Autosomal Dominant Polycystic Kidney Disease Inflammation Biomarkers in the Tolvaptan Era

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1121 - 1121

Published: Jan. 28, 2025

With the approval of tolvaptan as first specific medicine for treatment rapidly progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD), biomarker discovery has gained renewed interest it is widely recognized that these will be crucial in clinical decision-making, serving either prognostic or predictive tools. Since marketing authorization was issued 2015 ADPKD, remained sole pharmacological compound specifically targeting disease. For ADPKD patients an invaluable retarding disease progression. Although field overall and validation been detailed several publications, role inflammation remains largely overlooked ADPKD. The current work aims to provide reader with updated review biomarkers research highlighting urinary MCP-1 (monocyte chemoattractant protein-1) most promising tool.

Language: Английский

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G-quadruplex stabilization provokes DNA breaks in human PKD1, revealing a second hit mechanism for ADPKD

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Abstract The “secondhit” pathway is responsible for biallelic inactivation of many tumor suppressors, where a pathogenic germline allele joined by somatic mutation the remaining functional allele. mechanisms are unresolved, but human PKD1 suppressor good experimental model identifying molecular determinants. Inactivation results in autosomal dominant polycystic kidney disease, very common disorder characterized accumulation fluid-filled cysts and end-stage renal disease. Since follows second hit mouse Pkd1 heterozygotes do not, we reasoned that there likely difference explains elevated mutagenesis gene. Here demonstrate guanine quadruplex DNA structures abundant throughout human, not mouse, they activate damage response. Our suggest DNAs provoke breaks , providing potential mechanism cystogenesis disease specifically quadruplex-rich suppressors generally.

Language: Английский

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Mechanisms of Cyst Expansion in Polycystic Kidney Disease

Journal of the American Society of Nephrology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany Correspondence: Prof. Dr. med. Kai M. Schmidt-Ott, email: [email protected] See related article, "Adamts1 Cyst Expansion in Polycystic Kidney Disease," on pages XXX–XXX.

Language: Английский

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STING Promotes the Progression of ADPKD by Regulating Mitochondrial Function, Inflammation, Fibrosis, and Apoptosis

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1215 - 1215

Published: Sept. 26, 2024

Autosomal dominant polycystic kidney disease (ADPKD) is a predominant genetic disease, which caused by mutations in PKD genes and associated with DNA damage cystic cells. The intrinsic stimulator of interferon (STING) pathway crucial for recognizing damaged the cytosol, triggering expression inflammatory cytokines to activate defense mechanisms. However, precise roles mechanisms STING ADPKD remain elusive. In this study, we show that

Language: Английский

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End-stage ADPKD with a low-frequency PKD1 mosaic variant accelerated by chemoradiotherapy

Human Genome Variation, Journal Year: 2024, Volume and Issue: 11(1)

Published: March 28, 2024

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is commonly caused by PKD1 , and mosaic variants result in milder phenotypes. We present the case of a 32 year-old male with chronic active Epstein–Barr virus who underwent bone marrow transplantation chemoradiotherapy at age 9. Despite low-frequency splicing variant, he developed severe renal cysts end-stage his 30 s. This highlights how environmental factors may contribute to genetic predisposition ADPKD.

Language: Английский

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Human

PubMed, Journal Year: 2024, Volume and Issue: 2024

Published: Jan. 1, 2024

Autosomal dominant polycystic kidney disease results from the loss of

Language: Английский

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Concomitant Wilms Tumor and Autosomal Dominant Polycystic Kidney Disease

Authorea (Authorea), Journal Year: 2024, Volume and Issue: unknown

Published: June 25, 2024

Background: Concomitant Wilms tumor (WT) and autosomal dominant polycystic kidney disease (ADPKD) is exceedingly rare, presenting a diagnostic technical challenge to pediatric surgical oncologists. The simultaneous workup management of these processes incompletely described. Procedure: We performed retrospective analysis patients treated at our institution with concomitant diagnoses WT ADPKD. also review the literature on underlying biology principles conditions. Results: present three diverse cases unilateral ADPKD who underwent nephrectomy. One patient had preoperative imaging consistent confirmatory testing postoperatively, one was found have contralateral renal cysts intraoperatively post-nephrectomy, diagnosed in childhood post-nephrectomy. All are alive last follow-up, longest follow-up has progressed end-stage failure requiring transplantation dialysis adulthood. germline were no cancer predisposition syndrome or pathogenic likely-pathogenic variants for WT. Conclusion: inheritance development extremely manifestations may not until late known predisposing condition When diagnosis made by family history, imaging, and/or genetic before treatment, need extensive characterization cystic lesions children increased risk post-nephrectomy warrant further discussion approach peri-operative strategies.

Language: Английский

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Kidney involvement in rare hereditary diseases

Terapevticheskii arkhiv, Journal Year: 2024, Volume and Issue: 96(6), P. 559 - 564

Published: July 7, 2024

Various rare inherited disorders can be associated with kidney involvement, including glomerulopathies, tubulopathies, multiple cysts, congenital anomalies of the kidneys and urinary tract, urolithiasis, malignant benign tumors. Genetic nephropathy should always considered in children, adolescents young patients or tract and/or positive family anamnesis. Extrarenal manifestations a valuable clue for diagnosis certain hereditary diseases, e.g. neurosensory deafness Alport syndrome photofobia nephropathic cystinosis. Diagnosis monogenic diseases verified by genetic testing. Specific drugs are available treatment involving kidney, Fabry disease, cystinosis, primary hyperoxaluria I type atypical hemolytic uremic syndrome.

Language: Английский

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Concomitant Wilms tumor and autosomal dominant polycystic kidney disease

Pediatric Blood & Cancer, Journal Year: 2024, Volume and Issue: 71(10)

Published: July 31, 2024

Abstract Background Concomitant Wilms tumor (WT) and autosomal dominant polycystic kidney disease (ADPKD) is exceedingly rare, presenting a diagnostic technical challenge to pediatric surgical oncologists. The simultaneous workup management of these processes are incompletely described. Procedure We performed retrospective analysis patients treated at our institution with concomitant diagnoses WT ADPKD. also review the literature on underlying biology principles conditions. Results present three diverse cases unilateral ADPKD who underwent nephrectomy. One patient had preoperative imaging consistent confirmatory testing postoperatively, one was found have contralateral renal cysts intraoperatively post nephrectomy, diagnosed in childhood All alive last follow‐up, longest follow‐up has progressed end‐stage failure requiring transplantation dialysis adulthood. germline were no cancer predisposition syndrome or pathogenic likely variants for WT. Conclusion inheritance development extremely manifestations may not until late known predisposing condition When diagnosis made by family history, imaging, and/or genetic before treatment, need extensive characterization cystic lesions children increased risk post‐nephrectomy warrant further discussion approach perioperative strategies.

Language: Английский

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Rare inherited diseases with kidney involvement: approaches to diagnosis and treatment

Clinical pharmacology and therapy, Journal Year: 2023, Volume and Issue: 38(3), P. 6 - 18

Published: Sept. 2, 2023

Many rare inherited disorders can be associated with the various types of kidney involvement, including glomerular disease, tubulopathies, congenital anomalies kidneys and urinary tract, urolithiasis, multiple cysts, malignant benign tumors. Hereditary nephropathy should always considered in children, adolescents young patients kdineys or tract and/or positive family anamnesis although certain genetic diseases manifest adult even elderly whereas proband members frequently show no signs disease. Extrarenal manifestations a valuable clue for diagnosis disorders, e.g. neurosensory deafness Alport syndrome, cornea verticillata angiokeratoma Fabry photofobia nephropathic cystinosis. Genetic tests are essential verification monogenic diseases. In nearest future, whole-exome genome sequencing at constantly decreasing cost may replace targeted known causal gene(s) gene panels, particularly when present similar clinical phenotypes.

Language: Английский

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