Autosomal dominant renal cysts and diabetes (RCAD): A novel syndrome of diabetes and cystic kidney disease resulting from hepatocyte nuclear factor - 1 beta gene mutations

Autosomal dominant polycystic kiney disease is a hereditary systemic disorder, characterized by the developement of cysts, mainly in the kidney and liver, also with gastrointestinal and cardiovascular abnormalities. It affects 4 to 6 million people wordwide and accounts for end-stage renal disease in 7-10% of dialysis patients. The genetic penetrance is 100%, all affected individuals develop renal cysts until 70 years of age, and because of a great renal function reserve only about 50% of patients develop some degree of renal failure until the age of 60. Autosomal dominant polycystic kiney disease is a heterogeneous disorder, from a clinical as well as from a genetic point of view. There are at least three genes responsible for the disease: PKD-1 gene localized on chromosome 16p in the 16p13.3 segment which encodes Polycystin 1 protein similar to membrane receptor, PKD-2 gene localized on chromosome 4q in 4q13-23 segment which encodes Polycystin 2 protein wery similar to voltage L type Ca++ channel as well as Na+ channel and PKD-3 gene of unknown localization. Specific proteins participate in regulation od cell proliferation, apoptosis, secretion, polarity, cell-matrix interactions as cell-cell interactions and lead to the developement of cystic kidney disease. Renal manifestations of disease include structural (cyst development), functional (concentration alility falls), endocrine (renin erythropoietin) abnormalities and extra- renal manifestations. A routine diagnostic methods are good case-history about cystic kidney disease in family, ultrasonographic examination of kidneys and computerized tomography. In therapy of autosomal dominant polycystic kiney disease, low protein diets may help, treatment of arterial hypertension with ACE inhibitors and angiotensin II receptor blockers, the vasopressin V2 antagonists (VSR), rapamycin and long-acting somatostatin analogue may have some benefit.

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Cystic Diseases of the Kidney

10.2310/nephro.12047 ◽

2017 ◽

Author(s):

Christian Riella ◽

Peter G Czarnecki ◽

Theodor I Steinman

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

Autosomal Dominant ◽

Disease Gene ◽

Renal Cysts ◽

Cystic Kidney Disease ◽

Cystic Kidney ◽

Polycystic Kidney ◽

Autosomal Dominant Polycystic Kidney ◽

End Stage

The spectrum of cystic kidney diseases encompasses a wide range of genetic syndromes with different identified disease genes, modes of inheritance, extrarenal organ manifestations, and clinical progression. Depending on the given disease gene and type of mutation in a respective cystic kidney disease, the age of onset, pathologic characteristics, and rate of progression to end-stage kidney disease vary considerably. This review covers disease definitions, etiology and genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, and treatment of cystic kidney disease. Additionally, simple and complex renal cysts in adults are discussed. Tables list the epidemiology of polycystic kidney disease, gene locus, and encoded protein, unified criteria for ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (APDKD), risk factors for progressive kidney disease in APDKD, differential diagnosis of cystic diseases of the kidney, Halt Progression of Polycystic Kidney Disease trial summary, and other extrarenal manifestations of ADPDK. Key Words: Cystic kidney disease; Autosomal dominant polycystic kidney disease; APDKD; Polycystic kidney disease; PKD; End-stage renal disease; Renal cysts; Progressive kidney disease

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Phthalate Esters, Cystic Kidney Disease in Animals and Possible Effects on Human Health: A Review

Human & Experimental Toxicology ◽

10.1177/096032719000900607 ◽

1990 ◽

Vol 9 (6) ◽

pp. 397-401 ◽

Cited By ~ 17

Author(s):

K.N. Woodward

Keyword(s):

Kidney Disease ◽

Human Health ◽

Phthalate Esters ◽

Renal Cysts ◽

Cystic Kidney Disease ◽

Cystic Kidney ◽

Peroxisome Proliferation ◽

Peroxisome Proliferators ◽

Prolonged Administration ◽

Route Of Exposure

1 Phthalate esters are known to cause hepatic peroxisome proliferation in rodents and, after prolonged administration, hepatocarcinogenesis. Peroxisome proliferators as a group are hepatocarcinogenic. The mechanism is not known but it does not appear to involve a direct genotoxic element. 2 DEHP and DBP have been shown to cause renal cysts in rodents and they also produce renal peroxisome proliferation. There are no data to causally link the two phenomena. 3 Although renal cysts have been noted in haemodialysis patients and haemodialysis is a route of exposure to DEHP, there are no data to suggest a cause and effect relationship. 4 More studies are needed on the mechanism of renal cystogenesis.

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New PAX2 Mutation Associated with Polycystic Kidney Disease: A Case Report

Clinical Medicine Insights Pediatrics ◽

10.1177/1179556521992354 ◽

2021 ◽

Vol 15 ◽

pp. 117955652199235

Author(s):

Jessica Maria Forero-Delgadillo ◽

Vanessa Ochoa ◽

Natalia Duque ◽

Jaime Manuel Restrepo ◽

Hernando Londoño ◽

...

Keyword(s):

Kidney Disease ◽

Novel Mutation ◽

Clinical Manifestations ◽

Renal Cysts ◽

Renal Dysplasia ◽

Cystic Kidney Disease ◽

Cystic Kidney ◽

Incomplete Penetrance ◽

Wide Range ◽

Stage Renal Disease

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage renal disease in children. Diagnosis by genetic testing has proven challenging due to its genetic and phenotypic heterogeneity, as well as incomplete penetrance. We report a case on a 16-months old female with a history of renal cysts and a PAX2 mutation. Case presentation: The patient presented with a prenatal diagnosis of Potter sequence and a postnatal diagnosis of renal cysts. An ultrasound at 20 weeks gestation revealed right renal agenesis and possible left renal dysplasia. Post natal genetic analyses identified a novel mutation in PAX2. Conclusion: Cystic kidney disease is often underdiagnosed due to its variable expressivity and wide range of clinical manifestations; PAX2 genetic screening should be considered for all patients with CAKUT.

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Hepatocyte nuclear factor-1β (MODY5) gene mutations in Scandinavian families with early-onset diabetes or kidney disease or both

Diabetologia ◽

10.1007/s001250050018 ◽

2000 ◽

Vol 43 (1) ◽

pp. 131-132 ◽

Cited By ~ 6

Author(s):

Not Available Not Available

Keyword(s):

Kidney Disease ◽

Early Onset ◽

Gene Mutations ◽

Nuclear Factor ◽

Hepatocyte Nuclear Factor ◽

Onset Diabetes

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Evolving role of genetic testing for the clinical management of autosomal dominant polycystic kidney disease

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy261 ◽

2018 ◽

Vol 34 (9) ◽

pp. 1453-1460 ◽

Cited By ~ 7

Author(s):

Matthew B Lanktree ◽

Ioan-Andrei Iliuta ◽

Amirreza Haghighi ◽

Xuewen Song ◽

York Pei

Keyword(s):

Genetic Testing ◽

Kidney Disease ◽

Polycystic Kidney Disease ◽

Autosomal Dominant ◽

Mutation Screening ◽

Cystic Kidney Disease ◽

Cystic Kidney ◽

Polycystic Kidney ◽

Autosomal Dominant Polycystic Kidney

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is caused primarily by mutations of two genes, PKD1 and PKD2. In the presence of a positive family history of ADPKD, genetic testing is currently seldom indicated as the diagnosis is mostly based on imaging studies using well-established criteria. Moreover, PKD1 mutation screening is technically challenging due to its large size, complexity (i.e. presence of six pseudogenes with high levels of DNA sequence similarity) and extensive allelic heterogeneity. Despite these limitations, recent studies have delineated a strong genotype–phenotype correlation in ADPKD and begun to unravel the role of genetics underlying cases with atypical phenotypes. Furthermore, adaptation of next-generation sequencing (NGS) to clinical PKD genetic testing will provide a high-throughput, accurate and comprehensive screen of multiple cystic disease and modifier genes at a reduced cost. In this review, we discuss the evolving indications of genetic testing in ADPKD and how NGS-based screening promises to yield clinically important prognostic information for both typical as well as unusual genetic (e.g. allelic or genic interactions, somatic mosaicism, cystic kidney disease modifiers) cases to advance personalized medicine in the era of novel therapeutics for ADPKD.

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