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.

Trial registration: ClinicalTrials.gov NCT00068224.

Figures

Figure 1.

Artist's rendering, ultrasound, and MRI findings showing the spectrum of kidney abnormalities in ARPKD. Percentages refer to the frequency of each pattern within our population of 62 clinically and molecularly diagnosed pretransplant patients. (A) Normal-sized kidneys with hyperechogenicity and ductal dilations involving parts of the medulla (white dots on artist's rendering). (B) Mildly enlarged kidneys with hyperechogenicity and ductal dilations involving most of the medulla but sparing the cortex. (C) Enlarged kidneys with diffuse hyperechogenicity and ductal dilations sparing only parts of the cortex. Some macrocysts (black) are present. (D) Massively enlarged kidneys with complete involvement of medulla and cortex and numerous macrocysts.

Figure 2.

Morphometric and laboratory data. (A) Kidney volume corrected for body surface area versus age for 42 ARPKD patients (y = 0.25x2 − 22.1x + 635, R2 = 0.18). Normal adult male kidney volume is 204 ± 36 ml (24). (B) Kidney survival comparing perinatally symptomatic and nonperinatal patients (P = 0.003, log-rank test). (C) CrCl plotted against kidney volume corrected for body surface area in children (y = −65.42ln(x) + 487.42, R2 = 0.51) and adults (y = −0.0545x + 83.706, R2 = 0.04) with ARPKD. Data for the inserted bar graph were analyzed for pediatric and adult patients together.