Future directions in ADPKD prognostication point toward multimodal frameworks that integrate AI-derived imaging features, genomic risk measures, clinical risk factors, and molecular biomarkers, which could help translate complex disease information into more consistent, clinically actionable guidance for treatment decisions and shared decision-making.
Abstract
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent hereditary kidney disorder. While the disease is well-defined, its clinical course is highly variable, making the prediction of individual patient outcomes a significant challenge for clinicians and a source of psychological distress for those affected. Current prognostic tools fall into two primary categories: imaging-based models and genetic scoring systems. However, these unimodal approaches have inherent limitations. Imaging-based metrics often lose prognostic resolution in advanced disease stages as fibrosis begins to outweigh cyst expansion. Meanwhile, genetic scoring often fails to account for intrafamilial variability and may underestimate risk in a significant percentage of rapid progressors. Upcoming tools seek to fill these gaps by exploring new dimensions of the disease, including genome-wide polygenic scores (GPS) to account for background genetic influences and imaging approaches that use artificial intelligence that can capture cyst architecture and parenchymal changes beyond conventional volumetric measures. Future directions in ADPKD prognostication point toward multimodal frameworks that integrate AI-derived imaging features, genomic risk measures, clinical risk factors, and molecular biomarkers. Integrated prognostic tools could help translate complex disease information into more consistent, clinically actionable guidance for treatment decisions and shared decision-making.
Autosomal recessive polycystic kidney disease (ARPKD) is a rare, genetic ciliopathy with significant associated morbidity and mortality. ARPKD kidney disease is characterized by diffuse kidney fusiform collecting duct dilatations (microcysts) leading to progressive kidney dysfunction. Patients with ARPKD can also develop clinically-significant congenital hepatic fibrosis and portal hypertension. Despite advances in clinical management, there are currently no disease-modifying therapies approved for ARPKD, and the development of clinical trials has been limited by the lack of sensitive, non-invasive biomarkers capable of detecting early disease progression in both the kidney and liver. MRI provides a unique opportunity to address this gap by offering multiparametric, quantitative assessments of tissue structure and function without ionizing radiation or, in many cases, contrast agents. This review summarizes emerging quantitative MRI-based techniques that show promise as imaging biomarkers for children and young adults with ARPKD. These advanced MRI approaches enable comprehensive characterization of the multi-faceted structural and functional changes in the kidney and liver associated with ARPKD. Continued development and harmonization of these quantitative imaging biomarkers across institutions will be critical for enabling multi-center studies and supporting future therapeutic trials aimed at improving outcomes for children and young adults with ARPKD.
Christina J MacAskill, Jacob B Smothers, Madison E. Kretzler et al.· Pediatric Radiology· 0 citations
Chronic kidney disease (CKD) is a heterogeneous, progressive condition where the measurement of functional aspects and clinical phenotypes might not be sufficient in evaluating the underlying structural damage. This review synthesizes evidence on clinicopathological correlation in CKD and evaluates how integrating histopathology with clinical assessment, laboratory markers, and imaging improves diagnostic precision and prognostic assessment. Key clinicopathological relationships are highlighted, including how proteinuria and active urinary sediment often signal glomerular injury, whereas declining renal function frequently aligns with the burden of tubulointerstitial fibrosis and vascular disease. The review also examines how pathological severity generally increases with advancing CKD stage, limiting reversibility and narrowing therapeutic windows. Importantly, discordance between presumed clinical diagnoses and biopsy findings is common in systemic and comorbidity-driven CKD, underscoring the value of tissue-based evaluation in selected cases. A multidisciplinary framework involving nephrology, pathology, radiology, and laboratory medicine is emphasized as essential for integrated interpretation and individualized care. Emerging biomarkers, advanced imaging approaches, and risk prediction models are discussed as tools that may enhance stratification and support personalized management, while ongoing challenges include disease heterogeneity, methodological limitations, and delayed recognition of progressive injury. Clinicopathological integration provides a robust pathway toward more accurate classification, targeted intervention, and improved outcomes in CKD.
P. Balaji, P. Shanmugasundaram, Shivangi Gupta et al.· Genetics and Molecular Resea...· 0 citations
Underused Drosophila melanogaster offers high genomic and pathway conservation, a wealth of genetic tools, and rapid generation times, making it a reliable and sustainable model for mechanistic, genome-wide, and precision medicine studies.
Jay Deloriea, Cody Casey, Lexee Shearer et al.· Journal of Developmental Bio...· 0 citations
The ease of use of MPS increasingly tempts non-specialized genetic laboratories to perform broad analyses of numerous diseases, which in specific cases may worsen the quality of investigations, i.e. for the relatively frequent ADPKD.
Arif B. Ekici, K. Knaup, C. Schaeffer et al.· American Journal of Kidney D...· 0 citations
Primary mitochondrial diseases (PMDs) are one of the most common genetic disorders with an estimated prevalence of 1 in 4300. This review article summarises the latest updates in the field of mitochondrial medicine over the last decade. The availability of exome and genome sequencing in clinical practice has empowered clinicians to unravel the phenotypic heterogeneity of PMD and to end the diagnostic odyssey experienced by many patients and families. In unresolved cases, the detection of variant(s) of unknown significance by next-generation sequencing creates diagnostic and clinical uncertainties, and integrating a multi-omics approach can improve diagnostic yield. Alongside breakthroughs in genomic technologies, there is growing interest in using fluid biomarkers to guide diagnosis, monitor disease progression, and potentially serve as clinical trial endpoints. However, the clinical application of these fluid biomarkers in unselected patient cohorts with different disease onset and phenotypes would require more robust evidence. Natural history studies derived from national and international collaborations have provided insights into genotype–phenotype relationships and prognostic factors across several genotypes, including m.3243A>G, MT-ATP6, POLG, and TK2. Advances in therapeutic discoveries and clinical trials are challenging the obsolete dogma that PMDs are untreatable and bringing hope to patients; four compounds have been licensed, and many trials are in progress. Many barriers and challenges to translating laboratory discoveries into clinical therapy in PMD remain, including preclinical models for efficacy and safety testing, sample size, trial design, and the selection of outcome measures and trial endpoints.
A. Lim, Aye Moe, R. Stefanetti et al.· Genes· 0 citations
Rare genetic diseases present with a broad spectrum of clinical manifestations, frequently affecting multiple organ systems or causing isolated, severe physical impairments. These disorders represent a profound public health and socioeconomic burden due to prolonged diagnostic delays, suboptimal clinical management, and the lack of targeted therapeutic options. While early detection remains paramount to establishing effective clinical care, rehabilitation protocols, and orthopedic interventions, the molecular etiologies of numerous musculoskeletal, neurodevelopmental, and immunological rare conditions remain completely unknown. Key drivers of this diagnostic gap include fragmented healthcare access, high costs of advanced genomic technologies, and a lack of integrated research pipelines capable of translating variants of uncertain significance into confirmed disease-causing genes. Identifying and functionally validating these genetic factors is essential for expanding the known Mendeliome, discovering novel diagnostic biomarkers, and revealing targetable pathways for future therapeutics. In this review, using an implementation model, we evaluate the global and regional burdens of undiagnosed rare genetic diseases and outline a strategic, multi-omics functional workflow tailored to address complex, hidden variants in the highly consanguineous population of Saudi Arabia.
Naif A. M. Almontashiri· Journal of Musculoskeletal S...· 0 citations
