Autosomal Recessive Polycystic Kidney Disease—The Clinical Aspects and Diagnostic Challenges

Abstract

Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common ciliopathies with kidney (nephromegaly, hypertension, renal dysfunction) and liver involvement (congenital hepatic fibrosis, dilated bile ducts). Clinical features also include growth failure and neurocognitive impairment. Plurality of clinical aspects requires multidisciplinary approach to treatment and care of patients. Until recently, diagnosis was based on clinical criteria. Results of genetic testing show the molecular basis of polycystic kidneys disease is heterogeneous, and differential diagnosis is essential. The aim of the article is to discuss the role of genetic testing and its difficulties in diagnostics of ARPKD in children.

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

“…These clinical trials are expected to provide data on the safety, tolerability, and efficacy of tolvaptan treatment and determinants of progression in ARPKD. The genetic data collected may improve the ability to diagnose and predict the course of ARPKD, which are challenging given the genetic complexity of the disease [ 5 , 12 , 33 ].…”

“…Feeding difficulties may arise from compression of the stomach by enlarged organs or from the effects of kidney function impairment on appetite and/or gastric motility. Inadequate nutrition, in conjunction with risk factors such as prematurity, low birth weight, repeated hospitalization, early onset CKF, chronic hypertension, and lung disease, increase the likelihood for impaired growth and neurocognitive deficits [ 5 ].…”

“…Autosomal recessive polycystic kidney disease (ARPKD) is a rare, inherited condition that occurs in approximately 1 in 25,000 births and is caused in most cases by pathogenic variants in the PKHD1 gene [1][2][3]. Characteristic features are the formation and growth of cysts in the distal tubules and collecting ducts of the kidney in utero, massive kidney enlargement, congenital hepatic fibrosis, and anomalies of the intrahepatic biliary ducts [4,5]. Patients with the most aggressive phenotypes are at risk of death in the neonatal period from respiratory insufficiency due to pulmonary hypoplasia [1,[6][7][8].…”

“…Patients with the most aggressive phenotypes are at risk of death in the neonatal period from respiratory insufficiency due to pulmonary hypoplasia [1,[6][7][8]. Disease manifestations among children with less aggressive phenotypes include arterial hypertension, chronic lung disease, continued kidney enlargement, progression to chronic kidney failure (CKF) with dialysis in early life, worsening hepatic fibrosis, portal hypertension, recurrent cholangitis, and need for kidney, liver, or combined kidney-liver transplantation, which impose a heavy health burden and negative consequences for quality of life [4,5,9]. Feeding difficulties may arise from compression of the stomach by enlarged organs or from the effects of kidney function impairment on appetite and/ or gastric motility.…”

Feline Polycystic Kidney Disease: An Update

“…For example, a clinical case was described in six kittens that died at seven weeks of age, in which the necropsy revealed the presence of renal and bile duct cysts, undiagnosed by the young age of the animals [30]. Recent studies in human medicine reveal high genetic and clinical heterogeneity of this disease [31]. Thus, although now only the PKD1 gene has been identified as the cause of the disease in cats, several studies found cases of animals with kidney cysts and a wild-type genotype of the PKD1 gene.…”