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

Abstract

Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of chronic kidney disease in children. The care of ARPKD patients has traditionally been the realm of pediatric nephrologists; however, the disease has multisystem effects, and a comprehensive care strategy often requires a multidisciplinary team. Most notably, ARPKD patients have congenital hepatic fibrosis, which can lead to portal hypertension, requiring close follow-up by pediatric gastroenterologists. In severely affected infants, the diagnosis is often first suspected by obstetricians detecting enlarged, echogenic kidneys and oligohydramnios on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. Surgical considerations can include the possibility of nephrectomy to relieve mass effect, placement of dialysis access, and kidney and/or liver transplantation. Families of patients with ARPKD also face decisions regarding genetic testing of affected children, testing of asymptomatic siblings, or consideration of preimplantation genetic diagnosis for future pregnancies. They may therefore interface with genetic counselors, geneticists, and reproductive endocrinologists. Children with ARPKD may also be at risk for neurocognitive dysfunction and may require neuropsychological referral. The care of patients and families affected by ARPKD is therefore a multidisciplinary effort, and the general pediatrician can play a central role in this complex web of care. In this review, we outline the spectrum of clinical manifestations of ARPKD and review genetics of the disease, clinical and genetic diagnosis, perinatal management, management of organ-specific complications, and future directions for disease monitoring and potential therapies.

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

“…1 It is caused by mutations in PKHD1, although mutations in other ciliary disease genes may phenocopy the disorder. 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).…”

A Rare Cause of Polyuria and Polydipsia in a Patient With Cystic Renal Disease: Maturity-Onset Diabetes of the Young Type 5

“…Given increased kidney size, multiple cysts with significant renal failure and the absence of family history suggested a diagnosis of ARPKD [2,10,11]. However, the size of kidneys which are not enlarged relative to body size, the lack of hepatic fibrosis and portal hypertension during the follow-up mainly by ultrasound in our patient was puzzling.…”

“…In ARPKD macrocysts are not routinely present at birth and kidney size stabilizes or may decrease over time and these patients do not show progressive macrocystic enlargement as in ADPKD. In addition, some patients may lack specific symptoms and results of imaging studies and liver tests may be in the normal range [10][11][12]. Although diabetes was diagnosed in our patient at second decade, further findings of endogenous insulin secretion (lowdose insulin requirement) and the absence of autoantibodies for diabetes and cystic kidneys prompted consideration of the diagnosis of MODY [8].…”

Bases moleculares e celulares das nefropatias hereditárias císticas

“…Ocorre em uma frequência estimada de 1 para 20000 nascidos vivos, porém a existência de casos graves acompanhados de óbito fetal sugere uma incidência maior 26 . Esta doença fibrocística apresenta um espectro clínico bastante variável, incluindo desde fenótipo neonatal grave até formas mais brandas de manifestações tardias.…”

“…A FHC progride ao longo do tempo, podendo levar à hipertensão portal grave. Como consequência, os pacientes podem apresentar inversão do fluxo hepatoportal, esplenomegalia e varizes de esôfago e do fundo gástrico 26 . Cerca de dois terços dos pacientes apresentam HAS, geralmente de início precoce e muitas vezes de controle difícil.…”