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To improve our understanding of both diagnosis and treatment of diseases of oxalate metabolism, we first set out to establish a new ion-chromatographic method to determine normal plasma levels of oxalate, citrate and sulfate from single plasma samples. In 50 infants and children (23 girls, 27 boys, aged 0.2 to 17 years) with normal renal function, blood was drawn in Li-heparin tubes, placed on ice and preserved immediately with 40 microliters M HCl/ml plasma in two ultracentrifugation steps. For measurement, plasma was injected onto an ion chromatography system with NaOH as the mobile phase, and then run as a linear gradient from 5 mM to 52.5 mM over 21 minutes. Analysis yielded measurable and reproducible oxalate (6.43 +/- 1.06 microM/liter), citrate (79.3 +/- 27.4 microM/liter) and sulfate (235.0 +/- 85.3 microM/liter) levels, without any age and gender specific differences. The least detectable plasma oxalate level was < 0.3 microM with a high reliability and reproducibility (coefficient of variance 1.95 to 4.75%). In conclusion, we established a reproducible, precise method to determine the relevant plasma anions involved in mineral metabolism, which heretofore have not been easily measurable. Studies of diseases of oxalate and citrate metabolism are ongoing on the basis of the normal plasma values achieved in this study.

Burn injury in children is associated with low bone formation and long-term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH-deficient patients, we studied the short-term effects of rHGH on bone fomation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg.day) or an equal volume of saline. Mean burn size and age were not different between the groups, and test substances were given from admission to time of wound healing (mean: 43 +/- 22 days). At wound healing, serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229% and 187% of the respective means of the placebo group (P < 0.025). Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level IGFBR-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP-3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.