Anemia is common in patients with chronic kidney disease (CKD) and contributes to cardiovascular alterations. Recent findings suggest that B-type natriuretic peptide (BNP) is a sensitive biomarker for left ventricular dysfunction, but relationship between hemoglobin and BNP in CKD patients is unclear. Hemoglobin, plasma BNP and serum creatinine levels were measured in 49 patients with CKD (without heart failure), divided in two groups according to the hemoglobin status (cut-off point 110 g/L). All patients underwent echocardiography in order to assess left ventricular (LV) morphology and function. The results showed that in the group of patients with hemoglobin levels under 110 g/L BNP levels were significantly elevated (p < 0.001), as well as left ventricular mass index (p < 0.001). Systolic and diastolic LV function were significantly better in patients with hemoglobin levels above 110 g/L (p < 0.001). Hemoglobin levels were inversely related to BNP values (r = -0.451, p < 0.001). Significantly negative correlation between BNP level and creatinine clearance (p = 0.009), and significantly positive correlation between BNP level and left ventricular mass index (LVMI) were established. A similar but positive relationship was observed between hemoglobin levels and creatinine clearance (p < 0.01). We established statistically significant negative correlation between hemoglobin levels and LVMI (r = -0.564, p < 0.001). In conclusion, BNP and hemoglobin levels depend on the renal function. Anemia may contribute to elevated BNP levels in CKD patients, and may represent an important confounder of the relationship between BNP and cardiac alteration in these patients.

AIM The effects of two immunosuppressive therapeutic protocols have been analyzed to evaluate the influence of treatments on the level of proteinuria, value of creatinine clearance and the level of serum albumin of patients with idiopathic membranous glomerulonephritis (IMGN) and nephrotic syndrome. PATIENTS AND METHODS We studied 30 patients with IMGN and NS. In one group, patients were treated with corticosteroids in dose of 1 mg/kg of body weight for 4 weeks, followed by gradual reduction of dose to 0.5 mg/kg, in combination with one monthly pulses of cyclophosphamide i.v. in dose of 10 mg/kg for six months, followed by pulses treatment in three months intervals. In second group cyclosporine therapy was used in dose of 3-5 mg/kg, maintaining the medication serum level at 120 +/- 20 ng/ml. The research encompassed time period from 2000 to the end of 2007, while the parameters were tested every 2 months up to 24 months in total. RESULTS The obtained results showed that a significant reduction of proteinuria (p < 0.05) was reached in both analysed groups during the period from 6 to 9 months from the beginning of therapy. The preservation of the stabile status of the kidney function was attained as well as the insignificant variation in serum creatinine, before and after the therapy in both analysed groups. Decrease in average serum creatinine values in cyclophosphamide group (from 133.9 to 115.5 micromol/l) and the increase in the cyclosporine group (from 85.0 to 100.3 micromol/l) point to somewhat better preservation of kidney function in the cyclophosphamide group. Complete remission of nephrotic syndrome was achieved in 40% of the patients in the cyclophosphamide group, while 60% achieved partial remission. In 27% of the cyclosporine group patients complete remission was achieved, in 60% partial remission, while in 13% of them decrease of proteinuria without remission of the nephrotic syndrome. CONCLUSION The cyclophosphamide therapy, in combination with steroids, proved to be a good choice, whereas the cyclosporine therapy proved as a prosperous alternative in treatment of patients with IMGN.

The aim of this retrospective study was to evaluate the results of the immunosuppressive regiment in managing of IgA nephropathy associated with primary nephrotic syndrome at the Nephrology Clinic, University of Sarajevo Clinics Centre in period of 1997-2007. We studied 19 patients (4 women and 15 men) with idiopathic nephrotic syndrome, where pathomorphologic changes of IgA nephropathy were proved by kidney biopsy. The levels of diuresis, proteinuria, albuminemia, lipidemia and kidney function, as measure of efficiency of used therapy, were monitored. The IgA nephropathy present with the nephrotic syndrome was shown in 15.8% (19) patients underwent renal biopsy due to primary nephrotic syndrome in the period of observation. The average age of patients with IgA nephropathy was 34.9+/-14.1 years. Eight patients from this group were treated with corticosteroid therapy (1-1.5 mg/kg of body weight for 4 weeks, followed by 0.5 mg/ kg of body weight until therapeutic response was achieved, and finally gradual exclusion of therapy after eight weeks in responsive patients), 6 patients with corticosteroids and bolus cyclophosphamide (10-15 mg/kg BW), and in 5/19 patients cyclosporine therapy was used (3 mg/kg BW). Complete remission of nephrotic syndrome was achieved in 42.1% of the patients. In conclusion, in adults patients with primary nephrotic syndrome associated with IgA nephropathy, used immunosuppressive therapy resulted in a high percentage of achieved remissions.

Strict therapy protocol, which would be used universally for certain morphological forms of primary nephrotic syndrome, does not exist. The aim of the study was to show the effects of used therapy protocol in treatment of primary nephrotic syndrome at the Institute of Nephrology, Clinical Center University of Sarajevo in period of 2000-2005. The retrospective analysis covered 48 patients (17 women and 31 men) with idiopathic nephrotic syndrome, where pathomorphological changes were proved by kidney biopsy. Minimal change disease was confirmed with 6 (12.5%) patients. All patients were initially treated with corticosteroids with dose of 1 mg/kg of body weight. Five patients were in the group of primary responders (83.3%) with long term total remission, and 1 patient (16.6%) was a primary responder with 3 relapses in 8 months with a therapy of corticosteroids and bolus of cyclophosphamide. Diffuse mesangial proliferative glomerulonephritis was shown in 13 patients (27.1%). Seven patients from this group were treated with corticosteroid therapy (1 mg/kg of body weight for 4 weeks, followed by 0.5 mg/ kg of body weight until therapeutical response was achieved, and finally gradual exclusion of therapy after eight weeks in responsive patients). Six patients were treated with corticosteroids and one-month of bolus cyclophosphamide during half of year (10-5 mg/kg of body weight). Total remission was achieved in 37,9% of the patients. The IgA nephropathy presented with the nephrotic syndrome was shown in 10.4% (5) of the patients. Three patients from this group were treated with corticosteroid therapy (1 mg/kg of body weight for 4 weeks, followed by 0,5 mg/ kg of body weight until therapeutical response was achieved, and finally gradual exclusion of therapy after eight weeks in responsive patients) and.2 patients with corticosteroids and cyclophosphamide (1.5 mg/kg of body weight) during 6 months. Complete remission of nephrotic syndrome from this pathomorphological category was achieved in 2 patients. Membranoproliferative glomerulonephritis was shown in 6 patients (12.5%). All were treated with corticosteroids plus bolus of cyclophosphamide. Partial remission was achieved in one patient. Membranous glomerulonephritis was confirmed in 18 patients (37.5 %). Combined therapy of corticosteroids and bolus of cyclophosphamide was used in 7/18 patients, in 2/18 patients therapy of corticosteroids and per os cyclophosphamide (2 mg/kg of body weight) and in 9/18 patients cyclosporine therapy (3 mg/kg of body weight). Complete remission was achieved in 38.8% of the patients. A high percentage of achieved remissions of primary nephrotic syndrome in adults shows the efficiency of immunomodulating therapy used. Membranoproliferative glomerulonephritis still remains a therapy problem.

BACKGROUND Cardiovascular diseases represent the leading cause of mortality in patients with end-stage renal disease treated by hemodialysis. Left ventricular hypertrophy (LVH), which is connected with various risk factors present in this population of patients, represents a major factor of high mortality. AIM To determine the plasma levels of parathormone (PTH, levels of serum calcium (Ca) and phosphorus (P) in patients treated by hemodialysis, and investigate the impact of PTH as a possible risk factor for LV morphology changes. PATIENTS AND METHODS The study included 50 patients with end-stage renal disease during the first two years of haemodialysis treatment. They were followed during the period of 12 months and had the same conditions of hemodialysis treatment. All participans have the echocardiography performed, as well as serial measurements of serum calcium and phosphorus by standard laboratory tests, and measurement of PTH by immunoradiometry. RESULTS More than 2/3 of selected patients (72%) showed signs of LVH at the beginning of the study. Patients with concentric LVH have significantly higher levels of PTH than those with normal echocardiography finding. Especially high levels of PTH were observed in patients with global sistolic-diastolic LV failure (more than 84,5% than the patients with normal echocardiography). PTH is significantly and independently associated with LV mass (p=0,002) and LV volume increment (p=0,040) noted by echocardiography. Ca x P product showed higher values in patient with sistolic-diastolic LV failure as compared to patients with normal LV echocardiography. CONCLUSION PTH appears to be an independent predictor of significant changes in LV mass and volume, which indicates that this "uremic toxine" has the importance of risk factor for uremic cardiomiopathy.

UNLABELLED Left ventricular hypertrophy (LVH) is commonly present in hemodialysis patients (HD pts) and is considered as an independent risk factor for high mortality. Many studies have confirmed sound connection between anemia and LVH in this patients. OBJECTIVE To analyse dystolic function of LVH in uraemic pts during the 6 months human recombinant erythropoectin (rHu-Epo) treatment of anemia, with emphasis on the role of nitric oxide (NO), whose role in regulation of LV diastolic distensibility has been hinted in some recent studies. PATIENTS AND METHODS The study included 20 HD pts, aged 39.6 +/- 5.3 yrs, with the same condition of HD treatment, signs of anemia and echocardiographically verified LVH. Pulse Doppler echocardiography confirmed LV diastolic function as a ratio of early to late diastolic mitral flow velocity (E/A). Nitrate concentration was determined by colorimetric method using Greiss reagent. Renal anemia was treated with rHuEpo. RESULTS Six months rHuEpo treatment of anemia in HD pts with LVH caused significant reduction of LV mass index (p = 0.008). However, we observed unfavourable fall in LV diastolic function (E/A = 0.83, p = 0.007). In the same time, it was found that the serum NO level was higher for 11.8% in HD pts with LVH as compared with the pts with normal LV mass. Also, the significant positive correlation was found between the level of NO and LV mass index before (p = 0.004) and after rHuEpo therapy (p = 0.03), as well as a significant positive correlation between NO and E/A in the same conditions (p = 0.002) and p = 0.049). Level of NO negatively correlates with blood hemoglobin level, but without statistical significance. CONCLUSIONS Correction of anemia with rHuEpo leads to the significant partial regression of LVH. Reduction of diastolic function of LV, observed after diminished LV mass index, could be related to the significant fall of NO level and damaged response of LV to NO. The results of the study strongy suggest that NO can present an important determinant of LV diastolic function in uraemic pts.

INTRODUCTION Anemia has been shown to be a key component of renal failure, as well as of the occurrence of left ventricular hypertrophy (LVH), with special attention paid to the paracrine mechanism of left ventricular remodelling. AIM The aim of the study was to analyze possible association of serum angiotensin-converting enzyme (ACE) activity and LVH in hemodialysis patients with anemia treated with human recombinant erythropoietin (rHuEpo) during six months. METHOD LV geometry was determined by echocardiographic analysis in 20 hemodialysis patients before and after erythropoietin treatment. Serum ACE activity was measured by spectrophotometric method using hippyril-l-histidyl-l-leucin as a substrate. RESULTS Serum ACE activity increased to 47.3% in hemodialysis patients with LVH as compared to patients with normal LV mass. A significant positive correlation was found between the level of ACE activity and LV mass index (p=0.004). Six-month erythropoietin treatment of anemia led to a significant reduction of LV mass index (p<0.008) and serum ACE activity (p=0.003) from the initial values. CONCLUSION The levels of serum ACE activity are associated with LV geometry. Our findings suggested the possibility of simultaneous and modest modulation of LV mass and serum ACE activity with rHuEpo correction of renal anemia.

Anaemia appears to play an important role in left ventricular (LV) enlargement in chronic kidney disease patients. The objective of this study was to evaluate LV echocardiography changes during anaemia correction with recombinant human erythropoietin (rHu-Epo) in chronic haemodialysis patients (HD pts) with signs of anaemia and LV hypertrophy (LVH). The study included 20 HD pts aged 39,6 +/- 5,3 yrs, with the same condition of HD treatment, anaemia and echocardiographically LVH verified. At the beginning of the rHu-Epo treatment haemoglobin (Hb) level was < 90 g/L and the target Hb level was 110 g/L. Echocardiography was performed at the beginning (baseline) and after six months of rHu-Epo treatment. LVH was defined as LV mass index >100 g/m2 in women and >131 g/m2 in men. We observed significant reduction of LV mass index (LVMI) (mean 26,4%, p=0.008), as well as LV volumen. There was a significant negative correlation between Hb level and LVMI with predictive LVMI reduction of 2,317 g/m2 for each 1g/L rising of mean Hb level. The results of the study confirm the importance of early anaemia correction in haemodialysis patients aimed to improve LV parameters.

BACKGROUND It's known that uremia is accompanying with different alteration of immune system. Also, different type of dialysis membranes can affect the immunological competence cells--lymphocytes and their function during hemodialysis (HD). AIM OF STUDY To establish the effect of single hemodialysis session with polysulfonic and cellulose--acetat membranes on lymphocyte subpopulations and their activation markers. METHODS In two groups of seven patients with end stage of renal disease (ESRD) on periodic HD we were investigated flow-cytometrical expression the following markers using monoclonal antibodies (BECTON DICKENSON): CD3 (T-Ly), CD19 (B-Ly), CD4 (T helper/inducer), CD8 (T-suppressor/cytotoxic), CD4/CD8 ratio, CD16 (NK cells), CD3/HLA-DR (late activated T-cells), CD4/CD 25 (IL-2R early activated T4), CD4/HLA-DR (late activated T8), CD8/CD25 (early activated T8), CD8/CD71 (late activated CD8). Blood samples were taken before HD, 30 minutes into HD and at the end of a four-hours HD session. RESULTS Demostrates statistical increased expression T helper cells on both membranes on minute 30 from beginning of HD procedure, but more on cellulose-acetat membranes and the significant falls to normal value at the end of HD: start 46.7% minute 30: 54.9%, minute 240: 42.7%. Significant changes were in expression of NK cells on cellulose-acetat membranes: start 12.7%; minute 30: 6.0; minute 240: 11.1%. No changes were noted in activations of T Ly, T4 and T8 on the both membranes. CONCLUSION No significant difference was found in expression of lymphocyte subpopulations and their activations during HD with polysulfone membranes. Significant changes of the expression of NK cells during HD with cellulose acetat, indicated that NK cells can be sensitive marker for biocompatibility of HD membranes.

Renal amyloidosis is a rare disease when compared to other kidney diseases. During the period of last fifteen years, at the Institute of Nephrology and Immunology in Sarajevo renal amyloidosis was diagnosed with 15 patients. The disease occurred more often with men than with women. Only during 1988, renal amyloidosis was revealed and followed up with five patients. The most common clinical manifestations of renal amyloidosis are nephrotic syndrome and chronic renal failure, with respective laboratory findings. Using immunofluorescent analysis of the kidney biopsy material, we discovered deposits of immunoglobulins of different intensity and deposits of lambda and kappa light chains of immunoglobulins. The intensity of lambda light chains is greater than that of kappa chains. The analysis of light microscopy showed nodular mesangial deposits and deposits along GBM without proliferation. The diagnosis of amyloidosis was confirmed by staining of amyloid. Application of therapy for amyloidosis was without any effect. Although renal amyloidosis is a rare disease, we want to point out disease as being an etiologic factor in nephrotic syndrome.