Correlation of Kidney Function, Volume and Imaging Findings, and PKHD1 Mutations in 73 Patients with Autosomal Recessive Polycystic Kidney Disease

Abstract

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.Clin J Am Soc Nephrol 5: 972-984, 2010.

Transplantation in autosomal recessive polycystic kidney disease: liver and/or kidney?

“…Kidneys with ARPKD do not increase in size after the first 2-3 years of life [1,2]. Those with corticomedullary involvement versus only medullary involvement have worse kidney function [11]. Survival into mid-adulthood without requiring liver or renal replacement therapy has been described [12,13].…”

“…The signs are hepatic enlargement or heterogeneous and echogenic appearance of the liver by ultrasound, splenomegaly, hypersplenism, esophageal varices, protein-losing enteropathy, and ascending cholangitis [2,3]. Enlargement of the left lobe of the liver is a consistent finding [11]. Patients with Caroli's disease are at risk for acute bacterial cholangitis leading to septicemia and biliary tract calculi from stasis.…”

“…As the child grows, the rate of growth of the kidneys slows down. High-resolution ultrasonography helps in determining the extent of renal involvement in patients with milder forms of renal disease where ductal dilatation may be present predominantly in the medullary region [11]. The prevalence of hepatic abnormalities is underestimated in children.…”

Polycystic kidney disease gene in the Lewis polycystic kidney rat is mapped to chromosome 10q21&ndash;q26

“…16,18,26 In all cases of PKD, congestive heart failure is a feature that cannot be avoided. 27,28 To the present, many murine models have been identified and used to study and understand the development and progression of PKD. 10,14,29 However, the polycystic kidney (PCK) rat model seems to present with PKD phenotypes that resemble human PKD phenotypes.…”

Autosomal Recessive Polycystic Kidney Disease: A Hepatorenal Fibrocystic Disorder With Pleiotropic Effects

“…35,[37][38][39][40] However, not all missense mutations lead to a more benign outcome; indeed, a number of missense mutations result in severe phenotypes when present with a truncating mutation or in homozygous form. 6,37,41 Numerous groups have attempted to categorize sequence variations based on likelihood of pathogenicity, 6,37,[42][43][44] many of which are cataloged in the ARPKD Mutation Database. 33 However, because many patients will be found to have novel PKHD1 variants, interpretation of genetic testing results can be challenging.…”