Spurious hyperbilirubinemia in uremic patients on propranolol therapy.

Chronic, low-grade, unexplained increases of total serum bilirubin concentration were observed in 16 of 132 (12%) chronic dialysis patients. Cessation of antihypertensive medication in four patients resulted in disappearance of hyperbilirubinemia. Propranolol was the only antihypertensive drug common to all 16 patients. Daily dosage varied among the patients, but the mean dose was 308 mg (+/- 51 SEM). Serial determinations of sera from individual patients given different doses and from the group as a whole demonstrated a linear relationship between propranolol dose and apparent total serum bilirubin concentration with continuous-flow analysis. When serum specimens from uremic patients receiving propranolol were treated with diazotized fulfanilic acid and examined spectrophotometrically, an absorbance peak distinct from but overlapping that of bilirubin was consistently demonstrated. The material producing the peak disappeared when the drug was stopped, did not dialyze, and was not reproduced by the in vitro addition of propranolol to uremic serum. We postulate that a metabolite(s) of propranolol is retained in uremic serum and interferes with the bilirubin determination.

The determination of thiamin pyrophosphate in blood and other tissues, and its correlation with erythrocyte transketolase activity.

A sensitive method for the specific measurement of thiamin pyrophosphate (TPP) has been developed using the apoenzyme recombination concept. Yeast pyruvic decarboxylase apoenzyme can be reconstituted by the addition of TPP or samples containing TPP, yielding the holoenzyme with activity proportionate to the amount of TPP added. Using this technique, reaction mixtures containing 0.2 to 1.5 ng TPP can be assayed. Normal human erythrocyte TPP ranges from 50 to 150 ng per ml packed cells. When rats are fed a thiamin deficient diet, the erythrocyte TPP level falls more rapidly than the erythrocyte transketolase activity. After 8 days, the level of TPP in the erythrocytes of deficient animals was 10% of the level in pair-fed controls. At this time, however, there was no appreciable decrease in their respective transketolase activities. The level of TPP in the liver also is decreased drastically after 8 days. Therefore it appears that erytyrocyte and liver TPP stores have begun to be depleted and suggest that erythrocyte TPP levels are a more sensitive indicator of thiamin status.

Vitamin B6 deficiency in uremia.

Significant decreases in plasma pyridoxal-5-phosphate (PLP), plasma glutamic-oxaloacetic transaminase (PGOT) and erythrocyte glutamic-oxaloacetic transaminase (EGOT) were found in 29 uremic patients including 14 who had been on hemodialysis an average of 15.8 months. The mean PLP values of the uremic patients (5.39 +/- 0.37 ng/ml) were clearly lower than the values obtained for the normal group (9.30 +/- 0.80 mg/ml). The mean PGOT values of the uremic patients (dialyzed 4.07 +/- 0.29 U/liter, undialyzed 5.31 +/- 0.49 U/liter) were significantly lower than the normal group (6.57 +/- 0.39 U/liter). The mean EGOT value of the uremic patients (325 +/- 17 U/liter) was also lower than normal subjects (416 +/-21 U/liter). Stimulation of the EGOT by exogenous PLP (EGOT index) was less in dialyzed patients (1.60) than normal subjects (1.80) while the undialyzed uremic subjects had a greater than normal stimulation (2.12). All of these results indicate that uremic patients are vitamin B6 deficient and that those undergoing hemodialysis may have decreased amounts of the EGOT apoenzyme.