The dominant findings of a recessive man: from Mendel’s kid pea to kidney DOI Creative Commons
Kálmán Tory

Pediatric Nephrology, Journal Year: 2023, Volume and Issue: 39(7), P. 2049 - 2059

Published: Dec. 5, 2023

The research of Mendel, born two centuries ago, still has many direct implications for our everyday clinical work. He introduced the terms "dominant" and "recessive" characters determined their 3:1 ratio in offspring heterozygous "hybrid" plants. This distribution allowed calculation number phenotype-determining "elements," i.e., alleles, been used ever since to prove monogenic origin a disorder. Mendelian inheritance kidney disorders is great help distinguishing them from those with multifactorial practice. Inheritance most fits Mendel's observations: equal contribution parents complete penetrance or correlation between frequency recessive character degree inbreeding. Nevertheless, beyond truth these basic concepts, several observations have expanded genetic characteristics. extreme heterogeneity, pleiotropy causal genes role modifiers ciliopathies, digenic parental imprinting some tubulopathies, incomplete eventual interallelic interactions podocytopathies, reflect this expansion. For all reasons, transmission pattern natural setting may depend not only on "character" but also gene variant. passion combined his modest personality meticulous approach can serve as an example work required understand non-Mendelian universe genetics.

Language: Английский

KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) DOI Creative Commons
Olivier Devuyst, Curie Ahn, Thijs R.M. Barten

et al.

Kidney International, Journal Year: 2025, Volume and Issue: 107(2), P. S1 - S239

Published: Jan. 21, 2025

Language: Английский

Citations

6
Biomarkers of Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease DOI Creative Commons
Ahmad Ghanem,

Abdul Hamid Borghol,

Fadi George Munairdjy Debeh

et al.

Kidney International Reports, Journal Year: 2024, Volume and Issue: 9(10), P. 2860 - 2882

Published: July 14, 2024

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic disorder and fourth leading cause of failure (KF) in adults. Characterized by a reduction glomerular filtration rate (GFR) increased size, ADPKD exhibits significant variability progression, highlighting urgent need for reliable predictive biomarkers to optimize management treatment approaches. This review explores roles diverse biomarkers-including clinical, genetic, molecular, imaging biomarkers-in evaluating progression customizing treatments ADPKD. Clinical such as biological sex, predicting renal outcome

Language: Английский

Citations

9
Autosomal Dominant Polycystic Kidney Disease DOI
Fouad T. Chebib, Christian Hanna, Peter C. Harris

et al.

JAMA, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Importance Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of cysts and the most common inherited disorder worldwide. ADPKD accounts for 5% to 10% failure in US Europe, its prevalence 9.3 per 10 000 individuals. Observations typically diagnosed individuals aged 27 42 years primarily caused pathogenic variants PKD1 (78%) or PKD2 (15%) genes. Most persons with have an affected parent, but de novo suggested 25% families. More than 90% patients older 35 hepatic cysts, which may cause abdominal discomfort occasionally require medical surgical intervention. Hypertension affects 70% 80% ADPKD, approximately 9% 14% develop intracranial aneurysms, a rupture rate 0.57 1000 patient-years. Approximately 50% replacement therapy 62 age. The severity can be quantified using Mayo Imaging Classification (MIC), stratifies based on total volume adjusted height age ranges from 1A 1E. Patients MIC 1C 1E larger kidneys because more rapid growth (6%-10% year) compared those 1B (1%-5% earlier progression therapy, occurs at mean 58.4 1C, 52.5 1D, 43.4 Optimal management includes systolic blood pressure lower 120 mm Hg patients, 110/75 who estimated glomerular filtration (eGFR) greater 60 mL/min/1.73 m 2 are younger 50 years, dietary sodium restriction (<2000 mg/d), weight management, adequate hydration (>2.5 L daily). vasopressin type receptor antagonist tolvaptan reduces annual eGFR decline 0.98 1.27 indicated 3 year slow delay onset failure. Conclusion genetic worldwide cysts. hypertension liver aneurysms. First-line treatment control, hydration. Tolvaptan high risk

Language: Английский

Citations

1
State of the Science and Ethical Considerations for Preimplantation Genetic Testing for Monogenic Cystic Kidney Diseases and Ciliopathies DOI
Whitney S. Thompson, Samir Babayev, Michelle L. McGowan

et al.

Journal of the American Society of Nephrology, Journal Year: 2023, Volume and Issue: 35(2), P. 235 - 248

Published: Oct. 26, 2023

There is a broad phenotypic spectrum of monogenic polycystic kidney diseases (PKDs). These disorders often involve cilia-related genes and lead to the development fluid-filled cysts eventual function decline failure. Preimplantation genetic testing for (PGT-M) has moved into clinical realm. It allows prospective parents avoid passing on heritable their children, including PKD. The PGT-M process involves embryo generation through in vitro fertilization, with subsequent embryos selective transfer those that do not harbor specific disease-causing variant(s). growing body literature supporting success autosomal-dominant autosomal-recessive PKD, although important technical limitations some cases. This technology can be applied many other types PKD ciliopathies despite lack existing reports literature. like forms assisted reproductive technology, raises ethical questions. When considering diseases, as well potential disease future generations, there are regulatory considerations. include limited government regulation unstandardized consent processes, errors, high cost equity concerns, risks associated pregnancy mothers disease, impact all involved process, children who were made possible this technology.

Language: Английский

Citations

11
Characteristics of patients with autosomal polycystic kidney disease reaching kidney failure by age 40 DOI

Stijn Wigerinck,

Pieter Schellekens, Byron H. Smith

et al.

Pediatric Nephrology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Extrarenal clinical features are reported for most genes implicated in genetic kidney disease DOI Creative Commons
Benjamín Serrano, Judy Savige

Kidney International Reports, Journal Year: 2025, Volume and Issue: 10(4), P. 1196 - 1204

Published: Feb. 5, 2025

Language: Английский

Citations

0
Overexpression of the NEk8 kinase inhibits homologous recombination DOI Creative Commons

Joshua L. Turner,

Gregory J. Moore,

Tyler J. McCraw

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

ABSTRACT Homologous recombination maintains genome stability by repairing double strand breaks and protecting replication fork stability. Defects in homologous results cancer predisposition but can be exploited due to increased sensitivity certain chemotherapeutics such as PARP inhibitors. The NEK8 kinase has roles the response recombination. is overexpressed breast cancer, impact of overexpression on not been determined. Here, we demonstrate inhibits RAD51 focus formation resulting a defect degradation stalled forks. Importantly, sensitizes cells inhibitor, Olaparib. Together, our suggest overexpressing tumors may recombination-deficient respond that target defects

Language: Английский

Citations

0
Polycystic Kidney Disease in Children: The Current Status and the Next Horizon DOI
Melissa A. Cadnapaphornchai, Katherine MacRae Dell, Charlotte Gimpel

et al.

American Journal of Kidney Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Autosomal dominant polycystic kidney disease: an overview of recent genetic and clinical advances DOI Creative Commons

Abdul Hamid Borghol,

Mikhail D. Antoun,

Christian Hanna

et al.

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: April 23, 2025

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney disease, characterized by progressive development of multiple cysts, leading to a gradual decline in function. ADPKD also fourth cause failure (KF) adults. In addition manifestations, associated with various extrarenal features, including liver cardiovascular abnormalities, intracranial aneurysms, and chronic pain significant impact on patients' quality life. While several disease-modifying agents have been tested ADPKD, tolvaptan remains only approved drug US Food Drug Administration. The Mayo Imaging Classification currently practical tool for predicting rate disease progression ADPKD. This review provides comprehensive overview focusing its genetics, pathophysiology, clinical presentation, management, prognostic tools. Advances diagnostic imaging genetic testing improved early detection allowing better classification patients prediction KF. discusses current therapeutic approaches tolvaptan, vasopressin V2-receptor antagonist. Additionally, we address specific issues children pregnant individuals Despite substantial progress understanding there large need additional effective treatments markers provide more personalized care these patients.

Language: Английский

Citations

0
Functional Analysis of a De Novo Monoallelic NEK8 Variant Supports Pathogenicity for a Polycystic Kidney Disease Phenotype DOI Creative Commons
Whitney S. Thompson, Chuan Chen, Hana Yang

et al.

Kidney International Reports, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0