Elevated plasma 4-pyridoxic acid in renal insufficiency.
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.


METHODS
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.
Coburn
Stephen P
SP
Department of Biochemistry, Fort Wayne State Developmental Center, Fort Wayne, IN 46835, USA. coburn@ipfw.edu
Reynolds
Robert D
RD
Mahuren
J Dennis
JD
Schaltenbrand
Wayne E
WE
Wang
Yao
Y
Ericson
Karen L
KL
Whyte
Michael P
MP
Zubovic
Yvonne M
YM
Ziegler
Paula J
PJ
Costill
David L
DL
Fink
William J
WJ
Pearson
David R
DR
Pauly
Thomas A
TA
Thampy
K George
KG
Wortsman
Jacobo
J
D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007774:Lactation / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011735:Pyridoxic Acid / Q000097:blood*; D051437:Renal Insufficiency / Q000378:metabolism*; D025101:Vitamin B 6 / Q000378:metabolism*
D011735:Pyridoxic Acid; D025101:Vitamin B 6; D003404:Creatinine; D000469:Alkaline Phosphatase