[Remissions and progression of C3 glomerulopathy].

AIM: To analyze the outcomes of C3-glomerulopathy (C3-GP) and determine the associated factors. MATERIALS AND METHODS: A retrospective single-center study included 60 patients with newly diagnosed C3-GP (with primary C3-GP pC3-GP 82%). Of these, 48 (80%) patients had clinical data to assess the following disease outcomes: development of remission and disease progression (by a composite endpoint that included initiation of chronic dialysis or a decrease in estimated glomerular filtration rate eGFR 15 mL/min/1.73 m2 or a decrease in eGFR30% of baseline at the time of renal biopsy). The median follow-up period was 25 (7; 52) months. RESULTS: At early follow-up (median 4 [3; 9] months) remission was registered in 35% of patients; at the end of follow-up, in 48% (for pC3-GP, 32 and 41%). Disease progression occurred in 17 patients. In the overall group the likelihood of achieving early remission was higher with treatment (Exp=6.4, 95% confidence interval CI 1.429.3; p=0.017). Early remission was associated with the presence of remission at the end of follow-up (Exp=6.3, 95% CI 2.218.4; p=0.001). Specific treatment (Exp=0.308, 95% CI 0.1080.881; p=0.028) and late remission (Exp=0.079, 95% CI 0.0170.368; p=0.001) were associated with reduced risk of disease progression in multivariable models (adjusted for eGFR, mean blood pressure). The same results were obtained for the group of patients with pC3-GP. CONCLUSION: C3-GP is a variant of severe complement-mediated glomerular damage with unfavorable renal prognosis, which requires timely personalized expert-level diagnostics with clarification of etiopathogenesis of the disease followed by therapy aimed at achieving remission to improve outcomes.

[A novel approach to rapid induction of remission in primary membranous nephropathy].

AIM: То evaluate the effectiveness of a novel multi-targeted treatment approach including rituximab (RTX), cyclophosphamide (CPH) and steroids (S) to the induction of remission in patients with primary membranous nephropathy (PMN) compared to standard immunosuppression (IST). MATERIALS AND METHODS: An open-label prospective comparative study included 56 PMN patients (pts) with nephrotic syndrome (NS) and high serum level of antibodies to the phospholipase A2 receptor anti-PLA2R (mean age 5112 years, men 70%). We recorded demographic and clinical parameters at the time of kidney biopsy, data from light-optical and immunomorphological studies. All pts were on stable doses of the renin-angiotensin systems blockers. We compared the effectiveness of different treatments in the inductions of clinical and immunological remissions in pts who received experimental treatment with RTX, CPH and S (RTX+CPH+S group, n=14) and two control groups: high-dose RTX therapy (group RTX, n=12), cyclosporine and steroids (group CsA+S, n=30). RESULTS: In the RTX+CPH+S group, remission was achieved in 100% of cases (of which complete remissions CR in 21.4%). The median time-to-remission (2.5 [1.0; 3.5] months) was significantly lower compared to both control groups: RTX (8.7 [6.6; 14.0] months, p=0.005) and CsA+S (12.4 [6.5; 19.9] months, p0.001). The cumulative incidence of clinical and immunological remissions was also significantly higher in the RTX+CPH+S group than in the control groups. These results were confirmed in comparative analyzes in the same treatment groups after propensity score matching. The cumulative incidence of clinical and immunological remissions in the RTX+CPH+S group was higher than in the combined group of patients who received other therapies (p0.001). The incidence of serious adverse events was low and did not differ between groups. CONCLUSION: The use of multi-targeted therapy with rituximab, cyclophosphamide, and steroids seems to be an effective approach for the rapid induction of PMN remission and prevention of NS complications.

[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 analysis of treatment of Immunoglobulin A-nephropathy].

AIM: An evaluation of the effectiveness of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: A retrospective cohort of the study included cases with biopsy proven primary IgAN (n=367, age 3412 years, men 55%). We used demographic and clinical and morphological parameters at the time of biopsy. Median followup period was 26 (10; 61) months. Outcomes were remission (complete or partial) and the progression of IgAN (defined as the start of dialysis or a decrease in glomerular filtration rate 50% from baseline). All patients received treatment with renin angiotensin system blockers. Evaluation of the effectiveness of therapy was carried out using propensity score (PS) methods matching, conventional double robust regression models with PS as independent covariate, and inverse probability weighting. Following patient subgroups were used for comparative analyses: with IST (n=176) and without IST (n=191); with TE (n=63) and without TE (n=304); without IST and without TE (IST-TE-; n=162); with TE and without IST (IST-TE+; n=29); with IST and without TE (IST+TE-; n=142); with IST and with TE (IST+ TE+; n=34). RESULTS: All PS methods used gave close estimates of the comparative effectiveness of treatment in different subgroups: 1) patients on monotherapy with corticosteroids (CS) and combination of CS with other immunosuppressants did not have significant differences in probabilities of IgAN progression (hazard ratio 0.919; 95% CI 0.3332.950) and remission (odds ratio 0.919; 95% CI 0.3792.344) and were further combined into a group of IST; 2) IST was significantly associated with the lower risk of disease progression and increased odds ratio for remission; 3) the positive effects of IST were limited to cases with proteinuria 2 g/24 h; 4) the likelihood of IgAN remission and progression did not differ significantly between TE+ and TE-, IST-TE+ and IST-TE- groups. There were no cases of disease progression in the IST+TE+ group. The cumulative renal survival was higher in the IST+TE+ group compared to IST+ TE- group (p=0.010), while the probability of remission did not differ. CONCLUSION: IST was associated with a lower risk of IgAN progression and increased probability of remission, while these effects of IST were limited to patients with proteinuria 2 g/24 h. TE in combination with IST is associated with an additional reduction in the risk of disease progression.

Membranoproliferative glomerulonephritis in Russian population.

AIM: Analysis of etiology, clinical and morphological manifestations, approaches to therapy and prognosis of membranoproliferative glomerulonephritis (MPGN). MATERIALS AND METHODS: Cases of MPGN were retrospectively identified in the period 2000-2017 with subsequent analysis of etiology, clinical data and morphology (including deposits of immunoglobulins (Ig) and C3 complement fractions). The achievement of complete and partial remissions (PR, CR), overall survival, progression (by composite endpoint: decrease in the estimated GFR (eGFR) ≥50% from the baseline or eGFR <15 ml/min/1.73 m2 or the onset of dialysis). RESULTS: 214 cases of MPGN entered the study with the average age of 44±16 years. Most patients had nephrotic syndrome and significant hematuria. In 58.4% of cases, eGFR was <60 mL/min/1.73 m2, and every fifth patient had CKD 4 or 5 stages. The prevalence of MPGN among all biopsy-confirmed glomerulopathies was 9.3%. Idiopathic MPGN (iMPGN) was detected in 30.4% of cases, secondary MSGN (sMPGN) - in 69.6% (autoimmune diseases - 34.1%, infectious diseases - 16.4%, monoclonal gammopathies - 9.3%, complement-mediated damage - 9.8%). Ig+C3+MPGN was mainly associated with autoimmune diseases and infections; C3-glomerulopathy or thrombotic microangiopathy were most often causes of Ig-C3+MPGN; Ig-C3-/Ig+C3-MPGN had heterogeneous etiology. The median follow-up period was 28 [7; 37] months. The 10-year total cumulative patient and renal survival rates were 71 and 50%, respectively (without differences between sMPGN and iMPGN). The frequency of the PR/CR was 50% (iMPGN - 46.2%, sMPGN - 51.3%) depending on the etiology of the MPGN (p=0.049). The cumulative 10-year progression-free renal survival was nearly 100% in cases with PR/CR and 0% in non-responders. CONCLUSION: MPGN is a severe variant of glomerular damage with a heterogeneous etiological structure and an unfavorable prognosis. Targeted clinical and morphological diagnostics of MPGN allows to identify the cause of the disease in most cases. This approach is reliable for the adequate treatment choice and improvement of outcomes in MPGN.

[Membranous nephropathy in a Russian population]. / Membranoznaia nefropatiia v rossiiskoi populiatsii.

AIM: To analyze the clinical and morphological manifestations of membranous nephropathy (MN) and to evaluate the efficiency of its therapy. MATERIAL AND METHODS: MN cases in 2009 to 2016 were retrospectively detected with a subsequent analysis of patients with primary MN (PMN). The titer of IgG-autoantibodies to phospholipase A2 receptor (anti-PLA2R Ab) was determined by an indirect immunofluorescence assay. Treatment outcomes, such as the time course of changes in proteinuria, nephrotic syndrome (NS), and the development of complete and partial remissions (CR and PR), were assessed. RESULTS: MN was detected in 201 cases; the secondary etiology of the disease was established in 24.9%. The prevalence of MN among morphologically confirmed glomerulopathies was 14%; that of PMN was 10.4%. The median period to diagnosis PMN was 8 (5; 19) months. 150 patients with PMN (66.7% were men; age was 50±15 years) were distributed according to the following morphological stages: Stages I (23.9%), II (48.5%), III (26.1%), and IV (1.5%). Elevated anti-PLA2R Ab levels were found in 51.6% of cases; NS in the presence of proteinuria was detected in 85.6% of patients. An estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 was seen in 25% of cases. Treatment outcomes were evaluated in 80 cases; the median follow-up period was 19 (8; 40) months. 68% of cases had CR (32%) or PR (36%) with a median follow-up of 26 (13; 44) months. Spontaneous CRs or PRs were observed in 7.5% of the patients. Multivariate analysis showed that the probability of CR or PR increased 3.2-fold in the use of cyclophosphamide and/or cyclosporine and decreased as eGFR dropped. CONCLUSION: In Russia, PMN is a common type of glomerulopathy, the specific features of which should include the low rates of spontaneous remissions and detection of anti-PLA2R Abs. For renal protection, the majority of patients with PMN require timely diagnosis and treatment; individualization of the choice of treatment and its enhanced efficiency call for further investigations.

[Nephrological aspects of complement-mediated thrombotic microangiopathy]. / Nefrologicheskie aspekty komplement-oposredovannoi tromboticheskoi mikroangiopatii.

AIM: To analyze cases of complement-mediated thrombotic microangiopathy (C-TMA) in the daily practice of a hospital nephrology department, relative to the general aspects of the clinical course, therapy, and short-term outcomes. SUBJECTS AND METHODS: The prospective study conducted in the period June 1, 2015 to June 1, 2016 included 10 patients with C-TMA newly diagnosed during hospitalization. Standard demographic parameters, generally accepted clinical data showing the severity of TMA and the involvement of vital organs were recorded at admission. Short-term outcomes of therapy (plasma therapy and/or eculizumab therapy), such as achievement of hematological remission and the need for maintenance therapy and renal replacement therapy (RRT), were evaluate. RESULTS: The median time from the onset of symptoms of the disease to diagnosis in the analyzed cases was 5 months (range 1 week to 26 months). The incidence of C-TMA among the inpatients of nephrology departments was 6.4 per 1,000 patients per year. Five patients were admitted to a clinic with symptoms of obvious extrarenal organ disorders; 4 of them had multiple organ dysfunction. Evident clinical symptoms of renal dysfunction were detected in all the patients, which necessitated RRT in 8 out of the 10 patients. Renal biopsy was performed in 7 patients. All were found to have typical morphological manifestations of acute and chronic TMA. All the patients received plasma therapy; most of them had plasma exchanges; 4 patients took eculizumab. There were no fatal outcomes. All achieved hematological remission. Three of the 8 cases could achieve varying recovery of kidney function and stop dialysis. CONCLUSION: Analysis of this series of cases confirms the idea about the severity of TMA due to multiple organ dysfunction and the high risk of end-stage renal failure at late diagnosis. The key points of better renal prognosis are the earliest detection and treatment of the disease.

[Acute kidney injury and tubular biomarkers after hematopoietic stem cell transplantation].

AIM: To determine the value of molecular biomarkers (BMs) associated with tubular epithelial damage in developing and predicting acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT). SUBJECTS AND METHODS: The open-label observational prospective study enrolled 90 patients (46 males and 44 females) who had undergone HSCT. The concentrations of BMs (calbindin, clusterin, interleukin-18 (IL-18), kidney injury molecules-1 (KIM-1), glutathione S-transferase-π (GST-π), and monocyte chemoattractant protein-1 (MCP-1) were measured in urinary samples 7 days before HSCT (week 0) and at weeks 1, 2, 3, 4, and 5. Main clinical parameters were simultaneously monitored. AKI was diagnosed and stratified according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. RESULTS: At weeks 1, 2, 3, 4, and 5 after HSCT, the proportion of AKI cases was 7.8, 8.9, 12.5, 27.3, and 35.9%, respectively. The elevated urinary levels of BMs (above the median) were found to be substantially more common than AKI cases. The urinary excretion of the majority of BMs dramatically increased in the early HSCT period. The median number of simultaneously elevated BMs was 3 (2; 5) during the entire follow-up period. Clusterin, MCP-1 and KIM-1 positively and significantly correlated with serum creatinine at the week following the determination of BMs in the multivariate linear regression models adjusted for other confounders. The higher urinary KIM-1 and/or MCP-1 excretion regardless of other clinical indicators was associated with the higher relative risk (RR) of AKI, which increased by 2.3 times with a rise in one of these indicators and by 3.4 times with a rise in both indicators. CONCLUSION: Multiple renal toxic effects after HSCT result in a substantial and simultaneous elevation of urinary excretion of BMs for tubular damage. Among the BMs studied, KIM-1 and MCP-1 seem to be the most suitable molecules for assessing the risk of AKI in this cohort of patient within the predictive diagnostic approach.

[A case of diagnosing lipoprotein glomerulopathy in Russia]. / Sluchai diagnostiki lipoproteinovoi glomerulopatii v Rossii.

Lipoprotein glomerulopathy (LPG) is a rare disease characterized by specific histological, immunomorphological, and ultrastructural changes. The main pathomorphological signs of LPG are lipoprotein thrombi in the lumen of the capillary loops, proteinuria, and dyslipoproteinemia as an increased concentration of apolipoprotein E (phenotypes E2/E3, E2/E4). A patient aged 47 years had nephrotic syndrome with a daily protein loss of 12.4 g/ day. Light optical microscopic examination of a renal biopsy specimen revealed Sudan III-positive, weakly PAS, and eosin-positive friable thrombi in the lumen of the capillary loops. No deposits of immunoglobulins were immunomorphologically detected in thrombotic masses. The ultrastructure of thrombotic masses was composed of granular masses with numerous vacuoles that formed concentric layers. Thus, LPG was diagnosed as a manifestation of type 3 hyperlipoproteinemia that had characteristic pathological, clinical, and laboratory signs of this disease.

[Renal revascularization and long-term cardiovascular survival of patients with atherosclerotic renovascular disease].

The prospective investigation of 185 patients (118 men and 67 women in the age of 35-79 years (on the average 60+/-9 years) with atherosclerotic renovascular disease was carried out. The disease was detected by one- (62%) and two- (38%) hemodynamic value (>50%) of renal artery stenosis. Renal function, arterial pressure, cardiovascular death cases were estimated in 4 groups of patients during the period of 2,5-126 months (on the average 33 months). The patients of the first group (n=103) were undergone the renal revascularization (51 open and 80 endovascular). The patients of the second group (n=20) were after combined open renal revascularization (25) and after performed reconstruction of abdominal aorta and its branches and lower extremities arteries concerning aneurysmatic and occlusive lesions. The patients of the third group (n=19) had only reconstruction of lower extremities arteries concerning their ischemia without renal revascularization. The patients of the fourth group (n=43) haven't been operated because of the refusal of intervention. The lowest rate of survival was in the fourth group, who used the conservative therapy. Long-term survival didn't differ after open and endovascular therapy. The Koks regression analysis showed, that the improvement of long-term survival of the patients was associated with renal revascularization [Exp(B)=0,25, p<0,001] and didn't depend on the method of renal arteries reconstruction. A strategy of careful selection of patients with the application of interdisciplinary approach should be the base of clinical practice in renovascular disease.

[Phosphorus and calcium metabolism and the cardiovascular system status in patients with early-stage chronic renal disease].

AIM: To define the impact of phosphorus and calcium metabolic disturbances in patients with early-stage chronic renal disease (CRD) on the cardiovascular system. SUBJECTS AND METHODS: The levels of phosphate (P), calcium, parathyroid hormone (PTH), 25(OH) vitamin D and 1,25(OH)2 vitamin D, serum lipidogram, carotid artery intima-media thickness (IMT), and X-ray degree of abdominal artery calcification (AAC) were determined and echocardiography, electrocardiography and blood pressure monitoring were made in 465 patients with Stages I-V CRD who did not receive renal replacement therapy (of them, 73.5% of the patients had early (I to III) stages). RESULTS: Blood 1,25(OH)2D was related inversely to left ventricular (LV) posterior wall thickness, blood pressure (BP), triglycerides, and the degree of AAC and correlated directly to the severity of LV diastolic dysfunction and inversely to IMT, the presence of coronary heart disease and heart failure (HF). ACC, LV hypertrophy, and arterial hypertension (AH) were more significant in patients with higher serum levels PTH and P. CONCLUSION: In patients with early-stage CRD, phosphorus and calcium metabolic disturbances promote the development of AH, vascular and cardiac valvular calcification, myocardial hypertrophy, and HF.

[Heart valve calcification in patients with chronic kidney disease].

The aim of the study was to identify factors related to heart valve calcification (HVC) and effect of HVC on intracardiac hemodynamics in patients with chronic kidney disease (CKD). 377 CKD patients of the control group and 132 ones treated by hemodialysis (HD) were examined using echocardiography, cardiomonitoring, measurement of the carotid intima-media thickness and mineral bone density, X-ray imaging of calcified abdominal aorta. HVC was diagnosed in 38.9 and 27.3% of the CKD patients on hemodialysis and without it respectively. In both groups, patients with HVC were older than HVC-free ones, more of them had coronary heart disease, cardiac insufficiency, aortic calcinosis, and biochemically identifiable inflammation. In the absence of hemodialysis, patients with HVC had thicker intima-media compex, lower glomerular filtration rate, higher arterial pressure, and increased occurrence of diabetes mellitus. In HVC patients receiving hemodialysis, its duration was longer, blood PTH and calcium levels higher, forearm MOC lower. HVC associated with stenosis of mitral and aortic valves, aortic regurgitation, enlarged left and right atrium, thickened left and right ventricular wall. Multifactor analysis showed that HVC in patients receiving hemodialysis was related to the age, disbalance of phosporus and sodium, and duration of hemodialysis; in its absence, it was related to intima-media thickness and diabetes mellitus. Thus, in patients of the latter group, HVC was in the first place associated with atherosclerosis aggravated by a decrease of glomerular filtration rate and with the presence of diabetes. In patients receiving hemodialysis, HVC correlated with phosporus/sodium disbalance and atherosclerosis. The study revealed negative effect of HVC on intracardiac hemodynamics and for the first time demonstrated decreased MOC in patients with HYC.

[Contribution of irreversible morphological changes of different renal structures to development of anemia in immune glomerulopathies].

AIM: To find out correlations between severity of sclerotic affection of the glomeruli, tubules, interstitium, vessels and development of anemia in patients with glomerulopathy. MATERIAL AND METHODS: Assay of global and segmentary sclerosis, semiquantitative morphometry of severity of atrophic tubular changes, diffuse interstitial fibrosis, vascular changes (arteriolohyalinosis, elastofibrosis and perivascular sclerosis) were made in parallel with analysis of clinical laboratory data in 276 cases of chronic primary glomerulopathy with morphologically verified diagnosis by vital renal biopsy. RESULTS: Hemoglobin concentration and advance of anemia correlate negatively with severity of diffuse interstitial fibrosis and atrophic tubular alterations. However, no correlation was found between onset of anemia, severity of global and segmental glomerular sclerosis, the presence of vascular changes in the form of arteriolar hyalynosis, elastofibrosis of small arteries and perivascular sclerosis. CONCLUSION: The findings suggest that development of anemia in patients with primary glomerulopathy may be the result of structural-functional disturbances in tubular epithelium and renal stroma.

[Prevalence of subnormal glomerular filtration rate in patients with diabetes mellitus].

AIM: To evaluate prevalence of subnormal glomerular filtration rate (GFR) in diabetes mellitus (DM) patients with reference to albuminuria level. MATERIAL AND METHODS: GFR by MDRD and urine excretion of protein/albumin were estimated in 851 diabetic patients (473 with type 1 DM and 378 with type 2 DM). RESULTS: Normoalbuminuria (NAU), microalbuminuria (MAU) and proteinuria were detected in 54, 16 and 30% type 1 diabetics, respectively; 77% had subnormal GFR, in NAU 8.3% had GFR decline (< 60 ml/min) corresponding to stage III-IV chronic disease of the kidneys. In MAU the latter was present in 16.4%, in proteinuria--in 62.8%. Type 2 diabetics had NAU in 33.6% cases, MAU--in 17.7%, proteinuria--in 48.7%. Subnormal GFR < 60 ml/min was found in 40% cases with NAU and MAU. Most patients with proteinuria had chronic disease of the kidneys of stage III-V In a normal creatinine concentration in blood serum subnormal GFR < 60 ml/min was observed in type 1 DM in 7.6, in type 2 DM--in 33% cases. CONCLUSION: Prevalence of subnormal GFR in diabetic patients with NAU and MAU is rather high. This necessitates wide introduction of this index in screening, follow-up and classification of renal damage severity in DM as well as estimation of albuminuria/proteinuria.

[Renal tubular epithelocytic changes in hypercysteinemia and experimental chronic renal failure].

One group of adult male Wistar rats received DL-homocysteine, 13.4 mg/kg body weight every day (an HC-group) while the rats underwent subtotal nephrectomy (a SN-group) and were killed 3 weeks later. Both light and electron microscopies were used to analyze obtained renal specimens. A total loss of the brush border in some proximal tubular (PT) cells and an increase of autophagosomes and emergence of the loci of disorganized cytoplasm were observed in the HC-group, while in the SN-group there was a significant increase in the number and size of secondary lysosomes and of foci of the cytoplasmic disorganization.

[Elevated plasma homocysteine and glutathione level in patients with renal failure].

The levels of homocysteine (Hcy) and glutatione (Glt) were determined in plasma of 219 patients with different stages of chronic kidney disease (CKD) (94 patients received chronic bicarbonate hemodialysis and 125 patients were at predialysis stage). The elevated Hcy level was detected in an early stage of CKD and reached maximal values and spreading in the hemodialysis patients. The levels of total and reduced Hcy (tHcy and rHcy, respectively) were also higher in CKD patients: the proportion of rHcy in total pool of plasma Hcy was significally higher than in healthy subjects. In the group of non-dialysed patients the reverse dependance between glomerular filtration rate (GFR) value and Hcy plasma concentration was found. We did not find any correlation between Glt and GFR in predialysis patients, but there was direct dependance between Glt and tHcy plasma levels in this group. Glt plasma levels in dialysis patients were reliably lower than in predialysis ones. There was a lack of some correlation between Glt and tHcy in the haemodialysis group.

[Epidemiology and risk factors of chronic renal diseases: a regional level of the problem].

AIM: Assessment of chronic renal disease (CRD) prevalence and morbidity rate and approaches to early CRD in one of the regions of the RF (Tyva Republic). MATERIAL AND METHODS: A population study in the Tyva Republic performed from 01.07.2003 to 30.06.2004 included patients with glomerular filtration rate (GFR) < 30 ml/min, nephrosclerosis signs at autopsy, terminal GFR < 30 ml/min, on replacement renal therapy (RRT). CRD prevalence and morbidity were estimated (stage IV-V). Examination of 374 Tyva citizens was made for estimation of early CRD and risk factors of developing CRD (the sectional study). The participants of the sectional study were examined clinically and biochemically with measurement of albuminuria, calculation of urine albumin/creatinine (ACR) and study of some molecular-genetic characteristics. RESULTS: Prevalence of CRD stage IV-V in Tyva population was 493 cases per million, prevalence of RRT--126 cases per million. Elevated ACR was found in 4.7% of healthy subjects and 15.9% of hypertensive subjects. Initial lowering of GFR occurred in some healthy subjects and in 1 of 12 hypertensive patients. Significant predictors of albuminuria were serum albumin concentration (p < 0.00001), GFR (p < 0.0002), a male sex (p < 0.004), diabetes mellitus (DM) (p = 0.0057) and left ventricular myocardial mass index (p = 0.0253). GFR depended significantly on age (p < 0.000001), male sex (p < 0.000001), uric acid concentration in the serum (p < 0.000001), presence of DM (p = 0.000019), ACR (p = 0.0059), diastolic pressure (p = 0.0347), triglyceridemia (p = 0.0369). Citizens of Tyva had more frequently than citizens of other regions of Russia IlI-genotype of angiotensin 1-converting enzyme (ACE) (p < 0.0001), T-allele of methylentetrahydrofolatereductase (p < 0.0001), E3-allele of gene of apoprotein E (p < 0.0001). Prevalence of aa, ab, bb genotypes of eNO-synthetase was 82.3%, 15% and 2.7% in the group of Tyva examinees vs 62, 31 and 7% in European Russians (p < 0.01). CONCLUSION: Prevalence of both early and advanced stages of CRD among population of Tyva Republic is rather high. CRD morbidity may depend, besides conventional risk factors, some genetic specific features. Screening studies require continuation for early detection of CRD and timely planning of therapeutic and preventive measures.

[Epidemiology of chronic renal disease in the North-West of Russia: setting-up the register]. / épidemiologiia khronicheskoi bolezni pochek v Cevero-zapadnom regione Rossii: na puti k sozdaniiu registra.

AIM: To study epoidemiology of chronic renal disease (CRD) in the North-West region of the Russian Federation. MATERIAL AND METHODS: A population retrospective trial was performed from 01.07.98 to 30.06.99 in the Vologda region, towns Veliky Novgorod and Syktyvkar (total population 1840000). 490 cases of chronic renal failure (CRF) with creatinin levels > 300 mcmol/l corresponding to CRD stage IV and V by glomerular filtration rate were detected. CRD stage IV-V prevalence, morbidity including sex- and age-specific parameters, cumulative survival in different etiology of CRD regarding replacement therapy (RT) and nephrologist supervision were estimated. RESULTS: Mean prevalence and morbidity were 266 and 108 cases per million. Number of affected males and females was the same. CRD was provoked by chronic glomerulonephritis (CGN)--41%, chronic interstitional nephritis--16%, diabetes mellitus--14%, renal polycystic disease--8%, amyloidosis--6%, hypertension nephrosclerosis--2%, other causes--3%, cases of unclear etiology--10%. Among patients with primary renal pathology on RT, number of CGN patients was higher--61% while diabetic and amyloidosis shares were much lower 1.6 and 0.8%. 31.1% patients given no RT had Cr > 500 mcmol/l and glomerular filtration rate < 10 ml/min. Incidence of CRD stage IV-V in RT patients was 80 per million, 8 patients per million for 1 year started RT for the first time. CRF mortality was 85 patients per million a year. 88.4% of deaths in patients given no RT was due to uremia. Cumulative survival for RT patients and RT untreated was 90 and 50% a year, respectively. Survival of the RT untreated observed by the nephrologist was significantly higher (p = 0.003). CONCLUSION: New cases of CRD stage IV-V were comparable in number to European incidence rate while prevalence was much less because of lower number of old patients and RT treated. The problem of CRD treatment is urgent for RF and requires updating nephrological service and development of RT programs.

[Risk of chronic renal failure in patients with non-insulin dependent diabetes mellitus with diabetic nephropathy and the stage of permanent proteinuria and arterial hypertension: role of clinical factors]. / Risk razvitiia khronicheskoi pochechnoi nedostatochnosti u bol'nykh s diabeticheskoi nefropatiei v stadii postoiannoi proteinurii i arterial'noi gipertoniei: znachenie klinicheskikh faktorov.

AIM: To reveal prognostic factors which determine the risk of development of chronic renal failure (CRF) in patients with diabetes mellitus (DM) type II associated with diabetic nephropathy (DN) at the stage of continuous proteinuria in combination with arterial hypertension (AH). MATERIAL AND METHODS: A total of 60 AH patients suffering from type II DM with permanent proteinuria were examined. Chronic renal failure was registered in 21 patients. RESULTS: Among CRF patients, more frequent were males, high proteinuria and nephrotic syndrome, IHD, macroangiopathy of the lower limbs, VLDLP. CONCLUSION: Independent predictors of CRF in diabetes mellitus type II with AH and proteinuria were male gender, overweight, faster development of stable proteinuria from the time of diabetes diagnosis.