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Aim: To determine the nature and magnitude of changes in the detectable serum and urinary biomarkers of water-salt metabolism in patients with proteinuric forms of chronic glomerulonephritis (CGN), their importance for assessing the activity and prognosis of the disease., Subjects and Methods: Forty-seven patients with CGN were examined. Group 1 included 10 patients with nephrotic syndrome (NS) and decreased renal function; Group 2 comprised 16 patients with persistent NS and normal renal function; Group 3 consisted of 10 patients with partial remission of NS; Group 4 included 11 patients with active hematuric CGN. A control group consisted of 9 healthy individuals matched for gender and age with the patients with CGN. The serum level of copeptin and the urinary excretion of aquaporine-2 (AQP-2) and kidney injury molecule-1 (KIM-1) were determined by indirect enzyme-linked immunosorbent assay (ELISA)., Results: In the NS patients with and without renal dysfunction, the serum copeptin concentration was significantly higher than that in those with partial remission of NS or hematuric CGN and in the controls. In the patients with hematuric CGN, this indicator was virtually different from that in the control group. Urinary AQP-2 excretion was significantly similar in 3 NS groups. In the patients with hematuric CGN, the urinary AQP-2 concentration was higher than that in those with NS, but it was significantly lower than in the control group. The highest urinary excretion of KIM-1 was found in the patients with NS and diminished renal function while its excretion was significantly lower in the patients with NS and stable renal function, as in those with partial remission of NS. The lowest values were seen in the patients with hematuric CGN and in the control group; the differences between these groups were statistically insignificant. Correlation analysis showed that there was an inverse correlation between serum copeptin and urinary AQP-2 levels and between urinary AQP- 2 and KIM-1 levels., Conclusion: Serum copeptin levels and urinary AQP-2 secretion may be used to assess the activity of CGN and NS and to evaluate therapeutic effectiveness. The determination of urinary KIM-1 excretion may be of the same practical value in patients with NS. It has been shown that the concentrations of copeptin, APQ-2, and KIM-1 may be used as a differential diagnostic criterion for hematuric CGN.

Aim: To identify the risk factors of kidney injuries in hypertensive patients with uric acid (UA) metabolic disorders in order to choose the optimal management tactics, by analyzing the changes in markers for endothelial dysfunction (endothelin-1 (ET-1), microalbuminuria (MAU), intima-media thickness (IMT)) and tubulointerstitial tissue lesion (beta2-microglobulin (beta2-MG, monocyte chemotactic protein-1 (MCP-1))., Subjects and Methods: Eighty-one patients with grade 1 hypertension without associated diseases, diabetes mellitus, or metabolic syndrome were examined. There were 3 study groups: 1) hyperuricosuria (n = 7); 2) hyperuricemia (n = 53); 3) hyperuricemia and renal failure (n = 6); and a control group of 15 hypertensive patients without UA metabolic disorders who were matched for age and gender with the patients of the study groups., Results: The hypertensive patients with hyperuricemia, as compared with those without UA metabolic disorders, showed higher plasma concentrations of ET-1 (p = 0.003) and MAU (p = 0.009) and more marked increases in common carotid IMT (p = 0.044), urinary excretion of beta2-MG (p = 0.010), and MCP-1 (p = 0.030). There were direct correlations between all the examined biomarkers and the degree of uricemia (Rs = 0.453; p < 0.001; Rs = 0.411; p < 0.001; Rs = 0.322; p = 0.067; Rs = 0.537; p < 0.001; and Rs = 0.318; p = 0.004, respectively) and between the markers of endothelial dysfunction and those of tubulointerstitial tissue lesion (Rs = 0.295 for ET-1 and MCP-1; p = 0.008; Rs = 0.399 for ET-1 and beta2-MG; p < 0.001; Rs = 0.462 for MAU and beta2-MG; p < 0.001; and Rs = 0.188 for MAU and MCP-1; p = 0.094). Multivariate analysis of the clinical and laboratory parameters under study confirmed the role of serum MCP-1, beta2-MG, MAU, creatinine levels as independent predictors for decreased relative urinary gravity, the clinical sign of tubulointerstitial tissue lesion/fibrosis, and that of a wider range of the indicators, such as MAU, ventricular septal thickness, glomerular filtration rate, relative urinary gravity, systolic blood pressure, MPC-1, low-density lipoproteins, as risk factors for renal filtrating dysfunction.

Aim: To study the role of the morphogenetic proteins FGF-23 and Klotho in the progression of chronic kidney disease (CKD) and in the development of cardiovascular events, inflammation, protein-energy deficiency, and other complications., Subjects and Methods: Examinations were made in 70 patients with Stages I-VD CKD: 41 with chronic glomerulonephritis (including 10 with nephritis in the presence of diffuse connective tissue diseases), 22 with tubulointerstitial nephritis, and 7 with hypertensive nephrosclerosis. There were a total of 30 men and 40 women whose age was 20 to 84 years; the mean age at the study inclusion was 41 +/- 6.7 years. The serum levels of FGF-23 (Human FGF-23 ELISA kit using monoclonal antibodies to complete molecule of FGF-23) and Klotho (Human alpha-K1 ELISA using anti-Klotho antibodies) were investigated in all the 70 patients with CKD., Results: The sera of all the examinees with CKD showed elevated FGF-23 and decreased Klotho levels, the magnitude of a change in which increased from Stage I to VD. In patients with different stages of CKD, the increase in FGF-23 levels, as glomerular filtration rate reduced, outstripped that in the serum levels of phosphorus and intact parathyroid hormone. There was a strong correlation of the serum level of the morphogenetic proteins, Klotho in particular, with proteinuria, C-reactive protein level, protein-energy deficiency, indicating the pleiotropic effects of these proteins. There was also a strong correlation between serum Klotho and ferritin levels and transferrin saturation percentage, which suggests that Klotho may be involved in iron regulation., Conclusion: The results of the investigation lend credence to the experimental and clinical findings that the serum levels of the morphogenetic proteins FGF-23 (an increase) and Klotho (a decrease) are early markers for progressive CKD and that their changes begin just in Stage III CKD and progress as renal failure worsens.

Aim: To determine the levels of 70-kDa heat shock protein (HSP70) in urine and anti-HPS70 antibodies (Abs) in serum and to assess their clinical and prognostic value in patients with different forms of chronic glomerulonephritis (CGN)., Subjects and Methods: Seventy-nine patients with CGN, including 15 with inactive nephritis (Group 1), 35 with active CGN and preserved renal function (Group 2), 14 with the highest CGN activity and transient creatininemia (Group 3), and 15 with persistent proteinuria and chronic renal failure (Group 4) were examined. ELISA was used to estimate urinary HSP70 levels and serum anti-HSP70 Abs in the examined groups., Results: The patients with active CGN were found to have higher excretions of urinary HSP70 and serum anti-HSP70 Abs. Urinary HSP70 excretion was significantly higher in the patients with transient renal function (Group 3) than in those from the other groups. At the same time, there was a decrease in serum anti-HSP70 Abs, which was a poor factor of persistent nephrotic syndrome despite immunosuppressive therapy (IST). Despite long-term IST, the nephrotic syndrome was persistent in 9 (60%) of the 15 patients with low serum Ab titers. At the same time, 8 (80%) of the 10 patients with higher serum Ab titers responded to IST during 9 months., Conclusion: The investigation demonstrates the great value of HSP70 as an index of the severity of lesion and the activation of kidney self-defense mechanisms in patients with CGN. Determination of serum anti-HSP70 Abs may be used to assess the prognosis of CGN.

Aim: To study the clinical significance of determining the serum concentration of phosphorus and calcium metabolism regulators--the morphogenetic proteins FGF-23 and Klotho in patients with different stages of chronic kidney disease (CKD)., Subjects and Methods: The serum levels of FGF-23 (a human FGF-23 ELISA kit with full-length anti-FCF-23 monoclonal antibodies) and Klotho (a human alpha-K1 ELISA with anti-Klotno antibodies) were investigated in 70 patients with Stages I--VD CKD (41 patients with chronic glomerulonephritis, including 10 with nephritis in systemic diseases, 22 with tubulointerstitial nephritis, and 7 with hypertensive nephroslerosis). The morphogenetic proteins were studied by the specialists of the LiTECH diagnostic laboratory according to the standard protocol., Results: As CKD progressed from Stage I to VD, there were increased FGF-23 concentrations and decreased Klotho levels in the examinees' serum. The highest FGF-23 level and low Klotho concentration were noted in the group of patients on regular hemodialysis treatment (Stage VD). There was a strong inverse correlation between Klotho levels and proteinuria, C-reactive protein, and protein-energy insufficiency, which suggests that these factors influence the serum level of Klotho. The serum levels of FGF-23 and intact parathyroid hormone correlated with these values to a lesser degree. Analysis of the content of the morphogenetic proteins in patients with anemia versus those with CKD of the same stages and target hemoglobin values revealed low Klotho concentrations and high FGF-23 levels (r = 0.602; p < 0.01 and r = -0.450; p < 0.01, respectively). Forty-nine hypertensive patients showed a direct strong relationship between elevated serum FGF-23 levels and an inverse strong one between the reduced serum Klotho levels and the increased posterior left ventricular wall (r = 0.552; p < 0.01 and r = -0,587; p < 0.01, respectively). The same strong association was found between the higher serum level of FCF-23 (r = 0.492; p < 0.01) and the concentration of Klotho (r = -0.537; p < 0.01) and peripheral vascular resistance index (as evidenced by Doppler ultrasound study)., Conclusion: Along with the active participation of the morphogenetic proteins (FGF-23 and Klotho) in mineral metabolism and its disturbances in CKD, their role is apparent in the development of cardiovascular events (in particular, through the involvement in the processes of vascular calcification and cardiac remodeling), anemia (through the possible effect on iron metabolism, enhanced ischemia of renal interstitial tissue with impaired Klotho production), and protein-energy insufficiency (through the participation in the processes of inflammation, oxidative stress, and protein synthesis).

The paper gives current general data on the structure of amyloid fibril and the principles in the classification of amyloidosis, information on the clinical course of cardiac and renal involvements in systemic AL and AA amyloidosis, and that on diagnostic and prognostic criteria and the specific features of cardiorenal links. The authors draw the conclusion that the identification of acute and chronic cardiorenal links is of practical value for systemic amyloidosis. Cardiorenal and renocardiac syndromes are not always differentiated clearly in the systemacy of involvement.

The paper reviews the literature on the role of hyperuricemia as a risk factor for chronic kidney disease and as one of the factors for the progression of existing kidney disease. It gives epidemiological information on a relationship between hyperuricemia and kidney lesion. The mechanisms for the damaging action of uric acid on kidney tissue, which have experimentally and clinically observed, are considered. The main areas of hyperuricemia correction and its place in the total nephroprotection strategy are defined.

A significant progress in the field of molecular-biological investigations resulted in definition of a new group of systemic diseases referred to as autoinflammatory. This group comprises familial periodic fevers: periodic disease (mediterranean fever), Muckle-Wells syndrome, others cryopirinopathy, TRAPS-syndrome. As shown by case reports, Muckle-Wells syndrome is not a rare disease, its sporadic forms are encountered as well as a less severe variant of cryopirinopathy - nonallergic cold urticaria. Awareness of the physicians in respect of this pathology is essential especially because early diagnosis enables control of this disease with use of biological preparations the spectrum of which tends to expansion. Moreover, arrest of inflammation is necessary for prevention of development and progression of such prognostically poor complication as AA-amyloidosis.

Aim: To estimate serum and urine IL-6 levels and to study its role in diagnosis of nephritis activity in patients with cryoglobulinemic glomerulonephritis (CGN) associated with chronic hepatitis C (CHC)., Material and Methods: Enzyme immunoassay was used to assay IL-6 in blood serum of 124 patients having different stages of CHC. IL-6 was also estimated in the urine of 57 patients with CHC systemic manifestations including renal damage., Results: Abnormal serum IL-6 level was seen in 36% CHC patients. Patients with elevated level of IL-6 in the serum vs. patients with normal IL-6 level had cryoglobulinemia (CGE) (56% vs. 26%, p < 0.01) and related systemic manifestations including cryoglobulinemic glomerulonephritis (30% vs. 9%, p < 0.01). Most of (90%) patients with CHC-associated CGN had urinary IL-6 excretion correlating with severity of renal damage: the highest urinary level of IL-6 was seen in development of acute nephritic and nephritic syndromes (from 83.5 to 250 pg/ml). It did not correlate with IL-6 in the serum and proteinuria. This is evidence that IL-6 in the urine had a local origin (intrarenal), reflecting activity of immune inflammation in the kidney., Conclusion: Control of IL-6 levels in the blood serum and urine of patients suffering from CHC with cryoglobulinemic syndrome and renal damage can be used for monitoring of the disease activity.

Aim: To evaluate severity of nephrinuria (NU) as a marker of podocyte dysfunction (PD) in patients with proteinuric forms of chronic glomerulonephritis (CGN) and to specify efficacy of this test for assessment of activity and prognosis of CGN., Material and Methods: We examined 74 CGN patients: 18 with inactive nephritis (group 1), 18--with subnephrotic proteinuria (group 2), 38--with nephrotic syndrome--NS (group 3). The control group consisted of 10 healthy subjects. Urinary excretion of nephrin was studied with indirect enzyme immunoassay. A response to immunosuppressive treatment (IST) was studied in 23 NS patients depending on a baseline NU level., Results: An NU level was higher in patients with proteinuric forms of CGN (groups 2 and 3) than in inactive disease and in healthy subjects, in NS patients significantly higher than in less severe proteinuria. NU was significantly higher in arterial hypertension, in persistent NS. Remission of NS was achieved within 6 months of treatment in 9 of 11 (82%) patients with a baseline NU level < 17 ng/ml. Eight from 12 (67%) patients with high NU did not respond to IST conducted for 9 months to 2 years. ROC-curve construction showed that NU assessment in NS patients has high informative value in assessment of prognosis and efficacy of treatment in 6 months to come., Conclusion: The NU test in CGN patients is an informative diagnostic test allowing prognosis of a response to IST and assessment of PD severity.

Aim: To reveal clinical and morphological characteristics of renal damage in patients with cryoglobulinemia (CGE) associated with chronic viral hepatitis C (CVH-C) for upgrading diagnosis, prognosis and optimization of the treatment methods., Material and Methods: Two groups of CVH-C patients were studied: with CGE (group 1, n = 64) and free of CGE (group 2, n = 62) matched for gender, age and duration of the disease. Biopsy of the liver for assessment of the histological activity index and histological sclerosis index by METAVIR scale was conducted in 63 patients. Of patients with CGE-related damage to the kidneys, 48 were examined for clinical picture with morphological investigation of renal tissue in 15 of them including semiquantitative evaluation of fibrosis degree and activity., Results: Patients with CVH-C and CGE had a wider spectrum of systemic lesions than CVH-C patients without CGE. Only CGE patients demonstrated more severe affection of the skin, joints, kidneys and the nervous system. Therefore, CGE can be considered as a marker of poor prognosis. Liver biopsy showed that CGE patients had more pronounced fibrosis (3-6 points) versus 0-2 points in 80% patients from group 2. Duration of CVH-C from probable infection to renal damage in 48 patients with CGE glomerulonephritis (GN) averaged 197.05 +/- 18.5 months. Renal biopsy diagnosed CGE mesangiocapillary GN in 13 patients and membranoproliferative GN in 2 patients. Patients with HCV infection had a more severe proliferative form of nephritis--mesangiocapillary GN. In 48 GN patients with HCV-infection and CGE, GN ran latently with moderate urinary syndrome in 29 (60.4%) patients, with nephrotic syndrome--in 9 (18.6%), with acute nephritic syndrome--in 10 (21.0%) patients. Most of the patients had arterial hypertension, 13 patients had creatinemia (3.02 +/- 0.55 mg/dl), rapidly progressive GN was diagnosed in 4 patients., Conclusion: Persistent CGE marks poor prognosis in CHC patients and is an indication for antiviral treatment to prevent severe organ lesions, first of all of the kidneys. Development of CGE vasculitis with severe damage to the kidneys demands immunosuppressive therapy in combination with plasmapheresis or cryapheresis followed by antiviral drugs. As shown by pilot results, a new approach with rituximab is perspective but further evidence is needed for final conclusions.

Calcitriol is important in nephroprotective strategy in chronic disease of the kidneys (CDK). However, its long-term use often results in hypercalciemia with metastatic calcification. Compared to calcitriol, paricalcitol (zemplar)--metabolite of vitamin D2--leads to hypercalciemia less frequently, has a more potent nephroprotective effect and more rapidly decreases blood levels of parathyroid hormone. Paricalcitol in combination with lozartan has more pronounced nephroprotective effect. Morphological analysis detected inhibition of development of glomerulosclerosis and tubulointerstitial fibrosis. A cardioprotective effect of paricalcitol manifests with reduction of mortality from cardiovascular complications both at CDKpredialysis stage and in regular hemodialysis.

Aim: To determine clinical significance of measuring blood levels of protein precursors of AA- and AL-amyloidosis - SAA and immunoglobulin free light chains (ILC), respectively., Material and Methods: SAA concentrations were studied with ELISA in 43 rheumatoid arthritis (RA) patients including complicated with reactive AA-amyloidosis (n = 31). Inflammation activity and its severity were studied (indices Li, richi, HAQ, DAS4). A modern quantitative nephelometric method Freelite estimated ILC levels in 31 patients with AL-amyloidosis., Results: Patients with RA complicated with AA-amyloidosis and free of it had a strong correlation between blood serum SAA concentration and activity of joint disease. Elevated SAA concentrations to 160 mg/l (normal 10 mg/l) were detected in many patients with clinical remission of the joint syndrome. Significal inhibition of AA-amyloidosis progression was seen only in SAA concentration drop under 60 mg/l. For AL-amyloidosis patients ILC fall by less than 3 normal value means a 6-time increase in chances of a favourable outcome., Conclusion: Monitoring of blood levels of proteins precursors of AA- and AL-amyloidosis is a key factor in prognosis of the disease and treatment efficacy.

Aim: To determine clinical significance of urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis in essential hypertension (EH)., Material and Methods: Examination of the kidneys was made in 71 patients with EH degree 1-3. Renal function was assessed by 24-h albuminuria, calculated glomerular filtration rate (GFR) by Cockroft-Golt. Early signs of renal damage were microalbuminuria--MAU (diurnal albuminuria 30-300 mg/day), reduction of GFR (< 90 ml/min/1.73 m2). EH patients with hypercreatininemia and GFR under 60 ml/min/1.73m2 corresponding to stage III of chronic kidney disease were not included in the study. An additional nephropathy marker was an elevated index of resistance of interlobular renal arteries (RI > 0.65) as shown by dopplerometry. ELISA examined urinary biomarkers of intercellular and cell-matrix interactions in the kidney in EHpatients and healthy controls (n = 12)., Results: MAU was detected in 54 (76%) of 71 EH patients, elevated RI > 0.65--in 37 (52%) patients. Urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis were higher in EH patients then in the controls. Urinary excretion of PAI-1, TGF-beta1, VEGF and collagen of type IV in EH patients with MAU was significantly higher than in patients with normoalbuminuria. A strong direct correlation between MAU and the rest above urinary biomarkers was found as well as between urinary excretion of collagen IV and RI. An inverse negative relationship was seen between RI and GFR., Conclusion: Renal impairment in EHpatients is a progressive disorder. Each stage of this process has its own clinicodiagnostic markers. Urinary biomarkers ofproteolysis/fibrinolysis and fibroangiogenesis in the kidney are informative for monitoring of early HNP.

Aim: to define the clinical value of various concentrations of immunoglobulin light chains (ILCs) in patients with AL amyloidosis., Subjects and Methods: The content of free ILCs was studied by a nephelometric technique after their fixation in the blood of 31 patients with AL amyloidosis; monoclonal gammapathy was associated with the hyperproduction of monoclonal ILCs of lambda- and kappa-type in 14 and 17 patients, respectively. The obtained value was compared with the data of physical examination and laboratory and instrumental studies indicating lesions to target organs and with the course of the disease., Results: In patients with the good course of AL amyloidosis, the average level of free ILCs was 1.8 (range 0.77-3) times greater than the normal values (the range of ILCs of lambda and kappa-type was 20.24 to 67.4 and 20.14 to 81.38 mg/l, respectively); in those with the poor course, the excess of ILCs was 5.8 (range 3.7-13) times higher than the normal values (the range of lLCs of lambda and kappa-type was 54.32 to 286.7 and 117.06 to 2606.0 mg/l, respectively). The optimal range of diagnostic sensitivity (75%) and specificity (75%) in the estimation of prognosis was determined at the ILC levels that were three times greater (64.5 mg/l for kappa-ILCs and 80 mg/l for lambda-ILCs). Among the patients with a blood free ILC level of < 3 times more than the normal values, the good and poor courses of AL amyloidosis were noted in 13 and 4 cases, respectively., Conclusion: The determination of serum ILC concentration by the Freelite method may be used to diagnose AL amyloidosis and to specify the presence of appropriate organ dysfunction; this study over time makes it possible to monitor the course of the disease and to estimate its response to therapy.

Aim: to define the clinical value of changes in blood rheological properties and renal endothelial function in patients with hematuric and nephritic forms of chronic glomerulonephritis (CGN) and to ascertain whether the indices under study can be applied to assess the activity (progression) of nephritis and used as a prognostic criteria., Subjects and Methods: Sixty-one patients, including 30 with hematuric nephritis (Group 1) and 31 with nephrotic nephritis (Group 2), were examined. A control group consisted of 12 healthy individuals. The rheological properties of blood, such as its viscosity; kinetics of spontaneous aggregation and disaggregation of red blood cells in shear flow; their deformability; urinary excretion of functionally active von Willebrandt factor (WF), a plasminogen activator inhibitor type 1 (PAl-1); urine total fibrinolytic activity (UTFA), activity of urinary urokinase-type plasminogen activator (UPA) were studied., Results: The patients with CGN were found to have signs of impaired blood rheological properties (increased viscosity, an accelerated rapid phase of erythrocyte aggregation, increased strength of erythrocyte aggregates) and vascular endothelial dysfunction in the microcirculatory bed, among other factors, increased urinary excretion of functionally active WF, PA-1, which correlated with the activity of CGN. Data were obtained on the negative impact of the level of urinary PAl-1 excretion, red blood cell aggregation on the prognosis of CGN regardless of its form, the markers of endothelial damage/activation. Low urokinase activity and decreased red blood cell deformability in parallel with higher diurnal proteinuria are of poor prognostic value for hematuric nephritis., Conclusion: The findings illustrate two ways of the involvement of the endothelium in the mechanisms contributing to the development of tubular interstitial fibrosis, namely: endothelial dysfunction and as a substrate that links the processes of immune inflammation, hemorheology, and fibrinolysis/proteolysis in the kidney. The regularities revealed by clinical and laboratory comparison suggest that the indices under study may be used to determine the prognosis of the disease and may serve as a basis for the application of treatments aimed at correcting the detected disorders.

The paper deals with the analysis of studies of the role of the bone morphogenetic proteins fibroblast growth factor 23 (FGF-23) and Klothno in the development of vascular wall calcification in chronic renal disease (CRD). FGF-23 is shown to be an important phosphaturic hormone that inhibits hypercalcemic and hyperphosphatemic effects of elevated serum vitamin D concentrations. There is evidence that there is an association between high serum FGF-23 levels and vascular wall calcification irrespective of the content of phosphorus and parathyroid hormone. Most authors regard FGF-23 as a potential uremic toxin in patients with end-stage CRD. There are data that support the renoprotective value of the morphogenetic protein Klotho whose expression in CRD is decreased.

The paper describes a clinical case of congenital cardiomyopathy (left ventricular noncompaction) concurrent with secondary amyloidosis and renal involvement that develops at the outcome of long existing brochoectatic disease.

Aim: To assess the rate and clinical significance of impaired nutritional status and impact of low-protein diet on inhibition of renal insufficiency in patients of stage III-IV chronic disease of the kidneys (CDK)., Material and Methods: A total of 200 patients with CDK stage III-IV were randomized into three groups: group 1 consisted of 123 patients with chronic glomerulonephritis (73 with stage III and 50 with stage 1V), group 2--45 patients with systemic diseases (30 with stage III and 15 with stage IV), group 3 (a comparison group)--32 patients with CGN (17 with stage 111 and 15 with stage IV). Patients of groups 1 and 2 received low-protein diet (0.6 g protein kg/day) balanced by either high-calorie mix containing protein SUPRO 760 or ketosteril for 24-48 months. The nutritional status was studied by anthropometric data, absolute number of lymphocytes, levels of blood albumin and transferring, intake of protein, food calorie value according to 3-day diaries., Results: Among 200 patients impaired nutritional status was detected in 22 (11.0%) patients. More than half of them had glomerulonephritis in systemic diseases (SLE, systemic vasculitis). Only in patients with systemic diseases nutritional disorders manifested at stage III. These disorders grew with progression of renal insufficiency and were detected primarily in patients with stage IV CDK. Patients with CGN on low-protein diet for a year and longer demonstrated slowing of the fall of the glomerular filtration rate (GFR)., Conclusion: Early (predialysis) use of low-protein diet balanced by addition of amino- and keto-acids and high-energy nutritional mixes has a positive influence on nutritional status of patients with chronic renal insufficiency and can inhibit GFR lowering.

Aim: To assess the importance of renal affection and other systemic manifestations of infectious endocarditis (IE) among factors of unfavourable IE prognosis., Material and Methods: The examination including bacteriological blood test, transthoracic echocardiography was made in 54 patients with IE (35 males and 19 females aged 17-75 years). Transesophageal echocardiography and coagulogram examination were additionally performed in 11 and 45 patients, respectively., Results: Modern methods of statistic processing were employed to study systemic IE manifestations. Among them, prognostically significant were singled out and analysed including renal affection. Clinical variants of renal affection were determined in IE patients and their characteristics were determined: high incidence and severity of erythrocyturia, rare occurrence of arterial hypertension, frequent episodes of acute renal failure. A close correlation is shown between IE-associated renal affection, DIC symptoms and thrombocytopenia. Signs of renal damage in IE patients raise probability of other systemic manifestations including prognostically significant ones. This allows one to consider renal affection as a marker of an unfavourable IE course., Conclusion: A complex of significant factors of IE unfavorable outcome is determined including such systemic manifestations as severe renal affection, thromboembolism, splenomegaly. These factors are of importance in deciding on surgical intervention--valve replacement.

Aim: To evaluate contribution of endothelial dysfunction and impairment of endothelial proliferation/ regeneration to mechanisms of development of tubulointerstitial fibrosis (TIF) in chronic glomerulonephritis (CGN) basing on urinary levels of markers of endothelial activation/impairment and angiogenesis factors., Material and Methods: A total of 67 CGN patients entered the study: 19 patients with moderate urinary syndrome (group 1), 37 patients with nephrotic syndrome (group 2), 11 patients with nephrotic syndrome and persistent renal failure (RF). A control group consisted of 12 healthy subjects. The examination covered excretion with urine of Willebrand factor (WF), plasminogen activator inhibitor I (PAL-I), fibrin degradation products (FDP), vascular endothelial growth factor (VEGF). These values were compared with severity of fibrous changes in renal interstitium estimated by biopsy morphometry., Results: CGN patients had signs of affection of parietal effects of vascular endothelium. In particular, increased excretion of functionally active WF, PAI-I and FDP correlating with activity/severity of CGN. The changes were especially noticeable in patients with progressive forms of CGN (with NS and RF). Patients with morphologically verified TIF (interstitial area more than 20%) excretion of endothelial dysfunction markers was higher than in CGN patients free of TIF In a progressive course of nephritis endothelial dysfunction deteriorates by endothelial proliferation/regeneration impairment as shown by reduced urinary excretion of angiogenic factor VEGF and parallel elevation of functionally active WF in urine of patients with severe forms of CGN. Combined contribution of endothelial dysfunction and angiogenesis impairment to mechanisms of TIF development is seen from these values relations with severity of creatinemia and fibrous alterations in tubulointerstitial tissues of the kidney., Conclusion: The results point to participation of endothelium in mechanisms promoting development of TIF and RF in CGN both in terms of endothelial dysfunction and impairment of endothelial repair capacity. Clinicomorphological comparisons confirm the significance of WF, PAI-I and VEGF in assessment of local-renal endothelial changes and severity of fibrosis in renal tissue in CGN. Due to availability of the study material, perspectives of fibrogenesis monitoring in the kidneys with the tests appear which is essential for making prognosis and treatment policy in CGN patients.

Aim: To study efficacy and safety of long-term administration of epoetin and iron preparations in glomerulonephritis (GN) patients with chronic kidney disease (CKD) of stage III-IV in systemic diseases., Material and Methods: A total of 189 patients at predialysis stage of CKD (glomerular filtration rate between 15 and 60 ml/min) were randomized into 3 groups depending on GN etiology: primary GN (group 1, 123 patients), GN in systemic diseases (group 2, 45 patients), controls (group 3, 21 patients). Anemia was characterized not only by red cells indices but also by the level of serum ferritin, C-reactive protein (CRP), saturation of transferrin with iron. Remodeling of the heart was determined in all the patients at dopplerechocardiography estimating left ventricular myocardial mass, relative thickness of its wall., Results: Correction of anemia was achieved in all the patients with GN and CKD of stage III-IV in systemic diseases despite the activity of systemic disease (high blood level of CRP) and persistent nephritis activity (high proteinuria). In many patients from groups 1 and 2 who were initially diagnosed to have left ventricular hypertrophy (LVH) of excentric type LVH regressed after 6 months of anemia correction. In group 3 with untreated anemia frequency of LVH increased., Conclusion: Treatment of anemia in GN patients with CKD of stage III-IV in systemic diseases needed higher doses of epoetin and parenteral iron preparations compared to patients with the above stages of CKD with primary GN.

Aim: To estimate expression of smooth muscle alpha-actin (a-SMA) in renal glomeruli and interstitium of patients with chronic glomerulonephritis (CGN) for assessment of the disease progression and prognosis., Material and Methods: Expression of a-SMA in renal tissue was studied immunohistochemically, area of the interstitium and the degree of its interstitial inflammatory infiltration were investigated morphometrically in 45 biopsy specimens of renal tissue from patients with different morphological types of CGN and 7 specimens of normal renal tissue., Results: a-SMA expression in the glomeruli was higher in patients with proliferative morphological forms of CGN [34.3% (26.1-40.6)] than in patients with nonproliferative nephritis forms [22.3% (18.5-22.3)], p < 0.001; it was the highest in patients with sclerotic alterations in the glomeruli [55.3% (37-61.8)], p < 0.01. The degree of a-SMA expression in renal interstitium of CGN patients correlated most closely with severity of tubulo-interstitial fibrosis (Rs = 0.08, p < 0.001). There was no significant correlation between glomerular a-SMA expression in renal biopsies and proteinuria, creatinine level in the serum of CGN patients, while a-SMA interstitial expression correlated both with severity of proteinuria (rs = 0.5, p < 0.05) and that of renal failure (rs = 0.7, p < 0.001)., Conclusion: High expression of a-SMA in CGN occurs both in the glomeruli and interstitium of the kidney and evidences for activation of fibrogenesis but only interstitional expression can be considered as a morphological sign of CGN progression and as a factor of an unfavourable prognosis.

Aim: To measure urine and renal tissue levels of profibrogenic mediators (monocytic chemotaxic protein-1-MCP-1 and transforming growth factor beta1 - TGF-b1) in patients with chronic glomerulonephritis (CGN); to specify significance of these mediators for assessment of inflammation and fibrosis in the kidney and as prognosis criteria. ELISA, immunohistochemical tests, morphometry were used to study urine excretion of MCP-1 and TGF-b1, expression of TGF-b1 in renal tissue, interstitial area, respectively, in 63 patients with active proteinuric CGN., Results: Patients with active proteinuric forms of CGN have higher urine excretion of MCP-1 and TGF-b1 than healthy controls. Urine excretion of MCP-1 in patients with nephrotic syndrome was significantly higher than in patients with moderate urinary syndrome. The highest MCP-1 urine excretion was observed in patients with persistent renal failure. Urine excretion of TGF-b1 depended on the level of creatinemia being the highest in marked proteinuria and stable renal dysfunction. Intensive urine excretion of TGF-b1 occurred in CGN patients with expression of this cytokine in renal interstitium. This confirms its local-renal origin. A correlation was found between urine values of MCP-1, TGF-b1 and severity of tubulo-interstitial fibrosis (TIF). High informative value (sensitivity and specificity) of urine MCP-1 and TGF-b1 are for the first time shown as markers of interstitial fibrosis. They are also important for making prognosis of CGN., Conclusion: It is shown that MCP-1 and TGF-b1 are essential for remodeling of tubulointerstitium. The urinary parameters mark TIF and can be used as criteria of activity and prognosis of CGN.

Aim: To characterize renal amyloidosis in patients with rheumatoid arthritis and stages of amyloid nephropathy., Material and Methods: The trial covered 30 patients (6 males and 24 females) with documented rheumatoid arthritis (RA) complicated with secondary AA-amyloidosis. Amyloidosis diagnosis was confirmed in all the patients morphologically, the samples were studied with the peroxidase immunohistochemical method using specific monoclonal antibodies to SAA. Clinical manifestations of RA were assessed by the disease activity, functional impairment of the joints, x-ray alterations, extraarticular signs of RA, etc. All the patients were examined clinically, total blood count and biochemical tests were made., Results: In 23 (77%) of 30 examinees with RA, proteinuria as the first clinical symptom of AA-amyloidosis emerged with the first 15 years of RA. RA of the second-third degree of activity were diagnosed in 25 (83%) patients, 21 (70%) patients had apparent destructive changes in the joints (x-ray stage III-IV). Severe functional insufficiency of the joints was observed in 25 (83%) patients, deformation of the joints - in 27 (90%) patients. Clinically, renal amyloidosis was characterized by change of stages - from moderate proteinuria to nephrotic syndrome and renal failure. Prognosis of amyloid nephropathy in RA depends on duration of the proteinuric stage: if this stage is short (3 years maximum), the prognosis is worse than in its long duration., Conclusion: RA ranks first among causes of secondary AA-amyloidosis. Development of AA-amyloidosis in RA patients is most probable in the first 15 years of the course of the articular process. Amyloidosis is more frequent in patients with severe clinical manifestations of RA.

The authors present literature data and the results of their own studies of mixed cryoglobulinemia (MC) caused by chronic HCV infection, discuss issues concerning pathogenesis of MC as well as MC-associated cryoglobulinemic vasculitis and malignant lymphoproliferation, consider questions of MC influence on the course and prognosis of chronic HCV infection and anti-viral therapy effectiveness. MC was found in 43% of 207 patients with chronic hepatitis type C (CH-C), examined by the researchers. 30% of patients with CH-C and MC displayed clinical signs of vasculitis. The study established the direct correlation between MC severity and the frequency and degree of main clinical manifestations. The results show that more severe clinical variants of cryoglobulinemic glomerulonephritis are associated with MC type II. B-cell lymphoma, monoclonal immunoglobulinopathy and a range of autoimmune syndromes were observed in MC patients. The liver involvement in patients with MC was characterized by a significantly higher sclerosis index compared to the group of patients not having MC while medium liver process activity index was equal in both groups, which suggests possible existence of special mechanisms and faster progress of phibrosis in patients with MC.

The purpose of the study was to evaluate clinical significance of vascular purpura (VP) in diagnostics and establishing prognosis of chronic diffuse hepatic diseases (CDHD). The subjects were 660 patients with CDHD of viral and non-viral origin, who were under long hospital observation. 72 CDHD patients had cutaneous vasculitis. 11% of CDHD patients developed VP, which corresponded to the frequency of other cutaneous manifestations--minor hepatic signs (palmar erythema, spider-like blood vessels in the skin, xanthelasmas etc.) There was insignificant difference in the frequency of VP between the patients with type B and C hepatitis (9.6%), on the one part, and patients with non-viral hepatic diseases--primary sclerosing cholangitis, autoimmune hepatitis, and Wilson-Konovalov disease (14.2%). According to morphological data, 84.3% of CDHD patients with VP developed the latter or had a VP relapse at the cirrhotic stage (50%) or at the stage of forming hepatic cirrhosis (34.3%). Renal involvement, which was significantly more frequent in CDHD patients with VP vs. patients without VP (32% and 11.4%, respectively), may deteriorate the prognosis. The authors conclude that cutaneous vasculitits is a universal sign of viral and non-viral CDHD, which should be taken into consideration when diagnosing and establishing prognosis of these diseases. The fact that VP is revealed mainly at the cirrhotic stage suggests that an important role in its development is played by dysfunction of the liver, one of the main organs that clear antigen and immune complexes (including those of viral origin), appearing via the portal system or circulating in blood.

The authors describe various mechanisms (including cellular and molecular ones) that mediate the realization of interstitial inflammation under the influence of proteinuria components. The paper covers epithelial cell transdifferentiation processes, the role of angiotensin II, transforming growth factor beta, nuclear transcription factor NFkB, chemokines, endothelial factors etc. The effects of drugs routinely used in nephrology at present (angiotensin converting enzyme inhibitors, statines etc.) are presented in a new way according to the modern conception of the mechanisms of proteinuria-induced renal interstitial tissue remodeling in glomerulonephritis. The authors consider administration of antichemokine agents, which influences chemokine/chemokine receptor system, to be a prospective independent immunotherapeutic direction in treatment, aimed at prevention of glomerulonephritis progression.

Tubulointerstitial fibrosis (TIF) is thought now to be a key factor in progression of renal failure in chronic nephropathies. A similar pattern of changes in glomerulonephritis and amyloidosis suggests common mechanisms operating in progression of renal failure in these nephropathies. Of importance in the process of interstitial inflammation is activation of the nuclear factor of transcription (NFkB) in tubular cells due to components of proteinuria and their secretion of some proinflammatory mediators, first of all chemokines with formation of inflammatory infiltrate and accumulation of interstitial myofibroblasts--the main source of extracellular matrix (ECM) components. Our findings are of interest in the light of current ideas that among ECM components the number of fibronectin deposites most of all reflects the severity of structural renal tissue damage including TIF and correlates with severity of renal failure.

Aim: To determine early criteria of renal affection in hypertensive patients for improvement of diagnosis and treatment of hypertensive nephropathy., Material and Methods: 148 patients with essential hypertension (EH) were examined (82 males, 66 females, mean age 43.64 +/- 11.35 years). Of them, 46 patients (24 young males among them) had EH of new onset (NOH) and 102 patients had EH of long duration (LDEH). The examination included investigation of lipid, carbohydrate, uric acid metabolism, renal function, microalbuminuria, intrarenal hemodynamics (color dopplerography on ALOKA SSD-2000 MultiView., Results: 50% of NOH and 90% of LDEH patients had metabolic disorders: excessive body weight, hypercholesterolemia, hypertriglyceridemia, uric acid disbolism, impaired glucose tolerance. These disorders, except uric acid metabolism, correlated in severity with duration and severity of EH. Intensity of microalbuminuria depends on EH duration, severity of concomitant metabolic defects. Markers of early renal damage in EH patients are increased intrarenal peripheral vascular resistance and microalbuminuria. These alterations are detectable in 30% NOH patients (at the disease onset). Treatment with ACE inhibitors eliminates microalbuminuria, diminished hyperfiltration and improved intrarenal circulation. This justifies use of ACE inhibitors for nephroprotection in EH patients., Conclusion: Monitoring of the above early markers of renal damage and metabolic shifts is essential for assessing progression of hypertensive nephropathy and control over efficacy of antihypertensive treatment including ACE inhibitors.

The study results related with the rate of vascular purpura in 660 patients with different-type chronic diffusive hepatic pathologies both of the viral and other natures are described in the paper. The main regularities characterizing the phenomenon (spread and possible cause of purpura development) are defined. According to an analysis of actual materials, dermal vasculitis is not an exclusive feature of virus-associated hepatitis or liver cirrhosis. Vascular purpura can be regarded, on the basis of the obtained data, as a universal sign typical of any liver pathologies.

Aim: To determine the role of enhanced blood coagulation in pathogenesis of pulmonary hypertension (PH) at an early stage of fibrosing alveolitis (FA)., Material and Methods: Clinical, functional, roentgenological, coagulation and immunological examinations were performed in 17 patients with idiopathic FA (IFA), in 6 patients with exogenic allergic alveolitis (EAA), in 15 FA patients with diffuse diseases of the connective tissue (FA-DDCT). The diagnosis was verified with high resolution computed tomography (HRCT). Lesser circulation was assessed by Doppler echocardiography. Morphological impairment of the lungs was specified in all the patients using analysis of the bronchoalveolar lavage. In 9 FA patients the diagnosis was verified at thoracoscopic biopsy of the lung. The control group consisted of 16 healthy volunteers. Thrombin-antithrombin complex (TAT) and thrombocytic factor 4 (TF-4) were estimated with ELISA as stable, highly sensitive markers of thrombophilia., Results: The TF-4 level was elevated in all IPD patients (p < 0.05), the elevation being highest in FA-DDCT (p < 0.007). With FA progression, TF-4 concentration went down. A weak negative correlation (p < 0.047, r = -0.38) was found with average pressure in the pulmonary artery (PAAP). TAT was higher than control in all the groups (p < 0.05). Maximal TAT values were registered in EAA. If HRCT detected active inflammation and in development of irreversible fibrous changes TAT was higher vs control. A direct correlation between TAT level and PAAP was not found., Conclusion: Disorders in thrombocytic and plasmic links of hemostasis are detectable early in IPD. Stable markers of thrombophilia (TAT and TF-4) reflect activity of inflammation in FA. They can be also used as sensitive diagnostic tests for diagnosis of PH and diagnosis of patients with activated coagulation system in IPD.

Thirty-two patients with different forms of interstitial lung diseases (ILD), such as idiopathic fibrosing alveolitis (IFA) (n = 17) and fibrosing alveolitis concurrent with diffuse connective tissue diseases (FA-DCTD), were examined. Clinical, echocardiographic, computed tomographic, coagulative, and immunological studies were performed. Enzyme immunoassay was used to determine the levels of a complex of thrombin and antithrombin III (TAT) and platelet factor IV (PF-IV). There were significant increases in the levels of PF-IV (4.36 +/- 0.25 mg/l) and TAT (10.87 +/- 3.8 mg/l) in patients with ILD as compared to the control (2.75 +/- 0.47 and 1.8 +/- 0.2 mg/l, respectively; p < 0.05). In patients with early FA-DCTD with the predominance of the milk glass syndrome during high-resolution CT (HRCT), the level of PF-IV was greater than the normal levels (p < 0.05) and decreased with the progression of the disease and with the formation of the honeycomb lung. If there were HRCT signs of active inflammation, the level of TAT was higher than that in the control; this was also in the development of irreversible fibrous changes.

Aim: To elicit clinical features of nephropathy associated with antiphospholipid syndrome (APSN) in patients with primary antiphospholipid syndrome (PAPS)., Material and Methods: The analysis of clinical characteristics and course of APSN has covered 24 patients with PAPS (16 females and 8 males, mean age 34.3 years). Renal damage was represented by arterial hypertension (AH), urinary syndrome, functional decline. All the patients were tested for anticardiolipin antibodies and/or lupus anticoagulant. Renal biopsy was made in 7 patients., Results: PAPS patients developed renal affection in the onset of APS or within the first 5 years of its course. In the majority of patients APSN combined with abnormalities of CNS, heart and skin. Arterial/arteriolar thromboses prevailed. APSN manifested with: AH (n = 23, severe AH in 11), abnormal renal filtration (n = 17, creatinine rise in 8), urinary syndrome with proteinuria (n = 23, in 14 with hematuria). The following clinical variants of APSN were proposed: urinary syndrome with AH (n = 16; 67%), acute nephritic syndrome (n = 7; 29%), nephrotic syndrome (n = 1). Morphological studies of biopsies from APSN patients have revealed sclerotic changes, thrombotic microangiopathy, nonspecific alterations in the glomeruli., Conclusion: APSN is a variant of microvascular renal affection caused by thrombotic processes in intra-organ microcirculation. It is an early clinical marker of APS. Clinically, APSN manifests with vascular renal affection, the earliest symptom being inhibition of glomerular filtration. Clinical combinations of the symptoms allow to distinguish variant of APSN suggesting the existence of acute and chronic APSN. Combination of APSN with affection of the CNS, heart and skin points to a special PAPS subtype characterized by generalized ischemic damage to the organs as a result of intraorganic arterial and/or arteriolar thromboses.