Vol 84, No 6 (2012)

Aim. To study changes in apoptosis and endothelial function in patients with chronic kidney disease (CKD) stage I-IIIb (CKDsI-IIIb). Material and methods. A complex of biochemical, enzyme immunoassay and device investigations was used to examine 128 patients with CKDsI-IIIb. Results. In CKD stage I reduction of endothelium-dependent vasodilation (EDV) was detected in 34% patients, in stage II — in 52 %, in stage IIIa — у 52 %, in stage IIIb — in 70 %. An EDV decrease was associated with glomerular filtration rate (GFR), a homocysteine level and hemodynamic factors. Elevation of endothelin-1 (ET-1) level was seen in CKDsI in 41 %, in CKDsII — in 54 %, in CKDsIIIa — in 70 %, in stage IIIb — in 83 % patients. A negative correlation was observed between the level of ET-1 and GFR and positive — with diurnal proteinuria. A significant rise of annexin A 5 concentration versus normal was detected as early as in CKDsI (1,14 ± 0,68 ng/ml). In CKDsII annexin A 5 was 2,61 ± 0,75 ng/ml, in CKDsIIIa — 3,75±0,93 ng/ml and in CKDsIIIb — 5,16±1,01 ng/ml. Negative correlations were found between annexin A 5 level and GFR, a maximal growth of volumetric blood flow rate in skin vessels in the acetylcholine test, positive correlations with systolic blood pressure, body mass index. Conclusion. The levels of ET-1 and annexin A5 are factors having an independent impact on EDV in patients with CKDsI-II.

Aim. To evaluate frequency and risk factors of development of left ventricular hypertrophy (LVH) of the heart in patients with chronic kidney disease (CKD) of stage II-IV Material and methods. The trial enrolled 83 patients (42 - 51% males, 41 - 49% females, mean age 46.7 years) with stage II-IV CKD of non-diabetic origin. Glomerular filtration rate (GFR) estimated according to Cockroft-Goult formula was 37,7 ml/min (95% confidence interval from 33,9 до 41,4). Chronic renal failure duration averaged 2,7 years (95 % CI from 2.0 to 3.3). Arterial hypertension (AH) was diagnosed in 96% patients, hereditary predisposition to cardiovascular diseases - in 54 %, obesity — in 60 %, lipid disbolism - in 66%, anemia — in 34 % and hyperphosphatemia — in 45 %; 40% patients smoked. Echocardiography was performed in all the patients. Results. LVH was detected in 31 (37.3%) of 83 patients. With progression of renalfailure, frequency of registration of LVH increased. LVH onset was associated with conventional (age, AH, high level of total cholesterol) and renal (lowering of GFR, anemia, hyperphosphatemia) factors. Concentric remodeling, concentric LVH, eccentric LVH were detected in 31.3, 19.3 and 18.1% patients, respectively. Eccentric LVH developed more frequently under the influence of factors associated with renal failure (GFR, anemia, hyperphosphatemia, hypocalciemia). Concentric LVH was characterized with the highest systolic blood pressure. Conclusion. Patients with renal dysfunction develop LVH of different geometric model associated with both conventional and renal risk factors even at early stages of CKD.

Aim. To examine relations between hyperinsulinemia, insulin resistance (IR), components of metabolic syndrome (MS) and predisposition to renal damage. Material and methods. A total of 94 MS patients (64 males and 30 females, age 30-67 years, mean age 52±9 years) entered the study. The examination included measurement of waist and hip circumference, body mass index (BMI), HOMA index, estimation of lipids and immunoreactive insulin concentrations. Renal damage was assessed by glomerular filtration rate and urinary excretion of albumin. The patients were divided into groups by IR and BMI. Results. A strong correlation was found between IR markers and lipid metabolism disorders, hemodynamic parameters. Statistics show that IR is an independent unfavourable factor of renal damage in MS patients. Conclusion. IR is an essential component of MS and an independent factor of development of chronic kidney disease in MS patients.

Aim. To compare changes of hemorheological parameters in patients with lupus nephritis (LN) and IgA-nephropathy (IgA-N). Material and methods. Kinetics of spontaneous aggregation, disaggregation of red cells in shearing flow, red cell deformability were studied in 73 patients with LN including 6 patients with active LN with nephrotic syndrome, 38 patients with active LN with urinary syndrome, 29 with inactive LN; in 24 patients with a hematuric form of IgA-nephritis (IgA-N); in 24 healthy volunteers (controls). Results. Patients with LN and a hematuric form of IgA-H were found to have disorders of microrheological blood characteristics (accelerated formation of erythrocytic aggregates —EA of high density) depending on the form and activity of the disease. All LN and IgA-N patients exhibited increased time of "coin columbs" formation and accelerated aggregation. The largest EA were detected in IgA-H patients. Flow deformation ability of the red cells was poor in all the examinees. LN patients showed a positive correlation between maximal EA size and hematuria severity even in cases of trace proteinuria. A correlation was demonstrated in IgA-N patients between IgA level and EA density, between inhibition of GFR and erythrocytic deformability index. Conclusion. The above findings show deteriorated process of aggregation-disaggregation resultant from deterioration of red cell physical properties. Severity of hemorheological disorders depends on LN activity. Hematuria associated with increased size of EA is an important marker of the disease activity. Hemorheological disorders in patients with active LN and IgA-N are an additional pathogenetic component of hematuria.

Aim. Comparison of efficacy of 12-month treatment of anemia in patients with chronic kidney disease (CKD) of stage III — IV with a long-acting drug darbepoetin alpha — aranesp and short-acting drug erythropoietin beta — recormon. Material and methods. A total of 44 patients with CKD of stage III-IV were divided into two groups. Of them, 24 had chronic glomerulonephritis and 20 had tubulointerstitial nephritis with verified nephrogenic anemia. Group 1 consisted of 22 patients given long-acting erythropoetin (darbepoetin alpha) in an initial dose 0,75 mcg/kg each 2 weeks subcutaneously. Group 2 consisted of 22 patients matched by age, gender, severity of anemia and renal failure with group 1 patients given short-acting erythropoietin (erythropoietin beta) in an initial 20 IU 3 times a week subcutaneously for 12 months. In the phase of anemia correction and supporting therapy, the levels of packed red blood cells, Hb, free serum ferrum, ferritin, percentage of iron in transferrin, serum albumin in blood serum, creatinin, glomerular filtration rate were examined monthly. The patients themselves daily measured blood pressure, diuresis, body mass. Results. The target level of Hb 110-120 g/l was achieved faster in group 2 than in group 1 (3 and 4 months, respectively), p < 0.05). In the phase of supporting a target Hb level, on the opposite, darbepoetin alpha provided more stable hemopoetin effect than erythropoietin beta, darbepoetin alpha median dose being constant in the course of the study.

Aim. To assess efficacy of combined immunocorrection in the treatment of patients with chronic viral hepatitis C (CVHC). Material and methods. Routine clinicobiochemical tests, examination of immunological homeostasis (cellular immunity, the level of circulating immune complexes - CIC and their molecular composition, macrophagal phagocyting system — MPS) were made in two groups of CVHC patients: the study group (n=68) and control group (n=66). The control patients received standard treatment, the study group received also cyclopheron in combination with reamberin. Cyclopheron was given per os in a single daily dose 600 mg 2 days, then 3 times a week in a dose 150 mg for 48 weeks. Reamberin infusions in a single daily dose 400 m l were made for 5 — 7 days. Results. CVHC in exacerbation phase is characterized by the presence of secondary immunodeficiency running with T-lymphopenia, low count of peripheral blood lymphocytes with CD4+ phenotype and low immunoregulatory index CD4/CD8, depression of functional activity of T-cells as evidenced by lymphocyte blasttransformation test with phytohemagglutinin, inhibition of phagocyting activity of monocytes and inhibition of dermal macrophages. This shows subnormal functional activity of MPS. CVHC runs with accumulation of CIC in blood serum primarily due to increased content of most pathogenic mid- and low-molecularfractions of immune complexes. Addition of cyclopheron and reamberin in combined treatment of CVHC patients promotes normalization of immunological homeostasis which clinically occurs in parallel with achievement of persistent and long-term CVHC remission. Conclusion. The results of the above investigation support pathogenetic validity and prospects of cyclopheron and reamberin inclusion into combined treatment of CVHC.

The lecture considers mechanisms of potassium and water retention underlying nephrotic syndrome, clinical differences between hypo- and hypervolemic variants of nephrotic syndrome, risk factors of nephrotic crisis and its clinical symptoms, current approaches to its treatment.

A brief literature review analyses pharmacoprotective strategy in most widespread forms of chronic kidney disease: metabolic syndrome, hypertensive angionephrosclerosis, diabetic and non-diabetic nephropathy. Nephroprotective properties of the blockers of rennin-angiotensin-aldosteron system and other antiadrenergic drugs, diuretics, hypolipidemic, antianemic and hypouricemic drugs, active metabolites of vitamin D, metphormine and glytasones are reviewed. The highest efficacy of combined pharmaconephroprotection is demonstrated.