Correlation of kidney function, volume and imaging findings, and PKHD1 mutations in 73 patients with autosomal recessive polycystic kidney disease

Clin J Am Soc Nephrol. 2010 Jun;5(6):972-84. doi: 10.2215/CJN.07141009. Epub 2010 Apr 22.


Background and objectives: 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).

Design, setting, participants, & measurements: 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.

Trial registration: NCT00068224.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Biomarkers / urine
  • Child
  • Child, Preschool
  • Creatinine / urine
  • Cystatin C / blood
  • DNA Mutational Analysis
  • Disease Progression
  • Female
  • Genes, Recessive*
  • Genetic Predisposition to Disease
  • Glomerular Filtration Rate
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Kidney / diagnostic imaging
  • Kidney / pathology*
  • Kidney / physiopathology*
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • National Institutes of Health (U.S.)
  • Organ Size
  • Pedigree
  • Phenotype
  • Polycystic Kidney Diseases / genetics*
  • Polycystic Kidney Diseases / pathology
  • Polycystic Kidney Diseases / physiopathology
  • Polycystic Kidney Diseases / therapy
  • Prospective Studies
  • Receptors, Cell Surface / genetics*
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Ultrasonography
  • United States
  • Young Adult


  • Biomarkers
  • CST3 protein, human
  • Cystatin C
  • PKHD1 protein, human
  • Receptors, Cell Surface
  • Creatinine

Associated data