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  • CD36 in chronic kidney disease: novel insights and therapeutic opportunities
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Xiaochun Yang, Daryl M. Okamura, Xifeng Lu, Yaxi Chen, John Moorhead, Zac Varghese, Xiong Z. Ruan

    CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates the binding and cellular uptake of long-chain fatty acids, oxidized lipids and phospholipids, advanced oxidation protein products, thrombospondin and advanced glycation end products, and has roles in lipid accumulation, inflammatory signalling, energy reprogramming, apoptosis and kidney fibrosis. Renal CD36 is mainly expressed in tubular epithelial cells, podocytes and mesangial cells, and is markedly upregulated in the setting of chronic kidney disease (CKD). As fatty acids are the preferred energy source for proximal tubule cells, a reduction in fatty acid oxidation in CKD affects kidney lipid metabolism by disrupting the balance between fatty acid synthesis, uptake and consumption. The outcome is intracellular lipid accumulation, which has an important role in the pathogenesis of kidney fibrosis. In experimental models, antagonist blockade or genetic knockout of CD36 prevents kidney injury, suggesting that CD36 could be a novel target for therapy. Here, we discuss the regulation and post-translational modification of CD36, its role in renal pathophysiology and its potential as a biomarker and as a therapeutic target for the prevention of kidney fibrosis.

    更新日期:2017-09-20
  • CD36 in chronic kidney disease: novel insights and therapeutic opportunities
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-09-18
    Xiaochun Yang, Daryl M. Okamura, Xifeng Lu, Yaxi Chen, John Moorhead, Zac Varghese, Xiong Z. Ruan

    CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates the binding and cellular uptake of long-chain fatty acids, oxidized lipids and phospholipids, advanced oxidation protein products, thrombospondin and advanced glycation end products, and has roles in lipid accumulation, inflammatory signalling, energy reprogramming, apoptosis and kidney fibrosis. Renal CD36 is mainly expressed in tubular epithelial cells, podocytes and mesangial cells, and is markedly upregulated in the setting of chronic kidney disease (CKD). As fatty acids are the preferred energy source for proximal tubule cells, a reduction in fatty acid oxidation in CKD affects kidney lipid metabolism by disrupting the balance between fatty acid synthesis, uptake and consumption. The outcome is intracellular lipid accumulation, which has an important role in the pathogenesis of kidney fibrosis. In experimental models, antagonist blockade or genetic knockout of CD36 prevents kidney injury, suggesting that CD36 could be a novel target for therapy. Here, we discuss the regulation and post-translational modification of CD36, its role in renal pathophysiology and its potential as a biomarker and as a therapeutic target for the prevention of kidney fibrosis.

    更新日期:2017-09-20
  • Immunology: The renal sodium gradient in antimicrobial defence
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Susan J. Allison

    Urinary tract infections are common but rarely extend to the kidneys — an effect that has been attributed, at least in part, to the mechanical consequences of urine flow. New research now shows that the high interstitial sodium concentration in the renal medulla generates a

    更新日期:2017-09-19
  • Renal physiology: The sexually dimorphic kidney
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Shimona Starling

    Before the age of 60, females are protected from cardiovascular and renal disease relative to males. Alicia McDonough and colleagues show that there is a sexually dimorphic pattern of renal tranporters across the nephron and that this pattern may be associated with the 'female advantage'.

    更新日期:2017-09-19
  • Podocyte biology: Proteolytic processing in podocytes
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-08-07
    Grant Otto

    Podocytes are crucial components of the glomerular filtration barrier in the kidney. Podocyte function at this barrier is dependent on proteases, such as cathepsins and matrix metalloproteases. New research has analysed protein cleavage events in podocytes using a novel proteome-wide 'degradomics' approach. “The degradomics method

    更新日期:2017-09-19
  • Chronic kidney disease: PLD4 regulates kidney fibrosis
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Ellen F. Carney

    The transmembrane glycoprotein phospholipase D4 (PLD4) regulates fibrogenesis in the kidney, according to new findings from Vishal Vaidya, Priyanka Trivedi and colleagues. They suggest that targeting PLD4 could be a novel therapeutic strategy to reverse kidney fibrosis.“Our group previously identified PLD4 as one of

    更新日期:2017-09-19
  • Glomerular disease: Functional consequences of C5 nephritic factors in C3 glomerulopathies
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-31
    Ellen F. Carney

    C3 glomerulopathies (C3G) are caused by dysregulation of the alternative complement pathway. In >50% of cases, these diseases are associated with expression of autoantibodies known as C3 nephritic factors (C3Nefs), which stabilize the alternative pathway C3 convertase C3bBb. Now, researchers report a role of C5Nefs,

    更新日期:2017-09-19
  • Polycystic kidney disease: FPC in ARPKD
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-08-07
    Susan J. Allison

    Although mutations in PKHD1 are known to cause autosomal recessive polycystic kidney disease (ARPKD), very little is known about the function of its gene product, fibrocystin/polyductin (FPC). Recent research using a novel mouse model to enable tracking of full-length FPC and its cleaved C-terminus

    更新日期:2017-09-19
  • Chronic kidney disease: KDIGO CKD–MBD guideline update: evolution in the face of uncertainty
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Wei Chen, David A. Bushinsky

    Management of mineral and bone disorders in patients with chronic kidney disease (CKD–MBD) requires an understanding of the complex interactions among ions, hormones and their target organs. Since publication of the KDIGO CKD–MBD guideline in 2009, our understanding of disease pathophysiology has improved; however, a paucity of high-quality clinical evidence to support specific interventions remains. Using available data, KDIGO has now updated diagnostic and therapeutic recommendations for patients with CKD–MBD.

    更新日期:2017-09-19
  • Hypertension: A new genetic clue to unravel the origins of pre-eclampsia
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Eric M. George, Joey P. Granger

    Pre-eclampsia is a common disorder of pregnancy for which the underlying mechanism is poorly understood. A genome-wide association study has now identified a pre-eclampsia susceptibility locus located near the FLT1 gene. This study brings us a step closer to dissecting the underlying causes of pre-eclampsia.

    更新日期:2017-09-19
  • Pre-eclampsia: Screening and aspirin therapy for prevention of pre-eclampsia
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    James M. Roberts, Katherine P. Himes

    Aspirin therapy for the prevention of pre-eclampsia in unselected women is minimally effective. New data suggest that use of a screening strategy based on clinical, biochemical and biophysical factors to identify those at high risk of pre-term pre-eclampsia could improve the efficacy of preventive aspirin therapy.

    更新日期:2017-09-19
  • GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Marcel H. A. Muskiet, Lennart Tonneijck, Mark M. Smits, Michaël J.B. van Baar, Mark H. H. Kramer, Ewout J. Hoorn, Jaap A. Joles, Daniël H. van Raalte

    The gastrointestinal tract — the largest endocrine network in human physiology — orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects. The observation that the insulinotropic actions of GLP-1 are reduced in type 2 diabetes mellitus (T2DM) led to the development of incretin-based therapies — GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors — for the treatment of hyperglycaemia in these patients. Considerable interest exists in identifying effects of these drugs beyond glucose-lowering, possibly resulting in improved macrovascular and microvascular outcomes, including in diabetic kidney disease. As GLP-1 has been implicated as a mediator in the putative gut–renal axis (a rapid-acting feed-forward loop that regulates postprandial fluid and electrolyte homeostasis), direct actions on the kidney have been proposed. Here, we review the role of GLP-1 and the actions of associated therapies on glucose metabolism, the gut–renal axis, classical renal risk factors, and renal end points in randomized controlled trials of GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM.

    更新日期:2017-09-19
  • Mitochondrial energetics in the kidney
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-08-14
    Pallavi Bhargava, Rick G. Schnellmann

    The kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive these important functions and can adapt to different metabolic conditions through a number of signalling pathways (for example, mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways) that activate the transcriptional co-activator peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), and by balancing mitochondrial dynamics and energetics to maintain mitochondrial homeostasis. Mitochondrial dysfunction leads to a decrease in ATP production, alterations in cellular functions and structure, and the loss of renal function. Persistent mitochondrial dysfunction has a role in the early stages and progression of renal diseases, such as acute kidney injury (AKI) and diabetic nephropathy, as it disrupts mitochondrial homeostasis and thus normal kidney function. Improving mitochondrial homeostasis and function has the potential to restore renal function, and administering compounds that stimulate mitochondrial biogenesis can restore mitochondrial and renal function in mouse models of AKI and diabetes mellitus. Furthermore, inhibiting the fission protein dynamin 1-like protein (DRP1) might ameliorate ischaemic renal injury by blocking mitochondrial fission.

    更新日期:2017-09-19
  • T helper type 17 cells in immune-mediated glomerular disease
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-08-07
    Christian F. Krebs, Tilman Schmidt, Jan-Hendrik Riedel, Ulf Panzer

    CD4+ T cells are important drivers of tissue damage in immune-mediated renal diseases, such as anti-glomerular basement membrane glomerulonephritis, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis. The discovery of a distinct, IL-17-producing CD4+ T-cell lineage termed T helper type 17 (TH17) cells has markedly advanced current understanding of the pathogenic mechanisms of organ-specific immunity and the pathways that lead to target organ damage. TH17 cells are characterized by the expression of the transcription factor RORγt, the production of the pro-inflammatory cytokines IL-17A, IL-17F, IL-22, and high expression of the chemokine receptor C-C-motif chemokine receptor 6 (CCR6). An emerging body of evidence from experimental models and human studies supports a key role for these cells in the development of renal damage, and has led to the identification of targets to inhibit the production of TH17 cells in the intestine, their migration, or their actions within the kidney. Here, we describe the identification, regulation, and function of TH17 cells and their associated pathways in immune-mediated kidney diseases, with a particular focus on the mechanisms underlying renal tissue injury. We also discuss the rationale for the translation of these findings into new therapeutic approaches in patients with autoimmune kidney disease.

    更新日期:2017-09-19
  • Kidney cancer: Targeting Wilms tumour
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Grant Otto

    Kidney cancer: Targeting Wilms tumourNature Reviews Nephrology, Published online: 11 September 2017; doi:10.1038/nrneph.2017.131

    更新日期:2017-09-12
  • Nephrotic syndrome: Novel monogenic causes of Galloway–Mowat syndrome
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Ellen F. Carney

    Nephrotic syndrome: Novel monogenic causes of Galloway–Mowat syndromeNature Reviews Nephrology, Published online: 11 September 2017; doi:10.1038/nrneph.2017.130

    更新日期:2017-09-12
  • Transplantation: IdeS to desensitize organ allograft recipients
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-09-11
    Georg A. Böhmig, Lionel Rostaing

    Transplantation: IdeS to desensitize organ allograft recipientsNature Reviews Nephrology, Published online: 11 September 2017; doi:10.1038/nrneph.2017.128HLA sensitization greatly increases the risk of transplant rejection and failure. An IgG endopeptidase derived from Streptococcus pyogenes (IdeS) may be an attractive new therapy for desensitization. Recent data indicate that IdeS effectively depletes anti-HLA IgG, creating a therapeutic window for successful renal transplantation in sensitized recipients.

    更新日期:2017-09-12
  • Kidney cancer: Targeting Wilms tumour
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Grant Otto

    Kidney cancer: Targeting Wilms tumour Nature Reviews Nephrology, Published online: 11 September 2017; doi:10.1038/nrneph.2017.131

    更新日期:2017-09-11
  • Nephrotic syndrome: Novel monogenic causes of Galloway–Mowat syndrome
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Ellen F. Carney

    Nephrotic syndrome: Novel monogenic causes of Galloway–Mowat syndrome Nature Reviews Nephrology, Published online: 11 September 2017; doi:10.1038/nrneph.2017.130

    更新日期:2017-09-11
  • Transplantation: IdeS to desensitize organ allograft recipients
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Georg A. Böhmig, Lionel Rostaing

    Transplantation: IdeS to desensitize organ allograft recipients Nature Reviews Nephrology, Published online: 11 September 2017; doi:10.1038/nrneph.2017.128 HLA sensitization greatly increases the risk of transplant rejection and failure. An IgG endopeptidase derived from Streptococcus pyogenes (IdeS) may be an attractive new therapy for desensitization. Recent data indicate that IdeS effectively depletes anti-HLA IgG, creating a therapeutic window for successful renal transplantation in sensitized recipients.

    更新日期:2017-09-11
  • Pre-eclampsia: Screening and aspirin therapy for prevention of pre-eclampsia
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-09-04
    James M. Roberts, Katherine P. Himes

    Pre-eclampsia: Screening and aspirin therapy for prevention of pre-eclampsia Nature Reviews Nephrology, Published online: 4 September 2017; doi:10.1038/nrneph.2017.121 Aspirin therapy for the prevention of pre-eclampsia in unselected women is minimally effective. New data suggest that use of a screening strategy based on clinical, biochemical and biophysical factors to identify those at high risk of pre-term pre-eclampsia could improve the efficacy of preventive aspirin therapy.

    更新日期:2017-09-08
  • Cardiac surgery-associated acute kidney injury: risk factors, pathophysiology and treatment
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-09-04
    Ying Wang, Rinaldo Bellomo

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is the most common clinically important complication in adult patients undergoing open heart surgery, and is associated with increased mortality and morbidity. In patients in intensive care units, CSA-AKI is the second most common type of AKI after septic AKI. In this Review, we explore the definition of CSA-AKI, discuss its epidemiology and identify its risk factors. We discuss current theories of the pathophysiology of CSA-AKI and describe its clinical course. Furthermore, we introduce diagnostic tools with particular reference to novel biomarkers of AKI and their potential utility; we analyse currently applied interventions aimed at attenuating AKI in patients undergoing cardiac surgery; and describe evidence from randomized controlled trials aimed at preventing or treating CSA-AKI. Finally, we explore issues in the use of renal replacement therapy, its timing, its intensity and its preferred modalities in patients with CSA-AKI, and we discuss the prognosis of CSA-AKI in terms of patient survival and kidney recovery.

    更新日期:2017-09-08
  • GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-09-04
    Marcel H. A. Muskiet, Lennart Tonneijck, Mark M. Smits, Michaël J.B. van Baar, Mark H. H. Kramer, Ewout J. Hoorn, Jaap A. Joles, Daniël H. van Raalte

    The gastrointestinal tract — the largest endocrine network in human physiology — orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects. The observation that the insulinotropic actions of GLP-1 are reduced in type 2 diabetes mellitus (T2DM) led to the development of incretin-based therapies — GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors — for the treatment of hyperglycaemia in these patients. Considerable interest exists in identifying effects of these drugs beyond glucose-lowering, possibly resulting in improved macrovascular and microvascular outcomes, including in diabetic kidney disease. As GLP-1 has been implicated as a mediator in the putative gut–renal axis (a rapid-acting feed-forward loop that regulates postprandial fluid and electrolyte homeostasis), direct actions on the kidney have been proposed. Here, we review the role of GLP-1 and the actions of associated therapies on glucose metabolism, the gut–renal axis, classical renal risk factors, and renal end points in randomized controlled trials of GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM.

    更新日期:2017-09-08
  • Chronic kidney disease: PLD4 regulates kidney fibrosis
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Ellen F. Carney

    Chronic kidney disease: PLD4 regulates kidney fibrosis Nature Reviews Nephrology, Published online: 4 September 2017; doi:10.1038/nrneph.2017.125

    更新日期:2017-09-08
  • Hypertension: A new genetic clue to unravel the origins of pre-eclampsia
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-09-04
    Eric M. George, Joey P. Granger

    Hypertension: A new genetic clue to unravel the origins of pre-eclampsia Nature Reviews Nephrology, Published online: 4 September 2017; doi:10.1038/nrneph.2017.116 Pre-eclampsia is a common disorder of pregnancy for which the underlying mechanism is poorly understood. A genome-wide association study has now identified a pre-eclampsia susceptibility locus located near the FLT1 gene. This study brings us a step closer to dissecting the underlying causes of pre-eclampsia.

    更新日期:2017-09-08
  • Immunology: The renal sodium gradient in antimicrobial defence
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Susan J. Allison

    Immunology: The renal sodium gradient in antimicrobial defence Nature Reviews Nephrology, Published online: 30 August 2017; doi:10.1038/nrneph.2017.124

    更新日期:2017-09-08
  • Chronic kidney disease: KDIGO CKD–MBD guideline update: evolution in the face of uncertainty
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-08-21
    Wei Chen, David A. Bushinsky

    Chronic kidney disease: KDIGO CKD–MBD guideline update: evolution in the face of uncertainty Nature Reviews Nephrology, Published online: 21 August 2017; doi:10.1038/nrneph.2017.118 Management of mineral and bone disorders in patients with chronic kidney disease (CKD–MBD) requires an understanding of the complex interactions among ions, hormones and their target organs. Since publication of the KDIGO CKD–MBD guideline in 2009, our understanding of disease pathophysiology has improved; however, a paucity of high-quality clinical evidence to support specific interventions remains. Using available data, KDIGO has now updated diagnostic and therapeutic recommendations for patients with CKD–MBD.

    更新日期:2017-09-08
  • Renal physiology: The sexually dimorphic kidney
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Shimona Starling

    Renal physiology: The sexually dimorphic kidney Nature Reviews Nephrology, Published online: 21 August 2017; doi:10.1038/nrneph.2017.122

    更新日期:2017-09-08
  • Cardiac surgery-associated acute kidney injury: risk factors, pathophysiology and treatment
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 
    Ying Wang, Rinaldo Bellomo

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is the most common clinically important complication in adult patients undergoing open heart surgery, and is associated with increased mortality and morbidity. In patients in intensive care units, CSA-AKI is the second most common type of AKI after septic AKI. In this Review, we explore the definition of CSA-AKI, discuss its epidemiology and identify its risk factors. We discuss current theories of the pathophysiology of CSA-AKI and describe its clinical course. Furthermore, we introduce diagnostic tools with particular reference to novel biomarkers of AKI and their potential utility; we analyse currently applied interventions aimed at attenuating AKI in patients undergoing cardiac surgery; and describe evidence from randomized controlled trials aimed at preventing or treating CSA-AKI. Finally, we explore issues in the use of renal replacement therapy, its timing, its intensity and its preferred modalities in patients with CSA-AKI, and we discuss the prognosis of CSA-AKI in terms of patient survival and kidney recovery.

    更新日期:2017-09-07
  • Mitochondrial energetics in the kidney
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-08-14
    Pallavi Bhargava, Rick G. Schnellmann

    The kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive these important functions and can adapt to different metabolic conditions through a number of signalling pathways (for example, mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways) that activate the transcriptional co-activator peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), and by balancing mitochondrial dynamics and energetics to maintain mitochondrial homeostasis. Mitochondrial dysfunction leads to a decrease in ATP production, alterations in cellular functions and structure, and the loss of renal function. Persistent mitochondrial dysfunction has a role in the early stages and progression of renal diseases, such as acute kidney injury (AKI) and diabetic nephropathy, as it disrupts mitochondrial homeostasis and thus normal kidney function. Improving mitochondrial homeostasis and function has the potential to restore renal function, and administering compounds that stimulate mitochondrial biogenesis can restore mitochondrial and renal function in mouse models of AKI and diabetes mellitus. Furthermore, inhibiting the fission protein dynamin 1-like protein (DRP1) might ameliorate ischaemic renal injury by blocking mitochondrial fission.

    更新日期:2017-09-06
  • T helper type 17 cells in immune-mediated glomerular disease
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-08-07
    Christian F. Krebs, Tilman Schmidt, Jan-Hendrik Riedel, Ulf Panzer

    CD4+ T cells are important drivers of tissue damage in immune-mediated renal diseases, such as anti-glomerular basement membrane glomerulonephritis, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis. The discovery of a distinct, IL-17-producing CD4+ T-cell lineage termed T helper type 17 (TH17) cells has markedly advanced current understanding of the pathogenic mechanisms of organ-specific immunity and the pathways that lead to target organ damage. TH17 cells are characterized by the expression of the transcription factor RORγt, the production of the pro-inflammatory cytokines IL-17A, IL-17F, IL-22, and high expression of the chemokine receptor C-C-motif chemokine receptor 6 (CCR6). An emerging body of evidence from experimental models and human studies supports a key role for these cells in the development of renal damage, and has led to the identification of targets to inhibit the production of TH17 cells in the intestine, their migration, or their actions within the kidney. Here, we describe the identification, regulation, and function of TH17 cells and their associated pathways in immune-mediated kidney diseases, with a particular focus on the mechanisms underlying renal tissue injury. We also discuss the rationale for the translation of these findings into new therapeutic approaches in patients with autoimmune kidney disease.

    更新日期:2017-09-06
  • Diabetic nephropathy: Restoring podocyte proteostasis in DN
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-24
    Ellen F. Carney

    Impaired podocyte insulin signalling has been shown to promote maladaptive endoplasmic reticulum (ER) signalling in diabetic kidney disease (DKD). Now, Berend Isermann and colleagues report that the cytoprotective coagulation protease activated protein C (aPC) can compensate for defective insulin signalling and restore ER proteostasis in

    更新日期:2017-09-06
  • Cell biology: Connexin connections in GN
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-17
    Grant Otto

    Expression of the gap junction protein connexin 43 (Cx43) is upregulated in chronic kidney disease (CKD). Kavvadas et al. further examined the relationship between Cx43 and kidney injury: “Our goal was to test the efficiency of Cx43 blockade in a severe model of

    更新日期:2017-09-06
  • Polycystic kidney disease: SMYD2 is a novel epigenetic regulator of cyst growth
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-03
    Andrea Aguilar

    Autosomal dominant polycystic kidney disease (ADPKD), which is caused by mutations in PKD1 and PKD2, is the most common inherited kidney disease, but no FDA-approved treatment currently exists. In a new study, Xiaogang Li and colleagues report that the methyltransferase SMYD2 is an

    更新日期:2017-09-06
  • Infection: Impeding UPEC gut colonization
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-17
    Clemens Thoma

    Antibiotic resistance of uropathogenic Escherichia coli (UPEC) results in failure of standard treatments for UTI and recurrent infections in many patients. A new paper in Nature describes oral treatment with a mannoside compound that, by specifically blocking host cell binding via the adhesin

    更新日期:2017-09-06
  • Chronic kidney disease: Role of suPAR in APOL1-associated kidney disease
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-03
    Ellen F. Carney

    Researchers report that soluble urokinase plasminogen activator receptor (suPAR) synergizes with the apolipoprotein L1 (APOL1) risk variants G1 and G2 to activate αvβ3 integrin on podocytes. “Our findings provide an epidemiological and mechanistic explanation for renal disease in APOL1 risk

    更新日期:2017-09-06
  • Polycystic kidney disease: DZIP1L defines a new functional zip code for autosomal recessive PKD
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-24
    Erum A. Hartung, Lisa M. Guay-Woodford

    New findings demonstrate a link between mutations in DZIP1L and an autosomal recessive polycystic kidney disease (ARPKD)-like phenotype. Rather than focus on DZIP1L as a second genetic locus for ARPKD, we suggest these data identify the ciliary transition zone as a functional domain central to the pathogenesis of ARPKD.

    更新日期:2017-09-06
  • Diabetes mellitus: Cardiovascular and renal benefits of SGLT2 inhibition: insights from CANVAS
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-08-07
    Volker Vallon, Scott C. Thomson

    Inhibitors of renal sodium/glucose cotransporter 2 (SGLT2) are new anti-hyperglycaemic drugs that reduce proximal tubular glucose and sodium reabsorption. The Canagliflozin Cardiovascular Assessment Study (CANVAS) Program is the second major trial to demonstrate beneficial effects of SGLT2 inhibitors on the kidney and cardiovascular system in patients with type 2 diabetes mellitus.

    更新日期:2017-09-06
  • Uromodulin: from physiology to rare and complex kidney disorders
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-08-07
    Olivier Devuyst, Eric Olinger, Luca Rampoldi

    Uromodulin (also known as Tamm-Horsfall protein) is exclusively produced in the kidney and is the most abundant protein in normal urine. The function of uromodulin remains elusive, but the available data suggest that this protein might regulate salt transport, protect against urinary tract infection and kidney stones, and have roles in kidney injury and innate immunity. Interest in uromodulin was boosted by genetic studies that reported involvement of the UMOD gene, which encodes uromodulin, in a spectrum of rare and common kidney diseases. Rare mutations in UMOD cause autosomal dominant tubulointerstitial kidney disease (ADTKD), which leads to chronic kidney disease (CKD). Moreover, genome-wide association studies have identified common variants in UMOD that are strongly associated with risk of CKD and also with hypertension and kidney stones in the general population. These findings have opened up a new field of kidney research. In this Review we summarize biochemical, physiological, genetic and pathological insights into the roles of uromodulin; the mechanisms by which UMOD mutations cause ADTKD, and the association of common UMOD variants with complex disorders.

    更新日期:2017-09-06
  • Renal injury: Early apoptotic extracellular vesicles in injury and repair
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-08-18
    Benedetta Bussolati, Giovanni Camussi

    During injury, mitogenic signals from apoptotic cells may compensate for cell loss by promoting organ homeostasis and regeneration. A distinct type of early apoptotic extracellular vesicle with specific mitogenic activity has been identified. The detection of these vesicles in damaged mouse glomeruli highlights their possible role in response to renal injury.

    更新日期:2017-09-06
  • Diabetes mellitus: Complex interplay between metformin, AKI and lactic acidosis
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-24
    Connie M. Rhee, Kamyar Kalantar-Zadeh

    Debate exists regarding the safety of metformin and the risk of metformin-associated lactic acidosis, particularly in the setting of kidney dysfunction. Data from two studies examining the interplay between metformin, acute kidney injury, and complications including lactic acidosis suggest that metformin should be used conservatively in patients with kidney dysfunction.

    更新日期:2017-09-06
  • Extracellular vesicles in renal disease
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-24
    Diana Karpman, Anne-lie Ståhl, Ida Arvidsson

    Extracellular vesicles, such as exosomes and microvesicles, are host cell-derived packages of information that allow cell–cell communication and enable cells to rid themselves of unwanted substances. The release and uptake of extracellular vesicles has important physiological functions and may also contribute to the development and propagation of inflammatory, vascular, malignant, infectious and neurodegenerative diseases. This Review describes the different types of extracellular vesicles, how they are detected and the mechanisms by which they communicate with cells and transfer information. We also describe their physiological functions in cellular interactions, such as in thrombosis, immune modulation, cell proliferation, tissue regeneration and matrix modulation, with an emphasis on renal processes. We discuss how the detection of extracellular vesicles could be utilized as biomarkers of renal disease and how they might contribute to disease processes in the kidney, such as in acute kidney injury, chronic kidney disease, renal transplantation, thrombotic microangiopathies, vasculitides, IgA nephropathy, nephrotic syndrome, urinary tract infection, cystic kidney disease and tubulopathies. Finally, we consider how the release or uptake of extracellular vesicles can be blocked, as well as the associated benefits and risks, and how extracellular vesicles might be used to treat renal diseases by delivering therapeutics to specific cells.

    更新日期:2017-09-06
  • Treatment of membranous nephropathy: time for a paradigm shift
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-03
    Piero Ruggenenti, Fernando C. Fervenza, Giuseppe Remuzzi

    In patients with membranous nephropathy, alkylating agents (cyclophosphamide or chlorambucil) alone or in combination with steroids achieve remission of nephrotic syndrome more effectively than conservative treatment or steroids alone, but can cause myelotoxicity, infections, and cancer. Calcineurin inhibitors can improve proteinuria, but are nephrotoxic. Most patients relapse after treatment withdrawal and can become treatment dependent, which increases the risk of nephrotoxicity. The discovery of nephritogenic autoantibodies against podocyte M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain- containing protein 7A (THSD7A) antigens provides a clear pathophysiological rationale for interventions that specifically target B-cell lineages to prevent antibody production and subepithelial deposition. The anti-CD20 monoclonal antibody rituximab is safe and achieves remission of proteinuria in approximately two-thirds of patients with membranous nephropathy. In those with PLA2R-related disease, remission can be predicted by anti-PLA2R antibody depletion and relapse by antibody re-emergence into the circulation. Thus, integrated evaluation of serology and proteinuria could guide identification of affected patients and treatment with individually tailored protocols. Nonspecific and toxic immunosuppressive regimens will fall out of use. B-cell modulation by rituximab and second-generation anti-CD20 antibodies (or plasma cell-targeted therapy in anti-CD20 resistant forms of disease) will lead to a novel therapeutic paradigm for patients with membranous nephropathy.

    更新日期:2017-09-06
  • Mechanisms and consequences of carbamoylation
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-31
    Sigurd Delanghe, Joris R. Delanghe, Reinhart Speeckaert, Wim Van Biesen, Marijn M. Speeckaert

    Protein carbamoylation is a non-enzymatic post-translational modification that binds isocyanic acid, which can be derived from the dissociation of urea or from the myeloperoxidase-mediated catabolism of thiocyanate, to the free amino groups of a multitude of proteins. Although the term 'carbamoylation' is usually replaced by the term “carbamylation” in the literature, carbamylation refers to a different chemical reaction (the reversible interaction of CO2 with α and ε-amino groups of proteins). Depending on the altered molecule (for example, collagen, erythropoietin, haemoglobin, low-density lipoprotein or high-density lipoprotein), carbamoylation can have different pathophysiological effects. Carbamoylated proteins have been linked to atherosclerosis, lipid metabolism, immune system dysfunction (such as inhibition of the classical complement pathway, inhibition of complement-dependent rituximab cytotoxicity, reduced oxidative neutrophil burst, and the formation of anti-carbamoylated protein antibodies) and renal fibrosis. In this Review, we discuss the carbamoylation process and evaluate the available biomarkers of carbamoylation (for example, homocitrulline, the percentage of carbamoylated albumin, carbamoylated haemoglobin, and carbamoylated low-density lipoprotein). We also discuss the relationship between carbamoylation and the occurrence of cardiovascular events and mortality in patients with chronic kidney disease and assess the effects of strategies to lower the carbamoylation load.

    更新日期:2017-09-06
  • Experimental concerns regarding suPAR-related proteinuria
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-31
    Laurent Mesnard, Yosu Luque, Eric Rondeau

    We are writing in response to the News & Views commentary by L. Gallon and S. Quaggin (Glomerular disease: a suPAR kidney connection found in the bone marrow. Nat Rev Nephrol.13, 263–264; 2017), which discusses a recent study by Hahm

    更新日期:2017-09-06
  • Intravenous hydroxocobalamin and crystal nephropathy
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-31
    Matthieu Legrand, Vincent Mallet

    We read with great interest the excellent review by S. R. Mulay and H.-J. Anders on crystal nephropathies (Crystal nephropathies: mechanisms of crystal-induced kidney injury. Nat. Rev. Nephrol.13, 226–240; 2017). The authors list vitamin C as a cause of oxalate nephropathy,

    更新日期:2017-09-06
  • SuPAR and FSGS: is the jury still out?
    Nat. Rev. Nephrol. (IF 12.146) Pub Date : 2017-07-31
    Lorenzo Gallon, Susan E. Quaggin

    We thank L. Mesnard, Y. Luque and E. Rondeau for their comments (Experimental concerns regarding suPAR-related proteinuria. Nat. Rev. Nephrol. http://dx.doi.org/10.1038/nrneph.2017.108; 2017) regarding our News & Views commentary (Gallon, L. and Quaggin, S. E. A suPAR kidney connection found in the bone

    更新日期:2017-09-06
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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