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 protein’s 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: i) limited knowledge about the MGRS among hematologists and nephrologists; ii) lack of necessary diagnostic resources in most health-care facilities; iii) 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», 15-16 of March 2019, Pavlov First St-Petersburg State Medical University, St-Petersburg, Russia. 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 AIM: The analysis of clinical and morphological presentations and outcomes of primary systemic vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA-V) with dominant kidney involvement; the determination of clinical and morphological parameters associated with prognosis.

PATIENTS AND METHODS. Eighty nine patients with morphologically confirmed ANCA-associated kidney vasculitis on standard immunosuppressive therapy (IST) were included in this retrospective study. Clinical, immunological, and histological indices were analyzed at the time of the kidney biopsy, and early in the short-term (3-6 months) and in the long-term follow-up. The following outcomes were evaluated: the achievement of clinical and immunological remission of the disease; eGFR at the end of follow-up, the progression of renal disease (by the composite point: initiation of renal replacement therapy (RRT) or the estimated glomerular filtration rate (eGFR) <15 ml/min/1.73m2 or decrease in eGFR >50 %); all-cause mortality. The prognostic significance of clinical and morphological parameters was evaluated in multivariable regression models.

RESULTS. Most of cases (78 %) were represented by rapidly progressive or acute nephritic syndrome. Mean eGFR was 23 ml/min/1.73 m2. Fifteen percent of patients required acute dialysis. Dominant morphological phenotypes of glomerular lesions were sclerotic (34 %) and mixed (36 %) according to the International Pathology Classification (IPC). Median follow-up was 24 (8; 55) months. Cumulative 5-year and 10-year patient’s survivals and were 92 % and 86 %, respectively. Cumulative 5-year and 10-year renal survivals were 86 % and 68 %, respectively. The cumulative 5-year and 10-year proportions of cases without progression of kidney disease were 80 % and 55 %, respectively. Within 3-6 months of the induction IST 81 % of patients achieved clinical remission (complete (59 %) or partial (22 %)) (CR3-6), while 84 % of patients had immunological remission. Serum creatinine (Pcr) at the time of kidney biopsy was only the factor associated with the risk of renal progression (Expβ=1.73 (95 %CI 1.40-2.14) per 0.1 mmol/l increase). IPC classes and ANCA Renal Risk Score (ARRS) groups as well as other morphological indices of kidney injury had no independent associations with the renal outcomes in Cox models adjusted for Pcr. The independent factors associated with eGFR at the end of follow-up were: CR3-6 (β=0.36±0.08, p<0.001); age (β=-0.34±0.09, p<0.001), Pcr (β=-0.35±0.09, p<0.001) and the global glomerulosclerosis (β=0.28±0.08, p<0.001). CR3-6 (β=0.57±0.10, p<0.001), and the proportion of cellular crescents (β=0.26±0.12, p=0.023) and interstitial inflammation (β=0.27±0.11, p=0.026) were also independently associated with the change of eGFR by the end of follow-up.

CONCLUSION. An unfavorable renal prognosis for ANCA-V determined by severe renal dysfunction due to inflammatory and fibrotic alterations of the organ can be significantly improved by adequate therapy with the achievement of higher patient’s and kidney’s survival. The baseline serum creatinine is only the factor associated with the long-term risks of dialysis and kidney disease progression. In addition to baseline serum creatinine and the development of early clinical remission, the separate assessment of global glomerular sclerosis, cellular crescents, and interstitial inflammation may be more useful for the individual prediction of long-term eGFR changes than IPC classes or ARRS.

 AIM. The analysis of incidence, clinical and morphological manifestations, and the prognosis of IgA nephropathy in the Russian population.

PATIENTS AND METHODS. Six hundred cases with primary IgA nephropathy (IgAN) from 1999 to 2019 were enrolled in the single-center retrospective study. Demographic and clinical parameters, morphrology data, and the treatment were analyzed. Three hundred forty seven patients were included in follow-up study. The following outcomes were evaluated: the occurrence of complete (PR) or partial remission (CR), death from all causes, the need for renal replacement therapy (RRT). The composite endpoint (RRT or eGFR decrease ≥ 50 % from the time of biopsy) was used to evaluate the risk of IgAN progression and associated factors.

RESULTS. The period-average incidence of IgAN cases was 20.5 % of all indication biopsies and 31.7 % of primary immune glomerulopathies (with gradual increase to 41,5 % in last 5 years). At the time of the kidney biopsy, the proteinuria was 2.20 (1.10; 4.40) g/24h, eGFR – 69 ± 32 ml / min / 1.73 m2. Proportions of cases with arterial hypertension and with eGFR <60 ml / min / 1.73 m2 were 75 % and 36 %, respectively. The prevalence of histological changes in accordance with the MEST-C classification was as follows: M1 – 40.5 %, E1 -22.9 %, S1-70.2 %, T1-22 %, T2 – 9 %, C1-16.7 %, C2 – 4.4 %. Combined deposits of IgA and IgM (71.1 % of cases) were more frequent compared to IgA and IgG (9,6 %). In the followup period (27 (11; 61) month), 6 deaths from all causes were registered (1.7 %). The 10-year cumulative renal survival was 75 % (by dialysis) and 55 % (by composite endpoint). PR registered in 26 % of cases, CR – 24 %. PR / CR was more frequent in patients who received immunosuppression compared with patients on renin-angiotensin system blockers only (60 % vs. 40 %, p = 0.001). In multivariable Cox regression the independent factors associated with the risk of IgAN progression were: male gender, a younger age, higher blood pressure and hematuria, lower eGFR, interstitial fibrosis/ tubular atrophy (≥50 %), peritubular capillaritis and the presence of any crescents. Compared to the cohorts of other ethnic or geographical affiliation, analyzed IgAN cases were found to have more severe clinical and morphological presentations and faster progression rate.

CONCLUSION. While being the most common glomerulopathy, IgAN in the Russian population has more pronounced clinical and morphological presentations and an unfavorable prognosis.

INTRODUCTION. Acute Kidney Injury (AKI) is a common complication of acute coronary syndromes (ACS), and associated with higher mortality and adverse outcomes. Despite advances in research over the past years, effective treatments for current AKI are not available. Prevention and early intervention remain the most effective strategies for AKI of any entity. THE AIM: This study aimed to explore a risk factors and biomarkers for predictive and early diagnostic of AKI in ACS.

PATIENTS AND METHODS. Study was prospective and cohort, patients hospitalized with ACS in Pavlov First Saint Petersburg State Medical University were included. In case of exclusion of ACS, patients were determined in the comparison group, in case of confirmation of the diagnosis of ACS – in the study group. Biomaterial (blood and urine) was taken at admission (T1), 1 day after admission (T2) and 2 days after admission (T3). For the diagnosis of AKI, KDIGO 2012 criteria were used. The measured biomarkers at each point were NGAL, KIM-1, cystatin C, sST2, troponin I. RESULTS. The study included 73 patients, the diagnosis of ACS was confirmed in 40 patients and AKI development was in 15 patients, all from the ACS group. The most significant for predictive diagnosis was the assessment of the parameters of systemic hemodynamics and the severity of acute heart failure (AHF): heart rate>89 (AUC=0,798, p=0,001), GRACE Risk Score>133 (AUC=0,926, p=0,005). In evaluation the suitability of biomarkers in terms of prognostic diagnosis of AKI, urine NGAL>32 ng/ml (AUC=0,814 p=0,04) and sST2>23.4 ng/ml (AUC=0,718, p=0,02) showed the best results.

CONCLUSIONS. In study of biomarkers efficiency, the use of urine sST2 and NGAL is most promising. Together with hemodynamic parameters, biomarkers have high predictive ability in the diagnosis of AKI in ACS.

BACKGROUND. The number of patients with end-stage renal disease is steadily increasing. One of the main complications arising from the disorders of calcium-phosphorus metabolism in patients on hemodialysis is various types of renal osteodystrophy. The frequency of pathological fractures among patients receiving renal replacement therapy is twice as high as in the general population. The prevalence and structure of injuries, especially the diagnosis of injuries of the musculoskeletal system in hemodialysis patients, are not well understood. THE AIM: to determine the prevalence and structure of injuries and the consequences of pathological injuries of bones and joints undergoing hemodialysis in Saint-Petersburg. To achieve this goal, the authors developed a special questionnaire, consisting of 4 blocks, including 32 questions.

PATIENTS AND METHODS. An analysis of questionnaires of 798 patients from 15 hemodialysis centers of Saint-Petersburg was carried out.

RESULTS. A number of problems were identified, such as insufficient coverage of patients not only with specific instrumental examination methods (MSCT, MRI), but also with radiographic ones. Satisfaction with quality of life and physical activity was noted in less than half of patients. 46.4% had a history of fractures and injuries, while the proportion of operated patients was half that, which indicates the need for more active work of hemodialysis centers with city hospitals with traumatology and orthopedic departments.

CONCLUSION. Patients on HD require regular x-ray examination and densitometry to detect pathological damage to bones and joints. Based on the results of these studies, it is advisable to consult a traumatologist at least 1 time per year.

BACKGROUND. The molecular mechanisms of the initial stages of inorganic phosphate (Pi) metabolic disorders in chronic kidney disease (CKD) remain poorly understood.

THE AIM. To test the hypothesis about changes in canonical Wnt signaling pathway inhibitors biosynthesis and a concomitant decrease in bone turnover as one of early mechanisms of Pi imbalance in CKD.

MATERIAL AND METHODS. Creatinine (Cr), inorganic phosphate (Pi), serum parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), sclerostin (SOST) and Dickkopf-1 (DKK), renal SOST and DKK mRNA expression, albuminuria (Alb), proteinuria (uTP) levels, fractional (FEPi) and daily (uPi24) Pi excretion were analyzed in SHR rats (N = 52) with 3/4 nephrectomy (NE) or sham operation (SO) and observation periods of 2, 4, and 6 months.

RESULTS. Experimental model was comparable with 1-2 stages of CKD. In groups NE4 and NE6, the concentration of sPi and renal Pi excretion (FEPi and uPi24) were significantly higher vs corresponding controls SO4 (p = 0.006, p <0.010) and SO6 (p = 0.002, p = 0.028). Serum concentrations of FGF23 and PTH in NE and SO animals did not change significantly. In NE4 and NE6 groups, serum SOST and DKK concentrations were significantly higher vs controls (p <0.049, p <0.043), while the kidney expression SOST and DKK mRNA in NE rats did not change significantly or decreased (p = 0.002, p <0.011). The serum concentration of OPG was higher in the NE6 vs SO6 control (p = 0.028).

CONCLUSION. The initial stages of experimental CKD are characterized by an increase in serum concentrations of Dikkopf-1, sclerostin and osteoprotegerin. The obtained data suggest the possible role of canonical Wnt signaling inhibition and reduction of bone turnover in the pathogenesis of Pi metabolic disorders in early stages of CKD.

BACKGROUND. Increased salt intake is associated with a number of cardiovascular events, including increased blood pressure (BP) and the development of left ventricular hypertrophy (LVH). However, there is much evidence that a high content of sodium chloride in the diet does not always lead to an increase in BP, but almost inevitably causes cardiac remodeling, in particular, LVH. Many aspects of myocardial remodeling induced by high sodium content in the food have not been studied enough. THE AIM of the study was to trace the echocardiographic changes in Wistar rats fed the high salt ration and the high salt ration supplemented with soy proteins.

MATERIAL AND METHODS. Echocardiography and BP measurements were performed on male Wistar rats, divided into three groups. The first (control; n = 8) included rats that received standard laboratory feed (20.16 % animal protein and 0.34 % NaCl); the second (n = 10) – animals that received standard feed and 8 % NaCl (high salt ration). The third group (n = 10) consisted of rats who consumed a low-protein diet containing 10 % soy protein isolate (SUPRO 760) and 8 % NaCl. The follow-up period was 2 and 4 months.

THE RESULTS of the study showed that: (1) the intake of a large amount of salt with a diet does not necessarily lead to the formation of arterial hypertension; (2) despite the absence of a distinct increase in BP, under these conditions signs of cardiac remodeling, in particular, LVH, appear rather quickly; (3) supplementing a high-salt diet with soy isolates counteracts the development of LVH.

CONCLUSION. High salt intake with food can cause heart remodeling, regardless of blood pressure, while soy proteins can counteract this process.

INTRODUCTION. Vitamin D deficiency is commonly observed in patients with chronic kidney disease (CKD) due to decreased biosynthesis of 1,25(OH)2D3 in damaged renal tubules and increased catabolism of 1,25(OH)2D3 and 25OHD3. There is a growing evidence that vitamin D deficiency may contribute to impaired kidney function. Interventional studies have shown that vitamin D and its analogs attenuate the progression of renal fibrosis in experiment, and reduce proteinuria in patients with CKD. The renoprotective effects of vitamin D go far beyond its classical role in maintaining bone and mineral metabolism, which is a result of its pleiotropic action. THE AIM: to investigate the association between 25OH-hydroxyvitamin D (25OHD) level and renal fibrosis in spontaneously hypertensive rats (SHR) with early stages of experimental CKD.

MATERIAL AND METHODS. Systolic blood pressure (BP), proteinuria, albuminuria, creatinine (Cr), urea (Ur), inorganic phosphate (Pi), 25OHD in serum were measured in nephrectomized (NE) and sham operated (SO) spontaneously hypertensive rats SHR (follow-up period 2, 4 and 6 months) and SO Wistar Kyoto rats (follow-up period 2 months), morphological light-optical study of kidney tissue was performed.

RESULTS. The experimental model corresponded to the initial stages of CKD (Ur: 6.64 – 13.36 mmol/L). A significant increase in the area of renal fibrosis in animals with NE correlated with an increase in blood pressure (r = 0.51, p <0.001), serum Cr (r = 0.76, p <0.001), and albuminuria (r = 0.64, p <0.001) and proteinuria (r = 0.78, p <0.001) and a decrease in the concentration of 25OHD in serum (r = -0.67, p <0.001). In multiple regression analyzes, a reliable association of fibrosis with 25OHD was maintained (β = -0.28, p = 0.012). In addition, in ROC-analysis the largest value of the area under the curve was obtained for 25OHD (AUC = 0.95) to detect interstitial fibrosis more than 10 %.

CONCLUSION. 25OHD depression at the initial stages of experimental CKD and hypertension is independently associated with the development of renal fibrosis.