[Modern approaches to the detection of monoclonal gammopathy of undetermined significance (MGUS) in patients with kidney diseases].

Monoclonal gammopathy (MG) is not only the state preceding of hematological neoplasms, but also associated with non - hematological diseases, in particular kidney damage. AIM: To assess the diagnostic value of "Freelite" methods in addition to electrophoresis (EF) and immunofixation (IF) of serum and urine proteins for detecting MG in patients with kidney diseases. MATERIALS AND METHODS: 87 patients with kidney damage, in which MG was established using the method of electrophoresis of serum proteins (EF), immunofixation (IF) and the method of free light chains determination - FLC "Freelite" were selected. The diagnostic value of three - component serum panel was compared with EF and IF. RESULTS AND DISCUSSION: AL-amyloidosis with kidney involvement was diagnosed in 41% patients, cryoglobulinemic glomerulonephritis (cryo GN) - in 18%, chronic glomerulonephritis (CGN) - in 35%, also there was small number of patients with light chain disease and cast - nephropathy. Determination of MG using EP was possible only in 38 (44%). Adding to the serum electrophoretic methods instead of the "Freelite" method, the urine EF and IF reduced the number of missed patients with monoclonal gammopathy from 24 (27%) to 11 (13%), including in the subgroup of patients with AL-amyloidosis but did not reach the sensitivity of the three - component serum screening panel. In 10 (11.5%) MG was represented only by intact mIg with one type of light chain, either κ or λ. Most often - in 25% of patients, intact monoclonal gammopathy was observed in HCV (+) cryo GN. A combination of intact mIgM, mIgG or mIgA with mFLC, was detected in 37 (42.5%). In almost half (46%) of the patients, only mFLC was detected - an abnormal κ/λ ratio. CONCLUSION: The serum screening panel EF + IF + "Freelite" spreads the low - grade monoclonal gammopathy recognition (MGUS) and should be included in the algorithm of examining patients with kidney disease.

[Oligosecretory monoclonal gammopathy with renal involvement]. / Oligosekretornaya monoklonal'naya gammapatiya s porazheniem pochek.

The article deals with the so-called monoclonal gammopathy of undetermined significance (MGUS), which is being actively explored in the world and has been recently investigated in Russia. It indicates the principles of identifying the phenotypes of MGUS and criteria for assessing the risk of its progression to cancer. There is an update on the possible involvement of monoclonal proteins in the pathogenesis of certain non-neoplastic kidney diseases, renal injuries in particular. The paper gives their classification and enumerates differential diagnostic techniques, including the Freelite method, a highly sensitive one to determine free light chains (FLC), prognostic criteria, and approaches to treating each separate form in relation to the phenotype of a monoclonal protein. The authors present their own data on detection rates for MGUS at a multidisciplinary hospital and a clinical case of MGUS-associated membranoproliferative glomerulonephritis, by justifying a treatment regimen containing bortezomib (velcade).

[Kidney injury associated with monoclonal gammopathies: Perspectives on diagnosis and treatment].

It is currently well justified that monoclonal gammopathies are the most important predictor for kidney diseases, including glomerulonephritis. To determine a correlation of nephropathy with oligosecretory gammopathy is of fundamental importance, as the treatment of these patients necessitates the use of special chemotherapy regimens to eliminate a pathological clone of lymphocytes or plasmocytes. If this clone is not eliminated, injury of the organ may recur to develop its failure. The principles of this therapy have been presently tried out by the example of AL-amyloidosis and showed its efficiency and relatively low toxicity.

[Current methods of systemic amyloidosis diagnosis and monitoring of its course].

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.

[New possibilities of the diagnosis and monitoring of the course of AL-amyloidosis].

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.

[Pharmacodynamic characteristics of velcade efficacy in resistant and recurrent multiple myeloma: determination of free light chains of blood serum immunoglobulins].

AIM: To ascertain individual sensitivity to velkeid in patients with resistant and recurrent multiple myeloma (MM) by determination of free light chains (FLC) of serum immunoglobulins. MATERIAL AND METHODS: Fourteen patients with MM stage III (Gcappa-5, Glambda-2, Acappa-3, Alambda-1, BJcappa-3) aged 52-75 years with documented resistance to treatment or recurrence received second-line monotherapy with velkeid. The drug was injected intravenously (jet) in a dose 1.3 mg/m2 on the treatment day 1, 4, 8 and 11. Free light chains concentration was examined with antibodies to their latent determinants (Binding Site, UK) on nephelometer (Hitathi-911, Japan) on velkeid treatment day 1, 2, 3, 5, 9 and 12. RESULTS: Nine patients showed lowering of FLC concentration and responded to treatment by Durie criteria. CONCLUSION: Dynamic follow-up of FLC concentration of the tumor clone in resistant and recurrent MM evaluates pharmacodynamics of the drug. The method provides prognosis of late clinical results.

[Lymphocyte proliferation and differentiation in chronic lympholeukemia]. / Proliferatsiia i differentsirovka limfotsitov pri khronicheskom limfoleikoze.

Proliferative activity and differentiation levels of lymphocytes of lymph nodes and peripheral blood of practically healthy people and patients with chronic lymphocytic leukemia have been studied using the present physicochemical methods (autoradiography with labelled DNA and RNA precursors, microspectrocytometry, NMR spectroscopy, kinetic formaldehyde method, etc.). The following points have been stated: stage character of changes in normal and leukemic cells, differences in synthesis of nucleic acids in different periods of the cell cycle in norm and under chronic lymphocytic leukemia, proliferation peculiarities of lymphocytes in lymph nodes and in blood, presence of DNA defects in the process development, changes in lipids of lymphocytes and blood plasma at early stages of the disease and in the process of its development.

[Local despiralization of DNA in lymphocytes of patients with chronic lympholeukemia]. / Lokal'naia despiralizatsiia DNK limfotsitov krovi bol'nykh khronicheskim limfoleikozom.

DNA isolated from blood lymphocytes of 43 patients with chronic lymphoid leukemia was studied for the content of local despiralized sites by the kinetic formaldehyde method. The patients were classified into three groups: before, during and after chemotherapy by cytostatic drugs (cyclophosphamide or chlorambucil). It is found that DNA from leukosis lymphocytes contain more despiralized sites as against to DNA from normal lymphocytes and that after chemotherapy a degree of DNA despiralization decreases.

[Possibility of the evaluation of the functional activity of human erythrocytes using the 31P-NMR method]. / O vozmozhnosti otsenki funktsional'noi aktivnosti éritrotsitov cheloveka metodom 31P-IaMR.

Intact human erythrocytes from venous blood were investigated. It has been found that the width and form of signals of 2.3 DFG vary strongly, but for the given person these characteristics of the signals are stable parameters. These variations were shown to correspond to the degree of inhomogeneity of erythrocytes population in venous blood as regards their relative concentrations of Hb and HbO2. The width of the signals of 2.3 DFG, so far reflects functional activity of the human red blood cells in oxygen transport.

[Detection of the cytotoxic effect of tumor cells against the targets of normal killers]. / Obnaruzhenie éffekta tsitotoksichnosti opukholevykh kletok po otnosheniiu k misheniam normal'nykh killerov.

The cells of 2 mouse leukemias (L-1212 and EL-4), the cells of mouse sarcoma (MX-11) and blood lymphocytes from 5 subjects with chronic leukemia were shown to damage the membrane of K-562 and EL-4 cells maintained in vitro. The membrane damage manifested in the rise of the permeability by the pancreatic ribonuclease molecules (m. m. 12,000 d). Experiments with tumor cell suspension fractionation have shown that such permeability cannot be attributed to the admixture of lymphocytes and macrophages to the tumor effector cells. Experiments with cold inhibition have revealed that the damage of the target cell membrane can be produced only by the contact of the tumor cell with the target. It is not related to the deterioration of target metabolism in the presence of a considerable number of tumor cells, or to the accumulation of any toxic products in the culture medium.