Renal replacement therapy in the treatment of confirmed or suspected inborn errors of metabolism.

OBJECTIVE: Analysis of mortality and risk factors for mortality in the use of renal replacement therapy to correct metabolic disturbances associated with confirmed or suspected inborn errors of metabolism. STUDY DESIGN: A retrospective review of an institutional review board-approved pediatric acute renal failure data base at the University of Michigan. Eighteen patients underwent 21 renal replacement therapy treatments for metabolic disturbances caused by urea cycle defects (n = 14), organic acidemias (n = 5), idiopathic hyperammonemia (n = 1), and Reye syndrome (n = 1). RESULTS: There were 14 boys (74%) and 4 girls (26%), with a mean age and weight of 56.2 +/- 71.0 months and 18.5 +/- 19.2 kg, respectively, at the initiation of renal replacement therapy. Overall treatment mortality rate was 57.2% (12 of 21 treatments), with 11 of the 18 patients (61.1%) dying before hospital discharge. Two-year follow-up on those patients demonstrated that 5 patients (71.4%) remained alive. Initial therapy with hemodialysis was associated with improved survival. Ten treatments (47.6%) required transition to another form of renal replacement therapy to maintain ongoing metabolic control, with a mean duration of 6.1 +/- 9.8 days. Time to renal replacement therapy >24 hours was associated with an increased risk of mortality, whereas a blood pressure >5th percentile for age at the initiation of therapy and the use of anticoagulation were associated with a decreased risk of mortality. CONCLUSIONS: Renal replacement therapy can correct the metabolic disturbances that accompany suspected or confirmed inborn errors of metabolism. Our experience demonstrates an approximately 60% mortality rate associated with renal replacement treatment, with more than 70% of survivors living longer than 2 years.

Clearance of amino acids by hemodialysis in argininosuccinate synthetase deficiency.

We determined the dialytic clearance of amino acids involved in ammoniagenesis and nitrogen excretion in a neonate with argininosuccinate synthetase deficiency who underwent acute hemodialysis. Plasma ammonia and plasma and dialysate amino acid concentrations were obtained at baseline, 30-minute intervals during hemodialysis, and 30 minutes after the completion of hemodialysis. Plasma ammonia concentrations declined by 56% during the 90-minute hemodialysis treatment, whereas arginine, citrulline, glutamine, and glycine concentrations decreased by 65%, 55%, 40%, and 34%, respectively. Mean dialytic clearances for arginine, citrulline, glutamine, and glycine were 24, 282, 263, and 189 mL/min per 1.73 m(2), respectively. The high dialytic clearance of citrulline suggests a novel mechanism of hemodialysis removal of nitrogen. Dialytic clearances of glutamine and glycine may prevent further ammoniagenesis in hyperammonemic patients. However, our data suggest that hemodialysis affects the precursors of alternative pathway removal of ammonia. Further study is needed to optimize the intradialytic and interdialytic dosing of substrates.