title: Correlation of kidney function, volume and imaging findings, and PKHD1 mutations in 73 patients with autosomal recessive polycystic kidney disease.
abstract: OBJECTIVE
  Renal function and imaging findings have not been comprehensively and prospectively characterized in a broad age range of patients with molecularly confirmed autosomal recessive polycystic kidney disease (ARPKD).
  
  
  METHODS
  Ninety potential ARPKD patients were examined at the National Institutes of Health Clinical Center. Seventy-three fulfilled clinical diagnostic criteria, had at least one PKHD1 mutation, and were prospectively evaluated using magnetic resonance imaging (MRI), high-resolution ultrasonography (HR-USG), and measures of glomerular and tubular function.
  
  
  RESULTS
  Among 31 perinatally symptomatic patients, 25% required renal replacement therapy by age 11 years; among 42 patients who became symptomatic beyond 1 month (nonperinatal), 25% required kidney transplantation by age 32 years. Creatinine clearance (CrCl) for nonperinatal patients (103 +/- 54 ml/min/1.73 m(2)) was greater than for perinatal patients (62 +/- 33) (P = 0.002). Corticomedullary involvement on HR-USG was associated with a significantly worse mean CrCl (61 +/- 32) in comparison with medullary involvement only (131 +/- 46) (P < 0.0001). Among children with enlarged kidneys, volume correlated inversely with function, although with wide variability. Severity of PKHD1 mutations did not determine kidney size or function. In 35% of patients with medullary-only abnormalities, standard ultrasound was normal and the pathology was detectable with HR-USG.
  
  
  CONCLUSIONS
  In ARPKD, perinatal presentation and corticomedullary involvement are associated with faster progression of kidney disease. Mild ARPKD is best detected by HR-USG. Considerable variability occurs that is not explained by the type of PKHD1 mutation.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. mgaygun@mail.nih.gov
authors.forename: Meral
authors.initials: M
authors.lastname: Gunay-Aygun
authors.forename: Esperanza
authors.initials: E
authors.lastname: Font-Montgomery
authors.forename: Linda
authors.initials: L
authors.lastname: Lukose
authors.forename: Maya
authors.initials: M
authors.lastname: Tuchman
authors.forename: Jennifer
authors.initials: J
authors.lastname: Graf
authors.forename: Joy C
authors.initials: JC
authors.lastname: Bryant
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
authors.forename: Angelica
authors.initials: A
authors.lastname: Garcia
authors.forename: Hailey
authors.initials: H
authors.lastname: Edwards
authors.forename: Katie
authors.initials: K
authors.lastname: Piwnica-Worms
authors.forename: David
authors.initials: D
authors.lastname: Adams
authors.forename: Isa
authors.initials: I
authors.lastname: Bernardini
authors.forename: Roxanne E
authors.initials: RE
authors.lastname: Fischer
authors.forename: Donna
authors.initials: D
authors.lastname: Krasnewich
authors.forename: Neal
authors.initials: N
authors.lastname: Oden
authors.forename: Alex
authors.initials: A
authors.lastname: Ling
authors.forename: Zenaide
authors.initials: Z
authors.lastname: Quezado
authors.forename: Colleen
authors.initials: C
authors.lastname: Zak
authors.forename: Kailash T
authors.initials: KT
authors.lastname: Daryanani
authors.forename: Baris
authors.initials: B
authors.lastname: Turkbey
authors.forename: Peter
authors.initials: P
authors.lastname: Choyke
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Guay-Woodford
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D055316:Cystatin C / Q000097:blood; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D007684:Kidney Tubules / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009316:National Institutes of Health (U.S.); D009929:Organ Size; D010375:Pedigree; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D014463:Ultrasonography; D014481:United States; D055815:Young Adult
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface; D003404:Creatinine