ARPKD

Polycystic kidney diseases (PKDs) are genetic disorders characterized by the formation and expansion of numerous fluid-filled renal cysts, damaging normal parenchyma, and often leading to kidney failure (KF). Although, PKDs comprise a broad range of different diseases, with substantial genetic and phenotypic heterogeneity, an association with primary cilia represents a common theme. Great strides have been made in the identification of causative genes, furthering our understanding of the genetic complexity and disease mechanisms, but only one therapy so far has shown success in clinical trials and advanced to FDA approval...

Polycystic Kidney Diseases (PKDs) consist of a genetically and phenotypically heterogeneous group of inherited disorders characterized by numerous renal cysts. PKDs include autosomal dominant ADPKD, autosomal recessive ARPKD and atypical forms. Here, we analyzed 255 Italian patients using an NGS panel of 63 genes, plus Sanger sequencing of exon 1 of the PKD1 gene and MPLA ( PKD1, PKD2 and PKHD1 ) analysis. Overall, 167 patients bore pathogenic/likely pathogenic variants in dominant genes, and 5 patients in recessive genes...

Autosomal recessive polycystic kidney disease (ARPKD) is caused primarily by mutations in PKHD1, encoding fibrocystin (FPC), but Pkhd1 mutant mice failed to reproduce the human phenotype. In contrast, the renal lesion in congenital polycystic kidney (cpk) mice, with a mutation in Cys1 and cystin protein loss, closely phenocopies ARPKD. Although the nonhomologous mutation diminished the translational relevance of the cpk model, recent identification of patients with CYS1 mutations and ARPKD prompted the investigations described herein...

INTRODUCTION: Renal ciliopathies represent a collection of genetic disorders characterized by deficiencies in the biogenesis, maintenance, or functioning of the ciliary complex. These disorders, which encompass autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), and nephronophthisis (NPHP), typically result in cystic kidney disease, renal fibrosis, and a gradual deterioration of kidney function, culminating in kidney failure. AREAS COVERED: Here we review the advances in basic science and clinical research into ciliopathies which have yielded promising small compounds and drug targets, within both preclinical studies and clinical trials...

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a significant cause of morbidity and mortality in infants and children. In severe cases bilateral nephrectomies are considered but may be associated with significant neurological complications and life-threatening hypotension. CASE PRESENTATION: We describe a case of a 17 months old boy with genetically confirmed ARPKD who underwent sequential bilateral nephrectomies at the age of 4 and 10 months...

Autosomal dominant (ADPKD) and autosomal recessive (ARPKD) polycystic kidney disease are the most widely known cystic kidney diseases. They are significantly different from each other in terms of genetics and clinical manifestations. Hypertension is one of the main symptoms in both diseases, but the age of onset and secondary cardiovascular complications are significantly different. Most ARPKD children are hypertensive in the first year of life and need high doses of hypertensive drugs. ADPKD patients with a very early onset of the disease (VEOADPKD ) develop hypertension similarly to patients with ARPKD...

Mechanosensitive TRPV4 channel plays a dominant role in maintaining [Ca2+ ]i homeostasis and flow-sensitive [Ca2+ ]i signaling in the renal tubule. Polycystic kidney disease (PKD) manifests as progressive cyst growth due to cAMP-dependent fluid secretion along with deficient mechanosensitivity and impaired TRPV4 activity. Here, we tested how regulation of renal TRPV4 function by dietary K+ intake modulates the rate of cystogenesis and mechanosensitive [Ca2+ ]i signaling in cystic cells of PCK453 rats, a homologous model of human autosomal recessive PKD (ARPKD)...

We present a fetus with bilaterally enlarged and echogenic kidneys. Prenatal testing detected compound heterozygosity for a 0.676 Mb de novo deletion and an inherited pathogenic variant in PKHD1 . This is the first case of autosomal recessive polycystic kidney disease (ARPKD) with a prenatally detected disease-causing PKHD1 deletion.

(1) Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy characterized by progressively enlarged kidneys with fusiform dilatation of the collecting ducts. Loss-of-function mutations in the PKHD1 gene, which encodes fibrocystin/polyductin, cause ARPKD; however, an efficient treatment method and drug for ARPKD have yet to be found. Antisense oligonucleotides (ASOs) are short special oligonucleotides which function to regulate gene expression and alter mRNA splicing. Several ASOs have been approved by the FDA for the treatment of genetic disorders, and many are progressing at present...

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...

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a highly aggressive type of extranodal non-Hodgkin lymphoma, of which approximately 90% of the cases are diffuse large B-cell lymphoma (DLBCL). In recent years, the incidence of PCNSL has significantly increased in women and older men. Although advanced treatments such as high-dose methotrexate (HD-MTX) and targeted agents have been introduced, the prognosis of these patients remains poorer than those with other forms of non-Hodgkin's lymphoma...

Congenital hepatic fibrosis / Autosomal recessive polycystic kidney disease (CHF/ARPKD) is an inherited neonatal disease induced by mutations in the PKHD1 gene and characterized by cysts, and robust pericystic fibrosis in liver and kidney. The PCK rat is an excellent animal model which carries a Pkhd1 mutation and exhibits similar pathophysiology. We performed RNA-Seq analysis on liver samples from PCK rats over a time course of postnatal day (PND) 15, 20, 30, and 90 using age-matched Sprague-Dawley (SD) rats as controls to characterize molecular mechanisms of CHF/ARPKD pathogenesis...

BACKGROUND The polycystic kidney and hepatic disease 1 (PKHD1) gene codes for fibrocystin-polyductin, a protein that takes part in cell-signaling for cell differentiation, especially in kidney tubules and bile ducts. A homozygous or compound heterozygous defect in this gene can cause autosomal recessive polycystic kidney disease (ARPKD). Polycystic liver disease (PCLD) can also be caused by single heterozygous variants in the PKHD1 gene. ARPKD presents with renal insufficiency and cystic dilatation of bile ducts, although disease is not expected with a single heterozygous mutation...

INTRODUCTION: Autosomal recessive polycystic kidney disease (ARPKD) is associated with pathogenic variants in the PKHD1 gene. Autosomal dominant polycystic kidney disease (ADPKD) is mainly associated with pathogenic variants in PKD1 or PKD2. The present study aimed to identify the clinical and genetic features of Turkish pediatric ARPKD and ADPKD patients. METHODS: This multicenter, retrospective cohort study included 21 genetically confirmed ARPKD and 48 genetically confirmed ADPKD patients from 7 pediatric nephrology centers...

BACKGROUND: Impaired kidney concentration capacity is present in half of the patients with autosomal dominant polycystic kidney disease (ADPKD). The kidney concentrating capacity was further impaired within the animal model of autosomal recessive polycystic kidney disease (ARPKD). To date, only one small study has investigated it in children having ARPKD. Therefore, we aimed to study the kidney concentrating ability in a larger cohort of children with ARPKD. METHODS: Eighteen children (median age 8...

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a condition usually caused by a single gene mutation and manifested by both renal and extrarenal features, eventually leading to end-stage renal disease (ESRD) by the median age of 60 years worldwide. Approximately 89% of ADPKD patients had either PKD1 or PKD2 gene mutations. The majority (85%) of the mutations are in the PKD1 gene, especially in the context of family history. Objectives: This study investigated the genetic basis and the undiscovered genes that are involved in ADPKD development among the Saudi population...

Background : Hyperinsulinemic hypoglycemia (HH) is an important cause of persistent hypoglycemia in newborns and infants. Recently, PMM2 (phosphomannomutase 2) mutation has been associated with HH, especially in conjunction with polycystic kidney disease (PKD). PMM2 deficiency is one of the most common causes of congenital disorder of glycosylation (CDG). Renal involvement in PMM2-CDG manifests as cystic kidney disease, echogenic kidneys, nephrotic syndrome or mild proteinuria. Case Summary : Here, we describe a pair of siblings with HH associated with autosomal recessive polycystic kidney disease (ARPKD) and PMM2 mutation...

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cystic kidney disease, with patients often having a positive family history that is characterized by a similar phenotype. However, in atypical cases, particularly those in which family history is unclear, a differential diagnosis between ADPKD and other cystic kidney diseases is important. When diagnosing ADPKD, cystic kidney diseases that can easily be excluded using clinical information include: multiple simple renal cysts, acquired cystic kidney disease (ACKD), multilocular renal cyst/multilocular cystic nephroma/polycystic nephroma, multicystic kidney/multicystic dysplastic kidney (MCDK), and unilateral renal cystic disease (URCD)...

Autosomal recessive polycystic kidney disease (ARPKD) is an inherited pathology caused mainly by mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene, which usually leads to end-stage renal disease. Previous studies suggested that the P2X purinoreceptor 4 (P2X4 R) may play an important role in the progression of ARPKD. To test this hypothesis, we assessed the chronic effects of ivermectin (P2X4 R allosteric modulator) and 5-BDBD (P2X4 R antagonist) on the development of ARPKD in PCK/CrljCrl-Pkhd1pck/CRL (PCK) rats...

Autosomal recessive polycystic kidney disease (ARPKD) is an early onset genetic disorder characterized by numerous renal cysts resulting in end stage renal disease. Our study aimed to determine if metabolic reprogramming and tryptophan (Trp) metabolism via the kynurenine pathway (KP) is a critical dysregulated pathway in PKD. Using the Lewis polycystic kidney (LPK) rat model of PKD and Lewis controls, we profiled temporal trends for KP metabolites in plasma, urine, and kidney tissues from 6- and 12-week-old mixed sex animals using liquid and gas chromatography, minimum n  = 5 per cohort...