Urinary Type III Procollagen Is Associated With Chronic Allograft Dysfunction and Predicts Graft Survival

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A noninvasive method for monitoring kidney fibrosis and graft survival

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Renal transplantation is the treatment of choice for a minority of patients with end-stage renal disease. Marked improvements in early graft survival and long-term graft function have made kidney transplantation a more cost-effective alternative to dialysis. Over 375,000 kidney transplants have been performed in the United States. 191,400 patients were alive with a functioning transplanted kidney in 2012. The major causes of renal transplant loss are death from vascular, malignant, or infectious diseases. Loss of the allograft from chronic renal dysfunction is frequently associated with the development of graft fibrosis and glomerulosclerosis.
The reference analysis method is the histologic description of the fibrosis. Several renal specimens need to be collected from the patient, then carefully processed, stained with different reagents, and finally investigated thoroughly and analyzed by imaging techniques. As fibrosis is a long process, this should be repeated several times, on a given patient, even with all the risks associated with biopsies.
What if you had an easier, straightforward, and noninvasive solution to assess interstitial fibrosis in transplanted patients? That’s exactly what Rahmi Yılmaz demonstrated in this article. By studying the level of PIIIP in urine collected from patients suffering from Chronic Allograft Dysfunction (CAD), Rahmi Yılmaz showed that the level of this marker could be correlated with fibrosis progression in the transplanted kidney and with graft survival over 36 months.
If you had the choice between an invasive and a noninvasive method to assess kidney fibrosis progression and to predict graft survival in CAD patients, which would you choose? It is likely that you would prefer the second option!
Clearly, PIIIP is far from having revealed all its secrets for fibrosis investigation.


Chronic allograft dysfunction (CAD) is the most important clinical problem in solid organ transplantation. Interstitial fibrosis and tubular atrophy contribute to long-term renal allograft failure. Urinary type III procollagen N-terminal propeptide (PIIINP), has been shown to associate fibrotic processes. One hundred sixty patients with CAD who underwent allograft biopsies were evaluated, and 52 patients with chronic or sclerosing allograft nephropathy were enrolled in the study. The subjects were divided into 2 groups according to the level of urinary PIIINP to creatinine (u-PIIINP-to-Cr): high procollagen group and low procollagen group. The association between u-PIIINP-to-Cr level at the time of biopsy and renal endpoints during 36 months of follow-up was assessed by multivariate Cox analysis. Interstitial fibrosis and proteinuria were higher in the high procollagen group compared with the low urinary procollagen group. Correlation analysis showed that levels of u-PIIINP-to-Cr were positively associated with fibrosis scores. During the follow-up, glomerular filtration rate (GFR) decreased in both study groups; however, GFR declined more in the high procollagen group than in low procollagen group. Cox regression model showed that the u-PIIINP-to-Cr levels, GFR, and proteinuria were independent risk factors associated with graft survival. u-PIIINP-to-Cr level is a potentially useful noninvasive marker for graft survival in patients with CAD.


Transplantation Proceedings. 2017 Mar;49(2):281-287.I

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