BACKGROUND AND OBJECTIVES: Nephropathic cystinosis is a lysosomal storage disorder characterized by renal tubular Fanconi syndrome in infancy and glomerular damage leading to renal failure at ∼10 years of age. Therapy with the cystine-depleting agent cysteamine postpones renal failure, but the degree of compliance with this treatment has not been correlated with preservation of kidney function. METHODS: We assessed leucocyte cystine depletion by cysteamine and created the composite compliance score that incorporates the extent of leucocyte cystine depletion, as well as duration of cysteamine treatment, into a single integer. Age at renal failure was used to gauge preservation of renal function, and the Fanconi syndrome index (FSI), a measure of aminoaciduria, was used to assess renal tubular Fanconi syndrome. RESULTS: Age at renal failure varied directly and linearly with the composite compliance score (y = 0.3x +8.8; R(2) = 0.61). The slope indicated that for every year of excellent cystine depletion, nearly 1 year of renal function was preserved. Age at renal failure correlated roughly with mean leucocyte cystine level, but not with mean cysteamine dosage. There was no correlation between the FSI and the composite compliance score. CONCLUSIONS: Greater compliance with oral cysteamine therapy yields greater preservation of renal glomerular, but not tubular, function. Oral cysteamine therapy should be given at the maximum tolerated dose, within the recommended limits.
BACKGROUND AND OBJECTIVES:Nephropathic cystinosis is a lysosomal storage disorder characterized by renal tubular Fanconi syndrome in infancy and glomerular damage leading to renal failure at ∼10 years of age. Therapy with the cystine-depleting agent cysteamine postpones renal failure, but the degree of compliance with this treatment has not been correlated with preservation of kidney function. METHODS: We assessed leucocyte cystine depletion by cysteamine and created the composite compliance score that incorporates the extent of leucocyte cystine depletion, as well as duration of cysteamine treatment, into a single integer. Age at renal failure was used to gauge preservation of renal function, and the Fanconi syndrome index (FSI), a measure of aminoaciduria, was used to assess renal tubular Fanconi syndrome. RESULTS: Age at renal failure varied directly and linearly with the composite compliance score (y = 0.3x +8.8; R(2) = 0.61). The slope indicated that for every year of excellent cystine depletion, nearly 1 year of renal function was preserved. Age at renal failure correlated roughly with mean leucocyte cystine level, but not with mean cysteamine dosage. There was no correlation between the FSI and the composite compliance score. CONCLUSIONS: Greater compliance with oral cysteamine therapy yields greater preservation of renal glomerular, but not tubular, function. Oral cysteamine therapy should be given at the maximum tolerated dose, within the recommended limits.
Authors: Martijn J G Wilmer; Adriana de Graaf-Hess; Henk J Blom; Henry B P M Dijkman; Leo A Monnens; Lambertus P van den Heuvel; Elena N Levtchenko Journal: Biochem Biophys Res Commun Date: 2005-09-23 Impact factor: 3.575
Authors: M Town; G Jean; S Cherqui; M Attard; L Forestier; S A Whitmore; D F Callen; O Gribouval; M Broyer; G P Bates; W van't Hoff; C Antignac Journal: Nat Genet Date: 1998-04 Impact factor: 38.330
Authors: Mohamed A Elmonem; Koenraad R Veys; Neveen A Soliman; Maria van Dyck; Lambertus P van den Heuvel; Elena Levtchenko Journal: Orphanet J Rare Dis Date: 2016-04-22 Impact factor: 4.123
Authors: Emma J Brasell; Lee Lee Chu; Murielle M Akpa; Idit Eshkar-Oren; Iris Alroy; Rachel Corsini; Brian M Gilfix; Yojiro Yamanaka; Pedro Huertas; Paul Goodyer Journal: PLoS One Date: 2019-12-04 Impact factor: 3.240