Kidney International, Год журнала: 2024, Номер 106(3), С. 532 - 535
Опубликована: Июнь 27, 2024
Язык: Английский
Kidney International, Год журнала: 2025, Номер 107(2), С. S1 - S239
Опубликована: Янв. 21, 2025
Язык: Английский
Процитировано
7
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
Процитировано
1
Kidney International, Год журнала: 2023, Номер 104(5), С. 995 - 1007
Опубликована: Авг. 19, 2023
Язык: Английский
Процитировано
17
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
Процитировано
16
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
Процитировано
14
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
Процитировано
6
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
Процитировано
6
American Journal of Medical Genetics Part C Seminars in Medical Genetics, Год журнала: 2022, Номер 190(3), С. 309 - 324
Опубликована: Сен. 1, 2022
The clinical characteristics of autosomal dominant tubulointerstitial kidney disease (ADTKD) include bland urinary sediment, slowly progressive chronic (CKD) with many patients reaching end stage renal (ESRD) between age 20 and 70 years, inheritance. Due to advances in genetic diagnosis, ADTKD is becoming increasingly recognized as a cause CKD. Pathogenic variants UMOD, MUC1, REN are the most common causes ADTKD. ADTKD-UMOD also associated hyperuricemia gout. ADTKD-REN often presents childhood mild hypotension, CKD, hyperkalemia, acidosis, anemia. ADTKD-MUC1 present only This review describes pathophysiology, genetics, manifestation, diagnosis for ADTKD, an emphasis on testing counseling suggestions patients.
Язык: Английский
Процитировано
17
npj Genomic Medicine, Год журнала: 2023, Номер 8(1)
Опубликована: Июль 7, 2023
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of failure and primarily associated with PKD1 or PKD2. Approximately 10% patients remain undiagnosed after standard genetic testing. We aimed to utilise short long-read genome sequencing RNA studies investigate families. Patients typical ADPKD phenotype diagnostics were recruited. Probands underwent short-read sequencing, PKD2 coding non-coding analyses then genome-wide analysis. Targeted investigated variants suspected impact splicing. Those Oxford Nanopore Technologies sequencing. From over 172 probands, 9 met inclusion criteria consented. A diagnosis was made in 8 (89%) families on prior Six had impacting splicing, five regions PKD1. Short-read identified novel branchpoint, AG-exclusion zone missense generating cryptic splice sites a deletion causing critical intron shortening. Long-read confirmed one family. Most have splice-impacting describe pragmatic method for diagnostic laboratories assess validate splicing through targeted studies.
Язык: Английский
Процитировано
11
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
Процитировано
11