The Action of Pyridoxine in Primary Hyperoxaluria

Abstract

S U M M A R Y1. Evidence of deficiency of, antagonism to, or abnormal dependency upon pyridoxine has been sought in four patients with primary hyperoxaluria. The urinary excretion of kynurenine, 3-hydroxykyurenineY 3-hydroxyanthranilic acid, kynurenic acid and xanthurenic acid, before and after a loading dose of L-tryptophan was used to assess pyridoxine nutrition.2. Three of the four patients studied had abnormal L-tryptophan metabolite excretion patterns, but these were not of the type which is associated with abnormalities of pyridoxine nutrition.3. The changes which were observed are compatible with impaired conversion of kynurenine to 3-hydroxykynurenine by the NADH, dependent kynurenine 3-hydroxylase (EC 1.99.1.5) enzyme system. 4. Large doses of pyridoxine hydrochloride reduced the urinary oxalate excretion by two of the patients to levels which were intermediate between the normal range and the pre-treatment values. This effect was maintained for 6 months, which was the longest period of observation. 5.It is concluded that this action of pyridoxine is mediated by a mechanism which does not involve the correction of an abnormality of pyridoxine metabolism.Primary hyperoxaluria, in which calcium oxalate urolithiasis is accompanied by an elevated urinary oxalate excretion, accounts for only a small proportion of patients with calcium oxalate urinary stones. The urinary oxalate excretion is increased in severe experimentally induced pyridoxine deficiency in man (Faber et al., 1963) as well asin animals (Gershoff et al., 1959a; Andrus, Gershoff k Faragella, 1959), andGershoff, Mayer &Kulczycki (1959b) reported that pyridoxine reduced the urinary oxalate excretion of a group of institutionalized mental defectives who were not taking a pyridoxine deficient diet.Mayer et al. (1968) implicated pyridoxine deficiency as a factor in the causation of calcium

Renal calcium phosphate and oxalate deposition in prolonged vitamin B6 deficiency: studies on a rat model of urolithiasis

“…From the histopathological and ultrastructural data the following hypothesis is suggested; biochemical mechanisms [2,4,8] and histopathological aspects of vitamin B 6 deficiency [10,12,13] may cause the formation of calcium oxalate crystals, especially at the papillary level. These crystals, like any other noxious agent, induce an inflammatory infiltrate.…”

“…Samples were post-fixed in OsO 4 , dehydrated in ethanol and embedded in resin. Thin sections, counterstained in uranyl acetate and lead citrate, were examined in an electron microscope.…”

“…The administration of vitamin B 6 seems to reduce the production of oxalate from glyoxylate by enhancing the activity of alanine-glyoxylate transaminase, as pyridoxal phosphate, one of the biologically active forms of vitamin B 6 , is the cofactor for the enzyme [2][3][4]8,9]. Conversely, vitamin B 6 deficiency leads to increased hepatic synthesis and urinary reabsorption of oxalate [10][11][12][13].…”

“…The role of vitamin B 6 in the pathogenesis of kidney stones has been widely investigated, since it was reported to be beneficial in treating patients with type I primary hyperoxaluria [1][2][3][4][5][6][7]. The administration of vitamin B 6 seems to reduce the production of oxalate from glyoxylate by enhancing the activity of alanine-glyoxylate transaminase, as pyridoxal phosphate, one of the biologically active forms of vitamin B 6 , is the cofactor for the enzyme [2][3][4]8,9].…”

Primary and secondary hyperoxaluria: Understanding the enigma

“…The recommended initial dose of pyridoxine is 5 mg/kg with a maximum dose of 20 mg/kg [79] . Pyridoxine has been demonstrated to be effective in only 30% of the patients [80,81] and therapeutic success is noted by a approximately 30% reduction in urine oxalate excretion after 3 mo of pyridoxine supplementation at the maximal dose [53,60] . Certain genotypes (508G>A (Gly170Arg) and 454T>A (Phe153Ile) are known to be more responsive to pyridoxine treatment than others [82,83] although pyridoxine therapy should be tested in all patients with PH1.…”