The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development o...The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate < 30 m L/min per 1.73 m^2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.展开更多
Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests tha...Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests that impaired cholesterol metabolism,increased lipid uptake or synthesis,increased fatty acid oxidation,lipid droplet accumulation and an imbalance in biologically active sphingolipids(such as ceramide,ceramide-1-phosphate and sphingosine-1-phosphate)contribute to the development of diabetic kidney disease(DKD).Currently,the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production,oxidative stress,inflammation,or cell death.Therefore,control of renal lipid dysmetabolism is a very important therapeutic goal,which needs to be archived.This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.展开更多
Lipid droplets(LDs)are lipid storage organelles with a central hydrophobic core of neutral lipids that is enclosed in a monolayer of phospholipids.Though the storage of lipids,mainly cholesterol and triglycerides,was ...Lipid droplets(LDs)are lipid storage organelles with a central hydrophobic core of neutral lipids that is enclosed in a monolayer of phospholipids.Though the storage of lipids,mainly cholesterol and triglycerides,was thought to be the primary function of LDs,studies have shown that they have important functions in maintaining lipid homeostasis and modulating various signaling pathways.Abnormal lipid accumulation has been recognized as a key feature in several human diseases such as obesity,diabetes,cancer,neurological diseases,cardiovascular diseases,insulin resistance,liver diseases and kidney diseases.LDs play an important role in innate immunity,in the fight against infections,and in the replication of SARS-CoV-2.Hence a tight regulation of LD metabolism is essential for proper functioning of a cell.展开更多
文摘The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate < 30 m L/min per 1.73 m^2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.
基金the National Institute of Health(Research in Dr.Alessia Fornoni’s laboratory),No.R01DK117599,No.R01DK104753,No.R01CA227493,No.U54DK083912,No.UM1DK100846,and No.U01DK116101the Miami Clinical Translational Science Institute,No.UL1TR000460and the Chernowitz Medical Research Foundation(Mitrofanova A and Burke G),No.GR016291.
文摘Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests that impaired cholesterol metabolism,increased lipid uptake or synthesis,increased fatty acid oxidation,lipid droplet accumulation and an imbalance in biologically active sphingolipids(such as ceramide,ceramide-1-phosphate and sphingosine-1-phosphate)contribute to the development of diabetic kidney disease(DKD).Currently,the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production,oxidative stress,inflammation,or cell death.Therefore,control of renal lipid dysmetabolism is a very important therapeutic goal,which needs to be archived.This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.
基金This project was supported by grants from National Institutes of Health(No.R01DK117599,R01DK104753 and R01CA227493)to A.F.and S.Mthe Miami Clinical Translational Science Institute(No.U54DK083912,UM1DK100846,U01DK116101 and UL1TR000460)to A.F,and the Ophthalmology mass spectrometry facility,Vision Core grant(No.EY14801).
文摘Lipid droplets(LDs)are lipid storage organelles with a central hydrophobic core of neutral lipids that is enclosed in a monolayer of phospholipids.Though the storage of lipids,mainly cholesterol and triglycerides,was thought to be the primary function of LDs,studies have shown that they have important functions in maintaining lipid homeostasis and modulating various signaling pathways.Abnormal lipid accumulation has been recognized as a key feature in several human diseases such as obesity,diabetes,cancer,neurological diseases,cardiovascular diseases,insulin resistance,liver diseases and kidney diseases.LDs play an important role in innate immunity,in the fight against infections,and in the replication of SARS-CoV-2.Hence a tight regulation of LD metabolism is essential for proper functioning of a cell.