Universität zu Köln

Hoyer-Kuhn, Heike, Kohbrok, Sina, Volland, Ruth, Franklin, Jeremy ORCID: 0000-0003-1536-0925, Hero, Barbara, Beck, Bodo B. and Hoppe, Bernd (2014). Vitamin B6 in Primary Hyperoxaluria I: First Prospective Trial after 40 Years of Practice. Clin. J. Am. Soc. Nephrol., 9 (3). S. 468 - 478. WASHINGTON: AMER SOC NEPHROLOGY. ISSN 1555-905X

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Abstract

Background and objectives Primary hyperoxaluria type I (PH I) is caused by deficiency of the liver-specific enzyme alanine-glyoxylate:aminotransferase (AGT). Many mutations are known to perturb AGT protein folding. Vitamin B6 (B6) is the only specific drug available for treatment. Although B6 has been used for >40 years, controlled data on B6 efficacy are lacking. Therefore, this study investigated the absolute and relative change of urinary oxalate (Uox) excretion under increasing dosages of B6, the first prospective trial to do so. Design, setting, participants, & measurements B6 response was studied in 12 patients (7 male patients) with genetically confirmed PH I (3 Gly170Arg homozygous, 5 compound Gly170Arg and/or Phe152Ile heterozygous, and 4 negative for Gly170Arg and/or Phe152Ile mutations) and noncompromised renal function. Efficacy was defined as a 30% relative reduction in Uox excretion. B6 was administered orally starting at 5 mg/kg body weight per day and given in increments of 5 mg/kg every 6 weeks, up to a final dosage of 20 mg/kg per day at week 24. Uox and serum B6 levels were measured every 6 weeks. Results Mean relative Uox reduction was 25.5%. Uox declined from 2.09 +/- 0.55 (mean +/- SD) at baseline to 1.52 +/- 0.60 mmol/1.73 m(2) per day (P=0.01) at week 24. Serum B6 levels increased from 22.5 +/- 8.7 to 1217 +/- 776 ng/ml (P<0.001). Six patients showed a >= 30% relative reduction of Uox at week 24. Conclusion This first prospective trial confirmed B6 efficacy in 50% of patients (three of three homozygous, one of five heterozygous, and two of four patients negative for the Gly170Arg and/or Phe152Ile mutations). Interestingly, no complete biochemical remission was observed, even in the homozygous Gly170Arg study participants. Future trials are necessary to learn more about genotype-related B6 response and B6 metabolism.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hoyer-Kuhn, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Kohbrok, Sina UNSPECIFIED UNSPECIFIED UNSPECIFIED Volland, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Franklin, Jeremy UNSPECIFIED orcid.org/0000-0003-1536-0925 UNSPECIFIED Hero, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Beck, Bodo B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-443476
DOI:	10.2215/CJN.06820613
Journal or Publication Title:	Clin. J. Am. Soc. Nephrol.
Volume:	9
Number:	3
Page Range:	S. 468 - 478
Date:	2014
Publisher:	AMER SOC NEPHROLOGY
Place of Publication:	WASHINGTON
ISSN:	1555-905X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALANINE-GLYOXYLATE AMINOTRANSFERASE; GENOTYPE-PHENOTYPE CORRELATION; GLOMERULAR-FILTRATION-RATE; OXALOBACTER-FORMIGENES; CLINICAL HETEROGENEITY; PEROXISOMAL ALANINE; MUTATION ANALYSIS; RENAL-DISEASE; TYPE-1; PYRIDOXINE Multiple languages Urology & Nephrology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44347