Nº 2 (2019)

The purpose of the study was to determine the effective and safe therapeutic dose of the new original long-acting erythropoiesis-stimulating agent BCD-іЗі (pegylated darbepoetin) upon repeated administration for the treatment of anemia in patients with end-stage chronic kidney failure on dialysis. Materials and methods. The international multicenter randomized open label comparative phase II clinical trial included 75 patients with anemia and end stage renal failure on dialysis, regularly receiving recombinant human erythropoietin. The trial consisted of two periods. During the first period it was planned to sequentially include patients in the three treatment groups of the investigational drug BCD-іЗі with the dose escalation: 1.05 ug/kg, 1.7 ug/kg and 2.75 ug/kg and parallel inclusion of participants in the group of active comparator Mircera. Drugs were administered once a month subcutaneously. During the first period of the trial we determined that two dose levels of BCD-іЗі i.05 ug/kg and i.7 ug/kg produce the sufficient pharmacodynamic and clinical effect, therefore the dose 2.75 ug/kg of BCD-іЗі was not used in the further research. During the second period the initially included participants and newly recruited patients (until the number of 25 person in each of the three treatment groups) continued to receive therapy with the investigational drug BCD-іЗі 1.05 ug/kg (group 1) or 1.7 ug/kg (group 2) and the reference drug (group 3) up to the 21st week. Results. During the 21 weeks treatment period the mean hemoglobin level was within the target range in all treatment groups (both doses of the investigational drug BCD-іЗі and Mircera). The calculated 95% CI for the difference in arithmetic mean values of the change in hemoglobin level between group 1 and group 3 was [-8.87; 4.47], does not exceed the predetermined equivalence limits і0,00 g/l and indicates the equivalent efficacy of the investigational drug BCD-іЗі 1.05 ug/kg and Mircera. The safety analysis demonstrated the absence of statistically significant differences between the three treatment groups in the frequency and spectrum of registered adverse events (AEs), including treatment-emergent AEs and thrombotic complications. Throughout the study no binding antibodies were detected. Conclusion. In this phase II clinical trial we determined the therapeutic dose of the new erythropoiesis-stimulating agent BCD-іЗі (pegylated darbepoetin). BCD-іЗі i.05 ug/kg and Mircera showed the equivalent efficacy. BCD-іЗі (both doses) and Mircera demonstrated the comparable and favorable safety profile, good tolerability and absence of the immunogenicity.

Objective. Evaluation of cardiovascular disorders and cytokine status, and their relationship with the glomerular filtration rate in men and women at the predialysis stage of chronic kidney disease (CKD). Material and methods. 170 patients aged 19 to 86 years who had CKD with high and very high (additional) cardiovascular risk were examined. The mean age of the examined patients was 56.2±13.9 years. CKD was diagnosed in accordance with the recommendations of the Russian Scientific Society of Nephrology. The serium interleukin-6 (IL-6), iL-10 levels were evaluated. Glomerular filtration rate (GFR) was calculated by the method of F.J. Hoek et al., proposed in 2003 (80.35/CystatinS-4.32=GFR). All patients underwent ultrasound examination of the heart and blood vessels, and central arterial pressure was measured. The patients were randomized into two age-, anthropometric- and hemodynamic parameter-matched groups: 1st (n=77) female, and 2nd (n=93) male. Results. A decrease in GFR less than 60 ml/min/1.73 m2 was detected in 49.4% of the examined patients. In the male group, C4-stage CKD was significantly more frequently recorded. The diameter of the left ventricular outflow tract (3.31±0.35 versus 3.11±0.40 cm; p<0.05), the carotid intima-media thickness (carotid IMT) (1.12 against 0.97 mm; p<0.05), left atrial size (3.98±0.57 versus 3.75±0.59 cm; p<0.05), left ventricle (LV) enddiastolic diameter (5.24±0, 66 vs 4.97±0.43 cm; p<0.05), the interventricular septum thickness (0.983±0.179 vs 0.925±0.180 cm; P<0.05), and LV mass (200.51±70.50 g versus 171.18±57.87 g; p <0.05) were significantly higher, and the LV ejection fraction (52.47±12.36 versus 58.28±5.79%; p<0.05), on the contrary, significantly lower in male group compared with female group. Concentric hypertrophy was significantly more common in men compared with women [16 (48.5%) versus 10 (33.3%); p<0.05], as well as concentric LV remodeling [12 (12.9%) versus 4 (5.1%); p<0.05]. At the same time, the number of patients with eccentric LV hypertrophy was significantly higher in women than in men [20 (66.7%) versus 17 (51.5%); p<0.05]. The values of the median and interquartile range of IL-10 [6,122 (2,381-7,204) versus 4,167 (1,761-7,500) pg/ml; p<0.05], the blood cystatin C and creatinine levels were significantly higher, and the GFR was lower in men compared with women. In men, a close relationship between the GFR and the central arterial pressure (r=-0.364; p=0.001) and the carotid IMT (r=-0.342; p=0.001) was also observed. At the same time, significant correlation between GFR and the serum IL-10 level was noted in the female group (r=-0.243; p=0.023).

Objective. Creation of a unified register of renal biopsies of the Kyrgyz Republic (RBKR). Establishment of relationship between morphological and clinical manifestations of glomerulopathy. Material and methods. The study included 245 patients who underwent a study of renal tissue samples obtained in vivo by percutaneous biopsy from 2015 to 2019. All patients underwent a complex of general clinical, biochemical, immunological, instrumental and morphological studies. Results. In the pediatric cohort, 41 (4і.8%) patients with hematuria combined with nephrotic proteinuria were followed-up, and it was the maximum number of all examined children. Patients with nephritic and nephrotic syndromes were detected with the same frequency in 27 (27.5%) and 22 (22.4%) patients, respectively. Isolated urinary syndrome was detected only in 8 (8.і6%) patients. In the adult cohort, nephritic-range proteinuria was more often recorded - in 96 (65.3%) patients. Isolated urinary syndrome was observed in 30 (20.4%) patients. It should be emphasized that the incidence of all clinical manifestations (proteinuria with and without hematuria) compared with children differed. Conclusion. The most common variants of glomerular lesion in adults includrd membranous glomerulonephritis (MN [38%]) and immunoglobulin A nephropathy (IgAN; 29.2%), whereas in children IgAN and the minimal change glomerulonephritis dominated, in 20.4 and і9.3%, respectively.

Nutcracker syndrome is a consequence of aorto-mesenteric compression of the left renal vein - compression of the left renal vein by the superior mesenteric artery with the development of left-sided renal phlebohypertension, pain in the left side and small pelvis, the appearance of proteinuria and hematuria. The relative rarity of the disease, the lack of clear clinical diagnostic criteria, the possible latent course with isolated urinary syndrome can lead to diagnostic errors. The article presents two cases of nutcracker syndrome, confirmed by data of multispiral computed tomography in 17- and 20-years old patients old, previously suffering from varicocele. Renal biopsy results excluded the suspected chronic glomerulonephritis as the cause of isolated urinary syndrome. The necessity of including aorto-mesenteric compression of the left renal vein with the development of renal venous hypertension in the diagnostic algorithm in patients with isolated urinary syndrome is emphasized.

Clinical manifestations of drug-induced hypersensitivity (DIH) can range from mild skin reactions (for example, maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis due to drug-induced eosinophilia with systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens-Johnson syndrome (SJS/toxic epidermal necrolysis (Ten - toxic epidermal necrolysis). In modern pharmacogenomic studies, important steps have been taken to prevent some forms of DIH by identifying relevant genetic variants, especially those that encode drug-metabolizing enzymes and human leukocyte antigens (HLA). In addition, advances in the field of immunological genetics have allowed to put forward new concepts of mechanisms for the development of DIH. As a result, models of drug presentation, explaining how small drug antigens can interact with HLA (human leucocyte antigens) and T-cell receptor (TCR) molecules in DIH, have been greatly enhanced and include today the concept of "pharmacological interaction", the model a modified peptide repertoire and a model of a modified TCR repertoire, in addition to hapten theory. a wide range of clinical manifestations of DIH and the participation of various drugs in its development, as well as the diversity of pathogenetic mechanisms make the diagnosis and management of DIH extremely difficult. This review highlights recent advances in studying the molecular mechanisms of DIH development and briefly discusses current approaches to its diagnosis.

The main milestones of the scientific and practical activity of Richard Bright (1789-1858) are considered. Little-known facts from the life of an English scientist and clinician are discussed. The scientific views and thoughts of the scientist are presented in detail. The article noted that in 1813 he defended his doctoral thesis "On a contagious erysipelas." He improved his knowledge in Cambridge, then in London, in various clinics in Vienna. Since 1820, he was a doctor at Guy’s Hospital in London for 30 years, giving a course of clinical lectures. It is shown that R. Bright made a major contribution to the study of internal diseases, especially kidney diseases, and is rightfully considered the founder of the scientific study of renal pathology. The fact that he identified the morphological forms of the main renal diseases - large white kidney, an enlarged or normal size irregular kidney, an, a small granular kidney - is analyzed. For the first time he described the clinical picture and the morphology of nephritis, indicated the causes for its development, created the principles of its treatment and prevention. It has been noted that bilateral inflammatory and dystrophic processes in the kidneys (nephritis, nephrosis) have been called Bright's disease for many decades. However, the term "Bright's disease" is a collective concept (differentiation of various forms of kidney diseases is necessary), therefore it is practically not used at present time. Meanwhile, it was shown that R. Bright was also engaged in natural history, geology, and taught botany.