title: Cystinosis: renal glomerular and renal tubular function in relation to compliance with cystine-depleting therapy.
abstract: OBJECTIVE
  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.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA, nesterovag@mail.nih.gov.
authors.forename: Galina
authors.initials: G
authors.lastname: Nesterova
authors.forename: Caitlyn
authors.initials: C
authors.lastname: Williams
authors.forename: Isa
authors.initials: I
authors.lastname: Bernardini
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002648:Child; D003543:Cysteamine / Q000008:administration & dosage / Q000627:therapeutic use*; D003553:Cystine / Q000097:blood*; D065104:Cystine Depleting Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003554:Cystinosis / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D005198:Fanconi Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D016014:Linear Models; D008297:Male; D020714:Maximum Tolerated Dose; D055118:Medication Adherence; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D065104:Cystine Depleting Agents; D003553:Cystine; D003543:Cysteamine