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- Haarhaus, Mathias, 1967-, et al.
(författare)
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Pharmacologic epigenetic modulators of alkaline phosphatase in chronic kidney disease
- 2020
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Ingår i: Current opinion in nephrology and hypertension. - : Lippincott Williams & Wilkins. - 1062-4821 .- 1473-6543. ; 29:1, s. 4-15
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: In chronic kidney disease (CKD), disturbance of several metabolic regulatory mechanisms cause premature ageing, accelerated cardiovascular disease (CVD), and mortality. Single-target interventions have repeatedly failed to improve the prognosis for CKD patients. Epigenetic interventions have the potential to modulate several pathogenetic processes simultaneously. Alkaline phosphatase (ALP) is a robust predictor of CVD and all-cause mortality and implicated in pathogenic processes associated with CVD in CKD.RECENT FINDINGS: In experimental studies, epigenetic modulation of ALP by microRNAs or bromodomain and extraterminal (BET) protein inhibition has shown promising results for the treatment of CVD and other chronic metabolic diseases. The BET inhibitor apabetalone is currently being evaluated for cardiovascular risk reduction in a phase III clinical study in high-risk CVD patients, including patients with CKD (ClinicalTrials.gov Identifier: NCT02586155). Phase II studies demonstrate an ALP-lowering potential of apabetalone, which was associated with improved cardiovascular and renal outcomes.SUMMARY: ALP is a predictor of CVD and mortality in CKD. Epigenetic modulation of ALP has the potential to affect several pathogenetic processes in CKD and thereby improve cardiovascular outcome.
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- Haraldsson, Börje, et al.
(författare)
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Glomerular filtration barrier
- 2009
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Ingår i: Current opinion in nephrology and hypertension. - 1062-4821 .- 1473-6543. ; 18:4, s. 331-335
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: In 2008, more than 376 papers were published on the glomerular barrier. Most of them dealt with the podocyte and its role in kidney disease.RECENT FINDINGS: There is new information on signaling pathways that are utilized in podocytes during proteinuria. Interestingly, the glomerular endothelium, with its fenestrae and glycocalyx, seems to be important for the maintenance of an intact glomerular barrier. All new advances at the molecular level are compatible with a highly size and charge-selective glomerular membrane and refute the concept of a 'leaky' glomerular barrier with tubular retrieval of intact albumin. Still, the hypothesis has its advocates, keeping a stimulating 'charge debate' alive.SUMMARY: Glomerular diseases account for 90% of chronic kidney disease requiring dialysis and transplantation at an annual cost of $20 billion in the USA. In clinical practice, we lack specific treatment of these diseases, giving us plenty of room for improvement. Future research should be directed toward deeper understanding of the signaling pathways involved in different conditions of proteinuria, the cross-talk between cell types in the glomerulus, and the identification of novel targets for treatment of acquired kidney disease.
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- Johnson, RS, et al.
(författare)
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Cutaneous control of blood pressure
- 2016
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Ingår i: Current opinion in nephrology and hypertension. - 1473-6543. ; 25:1, s. 11-15
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Tidskriftsartikel (refereegranskat)
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- Palm, Fredrik, et al.
(författare)
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Nitric oxide and kidney oxygenation
- 2009
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Ingår i: Current opinion in nephrology and hypertension. - 1062-4821 .- 1473-6543. ; 18:1, s. 68-73
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: The regulatory role of nitric oxide for tissue oxygen availability involves both oxygen delivery, through regulation of vascular tone, and oxygen consumption, through interference with mitochondrial respiration and tubular transport capacity. This review highlights recent findings regarding mechanisms of dysfunctional nitric oxide bioavailability in the kidney and the implications for oxygen availability and mitochondrial respiration. RECENT FINDINGS: It has been revealed that nitric oxide has several ways to influence and regulate kidney function during normal physiological conditions and that it is also involved in many of the mechanisms resulting in altered kidney function during disease. Recent reports show that nitric oxide regulates kidney oxygenation by influencing both oxygen utilization and supply. SUMMARY: Increasing evidence has accumulated during recent years for a dysfunctional nitric oxide system resulting in altered kidney oxygenation in several pathological conditions, which contributes to the development of kidney failure. We presently have extensive knowledge regarding the interplay between nitric oxide, oxygenation and kidney function; however, more effort is needed to clarify how dysfunctional nitric oxide regulation progresses to tissue hypoxia and kidney failure in various conditions, in order to identify potential therapeutic targets and develop strategies to prevent or alleviate these adverse effects and maintain adequate kidney function.
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