Effect of renal function on plasma levels of bone Gla-protein

Plasma bone Gla-protein (BGP) is a sensitive and specific marker for metabolic bone disease. Because BGP is removed from the circulation mainly by kidney clearance, increased plasma BGP in subjects with impaired renal function could be due to decreased renal clearance, increased bone metabolism, or both. These factors were evaluated in 62 patients with various degrees of renal failure in whom we measured plasma BGP, [125I]iothalamate clearance [a measure of glomerular filtration rate (GFR)], and [131I]o-iodohippurate clearance (a measure of effective renal plasma flow). In all patients with GFR greater than 30 ml/min X 1.73 m2, plasma BGP was within the normal range for age- and sex-comparable control subjects, and large increases in plasma BGP did not occur until GFR was below 20 ml/min X 1.73 m2. Nonlinear regression analysis showed that the variation in plasma BGP was substantially accounted for using the exponential of GFR. Similarly, plasma BGP was normal for values of effective renal plasma flow above 150 ml/min X 1.73 m2. Thus, for normal subjects and patients with mild to moderate renal failure, plasma elevations of BGP reflect increased bone turnover rather than decreased renal filtration.