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  • 1
    Online Resource
    Online Resource
    Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression
    MDPI AG ; 2018
    In:  Toxins Vol. 10, No. 7 ( 2018-07-19), p. 300-
    Details
    In: Toxins, MDPI AG, Vol. 10, No. 7 ( 2018-07-19), p. 300-
    Abstract: In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression. Some uremic toxins result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves, such as trimethylamine N-Oxide (TMAO), p-cresyl sulphate, indoxyl sulphate and indole-3 acetic acid. Increased intake of some nutrients may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of CKD progression. This offers the opportunity for therapeutic intervention by either modifying the diet, modifying the microbiota, decreasing uremic toxin production by microbiota, increasing toxin excretion or targeting specific uremic toxins. We now review the link between nutrients, microbiota and uremic toxin with CKD progression. Specific focus will be placed on the generation specific uremic toxins with nephrotoxic potential, the decreased availability of bacteria-derived metabolites with nephroprotective potential, such as vitamin K and butyrate and the cellular and molecular mechanisms linking these toxins and protective factors to kidney diseases. This information provides a conceptual framework that allows the development of novel therapeutic approaches.
    Type of Medium: Online Resource
    ISSN: 2072-6651
    URL: Article
    DOI: 10.3390/toxins10070300
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2518395-3
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  • 2
    Online Resource
    Online Resource
    Exploring Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors for Organ Protection in COVID-19
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 7 ( 2020-06-28), p. 2030-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 7 ( 2020-06-28), p. 2030-
    Abstract: Hospital admissions and mortality from the Coronavirus disease 2019 (COVID-19) pandemic are spreading throughout the world, and second and third waves are thought to be likely. Risk factors for severe COVID-19 include diabetes, chronic kidney disease and cardiovascular disease. Currently, there is no vaccine and no approved therapy. Therapeutic approaches are aimed at preventing viral replication and spread, limiting the impact of the inflammatory overdrive (cytokine storm), preventing thromboembolic complications and replacing or supporting organ function. However, despite organ support, mortality is currently 65% for those receiving advanced respiratory support and 78% for those requiring renal replacement therapies. Thus, efforts should be made to provide adjuvant organ protection therapy. This may imply novel therapies in clinical development (e.g., the Fas ligand trap asunercept), but uptake of repurposed drugs already in clinical use may be faster. In this regard, sodium glucose co-transporter-2 (SGLT2) inhibitors were recently shown to protect the heart and kidney both within and outside of a diabetic milieu context. Further, preclinical data support a beneficial effect for the lung. We now discuss the potential benefits and risks of SGLT2 inhibitors in COVID-19 and an ongoing clinical trial testing the impact of dapagliflozin on outcomes in COVID-19 patients with respiratory failure.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9072030
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 3
    Online Resource
    Online Resource
    The chaos of hypertension guidelines for chronic kidney disease patients
    Oxford University Press (OUP) ; 2019
    In:  Clinical Kidney Journal Vol. 12, No. 6 ( 2019-12-01), p. 771-777
    Details
    In: Clinical Kidney Journal, Oxford University Press (OUP), Vol. 12, No. 6 ( 2019-12-01), p. 771-777
    Abstract: Three major guidelines deal with blood pressure thresholds and targets for antihypertensive drug therapy in chronic kidney disease (CKD) patients: the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease; the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults; and the 2018 ESC/ESH Guidelines for the Management of Arterial Hypertension. However, a careful reading of the three guidelines leaves the practicing physician confused about the definition of CKD, how hypertension and secondary hypertension should be diagnosed in CKD patients and what the blood pressure thresholds, targets and compelling indications of antihypertensive drug therapy should be for this population. Current guidelines refer to different CKD populations and propose different definitions of hypertension, different thresholds to initiate antihypertensive therapy in CKD patients and different BP targets compelling antihypertensive drug use. The different bodies producing guidelines should work together towards a unified definition of CKD, a unified concept of hypertension and unified BP thresholds and targets for hypertensive drug therapy for CKD patients. Otherwise they risk promoting confusion and therapeutic nihilism among physicians and patients.
    Type of Medium: Online Resource
    ISSN: 2048-8505 , 2048-8513
    URL: Article
    DOI: 10.1093/ckj/sfz126
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2656786-6
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  • 4
    Online Resource
    Online Resource
    SGLT2 inhibitors for non-diabetic kidney disease: drugs to treat CKD that also improve glycaemia
    Oxford University Press (OUP) ; 2020
    In:  Clinical Kidney Journal Vol. 13, No. 5 ( 2020-10-01), p. 728-733
    Details
    In: Clinical Kidney Journal, Oxford University Press (OUP), Vol. 13, No. 5 ( 2020-10-01), p. 728-733
    Abstract: Sodium–glucose co-transporter-2 (SGLT2) inhibitors decreased cardiovascular (CV) events and improved renal outcomes in CV safety studies in type 2 diabetes melitus (T2DM) patients at high CV risk. Canagliflozin also improved kidney outcomes in diabetic kidney disease in the Canagliflozin and Renal Events in Diabetes and Nephropathy Clinical Evaluationtrial. More recently, the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial showed that dapagliflozin improved CV outcomes in patients with HF with or without diabetes. Protection from HF in non-diabetics was confirmed for empagliflozin in the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) trial. A meta-analysis of DAPA-HF and EMPEROR-Reduced confirmed reductions in all-cause and CV death and the combined risk of CV death or worsening HF, as well as in the composite renal endpoint {hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.43–0.90] } without differences based on the presence of diabetes or baseline estimated glomerular filtration rate (eGFR). Moreover, the Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (DAPA-CKD) showed that dapagliflozin as an add-on over renin–angiotensin system blockade in patients with chronic kidney disease (CKD; with or without T2DM) reduced the HR for the primary endpoint (time to the first occurrence of ≥50% eGFR decline, end-stage kidney disease or renal or CV death) to 0.61 (95% CI 0.51–0.72) and for the secondary endpoints of worsening renal function or death from kidney failure [HR 0.56 (95% CI 0.45–0.68)], hospitalization for HF or CV death [HR 0.71 (95% CI 0.55–0.92)] and all-cause mortality [HR 0.69 (95% CI 0.53–0.88)]. These beneficial effects were consistent in patients with and without T2DM. In conclusion, SGLT2 inhibitors offer CV and kidney protection in both diabetic and non-diabetic CKD and, additionally, improve glycaemic control in T2DM, making them first-line therapy for CKD independent from diabetic status.
    Type of Medium: Online Resource
    ISSN: 2048-8513
    URL: Article
    DOI: 10.1093/ckj/sfaa198
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2656786-6
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  • 5
    Online Resource
    Online Resource
    Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA)
    Oxford University Press (OUP) ; 2023
    In:  Clinical Kidney Journal ( 2023-06-24)
    Details
    In: Clinical Kidney Journal, Oxford University Press (OUP), ( 2023-06-24)
    Abstract: Chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D) represents a major public health issue; it develops in about 30%–40% of patients with diabetes mellitus and is the most common cause of CKD worldwide. Patients with CKD and T2D are at high risk of both developing kidney failure and of cardiovascular events. Renin–angiotensin system (RAS) blockers were considered the cornerstone of treatment of albuminuric CKD in T2D for more than 20 years. However, the residual risk of progression to more advanced CKD stages under RAS blockade remains high, while in major studies with these agents in patients with CKD and T2D no significant reductions in cardiovascular events and mortality were evident. Steroidal mineralocorticoid receptor antagonists (MRAs) are known to reduce albuminuria in individuals on RAS monotherapy, but their wide clinical use has been curtailed by the significant risk of hyperkalemia and absence of trials with hard renal outcomes. In recent years, non-steroidal MRAs have received increasing interest due to their better pharmacologic profile. Finerenone, the first compound of this class, was shown to effectively reduce the progression of kidney disease and of cardiovascular outcomes in participants with T2D in phase 3 trials. This clinical practice document prepared from a task force of the European Renal Best Practice board summarizes current knowledge on the role of MRAs in the treatment of CKD in T2D aiming to support clinicians in decision-making and everyday management of patients with this condition.
    Type of Medium: Online Resource
    ISSN: 2048-8505 , 2048-8513
    URL: Article
    DOI: 10.1093/ckj/sfad139
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2656786-6
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