Urinary amino-terminal propeptide of type III procollagen (PIIINP) as a marker of interstitial fibrosis in renal transplant recipients

Teppo, Anna‐Maija; Törnroth, T; Honkanen, Eero; Grönhagen‐Riska, Carola

doi:10.1097/01.tp.0000066809.60389.48

Cited by 58 publications

(60 citation statements)

References 26 publications

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“…The limited follow-up of the patients included in our study (Ͻ2 years), and thus the absence of significant modification of eGFR during follow-up (Table 1), precluded any analysis of the predictive value of UPIIINP/Cr for the decline in renal function. However, in a study of renal transplant recipients (10), UPIIINP/Cr correlated with the evolution of eGFR. During a mean follow-up of roughly 4 years, GFR increased or remained unchanged in patients with a UPIIINP/Cr Ͻ100 ng/mmol and decreased in 42% of patients with a UPII-INP/Cr Ͼ100 ng/mmol.…”

Section: Discussionmentioning

confidence: 99%

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Urinary Procollagen III Aminoterminal Propeptide (PIIINP)

Ghoul¹,

Squalli²,

Servais³

et al. 2010

Clinical Journal of the American Society of Nephrology

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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.

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Section: Discussionmentioning

confidence: 99%

“…Besides, two previous studies have suggested that serum and urinary PIIINP levels may prove useful in the assessment of renal fibrosis in the native as well as in the transplanted kidney (1,10).…”

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confidence: 99%

Urinary Procollagen III Aminoterminal Propeptide (PIIINP)

Ghoul¹,

Squalli²,

Servais³

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…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. PIIINP is 44 kD in size and therefore smaller than albumin.…”

Section: Discussionmentioning

confidence: 99%

“…21 Finally, Teppo and colleagues found that urine PIIINP concentrations were associated with tubulointerstitial fibrosis, whereas plasma PIIINP concentrations were not. 9 The strengths of our study include its relatively large sample size; concurrent measurement of eGFR, ACR, and plasma PIIINP; availability of follow-up for change in kidney function and ESRD; and evaluation of a community-living older adult cohort with largely preserved eGFR and low-grade or absent albuminuria at baseline. The study also has important limitations.…”

Section: Discussionmentioning

confidence: 99%

“…[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. 4 The purpose of this study was to determine the association of urine PIIINP concentrations with progression of CKD in community-living older adults.…”

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Urine Collagen Fragments and CKD Progression—The Cardiovascular Health Study

Biggs

Mukamal

et al. 2015

Journal of the American Society of Nephrology

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Tubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged $65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (6SD) was 7865 years, mean eGFR was 63618 ml/min per 1.73 m 2 , and median urine PIIINP was 2.6 (interquartile range, 1.4-4.2) mg/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals.

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A Novel High‐Throughput Immunoaffinity LC–MS/MS Assay for P‐III‐NP and Other Fragments of Type III Procollagen in Human Serum

Huynh,

Barahona‐Carrillo,

Moncrieffe

et al. 2024

Drug Testing and Analysis

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The amino‐terminal propeptide of type III procollagen (P‐III‐NP) is used with IGF‐I to detect the illicit use of growth hormone and to monitor growth hormone therapy. However, the only currently available assays for P‐III‐NP are immunoassays, which are not well harmonized. In addition, other fragments of type III procollagen may better evaluate collagen turnover. We aimed to develop a high‐throughput assay using immunoaffinity enrichment coupled to ultra‐high‐performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) to quantify peptides belonging to three different regions of type III procollagen in human serum simultaneously. To facilitate higher throughput, we transferred the assay from microcentrifuge tubes to a 96‐well plate format with partially automated pipetting. The method was linear (Pearson's R ≥ 0.994) over an estimated concentration range of 1.35–13.3 nM, 0.04–2.28 nM, and 0.26–5.1 nM for each surrogate peptide of P‐III‐NP, collagen degradation products, and the carboxyl‐terminal propeptide, respectively. Intra‐day and inter‐day imprecision were both < 13.6%, and the results of robustness testing were also encouraging. The method was successfully applied to capillary blood samples obtained using Tasso+ microsampling devices. Modest correlation of P‐III‐NP concentration was observed between our new method and a WADA‐approved immunoassay (N = 40, Pearson's R = 0.789) with a significant bias of −87.8%. Our method simultaneously quantifies four peptides belonging to three regions of type III procollagen in human serum. High bias between assays highlights the need for common higher‐order calibrators or reference materials to help improve the comparability of results across laboratories.

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Urinary amino-terminal propeptide of type III procollagen (PIIINP) as a marker of interstitial fibrosis in renal transplant recipients

Cited by 58 publications

References 26 publications

Urinary Procollagen III Aminoterminal Propeptide (PIIINP)

Urinary Procollagen III Aminoterminal Propeptide (PIIINP)

Urine Collagen Fragments and CKD Progression—The Cardiovascular Health Study

A Novel High‐Throughput Immunoaffinity LC–MS/MS Assay for P‐III‐NP and Other Fragments of Type III Procollagen in Human Serum

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