[The dapagliflozin and prevention of adverse outcomes in chronic kidney disease: results of the DAPA-CKD study].

AIM: The article presents the main results of a randomized, double-blind, parallel, placebo controlled trial of DAPA-CKD. MATERIALS AND METHODS: The study included patients with chronic kidney disease (CKD) and the possibility of using dapagliflozin at a dose of 10 mg once a day compared with placebo. The study involved 386 centers from 21 countries. A total of 4304 patients were included in the study, the average age was 61.8 years, men predominated, 2906 (67.5%) patients had an initial diagnosis of type 2 diabetes. Patients with diabetic and non-diabetic CKD were included with an estimated glomerular filtration rate (eGFR) of 25 to 75 ml/min/1.73 m2 and a urinary albumin/creatinine ratio of 200 to 5000 mg/g. RESULTS: The primary composite endpoint (time to eGFR reduction of 50% or more compared to baseline, time to end-stage renal disease defined as eGFR15 ml/min/1.73 m2, need for chronic dialysis or kidney transplantation, time to renal or cardiovascular death) was shown to occur in 9.2% of patients treated with dapagliflozin and in 14.5% of patients treated with placebo. Also, dapagliflozin therapy was less likely to have a secondary endpoint, such as a combination of a decrease in eGFR by 50% or more, end-stage kidney disease, or renal death. Less frequently, the dapagliflozin group experienced cardiovascular death or hospitalization for heart failure, as well as death from any cause. CONCLUSION: Thus, dapagliflozin demonstrated the ability, in comparison with placebo, to reduce the primary composite point and a number of secondary composite points in patients with both diabetic and non-diabetic CKD.

[Monoclonal gammopathy of renal significance: consensus of hematologists and nephrologists of Russia on the establishment of nosology, diagnostic approach and rationale for clone specific treatment].

Monoclonal gammopathy of renal significance (MGRS) is a new nosology in modern nephrology and oncohematology. MGRS is defined as kidney injury due to nephrotoxic monoclonal immunoglobulin produced by the B-cell line clone which does not reach the hematological criteria for specific treatment initiation. Monoclonal proteins pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: 1) limited knowledge about the MGRS among hematologists and nephrologists; 2) lack of necessary diagnostic resources in most health-care facilities; 3) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. Consensus document comprises the opinion of experts leading nephrologists and hematologists of Russian Federation on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy, 1516 of March 2019, Pavlov First Saint Petersburg State Medical University. The present Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses.

THE ROLE OF MYOSTATIN AND PROTEIN KINASE-B IN THE DEVELOPMENT OF PROTEIN-ENERGY DEFICIENCY IN PATIENTS WITH END-STAGE RENAL DISEASE ON HEMODIALYSIS.

In patients with chronic renal failure receiving hemodialysis, the development of protein-energy wasting (PEW) has a significant impact on the quality and duration of life. Myostatin (MSTN) and protein kinase-ß (AKT) play an important role in this process. The aim of our study was to assess the contribution of these molecular markers of muscle metabolism to the development of PEW in patients with chronic kidney disease stage 5D (CKD5D). The study included 80 patients with CKD5D. All patients underwent anthropometric research, hand dynamometry, bio-impedancemetry. MSTN and AKT levels were determined in the blood by ELISA. In the study, the prevalence of PEW was 90%. We have proposed a catabolic muscle tissue index (CMTI), which takes into account the complex effect of the relationship between MSTN and AKT on the development of PEW. An increase in this index in degrees from 0-2 characterizes the prevalence of catabolic processes in muscle tissue. There is an increase in CMTI with the progression of nutritional disorders in patients on hemodialysis (HD). An increase in CMTI is associated with a decrease in muscle strength, muscle mass (measured by the diameter of the shoulder). No correlation was found between CMTI and gender, age, or bio-impedance indicators, which requires further investigation.

FEATURES OF THE UBIQUITIN-PROTEASOME SYSTEM IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 5D.

The aim of the study was to assess the activity of the ubiquitin-proteasome system in patients with chronic kidney disease stage 5D (CKD5D) and its relationship with clinical and laboratory parameters. We examined 80 patients with CKD5D on hemodialysis (HD). The mean age was 51.7±11.6 years, the duration of HD was 33.5 (19.7; 58.25) months. All patients underwent physical examination, bio-impedancemetry. Hypoxia-inducible factor 1-alpha (HIF-1α) and 20S-proteasome (20S-PSM) levels were determined in the blood by ELISA. The hemoglobin level as well as its fluctuation over the preceding 12 months did not differ in the groups with normal and elevated 20S-PSM levels, however, there were some features of ferrokinetics depending on the level of serum transferrin (p=0.04), its fluctuations over the preceding 12 months (p=0.03) and its saturation (p=0.03). It was shown that as the level of 20S-PSM in the blood increases, the probability of detecting protein-energy wasting (PEW) increases (χ2=4.8, p=0.029). This is probably due to the implementation of the catabolic link of protein metabolism involving the ubiquitin-proteasome system. There was a strong negative correlation between the HIF-1a and 20S-PSM parameters (r=-0.86, p<0.05), which was confirmed when building the logistic regression model (χ2=65.9, p<0.0001). Depending on the level of hemoglobin and HIF-1a, we divided all patients into groups with hemoglobin and hypoxia-dependent 20S-PSM increase mechanisms. The found interrelations of these molecular markers with ferrokinetics parameters, features of renal replacement therapy (RRT) require additional study.