The natural history of chronic kidney disease describes a progressive decrease in renal function assessed by glomerular filtration rate. After the initial phase, this decrease is related to the occurence of physiological adaptation mechanisms independent of the primary renal disease. It is accompanied by the gradual appearance of clinical and metabolic abnormalities that can be largely prevented by early management including careful monitoring and appropriate treatments. The main determinants of the risk of progression to end-stage renal failure requiring the use of replacement therapy are initial glomerular filtration rate, as an index of residual renal mass, the amount of proteinuria, and the level of blood pressure. The last two factors are the main targets of nephroprotective treatment based on the blockade of the renin-angiotensin system. Other elements of nephroprotective treatment are parts of a multifactorial approach that identifies and corrects individual factors present in each patient, and prevents acute exacerbations related to intercurrent events or inappropriate interventions. Such a treatment strategy significantly reduces the risk of progression to end-stage renal disease, and of cardiovascular events to which these patients are particularly exposed.
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Sci Rep
December 2024
Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310000, People's Republic of China.
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December 2024
Department of Medical and Surgical Sciences, Institute of Cardiology, University of Bologna, Policlinico S.Orsola-Malpighi, via Massarenti 9, Bologna, 40138, Italy.
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December 2024
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
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December 2024
Department of Molecular and Medical Genetics, Oregon Health & Science University School of Medicine, Portland, OR, USA.
AAV vectors show promise for gene therapy; however, kidney gene transfer remains challenging. Here we conduct a barcode-seq-based comparison of 47 AAV capsids administered through different routes in mice, followed by individual validation. We find that local delivery of AAV-KP1, but not AAV9, via the renal vein or pelvis effectively transduces proximal tubules with minimal off-target liver transduction, while systemic AAV9, but not AAV-KP1, enhances proximal tubule and podocyte transduction in chronic kidney disease.
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December 2024
Department of Nephrology, Ankara Bilkent City Hospital, Ankara, Turkey.
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