The nephropathy of type I tyrosinemia after liver transplantation.

Type I tyrosinemia (HTI) is an autosomally recessively inherited disease caused by deficiency of fumarylacetoacetate hydrolase. The disease manifests with liver failure, renal tubular defects, and neurologic crises. Currently orthotopic liver transplantation (OLT) enables patients to survive. However, renal fumarylacetoacetate hydrolase deficiency is not corrected by OLT, and the long-term prognosis of the nephropathy is not known. We investigated tyrosine metabolism, GFR, renal tubular function, and histopathology before and 18-36 mo after OLT in eight patients with HTI. Progressive renal dysfunction was not documented despite continuing, although diminished, urinary succinylacetone excretion in all patients. The mean GFR was 82 mL/min/1.73 m2 before and 102 mL at 18 mo and 93 mL at 36 mo after OLT. All patients showed tubular dysfunction before OLT. At 18 mo, glucosuria occurred in one, amino aciduria and phosphaturia in three, and hypercalciuria in six patients. Only hypercalciuria was seen at 36 mo. Renal biopsies showed mild nonspecific changes caused either by minimal progression of the renal disease or by mild cyclosporine nephrotoxicity. In conclusion, patients with HTI had normal GFR, but showed signs of tubular dysfunction 18-36 mo after OLT. Renal function and histopathology should be monitored after OLT for HTI.

Simultaneous determination of tryptophan and its 5-hydroxy metabolites in human cerebrospinal fluid by reversed phase liquid chromatography with electrochemical detection.

A sensitive ion-pair reversed phase liquid chromatographic method for determining tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine (serotonin) and 5-hydroxyindole acetic acid has been developed. To separate these indoles in cerebrospinal fluid both octadecyl- and phenyl-bonded columns were tested. The effect of an ion-pair reagent (n-heptyl sulphonate) and pH of the mobile phase on the separation was examined. With the method described the concentrations of the four indoles can be determined within 45 min without sample pretreatment. The sensitivity obtained with electrochemical detection is 0.45 mumol/l for tryptophan and 2-4 nmol/l for 5-hydroxyindoles in human cerebrospinal fluid samples.

Assay for plasma 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 by "high-performance" liquid chromatography.

We describe a new, rapid, and simple column-chromatographic procedure for 25-OH vitamin D3 in plasma. The vitamin is extracted by use of Sep-pak C18 (octadecyl alkylated silicic acid), a short factory-packed reversed-phase column, and 25-OH vitamin D2 + 25-OH vitamin D3 fraction is eluted with methanol/water. The 25-OH D2 and 25-OH D3 are then well resolved on a high-resolution 3-micrometer silicic acid straight-phase liquid-chromatography column. The peaks are quantified against a 25-OH D3 standard by ultraviolet absorbance. Recovery was assessed by use of tritiated 25-OH D3. The within-assay coefficient of variation of the method was 5% and recovery 93%. The method was evaluated with 26 samples from control subjects and 17 samples from patients, seven with liver disease and 10 who had undergone ileo-ileostomy for hypercholesterolemia. The normal seasonal variation was observed for 25-OH D3 concentrations, and they correlated negatively and significantly with those of 25-OH D2. Post-ileo-ileostomy concentrations of 25-OH D3 in plasma were generally similar to those in normal individuals for the same reason (winter), but 25-OH D2 concentrations were insignificantly lower. The patients with chronic liver disease had significantly lower 25-OH D3 concentrations than normal persons but higher 25-OH D2 concentrations, with a significantly higher 25-OH D2/25-OH D3 ratio, indicating poor storage of vitamin D3.