs 3.7 ng/mgCr (interquartile range 3.6-9.6 ng/mgCr) in controls (p<0.001).

uCTGF did not correlate with creatinine clearance nor with proteinuria. A trend of correlation just below statistical significance was found between uCTGF and length of time occurred since transplant (P=0.06). uCTGF was not different in transplanted adults vs children.

"Low" and "high" uCTGF excretors were subdivided choosing as a cut-off the value higher than the 99th percentile for normal controls (6 ng/mgCr): children with uCTGF >6 ng/mgCr were found to have an older graft, with a time since transplant significantly longer than those with uCTGF <6 ng/mgCr (7.15 years vs 4.3, p 0.02).

This first report linking uCTGF with time since grafting appears to represent an encouraging useful marker of sclerosis which could be easily followed-up and monitored during the natural history of the transplant, particularly in children, potentially allowing a better screen for biopsy candidates and early alarm for sclerotic processes occurrence.

See also November 7, 2007 press release