Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
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Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A (GLA) gene, leading to a deficiency in α-galactosidase A. The lysosomal accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3) and its deacylated form, globotriaosylsphingosine (lyso-Gb3), results in progressive renal failure, cardiomyopathy associated with cardiac arrhythmia and recurrent cerebrovascular events, significantly limiting life expectancy in affected patients. In male patients, a definitive diagnosis of FD involves demonstrating a GLA deficiency in leucocytes. ⋯ These therapies facilitate cellular Gb3 clearance and an overall improvement of disease burden. However, ERT can lead to infusion-associated reactions, as well as the formation of neutralizing anti-drug antibodies in ∼40% of all ERT-treated males, leading to an attenuation of therapy efficacy. This article reviews the clinical presentation, diagnosis and interdisciplinary clinical management of FD and discusses the therapeutic options, with a special focus on precision medicine, accounting for individual variability in genetic mutations, Gb3 and lyso-Gb3 levels, allowing physicians to predict more accurately which prevention and treatment strategy is best for which patient.
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Nephrol. Dial. Transplant. · Dec 2019
Review Meta AnalysisPivotal clinical trials, meta-analyses and current guidelines in the treatment of hyperkalemia.
Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with advanced stages of chronic kidney disease (CKD), is a potentially life-threatening clinical condition due to an increased risk of fatal arrhythmias, and strongly impacts the quality of life and prognosis of CKD patients. Moreover, while renin-angiotensin-aldosterone system inhibitors (RAASIs) represent the most cardio-nephro-protective drugs used in clinical practice, the treatment with these drugs per se increases serum potassium (sK) values, particularly when heart failure and diabetes mellitus coexist. In fact, the onset or recurrence of HK is frequently associated with not starting, down-titrating or withdrawing RAASIs, and is an indication to begin renal replacement treatment in end-stage renal disease. ⋯ As such, there is an important unmet need for novel therapeutic options for the chronic management of patients at risk for HK. The development of new potassium binders may change the treatment landscape in the near future. This review summarizes the current evidence on the treatment of chronic HK in cardio-renal patients.
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Although hyperkalemia is much more common in patients with chronic kidney disease (CKD), the reported frequency of hyperkalemia varies markedly across studies, primarily due to differences in the ascertainment of hyperkalemia and the severity of CKD. Major risk factors for hyperkalemia among CKD patients include lower estimated glomerular filtration rate (eGFR), use of renin-angiotensin-aldosterone system inhibitors (RAASis), diabetes, older age and male gender. The use of two drugs to inhibit RAAS in diabetic CKD markedly increases the risk of hyperkalemia, as demonstrated in large multicenter clinical trials. ⋯ Sodium polystyrene sulfonate has been used commonly for decades to treat hyperkalemia in CKD patients, but without any high-quality clinical data to support its efficacy and with an increased risk of rare but serious colonic complications. The newer oral potassium-binding agents, patiromer and sodium zirconium cyclosilicate, have been shown to be effective and safe for the non-emergent treatment of hyperkalemia in CKD patients, including patients treated with RAASis. Although the long-term use of these medications may permit continuation of RAASis in CKD patients with hyperkalemia, the overall impact of this approach (as compared with down-titration of RAASis and/or up-titration of diuretics) on long-term morbidity, mortality and quality of life remains uncertain.
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Nephrol. Dial. Transplant. · Nov 2018
ReviewTargeting epigenetic DNA and histone modifications to treat kidney disease.
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease. ⋯ Several drugs targeting epigenetic regulators are in clinical development or use, most of them for malignancy. The BET inhibitor apabetalone is in Phase 3 trials for atherosclerosis, kidney function being a secondary endpoint, but nephrotoxicity was reported for DNA and HDAC inhibitors. While research into epigenetic modulators may provide novel therapies for kidney disease, caution should be exercised based on the clinical nephrotoxicity of some drugs.
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Nephrol. Dial. Transplant. · May 2018
Meta AnalysisRemote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials.
The main aim of this systematic review was to assess whether remote ischaemic preconditioning (RIPC) protects kidneys and the heart in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate a possible role of anaesthetic agents. ⋯ RIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB. In the subgroup on volatile anaesthetics only, RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury.