Design of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney disease.

PURPOSE: Autosomal recessive polycystic kidney disease (ARPKD) is a hereditary condition characterized by massive kidney enlargement and developmental liver defects. Potential consequences during childhood include the need for kidney replacement therapy (KRT). We report the design of 2 ongoing clinical trials (Study 204, Study 307) to evaluate safety, tolerability, and efficacy of tolvaptan in children with ARPKD. METHODS: Both trials are of multinational, multicenter, open-label design. Age range at enrollment is 28 days to < 12 weeks in Study 204 and 28 days to < 18 years in Study 307. Subjects in both studies must have a clinical diagnosis of ARPKD, and those in Study 204 must additionally have signs indicative of risk of rapid progression to KRT, namely, all of: nephromegaly, multiple kidney cysts or increased kidney echogenicity suggesting microcysts, and oligohydramnios or anhydramnios. Target enrollment is 20 subjects for Study 204 and ≥ 10 subjects for Study 307. RESULTS: Follow-up is 24 months in Study 204 (with optional additional treatment up to 36 months) and 18 months in Study 307. Outcomes include safety, tolerability, change in kidney function, and percentage of subjects requiring KRT relative to historical data. Regular safety assessments monitor for possible adverse effects of treatment on parameters such as liver function, kidney function, fluid balance, electrolyte levels, and growth trajectory, with increased frequency of monitoring following tolvaptan initiation or dose escalation. CONCLUSIONS: These trials will provide data on tolvaptan safety and efficacy in a population without disease-specific treatment options. TRIAL REGISTRATION: Study 204: EudraCT 2020-005991-36; Study 307: EudraCT 2020-005992-10.

Intrahepatic bile ductal ectasia in autosomal recessive polycystic kidney disease evaluated by fetal magnetic resonance imaging: a more frequent complication.

OBJECTIVE: This study aimed to evaluate liver malformations and intrahepatic bile ductal ectasia and dilatation (IBDED) in cases of prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD) using magnetic resonance imaging (MRI). METHODS: This retrospective study involved 209 cases referred for fetal MRI studies (f-MRI) from March 2004 and December 2019, suspicious of congenital renal disease. Fetuses that met the criteria for ARPKD were selected. RESULTS: Six cases were diagnosed as ARPKD (2.8%). The median gestational age at MRI examination was 28 weeks (24-36 weeks). IBDED was observed in 84% of cases. Moreover, 66% presented multilobar liver lesions, and 33% exhibited monolobar lesions. The "central dot sign" (CDS) was found in half of the cases. CONCLUSION: In this case series of prenatal diagnosis of ARPKD using f-MRI, IBDED was present in the majority of the cases, and the CDS was noted in half of the cases.

[Clinical feature and genetic analysis of a fetus with autosomal recessive polycystic kidney disease].

OBJECTIVE: To explore the genetic etiology of a fetus with autosomal recessive polycystic kidney disease (ARPKD). METHODS: Prenatal ultrasonography has revealed oligohydramnios and abnormal structure of fetal kidneys. After careful counseling, the couple opted induced abortion. With informed consent, genomic DNA was extracted from the muscle sample of the abortus and peripheral blood samples of the couple. High throughput whole exome sequencing was carried out to detect potential variants in relation with the disease. Suspected variants were verified by Sanger sequencing. RESULTS: Prenatal ultrasound revealed increased size of fetal kidneys, with multiple hyperechos from the right kidney, and multiple hyperechos with anechoic masses within the left kidney. DNA sequencing revealed that the fetus has carried heterozygous variants of the PKHD1 gene, including c.7994T>C inherited from its father, and two heterozygous variants of the PKHD1 gene c.5681G>A from its mother. CONCLUSION: The compound heterozygous c.7994T>C and c.5681G>A variants of the PKHD1 gene probably underlay the pathogenesis of ARPKD in this fetus. Above results can provide guidance for subsequent pregnancies of the couple.

Neonatal polycystic kidney disease: a novel variant.

Polycystic kidney disease (PKD) is a condition typified by multiple renal cysts and renal enlargement. Classification is usually determined by mode of inheritance-autosomal dominant PKD (ADPKD) or autosomal recessive PKD (ARPKD). ARPKD frequently presents in fetal life, but here we report a rare case of a family with two siblings diagnosed with ADPKD manifesting in utero with novel genetic findings. During the first pregnancy, enlarged cystic kidneys were noted at the gestational age (GA) of 18 weeks, which became progressively larger and anyhdramnios ensued by GA of 25 weeks. The couple opted to terminate the pregnancy. The second pregnancy similarly presented with bilateral enlarged cystic kidneys, but amniotic fluid remained normal throughout and she delivered at GA of 36 weeks. Genetic testing revealed the fetus to be heterozygous in AD PKD1, which is known to cause ADPKD and heterozygous for a hypomorphic allele for ADPKD of uncertain significance. The fetus was also found to be heterozygous in the AR PKHD1 gene with a variant not previously described in the literature. Where fetal features consistent with ARPKD are identified in the setting of familial ADPKD, this fetal manifestation of ADPKD, resulting from combined variants in the PKD1 gene, should be considered.

[Diagnosis of a case of autosomal recessive polycystic kidney disease with combined prenatal imaging and genetic testing].

OBJECTIVE: To explore the genetic basis for a fetus with renal abnormalities through whole exome sequencing and imaging examination. METHODS: Clinical data and result of medical imaging of the fetus was collected. Amniotic fluid sample was collected for the extraction of fetal DNA. Whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Prenatal ultrasonography showed that the fetus had bilateral enlargement of the kidneys with hyperechogenicity and diffuse renal cysts. Whole exome sequencing revealed that the fetus carried compound heterozygous variants of the PKHD1 gene, namely c.5137G>T and c.2335_2336delCA, which were derived from its mother and father, respectively. CONCLUSION: The fetus was diagnosed with autosomal recessive polycystic kidney disease through combined prenatal ultrasonography and whole exome sequencing. The compound heterozygous variants of the PKHD1 gene probably underlay the pathogenesis in the fetus. The results have enabled prenatal diagnosis and genetic counseling for its parents.

Two-dimensional (2D) morphologic measurements can quantify the severity of liver disease in children with autosomal recessive polycystic kidney disease (ARPKD).

PURPOSE: To evaluate the correlation of 2D shape-based features with magnetic resonance elastography (MRE)-derived liver stiffness and portal hypertension (pHTN) in children with ARPKD-associated congenital hepatic fibrosis. METHODS: In a prospective IRB-approved study, 14 children with ARPKD (mean age ± SD = 13.8 ± 5.8 years) and 14 healthy controls (mean age ± SD = 13.7 ± 3.9 years) underwent liver MRE. A 2D region of interest (ROI) outlining the left liver lobe at the level of the abdominal aorta was drawn on sagittal T2-weighted images. Eight shape features (perimeter, major axis length, maximum diameter, perimeter to surface ratio (PSR), elongation, sphericity, minor axis length, and mesh surface) describing the 2D-ROI were calculated. Spearman's correlation was calculated between shape features and MRE-derived liver stiffness (kPa) (n = 28). Shape features were compared between participants with ARPKD with pHTN (splenomegaly and thrombocytopenia), (n = 4) and without pHTN (n = 8) using the Mann Whitney U test. Receiver operating characteristic (ROC) curves were generated to examine the diagnostic accuracy of shape features in identifying cases with liver stiffness > 2.9 kPa. RESULTS: In ARPKD participants and healthy controls, all eight shape features, except elongation, showed moderate to strong correlation with liver stiffness (kPa); the perimeter surface ratio had the strongest correlation (rho = - 0.75, p < 0.001). In ROC analysis, a cut-off of PSR ≤ 0.057 mm-1 gave 100% (95% CI: 59.0-100.0) sensitivity and 100% (95% CI: 83.9-100.0) specificity in identifying ARPKD participants with liver stiffness > 2.9 kPa, with an area under the ROC curve (AUC) of 1.0 (95% CI: 0.88-1.00). Individuals with pHTN had a lower median PSR (mean ± SD = 0.05 ± 0.01) than those without (0.07 ± 0.01; p = 0.027) with an AUC of 0.91 (95% CI: 0.60-0.99) in differentiating the participants with and without pHTN. CONCLUSION: Shape-based features of the left liver lobe show potential as non-invasive biomarkers of liver fibrosis and portal hypertension in children with ARPKD.

Rapid B1-Insensitive MR Fingerprinting for Quantitative Kidney Imaging.

Background MR fingerprinting (MRF) provides rapid and simultaneous quantification of multiple tissue parameters in a single scan. Purpose To evaluate a rapid kidney MRF technique at 3.0 T in phantoms, healthy volunteers, and patients. Materials and Methods A 15-second kidney MRF acquisition was designed with 12 acquisition segments, a range of low flip angles (5°-12°), multiple magnetization preparation schema (T1, T2, and fat suppression), and an undersampled spiral trajectory. This technique was first validated in vitro using standardized T1 and T2 phantoms. Kidney T1 and T2 maps were then obtained for 10 healthy adult volunteers (mean age ± standard deviation, 35 years ± 13; six men) and three pediatric patients with autosomal recessive polycystic kidney disease (ARPKD) (mean age, 10 years ± 3; two boys) between August 2019 and October 2020 to evaluate the method in vivo. Results Results in nine phantoms showed good agreement with spin-echo-based T1 and T2 values (R2 > 0.99). In vivo MRF kidney T1 and T2 assessments in healthy adult volunteers (cortex: T1, 1362 msec ± 5; T2, 64 msec ± 5; medulla: T1, 1827 msec ± 94; T2, 69 msec ± 3) were consistent with values in the literature but with improved precision in comparison with prior MRF implementations. In vivo MRF-based kidney T1 and T2 values with and without B1 correction were in good agreement (R2 > 0.96, P < .001), demonstrating limited sensitivity to B1 field inhomogeneities. Additional MRF reconstructions using the first nine segments of the MRF profiles (11-second acquisition time) were in good agreement with the reconstructions using 12 segments (15-second acquisition time) (R2 > 0.87, P < .001). Repeat kidney MRF scans for the three patients with ARPKD on successive days also demonstrated good reproducibility (T1 and T2: <3% difference). Conclusion A kidney MR fingerprinting method provided in vivo kidney T1 and T2 maps at 3.0 T in a single breath hold with improved precision and no need for B1 correction. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Laustsen in this issue.

Infant presenting with pyloric stenosis and autosomal recessive polycystic kidney disease at 36 weeks' postmenstrual age (PMA).

This case report describes a premature male infant born after a pregnancy complicated by oligohydramnios of unknown aetiology but otherwise unremarkable prenatal scans. He had sudden onset of projectile emesis and severe hypertension in the third week of life, and further investigations revealed both pyloric stenosis and polycystic kidneys, at just 36 weeks' postmenstrual age (PMA). His course thereafter was complicated by severe refractory hypertension requiring multiple antihypertensive agents in order to gain control, although his renal function remained normal. Few case reports have previously described this unusual association, but none have presented with both entities at such an early PMA.

Bladder Agenesis and Bilateral Ectopic Ureters in an Infant Male With Cystic Renal Dysplasia, Imperforate Anus, and Penoscrotal Transposition.

Bladder agenesis is a rare congenital anomaly infrequently reported in the literature, with an incidence of 1/600,000 patients.1 Commonly associated with other fatal malformations, the condition is often incompatible with life.2 Prior reports estimate that over 90% of living children born with this malformation are female, owing to renal preservation resulting from low pressure drainage of urine into the vagina, uterus, and vestibule.3,4 Herein we report a rare case of an infant male born with penoscrotal transposition and end stage renal disease secondary to bilateral cystic renal dysplasia found to have concurrent bladder agenesis and bilateral ureteral ectopia.

Predictors of progression in autosomal dominant and autosomal recessive polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are characterized by bilateral cystic kidney disease leading to progressive kidney function decline. These diseases also have distinct liver manifestations. The range of clinical presentation and severity of both ADPKD and ARPKD is much wider than was once recognized. Pediatric and adult nephrologists are likely to care for individuals with both diseases in their lifetimes. This article will review genetic, clinical, and imaging predictors of kidney and liver disease progression in ADPKD and ARPKD and will briefly summarize pharmacologic therapies to prevent progression.

A case of TSC2-PKD1 contiguous deletion syndrome: Clinical features and effective treatment for epilepsy.

Polycystic kidney disease with Tuberous sclerosis is a disease caused by the deletions of the TSC2-PKD1 gene. The disease is rarely reported and the characterized manifestation is severe polycystic kidney growth. The diagnosis can be made by molecular analysis. We report the first case of PKDTS discovered in infancy in China with typical neurological and renal manifestations. The patient has infantile spasm, polycystic kidney, skin damage, hypertension, and hematuria after infection. After effective treatment of Rapamycin, the seizures were completely controlled. There was not been any renal function damage in the patient. At the same time, we review the related literature and further elaborate on the variety of clinical manifestations, treatment, and prognosis.

Multi-parametric MRI of kidney disease progression for autosomal recessive polycystic kidney disease: mouse model and initial patient results.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare but potentially lethal genetic disorder typically characterized by diffuse renal microcysts. Clinical trials for patients with ARPKD are not currently possible due to the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy. METHODS: In this study, animal and human magnetic resonance imaging (MRI) scanners were used to obtain quantitative kidney T1 and T2 relaxation time maps for both excised kidneys from bpk and wild-type (WT) mice as well as for a pediatric patient with ARPKD and a healthy adult volunteer. RESULTS: Mean kidney T1 and T2 relaxation times showed significant increases with age (p < 0.05) as well as significant increases in comparison to WT mice (p < 2 × 10-10). Significant or nearly significant linear correlations were observed for mean kidney T1 (p = 0.030) and T2 (p = 0.054) as a function of total kidney volume, respectively. Initial magnetic resonance fingerprinting assessments in a patient with ARPKD showed visible increases in both kidney T1 and T2 in comparison to the healthy volunteer. CONCLUSIONS: These preclinical and initial clinical MRI studies suggest that renal T1 and T2 relaxometry may provide an additional outcome measure to assess cystic kidney disease progression in patients with ARPKD. IMPACT: A major roadblock for implementing clinical trials in patients with ARPKD is the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy. A clinical need exists to develop a safe and sensitive measure for kidney disease progression, and eventually therapeutic efficacy, for patients with ARPKD. Mean kidney T1 and T2 MRI relaxation times showed significant increases with age (p < 0.05) as well as significant increases in comparison to WT mice (p < 2 ×10-10), indicating that T1 and T2 may provide sensitive assessments of cystic changes associated with progressive ARPKD kidney disease. This preclinical and initial clinical study suggests that MRI-based kidney T1 and T2 mapping could be used as a non-invasive assessment of ARPKD kidney disease progression. These non-invasive, quantitative MRI techniques could eventually be used as an outcome measure for clinical trials evaluating novel therapeutics aimed at limiting or preventing ARPKD kidney disease progression.

Magnetic resonance elastography to quantify liver disease severity in autosomal recessive polycystic kidney disease.

OBJECTIVES: To evaluate whether liver and spleen magnetic resonance elastography (MRE) can measure the severity of congenital hepatic fibrosis (CHF) and portal hypertension (pHTN) in individuals with autosomal recessive polycystic kidney disease (ARPKD), and to examine correlations between liver MRE and ultrasound (US) elastography. METHODS: Cross-sectional study of nine individuals with ARPKD and 14 healthy controls. MRE was performed to measure mean liver and spleen stiffness (kPa); US elastography was performed to measure point shear wave speed (SWS) in both liver lobes. We compared: (1) MRE liver and spleen stiffness between controls vs. ARPKD; and (2) MRE liver stiffness between participants with ARPKD without vs. with pHTN, and examined correlations between MRE liver stiffness, spleen length, platelet counts, and US elastography SWS. Receiver operating characteristic (ROC) analysis was performed to examine diagnostic accuracy of liver MRE. RESULTS: Participants with ARPKD (median age 16.8 [IQR 13.3, 18.9] years) had higher median MRE liver stiffness than controls (median age 14.7 [IQR 9.7, 16.7 years) (2.55 vs. 1.92 kPa, p = 0.008), but MRE spleen stiffness did not differ. ARPKD participants with pHTN had higher median MRE liver stiffness than those without (3.60 kPa vs 2.49 kPa, p = 0.05). Liver MRE and US elastography measurements were strongly correlated. To distinguish ARPKD vs. control groups, liver MRE had 78% sensitivity and 93% specificity at a proposed cut-off of 2.48 kPa [ROC area 0.83 (95% CI 0.63-1.00)]. CONCLUSION: Liver MRE may be a useful quantitative method to measure the severity of CHF and pHTN in individuals with ARPKD.

Use of patient derived urine renal epithelial cells to confirm pathogenicity of PKHD1 alleles.

BACKGROUND: PKHD1 is the main genetic cause of autosomal recessive polycystic kidney disease (ARPKD), a hereditary hepato-renal fibrocystic disorder which is the most important cause of end-stage renal disease during early childhood. ARPKD can also present in adulthood with milder phenotypes. In this study, we describe a 24-year-old woman with atypical polycystic kidney, no family history of renal disease and no obvious extra-renal manifestations who was referred for genetic investigation. METHODS: We used a combination of next generation sequencing, Sanger sequencing and RNA and microscopy studies performed on urine-derived renal epithelial cells (URECs) to provide a genetic diagnosis of ARPKD. RESULTS: A next generation sequencing panel of cystic ciliopathy genes allowed the identification of two heterozygous sequence changes in PKHD1 (c.6900C > T; p.(Asn2300=) and c.7964A > C; p.(His2655Pro)). The pathogenicity of the synonymous PKHD1 variant is not clear and requires RNA studies, which cannot be carried out efficiently on RNA extracted from proband blood, due to the low expression levels of PKHD1 in lymphocytes. Using URECs as a source of kidney-specific RNA, we show that PKHD1 is alternatively spliced around exon 43, both in control and proband URECs. The variant p.(Asn2300=) shifts the expression ratio in favour of a shorter, out-of-frame transcript. To further study the phenotypic consequence of these variants, we investigated the ciliary phenotype of patient URECs, which were abnormally elongated and presented multiple blebs along the axoneme. CONCLUSIONS: We confirm the power of URECs as a tool for functional studies on candidate variants in inherited renal disease, especially when the expression of the gene of interest is restricted to the kidney and we describe, for the first time, ciliary abnormalities in ARPKD patient cells.

Giant choledochal cyst and infantile polycystic kidneys as prenatal sonographic features of Caroli syndrome.

Caroli syndrome is a developmental disorder caused by complete or partial arrest of ductal plate remodeling, leading to dilated bile ducts along with fibrosis surrounding the portal tracts. It is most commonly associated with autosomal recessive polycystic kidney (ARPKD). We report a unique case of Caroli syndrome, diagnosed prenatally at 24 weeks of gestation in a 29-year-old Thai woman. Ultrasound findings revealed the association of a fetal giant choledochal cyst with ARPKD. Autopsy findings showed ductal plate malformation, typical of Caroli syndrome, associated with giant choledocal cyst and ARPKD.

Management of delivery of a fetus with autosomal recessive polycystic kidney disease: a case report of abdominal dystocia and review of the literature.

BACKGROUND: Autosomal recessive renal polycystic kidney disease occurs in 1 in 20,000 live births. It is caused by mutations in both alleles of the PKHD1 gene. Management of delivery in cases of suspected autosomal recessive renal polycystic kidney disease is rarely discussed, and literature concerning abdominal dystocia is extremely scarce. We present a case of a patient with autosomal recessive renal polycystic kidney disease whose delivery was complicated by abdominal dystocia, and we discuss the factors that determined the route and timing of delivery. CASE PRESENTATION: A 23-year-old Caucasian woman, G2 P0, with a prior unremarkable pregnancy was referred to our tertiary center at 31 weeks of gestation because of severe oligoamnios (amniotic fluid index = 2) and hyperechogenic, dedifferentiated, and enlarged fetal kidneys. She had no other genitourinary anomaly. Fetal magnetic resonance imaging showed enlarged, hypersignal kidneys and severe pulmonary hypoplasia. We had a high suspicion of autosomal recessive renal polycystic kidney disease, and after discussion with our multidisciplinary team, the parents opted for conservative care. Ultrasound performed at 35 weeks of gestation showed a fetal estimated weight of 3550 g and an abdominal circumference of 377 mm, both above the 90th percentile. Because of the very rapid kidney growth and suspected risk of abdominal dystocia, we proposed induction of labor at 36 weeks of gestation after corticosteroid administration for fetal lung maturation. Vaginal delivery was complicated by abdominal dystocia, which resolved by continuing expulsive efforts and gentle fetal traction. A 3300-g (P50-90) male infant was born with Apgar scores of 1-7-7 at 1, 5, and 10 minutes, respectively, and arterial and venous umbilical cord pH values of 7.23-7.33. Continuous peritoneal dialysis was started at day 2 of life because of anuria. Currently, the infant is 1 year old and is waiting for kidney transplant that should be performed once he reaches 10 kg. Molecular analysis of PKHD1 performed on deoxyribonucleic acid (DNA) from the umbilical cord confirmed autosomal recessive renal polycystic kidney disease. CONCLUSIONS: Management of delivery in cases of suspected autosomal recessive renal polycystic kidney disease needs to be discussed because of the risk of abdominal dystocia. The route and timing of delivery depend on the size of the fetal abdominal circumference and the gestational age. The rate of kidney growth must also be taken into account.

A teenage patient with autosomal recessive polycystic kidney disease, a splenorenal shunt, and congenital hepatic fibrosis: a case report / Doença renal policística autossômica recessiva, shunt esplenorrenal e fibrose hepática congênita em adolescente: relato de caso

ABSTRACT A 16-year-old female patient previously diagnosed with autosomal recessive polycystic kidney disease (ARPKD) presented with acute bilateral pneumonia, upper gastrointestinal bleeding caused by ruptured esophageal varices, ascites, and lower limb edema. She required intensive care and an endoscopic procedure to treat the gastrointestinal bleeding. The analysis of the differential diagnosis for chronic liver disease indicated she had a spontaneous splenorenal shunt. Ultrasound-guided biopsy revealed the patient had cirrhosis, as characteristically seen in individuals with ARPKD. She had no symptoms at discharge and was referred for review for a combined transplant.

RESUMO Relato de caso de uma paciente adolescente de 16 anos de idade com diagnóstico prévio de doença renal policística autossômica recessiva (DRPAR), que apresentou quadro agudo de pneumonia bilateral e hemorragia digestiva alta por ruptura de varizes esofágicas, bem como ascite e edema de membros inferiores. Necessitou de estabilização clínica intensiva e tratamento endoscópico do sangramento digestivo. Após investigação dos diagnósticos diferenciais da hepatopatia crônica, diagnosticou-se shunt esplenorrenal espontâneo, e realizou-se biópsia hepática guiada por ecografia com diagnóstico de cirrose, espectro típico da DRPAR. Recebeu alta hospitalar assintomática e foi encaminhada para avaliação de transplante duplo.

Ultrasound Elastography to Quantify Liver Disease Severity in Autosomal Recessive Polycystic Kidney Disease.

OBJECTIVES: To evaluate the diagnostic accuracy of ultrasound elastography with acoustic radiation force impulse (ARFI) to detect congenital hepatic fibrosis and portal hypertension in children with autosomal recessive polycystic kidney disease (ARPKD). STUDY DESIGN: Cross-sectional study of 25 children with ARPKD and 24 healthy controls. Ultrasound ARFI elastography (Acuson S3000, Siemens Medical Solutions USA, Inc, Malvern, Pennsylvania) was performed to measure shear wave speed (SWS) in the right and left liver lobes and the spleen. Liver and spleen SWS were compared in controls vs ARPKD, and ARPKD without vs with portal hypertension. Linear correlations between liver and spleen SWS, spleen length, and platelet counts were analyzed. Receiver operating characteristic analysis was used to evaluate diagnostic accuracy of ultrasound ARFI elastography. RESULTS: Participants with ARPKD had significantly higher median liver and spleen SWS than controls. At a proposed SWS cut-off value of 1.56 m/s, the left liver lobe had the highest sensitivity (92%) and specificity (96%) for distinguishing participants with ARPKD from controls (receiver operating characteristic area 0.92; 95% CI 0.82-1.00). Participants with ARPKD with portal hypertension (splenomegaly and low platelet counts) had significantly higher median liver and spleen stiffness than those without portal hypertension. The left liver lobe also had the highest sensitivity and specificity for distinguishing subjects with ARPKD with portal hypertension. CONCLUSIONS: Ultrasound ARFI elastography of the liver and spleen, particularly of the left liver lobe, is a useful noninvasive biomarker to detect and quantify liver fibrosis and portal hypertension in children with ARPKD.