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Almira Hadžović-Džuvo, E. Kučukalić-Selimović, E. Nakas-ićindić, S. Rašić, A. Begić, D. al Tawil, A. Valjevac, N. Avdagić et al.

The aim of this study was to assess echocardiographic changes in female patients with untreated dysfunctional thyroid states and whether the therapy aimed to normalize the thyroid dysfunction could lead to improvement in cardiac systolic and diastolic function. The study included 90 female subjects who performed control of thyroid hormonal status at the Institute of Nuclear Medicine at the University of Sarajevo Clinics Centre and who previously were untreated for the thyroid functional disorders. The study sample was divided in three groups based on the thyroid hormones levels: a) hyperthyroid group (n= 30) b) hypothyroid group (n=30) and c) euthyroid (control). Echocardiography measurements were performed on commercially available Toshiba, SSH 140. Before the therapy no statistically significant differences in the peak early and late mitral inflow velocities (E/A) values between the study groups was observed, but the mean left ventricular ejection fraction (LVEF) in hypothyroid group was significantly lower (58.30+/-1.05) compared to control (64.96+/-0.71) and hyperthyroid group (64.69+/-1.31) (p<0.001). In hypothyroid group we found significant increase in mean LVEF (58.30+/-1.05 vs. 64.95+/-0.86, p<0.01) and E/A (1.06+/-0.07 vs. 1.17+/-0.08; p=0.01) values after the normalization of thyroid hormone status.Thyroid dysfunctional states were not associated with impaired diastolic function, probably due to the short duration of thyroid dysfunction and timely and successful conversion therapy. Systolic function however was significantly reduced in hypothyroid patients but subsequently improved after the adequate therapy. Early diagnostic approach in patients with thyroid dysfunctional states is important for avoidance of cardiac complications that accompany these disorders.

Lupus nephritis (LN) is an immune inflammation of kidneys caused by systemic lupus erythematosus (SLE), a chronic inflammatory disease that affects the body's immune system. Aim of this study was to analyze clinical manifestation and treatment results of patients with LN. Forty one patients with clinical signs of LN were included in the study. Mean age of patients was 31.9+/-12.1 years in the moment of first diagnosis of LN, with female-male ratio 8:1. Renal disease was pathohistologically (PTH) verified in 53.7% of patients (4 pts with class III, 17 pts with class IV, one pt with class V of lupus nephrites). Patients with high nephrotic proteinuria were treated with pulse dose of methylprednisolone and pulse doses of cyclophosphamide (CYC) in induction therapy. Corticosteroid and CYC were continued according to treatment protocol. The other group of LN patients with lower nephrotic proteinuria was treated with mycophenolate mofetil (MMF) in induction therapy at a dose of 2x1 g/day for six months, and than in maintenance 2x0.5 g/day. The patients with non-nephrotic proteinuria and normal renal function were treated with oral prednisolone 0.75-1 mg/kg/day in a single morning dose, and then gradually reduced to the dose of maintenance. The mean time of patient's follow-up was 10.9+/-4.1 years. Partial renal remission was accomplished in 29.2% pts, and complete remission in 60.9% pts for period of 17.2+/-13.3 months from the beginning of the treatment. Duration of complete renal remission was 30.1+/-19.1 months. During the period of follow-up, 29.3% pts developed at least one nephritic flare and were treated again. These results confirmed that the aggressive form of lupus nephritis should be treated associating cyclophosphamide with corticosteroids therapeutical regiment. MMF is a new promising immunosuppressive drug for a treatment of this serious disease.

A. Mataradzija, H. Resić, S. Rašić, N. Kukavica, F. Masnic

INTRODUCTION Cardiovascular diseases are the most frequent causes of morbidity and mortality in patients with chronic renal disease. The aim of our paper is to evaluate the risk factors of cardiovascular complications in patients with various stages of chronic renal disease (CRD), with or without diabetes mellitus (DM). PATIENTS AND METHODS The study included 98 patients with different stages of the CRD, with creatinine clearance <60 ml/min/1.73m2, and laboratory parameters monitored: homocysteine, BNP, cholesterol, LDL, HDL, HbA1c, Body Mass Index (BMI). First group comprised 49 patients with DM, age 50-82 years, M 28/F 21. Second group comprised 49 patients without DM, age 35-80 years, M 18/F 31. The IMT (intima media thickness) was measured by B-mode ultrasonography, and all patients had echocardiography examination done by 2D Doppler ultrasonography. RESULTS The IMT values in diabetic patients had statistically significant positive correlation with homocysteine values of r=0.9393, p<0.034, and cholesterol r=0.289, p<0.05, compared to non-diabetics. A significant negative correlation was found between the ejection fraction (EF) and BMI in both groups, more prominent in non-diabetics r=0.289, p<0.044 (diabetics r=0.162, p>0.05). 47.4% of diabetics had arteriosclerotic changes on carotid arteries, 8.5% had stenosis of ACC, and 22.0% had rhythm abnormalities on ECG. A positive correlation between IMT and BMI was found in diabetics, but was not statistically significant r=0.111, p>0.05. In the diabetics group a significantly higher (p<0.05) values of BNP, HbA1c, proteinuria, BMI, and cholesterol were found, and significantly lowered EF (p<0.0001). CONCLUSION Risk factors for cardiovascular complications in patients with DM are various, and the most pronounced significance was found in the values of homocysteine, BNP and cholesterol.

The metabolic syndrome (MS) is a multi-factorial disorder which includes a main risk factors associated with the development of cardiovascular, neurologic, renal and endocrine diseases, especially type 2 diabetes. This study has been conducted to estimate the prevalence of the MS in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and its association with cardiovascular morbidity. The study included 37 patients (25 type 2 diabetic patients and 12 non-diabetic patients), who had been on peritoneal dialysis for > 3 months. At the beginning of CAPD treatment (baseline) and at the end of follow-up, we measured: body mass index (BMI), blood pressure, fasting blood glucose, triglycerides and high-density lipoprotein cholesterol (HDLC) and defined the prevalence of the MS using the modified National Cholesterol Education Program (NCEP; Adult Treatment Panel III) for peritoneal dialysis patients. The overall prevalence of the MS was 89.2%. The metabolic syndrome was estimated in all (100%) type 2 diabetic patients (vs. 60% patients on the beginning of CAPD treatment). In non-diabetic peritoneal patients, the MS was estimated in 50% cases, according to 33.3% at the beginning CAPD treatment. Development of the MS was significantly higher in the type 2 diabetic patients in compared with non-diabetic patients until the end of follow-up examination (p=0.0005). The prevalence of LVH in type 2 diabetic patients with the MS was significantly higher (p=0.002) than in non-diabetic peritoneal patients with the MS. We didn't found statistical significantly difference in the prevalence of ischemic heart disease between this two category of peritoneal dialysis patients (p=0.076). The results indicate that the metabolic syndrome is presented in high percentage in peritoneal dialysis patients, and it's also important risk factor of high cardiovascular morbidity rate in these patients, especially in type 2 diabetic patients.

The aim of this study was to analyze the importance of the peritoneal equilibration test (PET) in evaluation of the peritoneal membrane transport status in patients treated with continuous ambulatory peritoneal dialysis (CAPD). The study included 30 adult continuous ambulatory peritoneal dialysis (CAPD) patients, 16 male and 14 female, mean age 61 +/- 16.5 years with a prescription of four exchanges of 2 litres (L) per day, who underwent peritoneal equilibration test (PET). Eleven of patients were diabetics. A modified PET was performed during a 4 hours dwell using 4.25% glucose dialysis solution. The dialysate/ plasma ratio of creatinine (D/P) at the end of the procedure, and the dialysate 240 min/ initial dialysate ratio of glucose (D/Do) were calculated and used as parameter of solute transport. With the test, categorization of patients was possible into high (H), high-average (HA), low average (LA), and low (L) transporters. In multivariate analysis age, gender, time on dialysis, comorbid diseases, diabetes mellitus (DM), serum albumin, were considered as independent factors influencing the PET. Among 30 patients 5 (16.7%) were classified as H transporters, 6 (20%) as HA, and 19 (63.3%) as LA. There were no patients in low category. Creatinine D/P at 4 hours was not different DM and non-DM patients. There were significant differences in gender, comorbid disease, serum albumin, D4/Do glucose and volume drained in 4 hours. The high transporter group had higher proportion of man (p<0.05), higher proportion of patients with comorbid diseases, lower serum albumin concentration (p<0.001), lower D4/Do glucose (p<0.001), and lower drained volume (p<0.001). The PET was en easy, inexpensive, reliable test to assess peritoneal transport type and it also provided information about peritoneal clearance of solutes and ultrafiltration. Peritoneal transport type classification was recognized not only as aid for prescription, but also as a prognostic index.

Accelerated atherosclerosis and vascular calcification, with oxidative stress, endothelial dysfunction, and other factors causing the arterial stiffness, increases cardiovascular morbidity and mortality in patients on peritoneal dialysis. The aim of this paper is to assess changes in intima media thickness (IMT) at common carotid arteries (CCA) in patients with stable continuous ambulatory peritoneal dialysis (PD) and examine the relationship of these changes and other risk factors on the occurrence of atherosclerosis. The study was conducted on 35 stable PD patients (25 type 2 diabetic patients), aged 58.6 +/- 10.6 years. CCA-IMT was assessed using ultrasound B-mode technique, bilaterally. Other risk factors for the occurrence of atherosclerosis were monitored through regular laboratory control. One atheromatous plaque was found in 19 patients (54.3%). Among 25 type 2 diabetic patients, vascular calcifications were found in 80% patients. In all PD patients, CCA-IMT is 0.77 +/- 0.23, in PD patients with vascular calcifications CCA-IMT is 1.05 +/- 0.2 mm, while in group without vascular calcifications the value of this parameter is 0.56 +/- 0.09 (p<0.01 ). Significant differences were found between PD patients with and without vascular calcifications on CCA in patients age (p<0.001), as well as values of systolic blood pressure (p=0.001), serum phosphorus (p=0.017), product calcium and phosphorus (p=0.021), CRP (p=0.039), triglycerides (p<0.05) and lipoprotein (a) values (p=0.044). Our results suggest an important determination of common carotid arteries intima media thickness and its relation to other risk factors for the occurrence and progression of atherosclerosis in patients undergoing peritoneal dialysis.

Cardiovascular diseases (CVD) are a major cause of morbidity and leading cause of mortality in almost 50% of patients (pts) with chronic kidney disease (CKD), including kidney transplant recipients. Left ventricular hypertrophy (LVH) is the most common structural alteration and powerful risk factor for cardiovascular complications in the uremic patients. The aim of this study is to analyze predictors of the left ventricular remodelling in the first year after kidney transplantation based on comparison of echocardiographic findings, which had been done before and twelve months after transplantation. In five years retrospective study, we followed up 30 kidney transplant patients in the first post-transplant year. All patients data - blood pressure, BMI, ECG, blood haemoglobin, serum protein, calcium, phosphorus, product of calcium and phosphorus, the values of parathyroid hormone, serum creatinine and creatinine clearance were recorded just before kidney transplantation and in one month interval after transplantation in the first post-transplant year. Echocardiographic examination was done before transplantation and one year after kidney transplantation. Before transplantation, 33% of patients had normal echocardiographic finding and 67% of patients had echocardiographic signs of left ventricular hypertrophy. After first post-transplant year, 63% of patients showed normal echocardiographic finding of LV, while 37% of patients remained with LV hypertrophy. Diastolic dysfunction of LV until the end of study had been reduced in 40% of pts compared to 70% pts at the beginning of the study. The positive echocardiographic remodelling of LV significantly correlated with rising values of haemoglobin (p<0.05), creatinine clearance (p=0.039) and with the reduction of the serum creatinine values (p=0.047), as well as values of parathyroid hormone (p=0.022). These results confirmed positive relationship between echocardiographic remodelling of left ventricular hypertrophy and elimination uraemia-related risk factors after successful renal transplantation.

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.

The synergy and shared co-morbidity, certainly interplay between kidney and cardiovascular disease, where advanced renal failure influences on progression of cardiac disease in bi-direction relationship. Cardiovascular diseases are cause of death in almost 50% of uremic patients. Correction of uremia after successful renal transplantation leads to improved cardiovascular status in the majority of kidney transplanted patients. The aim of this study was an evaluation of the influence of renal allograft function on left ventricular remodelling in the first year after transplantation comparing echocardiographic findings before and twelve months after transplantation had been done. In retrospective-prospective study we followed up 30 patients with renal allograft in the first post transplant year. During the study values of serum creatinine and creatinine clearance were monthly monitored. Echocardiographic examination was done before transplantation and one year after the kidney transplantation. Results of our study showed that before transplantation 67% of patients had echocardiographic signs of left ventricular (LV) hypertrophy, while 33% of patients had normal echocardiographic findings. After first post transplant year, 63% of patients showed normal view of LV, and 37% remained with LV hypertrophy. Diastolic dysfunction of LV till the end of study had been reduced from 70% to 40% of patients. The positive echocardiographic remodelling of LV significantly correlated with the rise in creatinine clearance and with the reduction of the serum creatinine. These results confirm positive correlation between renal allograft functional status and remodelling of left ventricular hypertrophy after successful renal transplantation.

We present a case of 52 year old male with an acute renal failure that took place 4 days after open transabdominal surgery repair of infrarenal abdominal aneurysm along with aneurysm of left common iliac artery and dilatation of left external iliac artery. Patient was subjected to 13 hemodialysis treatments that resulted in satisfactory recovery of renal function. One month after aneurysm repair he developed the right ureteral leak, consequently urinoma and acute renal failure once again. We suppose that ureteral leak was related to segmental ischemic necrosis of right ureter but not to traction or other iatrogenic ureteral injury. Percutaneous nephrostomy and insertion of ureteral stent was resulted in complete recovery of renal function.

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.

AIM To evaluate relationship between echocardiography finding of LV mass and function and B-type natriuretic peptide (BNP) plasma level in patients with chronic kidney disease on different type of treatment. METHODS We performed comparative examine on a parallel groups of kidney patients with no clinical signs of heart failure: 25 patients with chronic kidney disease (CKD, creatinine klirens < 60 ml/min), 25 patients on peritoneal dialysis (PD), 34 patients on hemodialysis (HD) and 22 renal transplant patients. Each patient underwent echocardiography investigations and measured plasma level B-type natriuretic peptide. RESULTS It was determined that hemodialysis patients had higher value of left ventricular mass index (LVMI). The incidence of left ventricular hypertrophy (LVH) progressive increased from CKD patients to HD patients (78.6% vs. 88.9%), as well as a plasma level of B-type natriuretic peptide (174.2 vs. 1020.2 pg/ml). There was a significant positive correlation between LVMI and BNP plasma level in CKD (p = 0.008) and HD patients (p = 0.001), as well as significant negative correlation between BNP plasma level and LV diastolicfunction in CKD patients (p = 0.002). CONCLUSION Plasma BNP concentration was elevated in renal dysfunction. Plasma BNP levels and the incidence of LVH were significantly grater in HD patients than in other renal patients. Significant positive correlation between plasma BNP level and LVMI suggested simultaneous influence of renal dysfunction and plasma BNP level on development of LV dysfunction.

The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in gentamicin-induced acute tubular necrosis in rats using the iNOS inhibitor L-N6-(1-iminoethyl) lysine (L-NIL). Wistar rats, both sexes (n=18), were equally divided into three groups. Gentamicin group received intraperitoneally (i.p.) gentamicin in 0.9 % NaCl at a dose of 80 mg/kg/day for five consecutive days. L-NIL+gentamicin group received L-NIL at a dose of 3 mg/kg i.p. 36, 24 and 12 h before first dose of gentamicin. Control group received 0.9 % NaCl i.p. for five consecutive days at the equal volume as gentamicin group. Griess reaction was used for determination plasma level of NO. Semiquantitative histological analysis was used for the evaluation of kidney damage level. The plasma NO level and the level of kidney damage were statistically higher in gentamicin group in comparison to the control group (p=0.046). Application of L-NIL prior to gentamicin led to certain decrease in the plasma level of NO as well as in the level of kidney damage. Application of L-NIL, prior to gentamicin administration, did not provide complete protective effects of L-NIL on the kidney, which was demonstrated on kidney sections. The lack of anticipated protective effect of L-NIL on kidney tissue might be explained with the fact that we have used L-NIL prior but not during/after gentamicin administration. It would be necessary to examine the effects of L-NIL administration not only before, but as well during and possibly after the administration of gentamicin.

Microvascular diabetic complications are the most common causes of morbidity and mortality of patients with type 1 disease. Diabetic nephropathy is becoming the single most common cause of end stage renal failure, while diabetic retinopathy is the most common cause of blindness in working-age population. The main aim of the study was to evaluate the progression of late microvascular complications in type 1 diabetic patients treated by conventional or intensified insulin regimen over the period of 10 years. We selected a random sample of 32 patients, including 14 males and 18 females, aged 30,6 +/- 11,8 years, with average duration of the disease of 4,8 +/- 3,2 years. They did not show signs of overt diabetic nephropathy, while 5 patients had background retinopathy. All the patients had their fasting and postprandial glycaemia, HbAlc, 24/hour proteinuria, blood pressure, height and weight measured and body mass index calculated (BMI). There was a trend towards increasing values of HbAlc (6.9 +/- 0.8 vs. 7.4 +/- 1.0 %, p < 0.05), fasting glycaemia (6.8 +/- 08 vs. 7.8 +/- 1.2 mmol/l, p < 0.05), postprandial glycaemia (9.2 +/- 1.5 vs. 11.3 +/- 1.9 mmol/l, p <0.01), systolic and diastolic blood pressure values (120.0 +/- 10.8 vs. 128.5 +/- 16.8 mmHg, p<0.05; and 73.4 +/- 8.1 vs. 79.8 +/- 9.8 mmHg, p< 0.05) although no hypertensive patient was diagnosed. There were 11 persons (34.4%) with persistent proteinuria of 200 mg/24 hour or more and significant difference in overall proteinuria in 10 yrs period (121.3 +/- 37.3 vs. 312.8 +/- 109.9 mg/24 h, p< 0.001). Overall, 9 persons (28.1%) were diagnosed with simple, background retinopathy, but 6 of them (18.8%) had signs of proliferative form of the disease. The results indicate significant changes in progression of proteinuria in both groups although retinopathic progression was observed but was not significant in the intensively treated group.

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