Disorders in the System of Mineral and Bone Metabolism Regulators—FGF-23, Klotho and Sclerostin—in Chronic Kidney Disease: Clinical Significance and Possibilities for Correction

The chapter discusses the current understanding of the system of mineral and bone metabolism regulators—FGF-23, Klotho and sclerostin—disturbances in chronic kidney disease (CKD). In the chapter we presented the date, including our own results, which allow to suggest the change in the ratio of FGF-23-Klotho-sclerostin in CKD as an early biomarker not only for the chronic kidney damage but also for high cardiovascular (CV) risk. Results of studies show that disorders in FGF-23-Klotho-sclerostin ratio correlate with the frequency and severity of hypertension, vascular calcification, cardiac remodelling, anaemia, malnutrition, inflammation and strong aggravate CV risk in CKD. It was found independent from blood pressure (BP) action of increased serum FGF-23 on the myocardium as well as the correlation of serum high-sensitive troponin I with increased serum FGF-23 and low Klotho levels in CKD patients. At the same time, it was shown that renoprotective therapy, including renin-angiotensin blockers, low-protein diet with amino/keto acid supplementation and phosphate binders, erythropoiesis stimulators, vitamin D metabolites used to get the target levels of BP, serum phosphorus, haemoglobin, parathyroid hormone and nutritional status disorders correction can reduce the risk of CV events, as the major cause of death in CKD patients

Nutritional Status Disorders in Chronic Kidney Disease: Practical Aspects (Systematic Review)

Despite the significant achievements in the management of chronic kidney disease (CKD) patients, the mortality rate of these patients still remains high. Nutritional status disorders (NSD) are considered now as one of the prognostic risk factors not only for dialysis but also for predialysis CKD stages. Since the publication of KDIGO 2012 guidelines for CKD patient’s management, there has been some significant advancement in our understanding of main NSD mechanisms in CKD, including different nosological group patients (first, in diabetic and systemic diseases patients). At the same time, there is still an urgent need for randomized trials for better-informed decisions and future optimization of CKD patients’ care. This chapter provides the current data on all aspects of NSD in CKD: etiology, diagnosis, prevention, and treatment approaches, as well as on risk factors of NSD at predialysis stages and in chronic hemodialysis patients. Considerable attention was devoted to the diagnosis and differential diagnosis of NSD in CKD patients. It was determined that the overall strategy for dietary treatment contributed to improving the life quality of patients and slowing down of CKD progression. The review is written based on the published results of clinical studies performed on the position of evidence-based medicine

Anemia in Chronic Kidney Disease and After Kidney Allotransplantation (Systematic Review)

Anemia in chronic kidney disease (CKD) has been recognized as a separate independent risk factor of cardiovascular (CV) events. The aim of the review is to provide a literature summary concerning early diagnosis and treatment of anemia in CKD that may be useful for clinicians and contribute to decrease CV mortality. Literature searches were made in such major databases as: PubMed, Medline, Embase, Cochrane Library, CINAHL, Wiley Online Library, Scopus, Web of Science, e-library, and website of WHO. This search encompassed original articles, systematic reviews, and meta-analyses relevant to CKD and anemia over recent 15 years. A total of 54 references from 562 reviewed articles were selected as they met to the search criteria (anemia and CKD, including diabetes mellitus, systemic diseases and post-transplant anemia). The publications included 27 randomized controlled trials, 20 experimental studies representing new data on the links of CKD anemia and cardiovascular risk markers (cytokines, Klotho, fibroblast growth factor (FGF-23), hyperglycemia, hypoalbuminemia and some others), 4 systematic reviews and 3 clinical practice guidelines. The main attention was devoted to the analysis of the studies provided an early diagnosis of anemia, an ability to minimize the factors contributing to its severity that have allowed to improve CV and total outcomes and to reduce costs of hospital treatment of CKD patients with anemia

Agent-Based Modeling of Autosomal Recessive Deafness 1A (DFNB1A) Prevalence with Regard to Intensity of Selection Pressure in Isolated Human Population

An increase in the prevalence of autosomal recessive deafness 1A (DFNB1A) in populations of European descent was shown to be promoted by assortative marriages among deaf people. Assortative marriages became possible with the widespread introduction of sign language, resulting in increased genetic fitness of deaf individuals and, thereby, relaxing selection against deafness. However, the effect of this phenomenon was not previously studied in populations with different genetic structures. We developed an agent-based computer model for the analysis of the spread of DFNB1A. Using this model, we tested the impact of different intensities of selection pressure against deafness in an isolated human population over 400 years. Modeling of the “purifying” selection pressure on deafness (“No deaf mating” scenario) resulted in a decrease in the proportion of deaf individuals and the pathogenic allele frequency. Modeling of the “relaxed” selection (“Assortative mating” scenario) resulted in an increase in the proportion of deaf individuals in the first four generations, which then quickly plateaued with a subsequent decline and a decrease in the pathogenic allele frequency. The results of neutral selection pressure modeling (“Random mating” scenario) showed no significant changes in the proportion of deaf individuals or the pathogenic allele frequency after 400 years

Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study.

Objective To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. Methods We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab. Results 254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012). Conclusion Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial

Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study

To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice