KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Kidney International, Год журнала: 2025, Номер 107(2), С. S1 - S239

Опубликована: Янв. 21, 2025

Язык: Английский

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Autosomal Dominant Polycystic Kidney Disease

JAMA, Год журнала: 2025, Номер unknown

Опубликована: Март 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

Язык: Английский

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Certain heterozygous variants in the kinase domain of the serine/threonine kinase NEK8 can cause an autosomal dominant form of polycystic kidney disease

Kidney International, Год журнала: 2023, Номер 104(5), С. 995 - 1007

Опубликована: Авг. 19, 2023

Язык: Английский

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Cardiovascular Manifestations and Management in ADPKD

Kidney International Reports, Год журнала: 2023, Номер 8(10), С. 1924 - 1940

Опубликована: Авг. 4, 2023

Cardiovascular disease is the major cause of mortality in autosomal dominant polycystic kidney and contributes to significant burden disease. The manifestations are varied, including left ventricular hypertrophy, intracranial aneurysms, valvular heart cardiomyopathies, but most common presentation a modifiable risk factor hypertension. aim this review detail complex pathogenesis hypertension other extra-renal cardiac vascular conditions ADPKD drawing on preclinical, clinical epidemiological evidence. main drivers renin-angiotensin-aldosterone system polycystin-related endothelial cell dysfunction, with sympathetic nervous system, nitric oxide, endothelin-1 asymmetric dimethylarginine likely playing key roles different stages. reported rates some manifestations, such as have decreased due use anti-hypertensive therapies, others, ischemic cardiomyopathy, been increased prevalence longer survival higher chronic ADPKD-specific screening management guidelines exist for hypertension, hypertrophy these described review.

Язык: Английский

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Experimental Models of Polycystic Kidney Disease: Applications and Therapeutic Testing

Kidney360, Год журнала: 2023, Номер 4(8), С. 1155 - 1173

Опубликована: Июль 7, 2023

Polycystic kidney diseases (PKDs) are genetic disorders characterized by the formation and expansion of numerous fluid-filled renal cysts, damaging normal parenchyma often leading to failure. Although PKDs comprise a broad range different diseases, with substantial phenotypic heterogeneity, an association primary cilia represents common theme. Great strides have been made in identification causative genes, furthering our understanding complexity disease mechanisms, but only one therapy so far has shown success clinical trials advanced US Food Drug Administration approval. A key step pathogenesis testing potential therapeutics is developing orthologous experimental models that accurately recapitulate human phenotype. This particularly important for because cellular limited value; however, advent organoid usage expanded capabilities this area does not negate need whole-organism where function can be assessed. Animal model generation further complicated most type, autosomal dominant PKD, homozygous lethality very cystic phenotype heterozygotes while recessive mouse delayed modest disease, contrast humans. However, use conditional/inducible dosage resulted some best nephrology. These used help understand pathogenesis, facilitate interaction studies, perform preclinical testing. Whereas using alternative species digenic partially overcome these deficiencies. Here, we review currently available valuable therapeutic their applications, trials, advantages limitations, improvements needed.

Язык: Английский

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Combining genotype with height-adjusted kidney length predicts rapid progression of ADPKD

Nephrology Dialysis Transplantation, Год журнала: 2024, Номер 39(6), С. 956 - 966

Опубликована: Янв. 15, 2024

Our main objective was to identify baseline prognostic factors predictive of rapid disease progression in a large unselected clinical autosomal dominant polycystic kidney (ADPKD) cohort.

Язык: Английский

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How Does ADPKD Severity Differ Between Family Members?

Kidney International Reports, Год журнала: 2024, Номер 9(5), С. 1198 - 1209

Опубликована: Фев. 5, 2024

Thousands of pathogenic variants in more than 100 genes can cause kidney cysts with substantial variability phenotype and risk subsequent failure. Despite an established genotype-phenotype correlation cystic diseases, incomplete penetrance variable disease expressivity are present as is the case all monogenic diseases. In family members autosomal dominant polycystic (ADPKD), same causal variant responsible affected members; however, there still be striking discordance severity. This narrative review explores contributors to within-family ADPKD Cases biallelic digenic inheritance, where 2 rare cystogenic coexistent one family, account for a small proportion discordance. Genetic background, including cis trans factors polygenic propensity comorbid disease, also plays role but has not yet been exhaustively quantified. Environmental exposures, diet; smoking; alcohol, salt, protein intake, obesity, diabetes, hypertension, stones, dyslipidemia, additional diseases contribute phenotypic among members. Given that many contributing preventable, modifiable, or treatable, health care providers patients need aware these address them treatment ADPKD.

Язык: Английский

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State of the Science and Ethical Considerations for Preimplantation Genetic Testing for Monogenic Cystic Kidney Diseases and Ciliopathies

Journal of the American Society of Nephrology, Год журнала: 2023, Номер 35(2), С. 235 - 248

Опубликована: Окт. 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.

Язык: Английский

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Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family History

Kidney International Reports, Год журнала: 2024, Номер 9(9), С. 2685 - 2694

Опубликована: Июль 16, 2024

Recently, the monoallelic loss-of-function IFT140 variant was identified as a causative gene for autosomal dominant polycystic kidney disease (ADPKD). In patients with kidneys who have positive family history, >90% pathogenic variants in

Язык: Английский

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Quantifying variant contributions in cystic kidney disease using national-scale whole genome sequencing

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(19)

Опубликована: Авг. 27, 2024

BACKGROUNDCystic kidney disease (CyKD) is a predominantly familial in which gene discovery has been led by family-based and candidate studies, an approach that susceptible to ascertainment other biases.METHODSUsing whole-genome sequencing data from 1,209 cases 26,096 ancestry-matched controls participating the 100,000 Genomes Project, we adopted hypothesis-free approaches generate quantitative estimates of risk for each genetic contributor CyKD, across genes, variant types allelic frequencies.RESULTSIn 82.3% cases, qualifying potentially disease-causing rare established was found. There enrichment coding, splicing, structural variants known CyKD with statistically significant gene-based signals COL4A3 (monoallelic) PKHD1. Quantification (with replication separate UK Biobank study) revealed substantially lower associated genes more recently autosomal dominant polycystic disease, odds ratios some below what might usually be regarded as necessary classical Mendelian inheritance. Meta-analysis common did not reveal associations, but suggested this category variation contributes 3%-9% heritability European ancestries.CONCLUSIONBy providing unbiased quantification effects per gene, research suggests all contributors are equally likely manifest trait families. This information may inform testing counseling clinic.

Язык: Английский

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