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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).

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.

Aim: To study expression of topoisomerases (TI) I and II alpha (DNA-bound enzymes involved in transcription and replication) in renal tissue as markers of activity and prognosis of glomerulonephritis (GN) decisive for choice of immunodepressive therapy., Material and Methods: TI expression was studied immunohistochemically in renal biopsies from 177 patients with different morphological variants of GN and in the samples of unaffected kidney tissue removed in 12 patients for local tumors., Results: There are definite differences between proliferative and non-proliferative GN variants--elevation of TI levels and monocytic infiltration in proliferative GN. Focal-segmental glomerulosclerosis is characterized by a high TI II alpha level in mesangial cells and monocytic infiltration of the glomeruli which are typical for inflammation. A statistical relationship between TI levels in mesangial cells and glomerular epithelium suggests a pathogenetic relation between these links of the pathological process. Molecular markers of activation and proliferation of cells and direct inductors of the inflammatory process (cells of monocytic infiltrate) closely correlated with the activity index--an integral indicator of inflammatory activity, as well as with the integral indicator of sclerotic processes in renal tissue--sclerosis index. Monocytic infiltration in the interstitium correlated both with morphological manifestations of activity, progression of nephritis and their clinical equivalents. In high TI expression GN resistance to immunodepressive therapy rose. To overcome the resistance, immunodepressive therapy must be more active--large doses and duration of treatment. In patients with lupus nephritis and mesangiocapillary GN renal prognosis was worse in the presence of high TI expression in mesangial cells and epithelium of the renal canaliculi., Conclusion: The authors are the first to demonstrate TI expression in renal tissue of GN patients, correlation of its level with activity of renal process as well as its role in prediction of response to treatment and the rate of renal failure progression. It is suggested that high TI expression entails a progressive course of GN.