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Elevated plasma 4-pyridoxic acid in renal insufficiency^1,2,3,4

¹ From the Department of Biochemistry, Fort Wayne State Developmental Center, Fort Wayne, IN; the Department of Human Nutrition and Dietetics, University of Illinois, Chicago; the Metabolic Research Unit, Shriners Hospitals for Children, St Louis; the Department of Mathematical Sciences, Indiana University–Purdue University, Fort Wayne, IN; the Human Performance Laboratory and the Department of Nutrition, Ball State University, Muncie, IN; and the Department of Medicine, Southern Illinois University School of Medicine, Springfield, IL.

Background: Renal insufficiency is associated with altered vitamin B-6 metabolism. We have observed high concentrations of 4-pyridoxic acid, the major catabolite of vitamin B-6 metabolism, in plasma during renal insufficiency.

Objective: The objective was to evaluate the renal handling of 4-pyridoxic acid and the effects of renal dysfunction on vitamin B-6 metabolism.

Design: We measured the renal clearance of 4-pyridoxic acid and creatinine in 17 nonpregnant, 17 pregnant, and 16 lactating women. We then examined the influence of vitamin B-6 or alkaline phosphatase activity on the ratio of 4-pyridoxic acid to pyridoxal (PA:PL) in plasma in 10 men receiving a low (0.4 mg pyridoxine·HCl/d) or high (200 mg pyridoxine·HCl/d) vitamin B-6 intake for 6 wk, in 10 healthy subjects during a 21-d fast, in 1235 plasma samples from 799 people screened for hypophosphatasia, and in 67 subjects with a range of serum creatinine concentrations.

Results: Renal clearance of 4-pyridoxic acid was 232 ± 94 mL/min in nonpregnant women, 337 ± 140 mL/min in pregnant women, and 215 ± 103 mL/min in lactating healthy women. These values were approximately twice the creatinine clearance, indicating that 4-pyridoxic acid is at least partially eliminated by tubular secretion. Elevated plasma creatinine concentrations were associated with marked elevations in 4-pyridoxic acid and PA:PL. PA:PL was not affected by wide variations in vitamin B-6 intake or by the wide range of pyridoxal-P concentrations encountered while screening for hypophosphatasia.

Conclusions: Plasma 4-pyridoxic acid concentrations are markedly elevated in renal insufficiency. Plasma PA:PL can distinguish between increases in 4-pyridoxic acid concentrations due to increased dietary intake and those due to renal insufficiency.

Key Words: 4-Pyridoxic acid • vitamin B-6 • pyridoxal-P • pyridoxal • renal function • pregnancy • lactation • women

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