Cardiorenal continuum, pathogenetical grounds of preventive nephrology.

The problem of assessment of glomerular filtration rate in modern nephrology: a new indicator Cystatin C.

Current practice of disinfection of the «artificial kidney» apparatus.

THE AIM of the investigation is an analysis of clinicolaboratory and biophysical indices characterizing the metabolic shifts in chronic hemodialysis patients under continuous observation. PATIENTS AND METHODS. During 201 sessions of regular hemodialysis 108 patients with the terminal stage of CRF were examined. Repeated examinations were performed on 36 patients within 1.5 years after the observations were started, 22 patients were examined once more within 5.3 years. The level of parathyroid hormone in blood was determined in 59 patients. Reliability of differences in the data before and after the hemodialysis sessions (p<0.05) was estimated by the value of Student’s coefficient, the hemodialysis effectiveness  by the value Kt/V. Survival of the patients was calculated by the moment method, the average period of life at the hospital department and its dispersion were also determined. Acid hemolysis was performed after Terskov and Gitelzon, ultrasonic  with the apparatus of ultrasonic therapy UST 1.03 U. Osmotic resistance was determined in a 0.45% solution of NaCl calorimetrically. The immunoenzymic method was used to determine the content of parathyroid hormone in blood, all other clinical parameters were determined according to standard unified methods. RESULTS. For the recent decade the average term of life of these patients has become two times longer. Positive dynamics was noted in the indices of the state of the cardiovascular system: the duration of hemodialysis treatment had negative correlation with systolic arterial pressure (r = 0.246±0.070, p<0.001 before session; r = 0.349±0.067, p<0.0001after session), diastolic arterial pressure (r = 0.286±0.069, p<0.001 before session; r = 0.340±0.068, p<0.0001after session), and pulse pressure after session (r =  0.293±0.069, p<0.0001). A correlation was established of the electrolyte status of plasma with the duration of hemodialysis treatment: Na+ concentration before hemodialysis session decreased (r = 0.232±0.070, p = 0.001), and Ca2+  increased (r =0.327±0.068, p<0.0001). The increased intensity of protein metabolism was expressed as a gradually increased concentration of the total blood protein (r = 0.234±0.080, p = 0.001), albumin (r = 0.157±0.071, p= 0.028) and urea concentration in blood plasma (r = 0.229±0.070, p= 0.001). Dry weight of the patients decreased in due course (r = 0.264±0.068, p <0.0001). Stability of the erythrocyte membranes grew up: acid hemolysis time shortened (r = 0.152±0.071, p=0.034 before session), hematocrit increased (r = 0.190±0.070, p=0.008 before session). Coefficients of correlation of arterial pressure with the patients’ weight before and after hemodialysis sessions are presented as well as with the concentration of Na+ in blood plasma. Their sufficiently stable status was noted with the exception of the mineral metabolism indices. Even with the optimal values of the phosphoruscalcium product activity of alkaline phosphatase becomes 60% higher for 89 years of chronic hemodialysis treatment. An analysis of clinicolaboratory indices disclosed the most possible mechanisms of impairments of the cardio vascular system, proteinlipid metabolism, waterelectrolyte and nutritional status. The priority directions in correction are determined. CONCLUSION. In case of successful adaptation of the patient to regular hemodialysis treatment at the initial period his condition gradually becomes better in the following 23 years, and later for 79 years remains fairly stable. The high quality hemodialysis therapy effectively corrects the impaired protein and lipid metabolism, maintains nutritional status, adequately corrects anemia, and the cardiovascular system parameters do not deteriorate. The cellular structures become stable, the membrane systems improve. The state of mineral metabolism is the only thing that remains problematic.

THE AIM of the investigation was to compare quality of life (QL) indices of patients on hemodialysis (HD) and healthy subjects, to compare QL indices of Russian HD patients and those from other countries, to determine factors influencing QL of HD patients. PATIENTS AND METHODS. 1047 chronic hemodialysis patients were examined. To assess the healthrelated QL the Russian language version of the SF36 Health Status Survey was used. The indices of depression, asthenia, anxiety, personality features, life purposes and values, cliniclaboratory parameters were also determined for the assessment of their influence on patients’ QL. RESULTS. Patients on HD were found to have all indices of their physical functioning considerably lower than those in healthy subjects. It concerns the resistance to physical loads (PF), restricting effects of the physical state on the everyday activities (RP), general health condition (GH), intensity of pain (BP). According to the indices of mental health the decrease was less pronounced than normal. In Russian HD patients the tolerance indices to physical loads (PF), general activity (V) and the total index of physical health (PCS) were reliably higher than in US patients. The US patients possess an advantage in mental health (MH), total mental health index (MCS), freedom from pain (BP), general health condition (GH). Patients from Great Britain have lower rates of the majority of scales of the SF36 questionnaire than those from Russia and USA that seems to be associated with the lower level of hemoglobin in this group of patients. The blood serum albumin level is an independent predictor of safety of the total index of physical health (PCS). The degree of depression, patient’s age, duration of HD, number of days at the hospital for the last 6 months, and a coexisting pathology have negative influence on the total index of physical health (PCS). The total index of physical health (PCS) is dependent on the level of personal anxiety, depression and asthenia, age and time of HD treatment. CONCLUSION. QL of HD patients is substantially lower as compared to healthy subjects mainly at the expense of the indices of physical health. QL of HD patients is liable to effects of clinical and mental variables. It should be studied in future what underlies the established differences in QL between HD patients from different countries cultural, socialeconomic factors or the medical care quality.

THE AIM of the investigation was to study the mechanisms of renoprotective action of statins in 60 patients with chronic glomerulonephritis (CGN). PATIENTS AND METHODS. The main group consisted of 30 patients undergoing complex treatment including simvostatin in dose 10 mg/day in addition to glucocorticosteroids and cytostatics. The control group patients were treated by traditional therapy with glucocorticosteroids and cytostatics. In both groups of patients the effects of the used schemes of treatment on the indices of lipid metabolism, diurnal proteinuria, level of creatinine and cytokines in blood serum were assessed. RESULTS. It was found that the complex treatment including simvoststin resulted not only in a more pronounced decrease of the level of atherogenic fractions of lipoproteins than in the control group but in a more considerable antiproteinuric effect. In the main group, unlike the control one, the level of blood creatinine was not changed either. In addition, normalization of the ILβ level and statistically significant drop of the TNAα level were observed in the main group of patients. In the control group the ILβ level failed to reach normal values, while the TNAα level had a tendency to be decreased. CONCLUSION. The results of the investigation have shown that in addition to hypolipidemic effect statins also have a normalizing influence on the balance of plasma cytokines. The latter explains their antiinflammatory effect which appears to be the most important factor of their renoprotective action.

THE AIM of the work was to establish the ways of using the level of glycosylated hemoglobin (HbA1c) in nephrology. PATIENTS AND METHODS. The following patients were examined: 34 patients with diabetic nephropathy (DN), 11 patients with chronic glomerulonephritis (CGN) with the initial stage of chronic renal failure (CRF) and 11 with terminal renal failure. The method of isoelectrical focusing in the boratepolyolic system was used for determination of the HbA1c level. RESULTS. Glomerular filtration rate, blood creatinine level were found to substantially influence the proteinuria level (24P) in diabetes mellitus patients. A substantial effect of the HbA1c level was also found on the duration of CRF in CGN patients and on the main parameters of dialysis therapy. For example the influence of the HbA1c level on hemodialysis adequacy index according to urea (kt/v) was 65.6%, on the blood perfusion rate 61.3%, on the blood perfusion volume 89.1%. CONCLUSION. The HbA1c level might be a prognostic parameter for 24P in patients with DN and for the latent and initial CRF in patients with CGN. The data obtained allow HbA1c to be recommended as an additional indicator of a reliable control of the quality of programmed hemodialysis.

THE AIM of the investigation was to assess longterm outcomes (loss of transplant and its function) of transplantation of the kidneys from elderly (≥ 60 years) donors and compare them to a control group of donors <60 years. PATIENTS AND METHODS. Results of 154 renal transplantations from living related and nonrelated (spouses) donors performed between 1992 and May 2002 were analyzed. All patients were divided into two groups according to the donors’ age: group 1 (n=44) mean age of donor 66.4±4.9 (6078) years and group 2 (control group, n=110) mean age of donors 47.9±7.9 (2259) years. The maintenance immunosuppression consisted of cyclosporine, azathioprine or mofetil mycophenolate and prednisolone. The graft function was evaluated by serum creatinine concentration levels. The χ 2  test was used to compare differences between the groups. RESULTS. Transplants from elderly donors made up 28.6% of all living donor transplants. Mean age of the recipients (36.6±9.4 vs 30.2±11.4), percentage of retransplanted patients (4.5% vs 6.4%), HLA match (3.59 vs 3.1), number of sensitizated (PRA ≥ 50%) patients (6.8% vs 3.6%) were similar in both groups. In group 1 37 patients and 96 patients from group 2 were followed up for a year after transplantation. No statistically significant differences in the patients’ state and graft loss were found during the first year. The percentage of recipients with excellent and good graft function in group 1 was statistically significantly lower than in group 2: 81.1% vs 93.8% (χ2 =4.8604 p<0.05) in a year, 73.0% vs 89.6% (χ2 =5.5124 , p< 0.02) in 3 years and 50.0% vs 93.2% (χ2 = 15.3014, p<0.001) in 5 years respectively. CONCLUSION. The risk of chronic rejection of the transplanted kidney is independent of the donor’s age. Excellent and good state of the graft from elderly donors was observed more rarely than of the graft from younger donors.

THE AIM of the investigation was to evaluate the lipid peroxidation (LP) processes in platelets, antioxidative system (AOS), plateletvascular hemostasis and to determine their potential significance for pathogenesis of chronic pyelonephritis. PATIENTS AND METHODS. Indices of LP, AOS, plateletvascular hemostasis were determined three times in 48 chronic pyelonephritis patients (38 women and 10 men) aged from 18 to 50 in the phase of exacerbation. RESULTS. An analysis of the results obtained has demonstrated essential disorders in the lipid peroxidation system. It is documented by a significantly increased primary and secondary lipid peroxidation products in the platelets  isolated double bonds, dienic conjugates, conjugated triens, TBA responding products (p<0.001). The intensity of lipid peroxidation processes depends on the rate of chronic pyelonephritis activity. In patients with chronic pyelonephritis the intensification of LP is accompanied by essential suppression of the AOS activity (catalase, superoxide dismutase and total antioxidative activity of plasma (p<0.001). Furthermore, activation of platelet vascular hemostasis is observed in chronic pyelonephritis patients, more pronounced in patients with the III degree of the disease activity (p0.001). It should be noted that increased intensity of LP processes in the platelets, decreased activity of AOS is parallel to increased activity of the plateletvascular hemostasis. CONCLUSION. Thus, significant changes in the concentration of LP products in the platelets, AOS activity and plateletvascular hemostasis are observed in patients with chronic pyelonephritis. Changed indices and their degree seem to be a link in pathogenesis of the disease and require correcting therapy.

THE AIM of the investigation was to assess specific tubulostromalvascular changes in chronic glomerulonephrites and the effects of treatment on morphogenesis of tubulointerstitial component. PATIENTS AND METHODS. Nephrobiopsy was used to verify primary chronic glomerulonephritis in 143 examined patients. Repeated biopsy was performed in 19 (13.3%) of them within at the average 9.4±0.15 months after finishing the course of treatment. The method of light optical microscopy was used. RESULTS. Patients with mesangioproliferative glomerulonephritis were found to have mainly «tubular» lesions, and the treatment favored a decrease of the degree of dystrophy of the tubule epithelium. In mesangiocapillary variant of the disease «vascular» changes prevailed. Membranous nephropathy was characterized by frequently observed protein masses and glial cylinders in the tubule lumen, stroma edema and fibrinoid necrosis. In addition to a considerably decreased occurrence of stroma edema and plasmatic impregnation against the background of treatment there were greater tubular alterations as more frequent signs of dystrophy and necrosis of the epitheliocytes, impaired integrity of the tubule basal membrane. The main signs of impaired tubulointerstitium in focal segmental glomerulosclerosisglialinosis were «stromal» alterations stroma sclerosis and infiltration of it by cellular elements, which were more frequent after treatment, that points to progressing nephrosclerotic processes and accelerated formation of CRF. CONCLUSION. Underestimation of tubulointerstitial alterations in chronic glomerulonephritis is fraught with the progression of the disease in future with the outcome into CRF. Investigations aimed at studying the role of morphological and functional changes of the tubulointerstitium are expedient as well as of the effects of treatment on these processes.

THE AIM of the investigation was to find out the functional and structural consequences of experimental hyperhomocysteinemia (hHcy) in the rats’ kidneys. MATERIAL AND METHODS. Adult albino Wistar rats were exposed to daily parenteral homocysteine for three weeks in order to evaluate the influence of experimental hHcy on urinary albumine excretion (UAE), plasma creatinine concentration and creatinine clearance (CCr) as well as on the alterations of the glomerular and proximal tubular (PT) structures at the light and electron microscopy levels. RESULTS. The development of mild hHcy in experimental animals resulted in significantly increased UAE without a significant CCr change that was accompanied by moderate focal mesangial and endothelial cell proliferation, glomerular basement membrane hyperplasia, appreciably increased number of large apical vacuoles and secondary lysosomes, and focal loss of the brush border in certain PT cells. In addition, an increased number of autophagic vacuoles along with the epithelial cells with disorganized loci of the basal cytoplasm was noted. CONCLUSION. The data obtained are considered to be a direct evidence of the impairing effect of hHcy on the glomeruli and PT cells.

THE AIM of the investigation was to elucidate potentialities of the diagnostics of protective effects of GA40 on the course of sublimate nephropathy in rats. MATERIAL AND METHODS. Protective effects of GA40 were investigated in mature white male rats in the oliguric and polyuric stages of acute renal failure. In assessment of urine with the help of a vegetative resonance test «Imedis test+» the following parameters were determined by the bioindex scale: creatinine, ions of sodium, potassium, lithium, urea, thromboxan A2 , aldosterone, protein, Pg E2 , angiotensine 2, TNFα, Larginine, vasointestitial peptide, GA40. The lifetime testing of creatinine in blood and sublimate in the cortical substance of the rat kidneys, Pg E2,, angiotensine 2, TNFα, Larginine, vasointestitial peptide was performed through the reproducible biologically active point of a healthy volunteer. RESULTS. It was shown that GA40 had a protective effect on the course of sublimate nephropathy both in the oliguric and polyuric stages of the pathological process that was accompanied by a quicker elimination of sublimate from organism with urine, decrease of its content in the cortical substance of the kidneys, less degree of retentional azotemia at the expense of normalization of the balance of the hormonalmessenger systems of homeostasis of sodium ions. The method of the vegetative resonance test «Imedis test+» made it possible to find out GA40 in the rat’s urine that were previously given the substance. CONCLUSION. The perspective of scientific investigations is to continue using the vegetative resonance test «Imedis test+» for the lifetime assessment of biological parameters in experimental animals with diseases of the kidneys.

THE AIM of the investigation was to study the coagulation indices of urine in treatment of experimental Masuginephritis. MATERIALS AND METHODS. The investigation was performed in rabbits with body mass 2.03.7 kg. Pro and anticoagulatory as well as fibrinolytic properties of urine of healthy and sick animals were studied before and after treatment of the latter with a complex of drugs (plasma with high content of antithrombinIII, prodectin and phentalamine hydrochloride). The silicone, koalin time, partly activated thromboplastine time, index of the contact activation range, prothrombin, thrombin and heparine time, antithrombinIII, fibrinogen/fibrin degradation products (FDP) in urine, enzymatic and nonenzymatic fibrinolysis were determined. RESULTS. It has been found that treatment of Masuginephritis with a complex of drugs decreases activity of factors involved in formation of prothrombinase, the content of FDP in urine, heparin and ATIII, increases activity of both enzymatic and non enzymatic fibrinolysis, i.e. reestablishes the coagulatory potential of urine substantially impaired during the pathological process in the kidneys. CONCLUSION. The diseased kidneys change the pro, anticoagulatory and fibrinolytic indices of urine which become normal after the treatment of experimental nephritis with the complex of drugs (plasma with high content of antithrombin III, prodectin and phentalamine hydrochloride). The coagulation indices of urine can be used for the diagnosing of the development of kidney diseases as well as for control of effectiveness of the therapy.

THE AIM of the investigation was to study the renal transport of nitrates and nitrites in the intact kidney. MATERIALS AND METHODS. The selected for the experiments male rats with body mass 100200 g were randomly divided into 4 groups. The rats of the third and fourth groups were given sodium nitrite (0.2 mg/100g of body mass). The kidney function was studied under conditions of induced diuresis. Water and 3% solution of chemically pure sodium chloride (osmolality of the solution was 3 and 1050 mOsm/kg H2O) was used as a load which was administered by an intragastric probe at 5% of body mass. Water or aqueous solution of sodium nitrite was administered to rats of the 1st and 3rd (n=12) groups respectively. Saline solution was administered to rats of the 2nd group (n=13), the saline solution with sodium nitrite was administered to rats of the 4th (n=12) group. Nitrites, nitrates, creatinine and urine protein were determined in samples of urine and blood plasma. RESULTS. It has been found that a single administration of sodium nitrite, independent of the kind of load, is followed by a decrease of creatinine clearance, elevation of protein eliminated by the kidneys and does not result in higher concentration of nitriteions in blood plasma. At the same time the concentration of nitrites in blood plasma and their excretion by the kidneys increased. CONCLUSION. 1. Administration of sodium nitrite (0.2 mg/100g of body mass) results in the increased concentration of nitrates rather than nitrites in blood plasma and is followed by a moderate change of the functional state of the kidneys: lower creatinine clearance and higher excretion of protein. 2. The investigations performed suggest that detoxication of organism after administration of exogenous nitrites is realized at the expense of their accelerated oxidation into nitrates followed by higher rate of excretion of nitrateanion by the kidneys. 3. The kidneys play an important role in regulation of the nitrogen oxide cycle in organism after administration of exogenous sodium nitrite.

Nephrogenic edema of the lungs.

Is everything going smoothly in the doctrine of glomerulonephritis!?

Boris Ilyich Shulutko (to his 75th birthday).