Assessing bone formation in patients with chronic kidney disease using procollagen type I N-terminal propeptide (PINP): The choice of assay makes a difference.

Abstract

Measurement of procollagen type I N-terminal propeptide (PINP) concentration in serum reflects the rate of type I collagen synthesis and can therefore be used as a bone formation marker. There are two methods of PINP quantification; the first measures the trimeric propeptide (intact PINP) and the second measures both the trimeric and monomeric propeptides (total PINP). Trimeric PINP is excreted via hepatic endothelial cells, whereas monomeric PINP is cleared renally. Therefore, in renal failure, the total assay has a positive bias with respect to the intact assay, due to monomeric PINP accumulation. The aim of this study was to compare the performance of both assays across all stages of chronic kidney disease. Serum was taken from male (n = 111) and female (n = 105) patients attending a metabolic bone clinic, and these were partitioned into stages of chronic kidney disease 1-5. Each serum sample was analysed using the Roche electrochemiluminescence immunoassay for total PINP and the Immunodiagnostic Systems chemiluminescence immunoassay for intact PINP. Passing-Bablok regression analysis comparing both methods showed that with advancing chronic kidney disease there was a proportional positive bias affecting the total assay when compared with the intact assay. This proportional positive bias was statistically significant for chronic kidney disease stages 3b, 4 and 5. Based on this method comparison study, usage of the total PINP assay should be avoided in chronic kidney disease stages 3b, 4 and 5 (eGFR ≤44 mL/min/1.73 m2) and instead an intact assay used as the total assay overestimates PINP concentrations due to monomeric PINP accumulation.