Early clinical management of autosomal recessive polycystic kidney disease

Abstract

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but highly relevant disorder in pediatric nephrology. This genetic disease is mainly caused by variants in the PKHD1 gene and is characterized by fibrocystic hepatorenal phenotypes with major clinical variability. ARPKD frequently presents perinatally, and the management of perinatal and early disease symptoms may be challenging. This review discusses aspects of early manifestations in ARPKD and its clincial management with a special focus on kidney disease.

Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease

“…Typically, the most severe cases of ARPKD present in the late gestational or neonatal stage, with bilateral massively enlarged and echogenic kidneys with poor corticomedullary differentiation, retained reniform contour, and multiple tiny cysts [ 8 , 9 , 10 ]. In addition, they can present with oligo- or anhydramnios, resulting in the typical “Potter sequence” phenotype with pulmonary hypoplasia, characteristic facial features, and clubfoot contracted limbs [ 9 , 11 , 12 ]. In addition to the Potter sequence, the presence of other extrarenal manifestations is not common [ 13 ].…”

“…Note that prenatal diagnosis and termination of pregnancy are factors to consider in the epidemiology of the disease [ 15 , 17 ]. Another problem derived from kidney enlargement and pulmonary hypoplasia, in addition to early uremia and pulmonary immaturity, includes the difficulty of enteral feeding that could complicate nutrition, requiring persistent nasogastric feeding [ 11 , 18 ].…”

“…In most cases, the severe problem of ARPKD during the first few months of life is arterial hypertension, which requires treatment with multiple classes of pharmacological interventions. Tight blood pressure control is crucial to prevent further kidney damage from hypertension [ 11 , 12 ]. However, renal failure is not a very common cause of neonatal demise [ 19 ].…”

“…Kidney enlargement is due to extensive dilatations of the distal nephron, typically in the collecting duct. As the disease progresses, the kidney structure gradually resembles the pattern seen in ADPKD with renal macrocysts of different size and appearance, often accompanied by interstitial fibrosis [ 11 , 20 , 21 ]. This situation leads to almost 50% of end-stage renal disease (ESRD) in the first decades of life, requiring renal replacement therapy [ 9 , 14 , 17 ].…”

Is There a Functional Role of Mitochondrial Dysfunction in the Pathogenesis of ARPKD?

“…Typically, the kidneys show bilateral massive enlargement although they keep their reniform shape. Kidney disease results in a need for kidney replacement therapy (KRT) in around 50% of patients in the first two decades of life (2,3). Liver involvement is obligatory in ARPKD, typically presenting with congenital hepatic fibrosis and portal hypertension or with dilated bile ducts.…”