Correlation of kidney function, volume and imaging findings, and PKHD1 mutations in 73 patients with autosomal recessive polycystic kidney disease.
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.
Gunay-Aygun
Meral
M
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. mgaygun@mail.nih.gov
Font-Montgomery
Esperanza
E
Lukose
Linda
L
Tuchman
Maya
M
Graf
Jennifer
J
Bryant
Joy C
JC
Kleta
Robert
R
Garcia
Angelica
A
Edwards
Hailey
H
Piwnica-Worms
Katie
K
Adams
David
D
Bernardini
Isa
I
Fischer
Roxanne E
RE
Krasnewich
Donna
D
Oden
Neal
N
Ling
Alex
A
Quezado
Zenaide
Z
Zak
Colleen
C
Daryanani
Kailash T
KT
Turkbey
Baris
B
Choyke
Peter
P
Guay-Woodford
Lisa M
LM
Gahl
William A
WA
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
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface; D003404:Creatinine