| 1. |
- Ahlqvist, Emma, et al.
(författare)
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The genetics of diabetic complications.
- 2015
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Ingår i: Nature Reviews Nephrology. - : Springer Science and Business Media LLC. - 1759-507X .- 1759-5061. ; 11:5, s. 277-287
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Forskningsöversikt (refereegranskat)abstract
- The rising global prevalence of diabetes mellitus is accompanied by an increasing burden of morbidity and mortality that is attributable to the complications of chronic hyperglycaemia. These complications include blindness, renal failure and cardiovascular disease. Current therapeutic options for chronic hyperglycaemia reduce, but do not eradicate, the risk of these complications. Success in defining new preventative and therapeutic strategies hinges on an improved understanding of the molecular processes involved in the development of these complications. This Review explores the role of human genetics in delivering such insights, and describes progress in characterizing the sequence variants that influence individual predisposition to diabetic kidney disease, retinopathy, neuropathy and accelerated cardiovascular disease. Numerous risk variants for microvascular complications of diabetes have been reported, but very few have shown robust replication. Furthermore, only limited evidence exists of a difference in the repertoire of risk variants influencing macrovascular disease between those with and those without diabetes. Here, we outline the challenges associated with the genetic analysis of diabetic complications and highlight ongoing efforts to deliver biological insights that can drive translational benefits.
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| 2. |
- Biglarnia, Ali Reza, et al.
(författare)
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The multifaceted role of complement in kidney transplantation
- 2018
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Ingår i: Nature Reviews Nephrology. - : Nature Publishing Group. - 1759-5061 .- 1759-507X. ; 14:12, s. 767-781
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Forskningsöversikt (refereegranskat)abstract
- Increasing evidence indicates an integral role for the complement system in the deleterious inflammatory reactions that occur during critical phases of the transplantation process, such as brain or cardiac death of the donor, surgical trauma, organ preservation and ischaemia-reperfusion injury, as well as in humoral and cellular immune responses to the allograft. Ischaemia is the most common cause of complement activation in kidney transplantation and in combination with reperfusion is a major cause of inflammation and graft damage. Complement also has a prominent role in antibody-mediated rejection (ABMR) owing to ABO and HL A incompatibility, which leads to devastating damage to the transplanted kidney. Emerging drugs and treatment modalities that inhibit complement activation at various stages in the complement cascade are being developed to ameliorate the damage caused by complement activation in transplantation. These promising new therapies have various potential applications at different stages in the process of transplantation, including inhibiting the destructive effects of ischaemia and/or reperfusion injury, treating ABMR, inducing accommodation and modulating the adaptive immune response.
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| 3. |
- Bruchfeld, Annette
(författare)
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The COVID-19 pandemic: consequences for nephrology
- 2021
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Ingår i: Nature Reviews Nephrology. - : NATURE RESEARCH. - 1759-5061 .- 1759-507X. ; 17, s. 81-82
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The consequences of the COVID-19 pandemic have been devastating; however, evidence suggests that patients with, or at risk of, kidney disease are disproportionally affected. Patients on dialysis and kidney transplant recipients are at higher risk of adverse outcomes from COVID-19, whereas, conversely, patients with severe COVID-19 are at increased risk of acute kidney injury, with short-term and possibly long-term consequences for nephrological care.
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| 9. |
- Ekdahl, Kristina N, et al.
(författare)
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Cardiovascular disease in haemodialysis : role of the intravascular innate immune system.
- 2017
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Ingår i: Nature Reviews Nephrology. - : Springer Science and Business Media LLC. - 1759-5061 .- 1759-507X. ; 13:5, s. 285-296
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Forskningsöversikt (refereegranskat)abstract
- Haemodialysis is a life-saving renal replacement modality for end-stage renal disease, but this therapy also represents a major challenge to the intravascular innate immune system, which is comprised of the complement, contact and coagulation systems. Chronic inflammation is strongly associated with cardiovascular disease (CVD) in patients on haemodialysis. Biomaterial-induced contact activation of proteins within the plasma cascade systems occurs during haemodialysis and initially leads to local generation of inflammatory mediators on the biomaterial surface. The inflammation is spread by soluble activation products and mediators that are generated during haemodialysis and transported in the extracorporeal circuit back into the patient together with activated leukocytes and platelets. The combined effect is activation of the endothelium of the cardiovascular system, which loses its anti-thrombotic and anti-inflammatory properties, leading to atherogenesis and arteriosclerosis. This concept suggests that maximum suppression of the intravascular innate immune system is needed to minimize the risk of CVD in patients on haemodialysis. A potential approach to achieve this goal is to treat patients with broad-specificity systemic drugs that target more than one of the intravascular cascade systems. Alternatively, 'stealth' biomaterials that cause minimal cascade system activation could be used in haemodialysis circuits.
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| 10. |
- Garcia-Lopez, E, et al.
(författare)
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An update on peritoneal dialysis solutions
- 2012
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Ingår i: Nature reviews. Nephrology. - : Springer Science and Business Media LLC. - 1759-507X .- 1759-5061. ; 8:4, s. 224-233
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Gistera, A, et al.
(författare)
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The immunology of atherosclerosis
- 2017
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Ingår i: Nature reviews. Nephrology. - : Springer Science and Business Media LLC. - 1759-507X .- 1759-5061. ; 13:6, s. 368-380
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Haarhaus, Mathias, et al.
(författare)
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Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD
- 2017
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Ingår i: Nature Reviews Nephrology. - : NATURE PUBLISHING GROUP. - 1759-5061 .- 1759-507X. ; 13:7, s. 429-442
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Forskningsöversikt (refereegranskat)abstract
- Cardiovascular disease is the main cause of early death in the settings of chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and ageing. Cardiovascular events can be caused by an imbalance between promoters and inhibitors of mineralization, which leads to vascular calcification. This process is akin to skeletal mineralization, which is carefully regulated and in which isozymes of alkaline phosphatase (ALP) have a crucial role. Four genes encode ALP isozymes in humans. Intestinal, placental and germ cell ALPs are tissue-specific, whereas the tissue-nonspecific isozyme of ALP (TNALP) is present in several tissues, including bone, liver and kidney. TNALP has a pivotal role in bone calcification. Experimental overexpression of TNALP in the vasculature is sufficient to induce vascular calcification, cardiac hypertrophy and premature death, mimicking the cardiovascular phenotype often found in CKD and T2DM. Intestinal ALP contributes to the gut mucosal defence and intestinal and liver ALPs might contribute to the acute inflammatory response to endogenous or pathogenic stimuli. Here we review novel mechanisms that link ALP to vascular calcification, inflammation, and endothelial dysfunction in kidney and cardiovascular diseases. We also discuss new drugs that target ALP, which have the potential to improve cardiovascular outcomes without inhibiting skeletal mineralization.
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| 17. |
- Karpman, Diana, et al.
(författare)
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Extracellular vesicles in renal disease
- 2017
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Ingår i: Nature Reviews Nephrology. - : Springer Science and Business Media LLC. - 1759-5061 .- 1759-507X. ; 13:9, s. 545-562
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 18. |
- Kooman, JP, et al.
(författare)
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Chronic kidney disease and premature ageing
- 2014
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Ingår i: Nature reviews. Nephrology. - : Springer Science and Business Media LLC. - 1759-507X .- 1759-5061. ; 10:12, s. 732-742
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Tidskriftsartikel (refereegranskat)
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| 19. |
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| 21. |
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| 24. |
- Messerer, David A. C., et al.
(författare)
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Immunopathophysiology of trauma-related acute kidney injury
- 2021
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Ingår i: Nature Reviews Nephrology. - : Springer Nature. - 1759-5061 .- 1759-507X. ; 17:2, s. 91-111
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Forskningsöversikt (refereegranskat)abstract
- Physical trauma can affect any individual and is globally accountable for more than one in every ten deaths. Although direct severe kidney trauma is relatively infrequent, extrarenal tissue trauma frequently results in the development of acute kidney injury (AKI). Various causes, including haemorrhagic shock, rhabdomyolysis, use of nephrotoxic drugs and infectious complications, can trigger and exacerbate trauma-related AKI (TRAKI), particularly in the presence of pre-existing or trauma-specific risk factors. Injured, hypoxic and ischaemic tissues expose the organism to damage-associated and pathogen-associated molecular patterns, and oxidative stress, all of which initiate a complex immunopathophysiological response that results in macrocirculatory and microcirculatory disturbances in the kidney, and functional impairment. The simultaneous activation of components of innate immunity, including leukocytes, coagulation factors and complement proteins, drives kidney inflammation, glomerular and tubular damage, and breakdown of the blood-urine barrier. This immune response is also an integral part of the intense post-trauma crosstalk between the kidneys, the nervous system and other organs, which aggravates multi-organ dysfunction. Necessary lifesaving procedures used in trauma management might have ambivalent effects as they stabilize injured tissue and organs while simultaneously exacerbating kidney injury. Consequently, only a small number of pathophysiological and immunomodulatory therapeutic targets for TRAKI prevention have been proposed and evaluated. Acute kidney injury is a common complication of trauma. Here, the authors examine how, in addition to direct trauma to the kidneys, the pathophysiological responses to traumatic injuries in distant organs, including immune responses, can result in kidney dysfunction.
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| 25. |
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| 26. |
- Meuwese, CL, et al.
(författare)
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Nonthyroidal illness and the cardiorenal syndrome
- 2013
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Ingår i: Nature reviews. Nephrology. - : Springer Science and Business Media LLC. - 1759-507X .- 1759-5061. ; 9:10, s. 599-609
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Tidskriftsartikel (refereegranskat)
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| 27. |
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| 28. |
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| 29. |
- Prowle, John R., et al.
(författare)
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Postoperative acute kidney injury in adult non-cardiac surgery : joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative
- 2021
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Ingår i: Nature Reviews Nephrology. - : Springer Nature. - 1759-5061 .- 1759-507X. ; 17:9, s. 605-618
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Forskningsöversikt (refereegranskat)abstract
- The development of acute kidney injury (AKI) after major non-cardiac surgery is associated with substantial long-term morbidity and mortality. This joint Consensus Statement from the Acute Disease Quality Initiative and the PeriOperative Quality Initiative provides recommendations for the definition, prevention and management of postoperative AKI. Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.
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| 30. |
- Shiels, PG, et al.
(författare)
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The role of epigenetics in renal ageing
- 2017
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Ingår i: Nature reviews. Nephrology. - : Springer Science and Business Media LLC. - 1759-507X .- 1759-5061. ; 13:8, s. 471-482
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Tidskriftsartikel (refereegranskat)
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| 31. |
- Smith, Richard J.H., et al.
(författare)
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C3 glomerulopathy — understanding a rare complement-driven renal disease
- 2019
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Ingår i: Nature Reviews Nephrology. - : Springer Science and Business Media LLC. - 1759-5061 .- 1759-507X.
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Forskningsöversikt (refereegranskat)abstract
- The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy — dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) — have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Disease is driven by acquired factors in most patients — namely, autoantibodies that target the C3 or C5 convertases. These autoantibodies drive complement dysregulation by increasing the half-life of these vital but normally short-lived enzymes. Genetic variation in complement-related genes is a less frequent cause. No disease-specific treatments are available, although immunosuppressive agents and terminal complement pathway blockers are helpful in some patients. Unfortunately, no treatment is universally effective or curative. In aggregate, the limited data on renal transplantation point to a high risk of disease recurrence (both DDD and C3GN) in allograft recipients. Clinical trials are underway to test the efficacy of several first-generation drugs that target the alternative complement pathway.
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| 34. |
- Szili-Torok, T, et al.
(författare)
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Blockchain in nephrology
- 2023
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Ingår i: Nature reviews. Nephrology. - : Springer Science and Business Media LLC. - 1759-507X .- 1759-5061. ; 19:57, s. 421-422
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Tidskriftsartikel (refereegranskat)
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| 35. |
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| 36. |
- Windpessl, Martin, et al.
(författare)
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COVID-19 vaccines and kidney disease
- 2021
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Ingår i: Nature Reviews Nephrology. - : NATURE RESEARCH. - 1759-5061 .- 1759-507X. ; 17:5, s. 291-293
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Tidskriftsartikel (refereegranskat)abstract
- Patients with kidney diseases should be prioritized for COVID-19 vaccination and the available data suggest that replication-defective viral-vectored vaccines and mRNA vaccines are safe to use. As vaccine responses are likely to be lower in patients with kidney diseases than in the general population, highly potent vaccines should be preferred.
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| 37. |
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| 38. |
- Dmitrieva, Natalia I., et al.
(författare)
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Long-term health outcomes associated with hydration status
- 2024
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Ingår i: Nature Reviews Nephrology. - 1759-5061. ; 20:5, s. 275-294
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Forskningsöversikt (refereegranskat)abstract
- Body water balance is determined by fundamental homeostatic mechanisms that maintain stable volume, osmolality and the composition of extracellular and intracellular fluids. Water balance is maintained by multiple mechanisms that continuously match water losses through urine, the skin, the gastrointestinal tract and respiration with water gains achieved through drinking, eating and metabolic water production. Hydration status is determined by the state of the water balance. Underhydration occurs when a decrease in body water availability, due to high losses or low gains, stimulates adaptive responses within the water balance network that are aimed at decreasing losses and increasing gains. This stimulation is also accompanied by cardiovascular adjustments. Epidemiological and experimental studies have linked markers of low fluid intake and underhydration — such as increased plasma concentration of vasopressin and sodium, as well as elevated urine osmolality — with an increased risk of new-onset chronic diseases, accelerated aging and premature mortality, suggesting that persistent activation of adaptive responses may be detrimental to long-term health outcomes. The causative nature of these associations is currently being tested in interventional trials. Understanding of the physiological responses to underhydration may help to identify possible mechanisms that underlie potential adverse, long-term effects of underhydration and inform future research to develop preventative and treatment approaches to the optimization of hydration status.
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