[Chronic lymphocytic leukemia accompanied by renal failure].

AIM: To evaluate the efficiency and safety of monotherapy with bendamustine (B) and therapy with B in combination with rituximab (B + R) in patients with chronic lymphocytic leukemia (CLL) accompanied by renal failure (RF). SUBJECTS AND METHODS: The prospective pilot study included 8 patients (6 men, 2 women) with CLL concurrent with RF. The patients' median age was 63 years (51-77 years). The Binet classification stage of CLL corresponded to B in 2 cases and C in 6. The mean (± standard error) pretreatment concentration of creatinine was 218 ± 92 µmol/l and the glomerular filtration rate (GFR) was 33 ± 20 ml/min. The efficiency of monotherapy with B (n=5) and combination therapy with B + R (n=3) was evaluated. In progressive CLL, therapy was performed in specific treatment-naïve patients (n = 5) and in pretreated patients refractory to alkylating agents (cyclophosphan, chlorambucil) (n = 3). A total of cycles of B and B + R were carried out. RESULTS: After B monotherapy, one of the 5 cases achieved a complete remission, 3 a partial remission, and 1 a nodular partial remission. Three patients developed recurrence. In the B monotherapy group, the cumulative risk of recurrence was 70% at a median follow-up of 22 months and at a maximum follow-up of 27 months. In the B + R therapy group, all the 3 patients achieved a complete remission. The median follow-up was 7 months; the maximum follow-up was 1 year. There were no deaths or recurrences. During B monotherapy and B + R combination therapy, there was improved kidney function: the mean concentration of creatinine decreased from 218 ± 92 to 140 ± 57 µmol/l (p < 0.05); GFR increased from 33 ± 20.0 to 54 ± 25 ml/min; the mean increment was 20 ml/min (p < 0.01). Mild and moderate anemia and thrombocytopenia were most common during B and B + R therapies. Neutropenia with mild infection complications, as well as nonhematologic complications were detected in some cases. The drugs were observed to have no nephrotoxic effects. CONCLUSION: The performed pilot prospective indicated that the B + R combination therapy was effective in patients with RF-associated CLL. No toxic effect of B on kidney function was seen. During B therapy, there was better kidney function manifesting itself as a statistically and clinically important decrease in creatinine concentrations and a statistically and clinically important increase in GFR as compared to the baseline values.

[Morphological and immunochemical features of nephropathies in multiple myeloma and severe renal failure].

AIM: To study the pathomorphology of kidneys in patients with multiple myeloma (MM) and severe renal failure (RF) and to compare the results of morphological, immunohistochemical, and electron microscopic examinations of nephrobiopsy specimens with the pattern of monoclonal secretion and the type of proteinuria and paraproteinuria. SUBJECTS AND METHODS: A study group comprised 25 patients with MM and severe RF; 22 of them underwent programmed hemodialysis. Immunochemical study of serum and urine proteins, renal puncture biopsy with light, immunofluorescence and electron microscopy examination of its specimens were performed in all the patients. RESULTS: Cast nephropathy (CN) is the most common type of renal impairment in patients with MM and severe RF. CN concurrent with monoclonal immunoglobulin deposition disease was identified in 32% of cases. In the mixed lesion, it is CN that is a determinant in the development of acute and chronic RF. Rare variants of nephropathies as fibrillary glomerulonephritis, immunotactoid nephropathy, and crystalline histiocytosis were found in 16% of cases. In most cases, severe RF in MM develops in case of low monoclonal secretion. However, there are a larger number of secreted and excreted monoclonal light chains in CN than in other variants of kidney lesion. Urinary paraprotein G excretion suggests that the glomerular filter is damaged. Degenerative changes in the podocytes and a reduction in their small processes were detected in the majority of cases. In glomerular or mixed proteinuria, there were also unorganized and organized deposits in the glomerular basement membrane. CONCLUSION: The pattern of nephropathy does not determine a renal response after chemotherapy. The reversibility of CN in MM depends on the magnitude of interstitial fibrosis and podocyte changes. The pronounced changes in the podocytes as a reduction in their small processes serves as a poor sign in achieving renal responses following chemotherapy.

[The course of parvovirus B19 infection during pregnancy after kidney transplantation].

Having a tropism for erythroid progenitor cells, parvovirus B19 may cause partial red cell aplasia and thrombocytopenia. Early diagnosis of parvovirus B19 infection in immunocompromised patients is needed for timely antiviral therapy. A high-risk group for parvovirus B19 infection includes patients with blood diseases who receive multiple transfusions of blood components; those who have undergone donor organ transplantation and are long taking immunosuppressive drugs; and pregnant women. These patients require careful virological monitoring for major blood-borne viral infections. This paper describes a clinical case of parvovirus B19 infection in a pregnant woman who has undergone kidney transplantation and is continuously taking immunosuppressive medications. Identification of the cause of severe anemia and timely adequate therapy could lead to the recovery of effective erythropoiesis in the patient.

[Crystalline histiocytosis].

The paper describes a case of diagnosis of the rare monoclonal secretion-associated disease crystalline histiocytosis with kidney and bone marrow involvement. The female patient with multiple myeloma (MM) was found to have intralysosomal crystals in the cells of the bone marrow (histiocytes, plasmocytes), kidneys proper (mesangiocytes, podocytes), and subsequently in those of a kidney graft. Lower secreted monoclonal IgG and ceased Bence-Jones protein secretion after MM chemotherapy were accompanied by improved and stabilized kidney graft function. However, a repeat morphological study of a renal biopsy specimen showed that the crystalline inclusions were preserved in the podocytes. By comparing the immunological and renal responses, it is reasonable to suggest that monoclonal IgG rather than Bence-Jones protein is of value in the pathogenesis of crystal formation.

[The specific features of renal lesion in Burkitt's lymphoma].

AIM: To analyze the causes of renal lesion in patients with Burkitt's lymphoma (BL) and to develop optimal treatment policy. MATERIALS AND METHODS: The data of examination and treatment were analyzed in 20 patients with BL (14 men and 6 women aged 15 to 57 years (median age 24 years)) who had been followed up for renal lesion at the Hematology Research Center (HRC) in 2003 to 2011. When admitted to hospital, all the patients were found to have ureteric compression, renal parenchymal tumor infiltration, massive tumor cytolysis syndrome (MTCS). Polychemotherapy (PCT) was performed in accordance with the original intensive BL-M-04 protocol. The extent of the process was estimated according to the classification developed by S.B.Murphy: L3 variant B of acute lymphoblastic leukemia in 10 cases; Stage IV in 2; Stage III in 8. Acute renal failure (ARF) was identified in 13 patients. A control group comprised 36 patients with BL without ARF who had been followed up at the HRC in 2003 to 2011 and included into the BL-M-04 protocol. The ratio of patients with bone marrow lesion was 7:13 and 9:36 in the BL + ARF and BL-ARF groups, respectively. RESULTS: Decreased urine specific gravity and proteinuria (0.4 to 1.3 g/l) were the first manifestations of renal lesion and were seen in approximately 50% of all cases both on admission to hospital and in the first stages of PCT (10 and 9, 8 and 7 of the 20 cases, respectively). Microhematuria more commonly developed after initiation of PCT (7 and 3 of the 20 cases, respectively). ARF was diagnosed in 13 patients (24% of the 55 BL patients followed up at HRC in 2003 to 2011). One female patient developed ARF after the start of PCT. Twelve patients developed this condition at the onset of disease; in 4 patients, ARF existing prior to PCT began progressing after drug administration. The etiology of ARF was generally mixed. At the onset of disease, MTCS (n = 6) and specific renal parenchymal infiltration (n=6) were more common causes of ARF. Postrenal anuria was present in 2 cases. ARF after PCT initiation resulted from the toxic effects of methotrexate and MTCS (3 and 4 cases, respectively). ARF regressed in the early periods: in the prophase (n = 4) and during or the first PCT block A (n = 9). The BL patients with ARF, as compared to those without the latter, showed a statistically significant earlier onset of myelotoxic agranulocytosis (MTA): on day 3 of an intercourse interval (95 CI from 0 to 3 days) versus its day 5 (95% CI from 2 to 5 days) and a statistically significant longer duration of MTA--12 days (95% CI from 7 to 16 days) versus 7 days (95% Cl from 3 to 10 days); they were observed to have more severe mucositis. Despite the longer intercourse interval, 10 patients with ARF achieved remission; 4 patients died from therapy-refractory sepsis and 1 patient from thrombocytopenia. In the patients with ARF, mortality rates were significantly higher than in those without ARF (33% versus 10%; p = 0.04). CONCLUSION: Although there is a high risk of worsening renal dysfunction, PCT is a necessary condition for ARF resolution in BL.

[Nephropathy caused by non-amyloid organized and granular deposits as multiple myeloma syndrome].

A rare variant of nephropathy in multiple myeloma (MM) is reported. Nephropathy is characterized basing on the study of nephrobiopsy with light, immunofluorescent and electron microscopy. A repeat biopsy of the kidney was made after achievement of a complete clinicohematological remission. A MM patient's nephrobiopsy in a picture of glomerulonephritis had 3 types of deposits: granular, irregular fibrils of 12 nm in diameter and microtubes organized in bunches 19 nm in diameter. Congo red test was negative, cryoglobulinemia was absent. Immunofluorescent test detected deposit of monoclonal IgG in the mesangium and glomerular basal membrane (GBM) corresponding to monoclonal type of monoclonal secretion. After treatment and achievement of remission, neither IgG no light chains were found in nephrobiopsy. Electron microscopy registered complete resorption of granular deposits and microtubes with formation of electron-transparent cavities. However, fibrils seen before treatment only in mesangium appeared in the above hollow cavities. The presence of such fibrils in the mesangium and GBM did not influence clinical picture of the disease. After achievement of remission the patient had no clinical and laboratory signs of nephropathy, only insignificant selective glomerular proteinurea was observed (0,5 g/l). Thus, granular deposits and microtubes contained paraprotein, they were completely resorbed after achievement of MM remission. Fibrils seem to have another genesis unrelated to monoclonal gammapathy.

[An extremely high serum methotrexate concentration associated with acute renal failure in a patient with acute lymphoblastic leukemia after conduction of high dose consolidation].

Acute renal failure (ARF) is one of rare and severe methotrexate (MT)-induced complications in patients with acute lymphoblastic leukemia. A case of MT-induced renal dysfunction with an extremely high serum MT concentration is reported. This toxicity required conduction of hemodiafiltration for extracorporeal MT elimination. The presence of homozygous mutation of methylene-tetrahydrofolate reductase reflects an individual metabolism of MT and its renal clearance.

[Multiple myeloma in renal transplant recipients].

Severe renal failure (RF) may be the first and only clinical manifestation of multiple myeloma (MM). Occasionally the disease remains long unrecognized and the patients receive renal function replacement therapy, including renal transplantation (RT). To treat MM in renal transplant recipients is a complex medical and ethical problem. The paper presents the authors' experience in treating 3 patients with MM diagnosed after RT and evolving transplant lesion. Various morphological types of grafted kidney lesion were detected. These included fibrillar glomerulonephritis, cast nephropathy, and the latter concurrent with light-chain deposition disease. RF most rapidly progressed in cast nephropathy. The natural history of the disease was unfavorable in all patients; VAD and PAD chemotherapy programs proved to be ineffective. It is concluded that RT should not be performed in patients with extended-stage MM due to the fact that there is a considerable risk for renal transplant lesion and severe infectious complications that may occur during chemotherapy. Blood and urine immunochemical studies should be conducted in all the patients who are to undergo RT.

[A case of hemolytic-uremic syndrome with development of catastrophic antiphospholipid syndrome: diagnosis and clinical tactics].

The paper describes a case of practically simultaneous development of the hemolytic-uremic syndrome (HUS) and the catastrophic antiphospholipid syndrome (CAPS) complicated by mesenteric vessel thrombosis and small bowel necrosis. Multimodality treatment comprising volume plasmapheresis, fresh frozen plasma transfusion, hemodialysis, anticoagulant and disaggregant therapy could relieve thrombogenic events, such as pulmonary artery thromboembolism and intestinal necrosis.

[Monitoring the efficiency of heparin anticoagulation in patients on programmed hemodialysis].

The activated partial thromboplastin time (APTT) test is widely used to monitor heparin anticoagulation. The relationship of the APTT to the activity of administered unfractionated heparin was defined in 23 patients on programmed hemodialysis, by using six APTT reagents. A calibration curve was plotted for each reagent. The heparinized and nonheparinized plasma values of APTT depended on the reagent being used. During clinical heparin therapy, an APTT-heparin concentration relationship was also defined by the used reagent. The reagents showed varying heparin sensitivity both in vitro and in vivo studies. APTT was estimated for the therapeutic application of heparin for all the reagents in the examinees. The authors consider it necessary to define an APTT-heparin concentration relationship for each reagent being used.

[Renal monoclonal immunoglobuline deposition disease as a rare variant of renal damage in multiple myeloma].

A case of the immunoglobuline deposit disease diagnosis in MM patient having the symptoms of intensive proteinuria, macrohematuria and terminal renal failure is reported. The disease was diagnosed by the evidence from electron microscopy of the kidney and liver biopsies.

[Use of fractional plasma separation and adsorption (Prometheus technology) in the treatment of acute liver failure].

This paper presents the results of treating 8 patients with acute liver failure, by using the separation and adsorption of fractional plasma (Prometheus technology). Twenty-five procedures lasting 5-6 hours were performed. Anticoagulation with heparin was made under guidance of coagulogram parameters. The results of testing blood parameters before and after a procedure and hemodynamic parameters are given. The investigations have demonstrated the effectiveness and safety of the procedure.

[Rapidly progressive glomerulonephritis in ANCA-associated vasculitis: a course, treatment efficacy, prognosis].

AIM: To study efficacy of ANCA-RPGN treatment with corticosteroids and cyclophosphamide or mycophenolic acid drugs. MATERIAL AND METHODS: We treated 28 patients (17 males and 11 females aged 19-71 years) with morphologically verified ANCA-associated crescentic RPGN (crescentic median 79 (63:88)%. The patients received corticosteroids and cytostatics. RESULTS: The response to the treatment was registered in 22 (78%) patients in 8-16 weeks: a complete remission was achieved in 8 patients, a partial one--in 14 patients. In partial remission renal functions recovered incompletely (median Pcr 200 (180;255) mcmol/l) in persistence of moderate proteinuria (median 0.7 (0.6;1.3)g/day) and absence of microhematuria. Probability of the treatment success depended on severity of glomerulosclerosis and weakly depended on activity of extracapillary reaction. Severe renal failure was not an absolute predictor of treatment failure. CONCLUSION: In the absence of advanced nephrosclerosis early treatment with corticosteroid in combination with cytostatics can produce a positive effect in 70-80% patients with ANCA associated RPGN.

[Treatment and survival of multiple myeloma patients on programmed hemodialysis].

AIM: To analyse clinical picture of multiple myeloma (MM) and treatment results in MM patients on programmed dialysis (PD). MATERIALS AND METHODS: Case histories of 22 MM patients were analysed. They had a terminal stage of chronic renal failure (CRF) in the onset of the disease. Chemotherapy (CT) was performed in 20 patients (10 patients received VAD program, the other 10--melfalan). RESULTS: Early lethality was 28%. The patients died of septic complications. Neutropenia was observed significantly more frequently on melfalan treatment than on VAD therapy (9 and 2 patients, respectively; chi-square 5.6; p = 0.009). Survival median, excluding early lethality, was 16 months. Differences by therapy were not registered. Three patients on MP program survived more than 3 years. Function of the kidneys improved in 4 (20%) patients. Hemodialysis was avoided in 2 patients. Survival of patients with reestablished renal function was maximal (44 and 84 months). CONCLUSION: Standard CT for MM with terminal CRF is associated with high toxicity and frequent septic complications. Survival is better if renal function improves and HD discontinues. Reversibility of CRF at a terminal stage in MM does not depend on completeness of hematological response. Programs with melfalan CT provoke more frequent myelotoxic cytopenia, early lethality is higher but the number of longer survivals is more.

[Clinicohemadynamic and biochemical the effect of patients with coronary heart disease use combinated lactoovovegetarian diets and simvastatin].

This work is aimed at studying the effect of a lactoovovegetarian antiatherogenic well-balanced diet, combined with the hypolipidemic drug simvastatin, on clinicohemodynamic and biochemical parameters of patients with coronary heart disease and pronounced hypercholesterolemia (TC > 7.8 mmol/l). 43 patients suffering from coronary heart disease, stenocardia under loading (functional classes II-IV) were observed. The patients of the first group (n=17) were had an antiatherogenic vegetarian diet, the patients of the second group (n=26) had the antiatherogenic mixed diet IOC. Besides a standard antianginal therapy all the patients received simvastatin in a daily doze of 20 mg. By the end of the treat ment positive changes in clinicogemodynamic and biochemical parameters were methobolism lipid observed in both the groups of patients. The comparison of lipid parameters revealed a significant and reliable decrease in the first group.

[Renal lesion in hemoblastoses].

AIM: To study morphofunctional condition of the kidneys in patients with hematological malignancies. MATERIAL AND METHODS: Renal function, i.e. concentration ability, glomerularfiltration rate (GFR), concentration of electrolytes and beta2-microglobulin in blood serum and urine was studied at different stages of chemotherapy. Three cases are reported. All the patients have undergone transcutaneous fine-needle puncture biopsy of the kidney with histological and electron-microscopic study of biopsy specimens. RESULTS: Total urinalysis showed minimal changes. Concentration and filtration functions of the kidneys were impaired. Morphologically, glomerular damage was insignificant, there was dystrophy of tubular epithelium and focal interstitial sclerosis. Electron-microscopic examination revealed structural defects of the basal membrane of glomerular capillaries (focal thinning, focal insignificant thickening, the absence of three-layer structure at long distance) in all the patients. Dissection of the basal membrane was seen in one case. All the patients had cytoplasmic viruses: Epstein-Barr, cytomegalovirus, herpes simplex viruses type 1 and 2. In two cases mitochondria were affected with viruses. Dystrophic changes of podocytes and mitochondrial degradation were observed in all the cases. CONCLUSION: Chemotherapy may affect glomerular and tubular system of the kidney increasing probability of complications. Imbalance between cytolysis kinetics and natural clearance of the products of degradation of cells and drug metabolites may lead to nephropathy. Viral infection indicates immunodeficiency due to immunosuppression or is a direct cause of impairment of renal endothelium cells. No definite recommendations can be made still about therapeutic policy.

[The treatment of coronary heart disease by beta-adrenoblockers or tiazide diuretics preparation in combination with vegetarian diet].

Work make on 84 patients with coronare heart diseases were divided into two groups, equal quantity. The first groups were given athenolol (50 mg daily), the second--hypotiazide (25 mg daily). In every groupspart patients received an antiatherogenic lactoovovegetetarian diet, part--an standard antiatherogenic diet 10c. Time observation--24 daily. By the end of the treatment period with athenolol in backoground the vegetarian diet the level of total cholesterol decreased by 16%, low-density lipoproteins cholesterol decreased by 18%. In groups patients received an standard antiatherogenic diet these parameters practically did'nt change. In the vegetarian group the atherogenic coefficient (KA) decreased by 31%., while in the patients on standard antiatherogenic diet KA showed only a tendency for decreasing. By the end to the treatment period with hypotiazide the slight decrease in total cholesterol, KA levels and a slight increase in HDL cholesterol were observed only the vegetarian group.

[Use of continuous high-volume hemofiltration in patients with sepsis and multiple organ dysfunction].

The paper gives the authors' experience in performing continuous high-volume hemofiltration in 38 patients with sepsis and multiple organ failure. The kinetics of proinflammatory cytokines and a number of plasma enzymes as markers of substances having a relatively high molecular mass was studied. The advantages of a procedure using an artificial kidney apparatus equipped with an on-line substituting fluid preparation system are described. The possibilities of correcting the parameters of homeostasis are the principles of maintenance of a hemostatic system in this group of patients during the procedure are presented. The drawbacks of this technique are also described.

[The initial experience of using isolated ultrafiltration of the blood for the correction of severe respiratory failure in hemoblastosis patients]. / Pervyi opyt primeneniia izolirovannoi ul'trafil'tratsii krovi dlia korrektsii tiazheloi dykhatel'noi nedostatochnosti u bol'nykh gemoblastozami.

To correct acute respiratory failure in patients with hemoblastoses and taking into consideration the low efficacy of standard techniques, 8 operations of isolated ultrafiltration combined with low-flow extracorporeal oxygenation in 6 patients were performed. The first results have been analyzed. To attain the maximum positive result, it is recommended that the method may be included earlier in a complex of intensive therapy measures.

[Acute and chronic renal failure in patients with myeloma]. / Ostraia i khronicheskaia pochechnaia nedostatochnost' u bol'nykh mielomnoi bolezn'iu.

AIM: To analyze causes of reversible and irreversible renal failure in myeloma patients, lethal outcomes, treatment policy. MATERIALS AND METHODS: 43 myeloma patients with renal failure entered the trial. The replacement therapy consisted of hemodialysis, hemofiltration, hemodiafiltration. All the patients received full-dose polychemotherapy according to the programs M-2 and VAD. RESULTS: 69% of the patients retained normal renal function. 23% of the patients died. Partial recovery of renal function was observed in 1 patient who had to undergo dialysis once in 10-12 days. The patients survived from 5 days to 36 months (mean 20.6 months). The main causes of death in renal failure were sepsis (38%) and hemorrhagic stroke (14%).