LEADING ARTICLE
Living with chronic kidney disease (CKD) is associated with hardships for patients and their care-partners. Empowering patients and their care-partners, including family members or friends involved in their care, may help minimize the burden and consequences of CKD related symptoms to enable life participation. There is a need to broaden the focus on living well with kidney disease and re-engagement in life, including an emphasis on patients being in control. The World Kidney Day (WKD) Joint Steering Committee has declared 2021 the year of “Living Well with Kidney Disease” in an effort to increase education and awareness on the important goal of patient empowerment and life participation. This calls for the development and implementation of validated patient-reported outcome measures to assess and address areas of life participation in routine care. It could be supported by regulatory agencies as a metric for quality care or to support labelling claims for medicines and devices. Funding agencies could establish targeted calls for research that address the priorities of patients. Patients with kidney disease and their care-partners should feel supported to live well through concerted efforts by kidney care communities including during pandemics. In the overall wellness program for kidney disease patients, the need for prevention should be reiterated. Early detection with a prolonged course of wellness despite kidney disease, after effective secondary and tertiary prevention programs, should be promoted. WKD 2021 continues to call for increased awareness of the importance of preventive measures throughout populations, professionals, and policymakers, applicable to both developed and developing countries.
REVIEWS AND LECTURES
Over the past two decades, coronavirus infection has caused two major pandemics: SARS in 2002 and acute respiratory syndrome (MERS) in the Middle East in 2012. In December 2019, the novel coronavirus (CV) SARS-CoV-2 caused an outbreak of pneumonia in Wuhan, China. Experts from the World Health Organization (WHO) have confirmed the risk of this disease for the public health of the entire planet. SARS-CoV-2 was isolated from epithelial cells of the human respiratory tract. It was found that the genotype KB SARS-CoV-2 is closer to bat-SL-CoVZC45 and bat-SL-CoVZXC21, and the spike glycoprotein (SB) of the virus, which determines the ability to bind to the cellular receptor, is similar to the SARS-CoV coronavirus, which is responsible for the outbreak of severe acute respiratory syndrome (SARS / SARS) in 2002]. Angiotensin-converting enzyme 2 (ACE2) is an endogenous spike protein (spike glycoprotein with the S-domain) SARS-CoV-2, which, as part of the ACE2 + SARS-CoV-2 complex, binds to the ACE2 receptor located on the target cell membrane. The article discusses the mechanisms of infection with SARS-CoV-2, cell-cell interactions, and transmission routes. The issues of the epidemiology of COVID-19 and the prospects for the involvement of organs and systems other than the respiratory one in maintaining the viral load are covered in detail. The problems of the immune defense of the human body during infection with SARS-CoV-2 have been identified. Clinical parallels with progenitor viruses, namely SARS-CoV-1 and MERS-CoV, have been drawn. Highlighted risk factors for SARSCoV-2 infection, which make it possible to predict the nature of the course and probable outcomes of COVID-19.
Amlodipine and selective dihydropyridine Ca2+ channels blockers of the second generation in addition to ACE inhibitors or replacing them antagonists of AT1-angiotensin receptors don’t improve clinical renal outcomes in hypertensive patients with chronic kidney disease. These drugs don’t eliminate intraglomerular hypertension that underlies hypertensive nephropathy and can have an adverse effect on the neurohormonal status of the organism, triggering the activation of the sympathetic and renin-angiotensin-aldosterone systems. The review presents the results of clinical studies evaluating the effectiveness of the use in this patients population of a new dihydropyridine blocker L-Ca2+ channels third-generation lercanidipine, dual blocker T/L-Ca2+ channels benedipine and dual blocker N/L-Ca2+ channels cilnidipine, that differ from their predecessors expressed renoprotective properties.
Diabetic nephropathy (DN) is a chronic complication of diabetes and the most common cause of the end-stage renal disease (ESRD). Numerous factors have been considered, both contributing to the development of DN, and participating in its pathogenesis. However, to date, the molecular mechanisms, that lead to the development of DN, remain not fully understood. Recently, with the development of high-performance technologies, evidence demonstrating epigenetic mechanisms of regulation of gene expression, including DNA methylation, non-coding RNAs, and histone modifications that play a key role in the pathogenesis of DN through the secondary regulation of genes are starting to appear. All these data can contribute to the creation of new, more effective diagnostic and therapeutic technologies for DN.
One of the key roles in the development of diabetic nephropathy belongs to the renin-angiotensin-aldosterone system (RAAS), which is involved in the regulation of hemodynamics, systemic and intrarenal pressure, production of profibrogenic and growth factors, vascular remodeling. At the end of the twentieth century, local (tissue) RAAS elements from renin to aldosterone were found in tissues and target organs (including kidneys). Tissue RAAS plays a leading role in the development of vascular complications of diabetes mellitus (DM): cardiovascular disease, diabetic nephropathy, and retinopathy. It is this fact that explains in many ways the pathogenetic role of RAAS in the defeat of target organs even with normal or low plasma renin activity (ARP). RAAS activation occurs long before the clinical signs of diabetic nephropathy, which makes it possible for earlier prevention and correction of initial changes in the study of its components, as well as reducing disability and the output of patients in chronic kidney disease. Given the tendency to “rejuvenate” diabetes mellitus, the lability of the course of the disease in childhood, the high hormonal activity in this group of patients, and, therefore, the greater the risk of complications, the timely diagnosis of the initial manifestations of DN is of high relevance and relevance.
ORIGINAL ARTICLES. CLINICAL INVESTIGATIONS
BACKGROUND. Mechanisms of the initiation of renal interstitial inflammation and fibrosis caused by immunoglobulin monoclonal free light chains (mFLC) in monoclonal gammopathy are well established. As far as these damage pathways are considered to be universal we hypothesize that polyclonal free light chains (pFLC) could have a similar effect on tubular and interstitial tissue and lead to chronic kidney disease (CKD) progression in primary glomerulopathies. THE AIM of this retrospective study was to analyze the association of pFLC kappa (pFLC-κ) and lambda (pFLC-λ) assessed in serum by Freelite® with clinical and morphological parameters and CKD progression in IgA-nephropathy (IgAN) cohort.
PATIENTS AND METHODS. In this retrospective study, we enrolled 24 patients with IgAN proven by kidney biopsy (KBx). pFLC-κ and pFLC-λ levels were assessed in all cases at the time of KBx by Freelite® method (N pFLC-κ=3.3-19.4 mg/l, N pFLC-λ=5.7-26.3 mg/l). The normal κ/λ ratio was the inclusion criterion. In all cases, we determined serum creatinine, estimated glomerular filtration rate by CKD-EPI method (eGFRCKD-EPI), and daily proteinuria. Morphological findings were defined semiquantitatively by light and immunofluorescence microscopy. Oxford MEST-C score was evaluated as well as % of glomerulosclerosis. Correlation between parameters was assessed by Spearman’s coefficient. Cox proportional hazards regression was used to analyze the association of parameters with the progression of CKD estimated as an elevation of serum creatinine ≥25 % from the initial level or the initiation of renal replacement therapy at the end of the follow-up period (median was 28 (7; 37) months).
RESULTS. Median of pFLC-κ 30.2 (6.1; 67.5) mg/l, median of pFLC-λ 27.6 (11.1; 92.1) mg/l. Levels of pFLC-κ and pFLC-λ were increased in 66.7 % and 50 % of patients, respectively. eGFR CKD-EPI median was 41 (26; 65) ml/min/1.73m2. Serum creatinine correlates with pFLC-κ (R=0.62, p<0.01) and pFLC-λ (R=0.45, p=0.03). Among morphological parameters pFLC-κ correlates with interstitial inflammation (R=0.47, p=0.02), tubular atrophy (R=0.54, p<0.01), interstitial fibrosis (R=0.44, p=0.03), peritubular capillaritis (R=0.42, p=0.04), T-score (R=0.66, p<0.01) and combined MEST-C score (R=0.45, p=0.03). For pFLC-λ the correlations with tubular atrophy (R=0.45, р=0.03) and Т-score (R=0.56, p<0.01) were shown. In Univariate Cox regression analysis pFLC-κ and pFLC-λ were associated with CKD progression (Exp(ß)=1.053; 95,0 %CI 1.003-1.105; p=0.038 and Exp(ß)= 1.041; 95,0 %CI 1.002-1.082; p=0.038, respectively)
CONCLUSION. Polyclonal FLC, mostly pFLC-κ, were associated with tubulointerstitial inflammation and fibrosis in patients with IgAN. Increased levels of either pFLC-κ or λ could be proposed as a predictor of CKD progression in patients with IgAN.
BACKGROUND. Currently, there is no doubt that there is a close relationship between the condition of the kidneys and the cardiovascular system. Neurohormonal systems various parts long-term hyperactivation is important in the development of pathological processes. Natriuretic peptides provide cardio and renoprotective effects, inhibit the activity of the renin-angiotensin-aldosterone system (RAAS). AIM. To establish the prognostic significance of determining the concentration of natriuretic peptides in comparison with the activity of RAAS in children with congenital malformations of the urinary system to assess the risk of cardiovascular complications.
PATIENTS AND METHODS. 76 patients with congenital malformations OUS aged 3 to 18 years were examined: – 40 children with congenital vesicoureteral reflux, – 18 children with hydronephrosis, 18 children with other forms of OUS dysembryogenesis ( 10 patients with renal agenesis, 8-with hypoplasia). The control group consisted of 10 clinically healthy children of the appropriate age. The following parameters were determined in the blood by the enzyme immunoassay: renin, aldosterone, n-terminal propeptide of natriuretic hormone (NТ-рroВNР).
RESULTS. Hyperproduction of NТ-рroВNР was observed in 61.8 % of patients, stimulation of renin and/or aldosterone production in 39.5 % of cases. Elevated levels of natriuretic peptides were found in 32.8 % of cases in 25 children with congenital OUS defects without signs of arterial hypertension (AH) and left ventricular hypertrophy (LVH). Significantly higher concentrations of (NТ-рroВNР), renin, and aldosterone are recorded in patients with AH and LVH.
CONCLUSION. The increased level of natriuretic peptides is noted earlier than the clinical and instrumental signs of heart dysfunction are noticeable, it is important in identifying early stages of cardiovascular complications, evaluating the prognosis, and in justifying renoprotective treatment in pediatric Nephrology practice.
Obesity is considered one of the most common syndromes in medical practice. Over the past 40 years, the average body mass index (BMI) has increased by 10.3 % in men and by 9.4 % in women. It is believed that obesity, diagnosed by BMI, is a significant risk factor for the development of cardiovascular diseases, and, accordingly, negatively affects a person's life expectancy. Among the methods that make it possible not only to characterize the ratio of height and body weight but to give an idea of the amount of body fat, the most popular in our country are caliperometry and bioimpedance measurement. THE AIM: to assess the possibility of interchangeability of caliperometry and bioimpedance measurement in determining body fat mass in dialysis patients.
PATIENTS AND METHODS. The study involved 140 patients, including 66 men and 58 women, receiving HD treatment. In general, the surveyed group can be characterized as clinically stable. To determine the body composition, all patients underwent caliperometry using the TVES KETS 100 electronic caliper.
RESULTS. Fat mass according to caliperometry data was 40.0 % in women, 30.0 % in men, p = 0.0001. According to bioimpedance measurements – 39.9 and 28.3 %, respectively, p = 0.0001. During the ROC analysis, the area under the curve for caliperometry was 0.851 (CI 0.729-0.932), for bioimpedance measurements 0.839 (CI 0.715-0.932). The correlation between the two methods in determining body fat mass in kg was Rs = 0.991 p = 0.0001, and in % Rs = 0.985 p = 0.0001. When comparing the results of determining body fat by the Bland-Altman method, the average difference between the two methods was 0.6 ± 2.3 %, the degree of discrepancy was from -4 to + 5 %. The prevalence of obesity among dialysis patients by BMI was 29.4 % among women and 19.4 % among men. However, according to the results of both caliperometry and bioimpedance measurements, the real prevalence of obesity exceeded 90 %.
CONCLUSION. Diagnosing obesity by BMI does not provide an indication of the true prevalence of obesity in dialysis patients. For this purpose, it is necessary to use bioimpedance or caliperometry. Both methods give comparable results and can be considered interchangeable.
PRACTICAL NOTES
IgG4-related disease (IgG4-AD), is a fibro-inflammatory condition characterized by an increase of serum IgG4 and infiltration of the tissue of affected organs by IgG4-positive plasma cells. There is a significant cross between IgG4-AB and antineutrophilic cytoplasmic antibodies (ANCA) – associated vasculitis (AAV) because of clinical and morphological features of both pathologies. A positive ANCA test is considered highly specific for AAV and excludes other forms of systemic diseases. However, a number of recent publications have demonstrated a combination of IgG4-AD with positive serum ANCA in patients, which suggests a revision of the role of ANCA as a diagnostic criterion for AAV. In this work, we describe a clinical case of a combination of clinical and morphological markers of IgG4-AD and positive serum ANCA in an 8-year-old girl. She had a combination of lung and kidney injury. Kidney disease was manifested as pyelonephritis and incomplete nephrotic syndrome. Histologically, it was identified a combination of tubulointerstitial nephritis and membranous nephropathy, with severe IgG4 infiltration in the glomerulus. The search for serological markers of systemic diseases revealed a positive test for myeloperoxidase ANCA, which suggested the existence of AAV in the patient. However, the presence of membranous nephropathy, which is an uncharacteristic morphological pattern of AAV, and massive deposition of IgG4 in the kidney tissue suggests a different pathogenetic mechanism in this patient.
PROGRAM ON CONTINUOUS POSTGRADUATE EDUCATION ON NEPHROLOGY
This article is the continuation of analysis and discussion from the book by Professor AI Nevorotin "Matrix phraseological collection: a manual for writing a scientific article in English". The Matrix phraseological collection is a kind of catalog of text samples. The samples were from articles selected from the leading English-language scientific journals and were systematized in such a way that when writing an article in English, Russian researchers are able easy to find examples suitable for his/her own work. Furthermore, the selected samples can be transformed accordingly saving the semantic and syntactic relations between the elements and, finally, be inserted into the text. The next, fifth, article of this series is devoted to the comparative evaluation of experimental findings. Particular attention is drawn to the description nuances of the biological processes' course. Preferred phrases and most relevant terms are presented.
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