In both atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) complement plays a primary role in disease pathogenesis. Herein we report the outcome of a 2015 Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference where key issues in the management of these 2 diseases were considered by a global panel of experts. Areas addressed included renal pathology, clinical phenotype and assessment, genetic drivers of disease, acquired drivers of disease, and treatment strategies. In order to help guide clinicians who are caring for such patients, recommendations for best treatment strategies were discussed at length, providing the evidence base underpinning current treatment options. Knowledge gaps were identified and a prioritized research agenda was proposed to resolve outstanding controversial issues.
In uremic patients, the morbidity and mortality of cardiovascular disease are substantially higher than in the general population. This has led to the formulation of an 'accelerated atherogenesis' hypothesis in uremic patients and has been commonly linked with the metabolic alterations associated with uremia. Advancement in the understanding of the pathogenesis of atherosclerotic vascular disease now suggests a central contribution of inflammation to atherogenesis, with involvement of a number of key mediators and markers of the inflammatory process. Recent epidemiological data have documented associations between C-reactive protein (CRP), the prototypical acute phase response protein, and cardiovascular disease in general population. Given the lipoprotein binding and complement activation functions of CRP and its localization in atherosclerotic vessels, there is a strong likelihood that CRP may be involved in the atherosclerotic process. The uremic state is associated with an altered immune response, which is associated with elevated proinflammatory cytokine levels. CRP concentrations are increased in a significant proportion of end-stage renal disease patients and have been associated with certain clinical outcome measures, including all-cause and cardiovascular mortality. This review outlines the evidence linking CRP with atherosclerosis and proposes that elevated CRP concentrations may be involved in the initiation and progression of accelerated atherosclerosis in uremia.
Background Chronic kidney disease (CKD) and immunosuppression, such as in renal transplantation (RT), stand as one of the established potential risk factors for severe coronavirus disease 2019 (COVID-19). Case morbidity and mortality rates for any type of infection have always been much higher in CKD, haemodialysis (HD) and RT patients than in the general population. A large study comparing COVID-19 outcome in moderate to advanced CKD (Stages 3–5), HD and RT patients with a control group of patients is still lacking. Methods We conducted a multicentre, retrospective, observational study, involving hospitalized adult patients with COVID-19 from 47 centres in Turkey. Patients with CKD Stages 3–5, chronic HD and RT were compared with patients who had COVID-19 but no kidney disease. Demographics, comorbidities, medications, laboratory tests, COVID-19 treatments and outcome [in-hospital mortality and combined in-hospital outcome mortality or admission to the intensive care unit (ICU)] were compared. Results A total of 1210 patients were included [median age, 61 (quartile 1–quartile 3 48–71) years, female 551 (45.5%)] composed of four groups: control (n = 450), HD (n = 390), RT (n = 81) and CKD (n = 289). The ICU admission rate was 266/1210 (22.0%). A total of 172/1210 (14.2%) patients died. The ICU admission and in-hospital mortality rates in the CKD group [114/289 (39.4%); 95% confidence interval (CI) 33.9–45.2; and 82/289 (28.4%); 95% CI 23.9–34.5)] were significantly higher than the other groups: HD = 99/390 (25.4%; 95% CI 21.3–29.9; P < 0.001) and 63/390 (16.2%; 95% CI 13.0–20.4; P < 0.001); RT = 17/81 (21.0%; 95% CI 13.2–30.8; P = 0.002) and 9/81 (11.1%; 95% CI 5.7–19.5; P = 0.001); and control = 36/450 (8.0%; 95% CI 5.8–10.8; P < 0.001) and 18/450 (4%; 95% CI 2.5–6.2; P < 0.001). Adjusted mortality and adjusted combined outcomes in CKD group and HD groups were significantly higher than the control group [hazard ratio (HR) (95% CI) CKD: 2.88 (1.52–5.44); P = 0.001; 2.44 (1.35–4.40); P = 0.003; HD: 2.32 (1.21–4.46); P = 0.011; 2.25 (1.23–4.12); P = 0.008), respectively], but these were not significantly different in the RT from in the control group [HR (95% CI) 1.89 (0.76–4.72); P = 0.169; 1.87 (0.81–4.28); P = 0.138, respectively]. Conclusions Hospitalized COVID-19 patients with CKDs, including Stages 3–5 CKD, HD and RT, have significantly higher mortality than patients without kidney disease. Stages 3–5 CKD patients have an in-hospital mortality rate as much as HD patients, which may be in part because of similar age and comorbidity burden. We were unable to assess if RT patients were or were not at increased risk for in-hospital mortality because of the relatively small sample size of the RT patients in this study.
PatenT data indicate that hypertension is a highly prevalent but inadequately managed health problem in Turkey. There is an urgent need for population-based strategies to improve the prevention, early detection and control of hypertension.
Recently, the European Medicines Agency approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adult patients with chronic kidney disease stages 1–3 at initiation of treatment with evidence of rapidly progressing disease. In this paper, on behalf of the ERA-EDTA Working Groups of Inherited Kidney Disorders and European Renal Best Practice, we aim to provide guidance for making the decision as to which ADPKD patients to treat with tolvaptan. The present position statement includes a series of recommendations resulting in a hierarchical decision algorithm that encompasses a sequence of risk-factor assessments in a descending order of reliability. By examining the best-validated markers first, we aim to identify ADPKD patients who have documented rapid disease progression or are likely to have rapid disease progression. We believe that this procedure offers the best opportunity to select patients who are most likely to benefit from tolvaptan, thus improving the benefit-to-risk ratio and cost-effectiveness of this treatment. It is important to emphasize that the decision to initiate treatment requires the consideration of many factors besides eligibility, such as contraindications, potential adverse events, as well as patient motivation and lifestyle factors, and requires shared decision-making with the patient.
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