Autosomal Recessive Polycystic Kidney (Polycystic Kidney Disease, Infantile, Type I)

A genetic disorder with autosomal recessive inheritance, characterized by multiple CYSTS in both KIDNEYS and associated LIVER lesions. Serious manifestations are usually present at BIRTH with high PERINATAL MORTALITY.

Also Known As:

Polycystic Kidney Disease, Infantile, Type I; Polycystic Kidney, Autosomal Recessive; ARPKD; Polycystic Kidney Disease, Autosomal Recessive; Polycystic Kidney Disease, Infantile, Type 1; Polycystic Kidney and Hepatic Disease 1; Polycystic Kidney and Hepatic Disease 1 (Autosomal Recessive); Autosomal Recessive Polycystic Kidney Disease; Kidney, Polycystic, Autosomal Recessive

Networked: 290 relevant articles (16 outcomes, 38 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Autosomal Recessive Polycystic Kidney (Polycystic Kidney Disease, Infantile, Type I)
2.	Autosomal Dominant Polycystic Kidney (ADPKD)
3.	Liver Diseases (Liver Disease)
4.	Cysts
5.	Polycystic Kidney Diseases (Polycystic Kidney Disease)

Experts

1.	Harris, Peter C: 16 articles (11/2019 - 03/2002)
2.	Torres, Vicente E: 16 articles (11/2019 - 03/2002)
3.	Guay-Woodford, Lisa M: 15 articles (12/2018 - 04/2000)
4.	Avner, Ellis D: 14 articles (07/2017 - 04/2000)
5.	Bergmann, Carsten: 12 articles (01/2021 - 05/2002)
6.	Sweeney, William E: 12 articles (07/2017 - 04/2000)
7.	Hartung, Erum A: 10 articles (09/2022 - 09/2014)
8.	Zerres, Klaus: 10 articles (01/2021 - 04/2000)
9.	Masyuk, Tatyana V: 9 articles (01/2022 - 10/2003)
10.	Masyuk, Anatoliy I: 8 articles (01/2022 - 03/2007)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Autosomal Recessive Polycystic Kidney:

1.	Epidermal Growth Factor (EGF)IBA 06/01/1995 - "Epidermal growth factor ameliorates autosomal recessive polycystic kidney disease in mice." 01/01/1998 - "Functional activity of epidermal growth factor receptors in autosomal recessive polycystic kidney disease." 02/01/1995 - "EGFR mislocalization and overexpression may be mechanisms whereby the EGF-like factors in cyst fluid stimulate cystogenesis through an autocrine-paracrine cycle in ARPKD." 10/29/1993 - "An inborn error in epidermal growth factor prohormone metabolism in a mouse model of autosomal recessive polycystic kidney disease." 01/01/1998 - "As previously reported, in the C57BL-6Jcpk/cpk (CPK), BALB/c-bpk/bpk (BPK), and C3H-orpk/orpk (ORPK) murine models of ARPKD, as well as in human ARPKD and human ADPKD, the EGF-R is mislocated to the apical surface of cystic collecting tubule (CT) epithelial cells. "
2.	Proteins (Proteins, Gene)FDA Link 08/01/2012 - "In the current study, we employed, for the first time, a MS-based comparative proteomics approach to investigate the differently expressed proteins between kidney tissue samples of four ARPKD and five control individuals. " 04/01/2007 - "To further define the exact subcellular localization of FPC, the protein product encoded by the PKHD1 gene responsible for autosomal recessive polycystic kidney disease (PKD) in humans, and whether FPC has direct and/or indirect cross talk with PC2, which, in turn, is pivotal for the pathogenesis of autosomal dominant PKD, we performed double immunostaining and coimmunoprecipitation as well as a microfluorimetry study of kidney tubular epithelial cells. " 01/24/2023 - "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. " 06/17/2021 - "However, the function of the ARPKD proteins and the molecular mechanism of the disease currently remain incompletely understood. " 01/01/2021 - "Expression of the proteins of OXPHOS was downregulated sharply, in parallel with upregulated expression of the proteins involved in glycolysis in patients with ARPKD. "
3.	ErbB Receptors (EGF Receptor)IBA 08/01/2010 - "Autosomal recessive polycystic kidney disease epithelial cell model reveals multiple basolateral epidermal growth factor receptor sorting pathways." 12/01/2006 - "However, studies noted in this review suggest that therapeutic targeting of the cAMP and epidermal growth factor receptor (EGFR)-axis abnormalities in cystic epithelia may translate into effective therapies for ARPKD and, by analogy, autosomal dominant polycystic kidney disease (ADPKD). " 03/01/1998 - "A consistent phenotype observed in both human patients and several different mouse models of autosomal recessive polycystic kidney disease (ARPKD) is an increased activity of the epidermal growth factor receptor (EGFR) in the affected kidneys. " 10/01/2003 - "We have previously demonstrated an essential role for increased epidermal growth factor receptor (EGFR) activity in mediating renal cyst formation and biliary ductal ectasia (BDE) in murine models of autosomal-recessive polycystic kidney disease (ARPKD) such as the BPK mouse. " 01/01/2000 - "We have previously demonstrated an essential role for increased epidermal growth factor receptor (EGFR) activity in mediating renal cyst formation and biliary epithelial hyperplasia in murine models of autosomal recessive polycystic kidney disease (ARPKD). "
4.	Tolvaptan FDA Link 01/01/2023 - "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. " 01/01/2023 - "Design of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney disease." 04/01/2023 - "Tolvaptan is currently the sole approved treatment option available for ADPKD patients, while no approved treatment alternatives exist for ARPKD or NPHP patients. " 01/01/2021 - "Currently, there are no treatments for ARPKD, and tolvaptan is the only FDA-approved drug that alleviates the symptoms of ADPKD. " 09/01/2016 - "In spite of these differences, there is growing evidence to suggest that ADPKD and ARPKD are more related than previously suspected.3 Bilineal inheritance of PKD1 abnormalities has been reported to cause extremely severe disease resembling ARPKD.4 The use of Tolvaptan in the management of PKD in children is therefore expected to become more important. "
5.	Protein-Tyrosine Kinases (Tyrosine Kinase)IBA 01/01/2000 - "This study was designed to determine whether or not treatment with a newly developed inhibitor of EGFR tyrosine kinase activity (EKI-785) would reduce renal and biliary abnormalities in murine ARPKD. " 03/01/1998 - "These results suggest that changes in the expression of the EGFR contribute to the formation of cysts in the collecting ducts, and that drugs that target the tyrosine kinase activity of the EGFR may potentially be therapeutic in ARPKD." 03/01/1998 - "To determine whether this increased activity of the EGFR is a functional event that is directly part of the disease pathway of renal cyst formation, we used a genetic approach to introduce a mutant EGFR with decreased tyrosine kinase activity into a murine model of ARPKD. " 10/01/2003 - "if treatment with a second-generation inhibitor of EGFR tyrosine kinase activity, EKB-569, was effective in treatment of ARPKD; (2). "
6.	Phosphotransferases (Kinase)IBA 07/06/2017 - "This study demonstrates that: (1) in vivo pharmacological inhibition of multiple kinase cascades with TSV reduced phosphorylation of key mediators of cystogenesis: EGFR, ErbB2, c-Src and KDR; and (2) this reduction of kinase activity resulted in significant reduction of renal and biliary disease in both bpk and PCK models of ARPKD. " 07/06/2017 - "The data supports the hypothesis that this multi-kinase inhibitor TSV may provide an effective clinical therapy for human ARPKD." 09/01/2004 - "cAMP responses to maximally effective concentrations of renal agonists were determined together with measurements of transepithelial anion current and cellular proliferation and extracellular signal-related kinase (ERK 1/2) expression in primary cultures of epithelial cells from human ADPKD and ARPKD cysts. " 07/06/2017 - "To investigate the therapeutic potential of tesevatinib (TSV), a unique multi-kinase inhibitor currently in Phase II clinical trials for autosomal dominant polycystic kidney disease (ADPKD), in well-defined rodent models of autosomal recessive polycystic kidney disease (ARPKD). "
7.	XL647IBA 07/06/2017 - "Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease." 07/06/2017 - "To investigate the therapeutic potential of tesevatinib (TSV), a unique multi-kinase inhibitor currently in Phase II clinical trials for autosomal dominant polycystic kidney disease (ADPKD), in well-defined rodent models of autosomal recessive polycystic kidney disease (ARPKD). "
8.	Antihypertensive Agents (Antihypertensives)IBA 10/01/2014 - "Blood pressure parameters were similar between the two groups; however, ARPKD patients required a significantly greater number of antihypertensive medications to achieve similar BP levels. " 07/01/2014 - "Significant risk factors for AION were identified as median age (4 vs. 27 months; p < 0.001), autosomal recessive polycystic kidney disease (28.6 vs. 3.4%; p = 0.01), anephric status (53.8 vs. 6.8%; p < 0.001) and low to normal blood pressure evidenced by the number of patients having to be treated with antihypertensive medications (14.3 vs. 62.7%; p = 0.01). " 04/01/2016 - "GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). "
9.	Antisense OligonucleotidesIBA 01/01/2002 - "c-myc antisense oligonucleotide treatment ameliorates murine ARPKD." 02/10/2023 - "A Potential Therapy Using Antisense Oligonucleotides to Treat Autosomal Recessive Polycystic Kidney Disease."
10.	Cyclin D1IBA 01/01/2011 - "Proliferation and the increased nuclear expression of cyclin D1 and p-Rb coincide with the early phase of cyst growth in rats and humans, suggesting that there might be a therapeutic window in which cyclin-dependent kinase inhibitors are most effective in preventing kidney enlargement in ARPKD." 01/01/2011 - "Early cyst growth is associated with the increased nuclear expression of cyclin D1/Rb protein in an autosomal-recessive polycystic kidney disease rat model."

Therapies and Procedures

1.	Therapeutics 10/31/2023 - "Autosomal recessive polycystic kidney disease is an early onset inherited hepatorenal disorder affecting around 1 in 20,000 births with no approved specific therapies. " 01/01/2023 - "These data suggest that CFTR correctors can be useful as therapeutics for ARPKD. " 01/01/2022 - "Here, we unite organoids with organ-on-a-chip technology to unravel disease pathology and develop therapies for autosomal recessive polycystic kidney disease. " 05/29/2020 - "Precise molecular diagnosis of ARPKD has proven valuable for understanding its mechanism and selecting optimal therapy. " 01/01/2018 - "Quantitative magnetic resonance imaging assessments of autosomal recessive polycystic kidney disease progression and response to therapy in an animal model."
2.	Kidney Transplantation 11/01/2016 - "Combined liver-kidney transplantation in ARPKD is associated with increased mortality compared to kidney transplantation in our large observational study and was not associated with improved 5-year kidney transplant survival. " 04/01/2002 - "The aim of this study was to evaluate morbidity from CHF in ARPKD post renal transplantation. " 01/01/2017 - "With its obligate renal and hepatic involvement, ARPKD is one of the most important indications for liver and/or kidney transplantation in childhood. " 11/01/2014 - "Four pediatric patients with autosomal recessive polycystic kidney disease developed new-onset diabetes after renal transplantation." 05/01/2006 - "In case of associated ARPKD, renal transplantation is often indicated early on because of the more rapid progression of the renal component of the disease."
3.	Nephrectomy 07/01/2017 - "[Early bilateral nephrectomy in neonatal autosomal recessive polycystic kidney disease : Improved prognosis or unnecessary effort?]" 01/01/2023 - "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. " 02/01/2021 - "Early nephrectomy in neonates with symptomatic autosomal recessive polycystic kidney disease." 01/01/2021 - "Unilateral or bilateral early nephrectomy in infants with autosomal recessive polycystic kidney disease? " 01/01/2020 - "Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort."
4.	Liver Transplantation 05/01/2012 - "Kidney and liver transplantation in patients with autosomal recessive polycystic kidney disease: a multicentric study." 05/01/2012 - "Here, we report the results and outcome of renal and/or liver transplantation in a series of patients with ARPKD. " 05/01/2012 - "Fourteen ARPKD patients (age: 3-25 years) who underwent renal transplantation with or without liver transplantation were retrospectively identified in five French nephrology departments. " 12/01/2004 - "Between March 1997 and September 2002, three of 50 orthotopic liver transplantation (OLT) were performed because of CHF associated with ARPKD at Ege University Organ Transplantation and Research Center. " 01/01/2017 - "The hepatic manifestations of ARPKD can range from asymptomatic to portal hypertension and massively dilated biliary system that results in liver transplantation. "
5.	Ligation 08/01/2010 - "The main aim of this study was to screen ARPKD patients in whom only one pathogenic PKHD1 mutation was identified after bidirectional sequencing of the longest open reading frame, for gene copy number alterations by employing multiplex ligation-dependent probe amplification complemented with quantitative real-time polymerase chain reaction. "