Consensus Expert Recommendations for the Diagnosis and Management of Autosomal Recessive Polycystic Kidney Disease: Report of an International Conference

Abstract

Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) is a severe, typically early onset form of cystic disease that primarily involves the kidneys and biliary tract. Phenotypic expression and age at presentation can be quite variable1. The incidence of ARPKD is 1 in 20,000 live births2, and its pleotropic manifestations are potentially life-threatening. Optimal care requires proper surveillance to limit morbidity and mortality, knowledgeable approaches to diagnosis and treatment, and informed strategies to optimize quality of life. Clinical management therefore is ideally directed by multidisciplinary care teams consisting of perinatologists, neonatologists, nephrologists, hepatologists, geneticists, and behavioral specialists to coordinate patient care from the perinatal period to adulthood. In May 2013, an international team of 25 multidisciplinary specialists from the US, Canada, Germany, and the United Kingdom convened in Washington, DC, to review the literature published from 1990 to 2013 and to develop recommendations for diagnosis, surveillance, and clinical management. Identification of the gene PKHD1, and the significant advances in perinatal care, imaging, medical management, and behavioral therapies over the past decade, provide the foundational elements to define diagnostic criteria and establish clinical management guidelines as the first steps towards standardizing the clinical care for ARPKD patients. The key issues discussed included recommendations regarding perinatal interventions, diagnostic criteria, genetic testing, management of renal and biliary-associated morbidities, and behavioral assessment. The meeting was funded by the National Institutes of Health and an educational grant from the Polycystic Kidney Disease Foundation. Here we summarize the discussions and provide an updated set of diagnostic, surveillance, and management recommendations for optimizing the pediatric care of patients with ARPKD. Specialist care of ARPKD-related complications including dialysis, transplantation, and management of severe portal hypertension will be addressed in a subsequent report. Given the paucity of information regarding targeted therapies in ARPKD, this topic was not addressed in this conference.”

Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2

“…In contrast, about 30-40% of patients with ARPKD die in the neonatal period from complications of oligohydramnios. 4 Liver involvement is an obligate aspect of ARPKD and the presence of liver manifestations initially seemed to support a diagnosis of ARPKD in our patients. Liver abnormalities on imaging were noted in 8 patients, mostly showing scattered cysts and/or a heterogeneous echotexture.…”

“…2,3 Causative mutations are identified in approximately 85% of cases. 4 Here we investigated patients with an ARPKD-like clinical presentation that were genetically unsolved and prominently characterized by a concurrent clinical diagnosis of hyperinsulinemic hypoglycemia (HI). HI in itself is also a rare disorder with an estimated incidence of 1:50000 and most commonly associated with mutations in the ABCC8 and KCNJ11 genes involved in the regulation of insulin release from pancreatic β-cells.…”

Cystic Kidney Disease: A Primer

“…Although the pathophysiology of underlying hypertension is unclear, at least 1 study demonstrates intrarenal Renin-angiotensin-aldosterone system activation. 4 Infants often have hyponatremia, presumably because of defects in free water excretion. 4 Most ARPKD patients progress to ESRD, although the age of onset is variable.…”

“…4 Infants often have hyponatremia, presumably because of defects in free water excretion. 4 Most ARPKD patients progress to ESRD, although the age of onset is variable. The kidney survival rate of 1 large cohort of neonatal survivors was 86% at 5 years and decreased to 42% at 20 years.…”

Early and Severe Polycystic Kidney Disease and Related Ciliopathies: An Emerging Field of Interest

“…In addition to fibrocystic renal changes, affected individuals often present with extra-renal manifestations [1].…”