Urinary Procollagen III Aminoterminal Propeptide (PIIINP)

Abstract

Background and objectives: Kidney biopsy (KB), to date the only tool for the evaluation of renal fibrosis, carries specific risks, and its relevance is limited by the small size of renal parenchyma assessed. Thus, a noninvasive alternative to KB is required. Collagen type III amino-terminal propeptide (PIIINP) is a degradation product of collagen type III, the increase of which may reflect an ongoing fibrotic process.Design, setting, participants, & measurements: In a prospective study including 199 patients with various stages of chronic kidney disease (CKD), the association between urinary PIIINP/creatinine ratio (UPIIINP/Cr), patients' characteristics, and renal fibrosis was assessed.Results: A total of 118 of the patients had UPIIINP/Cr measured simultaneously with the performance of a KB. In patients, median UPIIINP/Cr was 290 ng/mmol versus 93.7 ng/mmol in controls. In univariate analysis, UPIIINP/Cr was correlated with serum creatinine, estimated GFR, CKD stage, presence of coronary artery disease, and nephropathy type (glomerulonephritis versus other types). In multivariate analysis, only estimated GFR and nephropathy type were correlated with UPIIINP/Cr. UPIIINP/Cr was closely correlated with the extent of interstitial fibrosis in KB assessed using two different methods. Moreover, UPIIINP/Cr >800 ng/mmol had a negative predictive value of 94% to detect patients in whom KB will eventually prove "noninformative" (KB leading neither to a definite diagnosis of nephropathy nor to specific treatment).Conclusions: UPIIINP/Cr is a promising fibro-test for the kidney and may alleviate the need for KB in some patients with CKD. Its predictive value for CKD progression deserves evaluation in prospective studies.

Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in Kidney Transplant Recipients: The FAVORIT Trial

“…(13) PINP and PIIINP are cleaved from type 1 and type 3 collagen fibrils during collagen deposition, which is an important step in fibrogenesis. (14) Urine PIIINP is the N-terminal fragment of type III collagen and is released during newly deposited collagen type III and is correlated with interstitial fibrosis (11) and kidney function decline(15) in patients with CKD of different etiologies (16) and in KTRs. (11)…”

New Computerized Color Image Analysis for the Quantification of Interstitial Fibrosis in Renal Transplantation

“…Similar studies on nontransplanted kidneys (27) suggest that the proposed technique could be easily adapted to different types of fibrosis studies in other organs such as liver and lung. Furthermore, as recent reports have revealed clini- cal significance of inflammatory fibrosis (28), our software could also be adapted to automatically differentiate inflammatory versus noninflammatory fibrosis.…”

Urine Collagen Fragments and CKD Progression—The Cardiovascular Health Study

“…10 Similar findings were reported by Ghoul and colleagues, who studied 118 patients with CKD. 8 Teppo and colleagues found that kidney transplant recipients with urine PIIINP/Cr.100 ng/mmol were more likely to lose GFR during follow-up than those with lower concentrations; however, they did not evaluate whether associations were independent of baseline eGFR, ACR, or other risk factors. 9 All three of these studies found direct correlations between urine PIIINP concentrations and the severity of tubulointerstitial fibrosis on biopsy.…”

“…Several prior studies evaluating kidney biopsy series have demonstrated that urine PIIINP concentrations are correlated with the severity of tubulointerstitial fibrosis on biopsy. [8][9][10] In one study among kidney transplant recipients, PIIINP/creatinine (Cr) concentrations .100 ng/mmol were associated with declining eGFR; however, this study did not adjust for baseline eGFR or proteinuria. 9 To our knowledge, no prior study has evaluated the association of urine PIIINP with loss of kidney function in older community-living individuals, an age group in which measurement of kidney function by creatinine is known to be insensitive to loss of GFR, 11,12 proteinuria is infrequent, and renal fibrosis is particularly common.…”