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Background. Systemic lupus erithematodes (SLE) is chronic, often febrile, multisystemic disease unknown origin and relapsing course which affects connective tissue of the skin, joints, kidney and serous membranes. Gastrointestinal manifestations are rarely the first sign of systemic lupus erythematosus. Case report. We presented a female patient, 35 years old, whose first symptoms of SLE were paralitic ileus (chronic intestinal pseudo-obstruction) and polyserositis (pleural effusion and ascites). Except for high parameters of inflammation, leucopenia and thrombocytopenia, all immunological and laboratory tests for SLE were negative in the onset of the disease. During next six months the patient had clinical signs of paralitic ileus several times and was twice operated with progressive malabsorptive syndrome. The full picture of SLE was manifested seven months later associated with lupus nephritis. Treatment with cyclophosphamide, corticosteroids and total parenteral nutrition (30 days) induced stable remission of the disease. Conclusion. The SLE can be initially manifested with gastroenterological symptoms without any other clinical and immunologic parameters of the disease. If in patients with SLE and gastrointestinal tract involvement malabsorption syndrom is developed, a treatment success depends on both immunosupressive therapy and total parenteral nutrition. [ABSTRACT FROM AUTHOR]

Background/Aim. Due to improved methods for removal of ABO isoagglutinins and novel immunosuppressive protocols, short and long term outcome in blood group incompatible is similar to blood group compatible kidney transplantation. The aim of this study was to determine the efficacy of our original method for removal of ABO isoagglutinins from the blood in ABO-incompatible kidney allograft recipients. Method. Between 2006 and 2008 twelve patients were transplanted from ABO incompatible living donors. Titers of ABO isoagglutinins were 4-128 (IgG). Immunosuppressive therapy started 14 days before kidney transplantation with rituximab, followed by a triple therapy (prednisone + tacrolimus + mycophenolate mofetil) and the first plasma exchange (PE) procedure, in which one plasma volume was substituted with albumin and saline on day 7 before transplantation. For selective extracorporeal immunoadsorption, the removed plasma was mixed with donor blood type filtered red blood cells, centrifuged and the supernatant separated and preserved. In the next PE procedure, the removed plasma was replaced with immunoadsorbed plasma, and so on. Titers of ABO agglutinins, renal allograft function and survival were followed-up. Results. The pre-transplant treatment consisting of 1-5 PE procedures and immunosuppressive therapy resulted in target ABO agglutinins titers below 4. During a 10-24 month follow-up three patients had an early acute rejection, one patient acute rejection and hemolytic anemia, two patients surgical complications and one of them lost his graft. In the post-transplant period, the titers of ABO antibodies remained below 4. All the patients had stable kidney allograft function with mean serum creatinine ± SD of 129 ± 45 µmol/l at the end of the study. Conclusion. Our method for removal of ABO antibodies was effective in a limited series of patients and short-term follow-up. [ABSTRACT FROM AUTHOR]

Background. Multiple myeloma is a plasmaproliferative disease characterized by the uncontrolled proliferation of a pathogenic plasma cell clone engaged in the production of monoclonal immunoglobulin. This condition affects the bone marrow, but it can be manifested in any other organ or tissue. The urinary bladder involvement is extremely rare. Case report. We reported a 70-year-old male with the history of multiple myeloma, receiving chemotherapy containing melphalan and prednisone (MP). Two years after the treatment, there was a renal failure associated with oligoanuria, hematuria and bilateral hydronephrosis. The urine cytology tests revealed the atypical cells, so was suspected obstructive uropathy to be caused by urothelium cancer. However, only upon the cystoscopy and biopsy performed on the urinary bladder mass, plasmacytoid infiltration diagnosis was confirmed. This extremely rare variant was presented throughout the illness period and proved to be resistant to the administered chemotherapy. Conclusion. When renal failure associated with hematuria and bilateral hydronephrosis is presented in a patient with multiple myeloma, this unusual and rare extramedular localization should be also considered. [ABSTRACT FROM AUTHOR]

Introduction. Hemorrhagic fever with renal syndrome (HFRS) is acute infective multisystemic disease followed by febrility, hemorrhages and acute renal insufficiency. Bleeding in the anterior pituitary lobe leading to tissue necrosis occurs in acute stage of severe clinical forms of HFRS, while atrophy of the anterior pituitary lobe with diminution of the gland function occurs after recovery stage. Case report. We presented a patient with the development of chronic renal insufficiency and hypopituitarism as complication that had been diagnosed six years after Hantavirus infection. Magnetic resonance of the pituitary gland revealed atrophy and empty sella turcica. Conclusion. Regarding frequency of this viral infection and its endemic character in some parts of our country partial and/or complete loss of pituitary function should be considered during the late stage of HFRS. [ABSTRACT FROM AUTHOR]

Background/Aim. Idiopathic retroperitoneal fibrosis (IRF) is an uncommon disease characterized by a retroperitoneal fibrotic tissue that often involve the ureters, leading to the obstructive nephropathy and variable impairment of renal function. Findings strongly suggest an autoimmune etiology. Surgery, medical treatment with immunosuppressive drugs, or a combination of both are proposed. The optimal treatment has not been established yet. The aim of this study was to present our experience with combined immunosuppressive therapy of IRF, steroids (S) and mycophenolate mofetil (MMF). Methods. We prospectively followed four patients with IRF from January 2004 to December 2006. Three patients had an active disease with bilateral hydronephrosis. In the two of them acute renal failure was presented, and ureteral catheters were inserted in one in order to manage ureteral obstruction. One patient has came to our unit with a relapse of IRF and incipient chronic renal failure after the prior therapy with ureterolysis and immunosuppressive drugs (azathioprine and tamoxifen). All patients received steroids and MMF. Two patients were treated with intravenous methylprednisolone pulses (250 mg each), for three consecutive days, followed by oral prednisone 0.5 mg/kg/day. The other two patients received oral prednisone at the same dose. Prednisone was gradually tappered to a maintenance dose of 10 mg/kg/day. Simultaneously, all patients received MMF, initially 1 g/day with the increase to 2 g/day. Results. After four weeks of the therapy all symptoms disappeared, as well as a hydronephrosis with a decrease of erythrocyte sedimentation rate and C-reactive protein (CRP) to normal level in all patients. Three patients remain in remission untill the end of the follow up. One patient had a relapse because of stopping taking the therapy after six months. He was treated by oral prednisone 0.5 mg/kg/day, which was gradually decreased. After twelve weeks hydronephrosis disappeared and CRP returns to the normal level. Conclusion. The combination of steroids and mycophenolate mofetil led to the remission of IRF with a strong and quick immunosuppressive effect. It also provided avoiding the long-term use of high steroid dose and surgical procedures. [ABSTRACT FROM AUTHOR]

Background/Aim. The efficacy and biocompatibility of hemodialysis have a singnificant impact on dialysis patient morbidity and mortality rate. The aim of our study was to compare the efficacy and biocompatibility of different hemodialysis modalities in our patients. Methods. A total of 55 patients were included in the study, and on the basis of dialysis modality, they were divided in four groups: group I -- postdilution on-line hemodiafiltration (n = 15), group II -- bicarbonate high-flux polysulphone hemodialysis (n = 15), group III -- bicarbonate low-flux polysulphone hemodialysis (n = 15), and groupe IV -- bicarbonate cuprophane hemodialysis (n = 10). The efficacy was evaluated on the basis of urea reduction rate (URR), urea Kt/V index and serum β2-microglobuline reduction rate, and the biocompatibility was evaluated on the basis of the leukocyte count fall during the first fiftheen minutes of dialysis session, and of the serum C-reactive protein (CRP) level. Results. The highest mean URR was achieved in the group I (70.53 ± 6.49 %), and it was significantly higher in comparison with the average URR in the group IV (54.8 ± 6.35%) (p = 0.001). The average value of urea Kt/V index in the group I (1.48 ± 0.22) was significantly higher in comparison with the average value in the groupe II 1.30 ± 0.22 (p < 0.05), group III (1.05 ± 0.22), and group IV (0.98 + 0.22) (p = 0.001). Serum β2-microglobuline reduction rate was 68.93 ± 8.25% in the group I, and 58.86 ± 7.98% in the groupe II (p = 0.01). During the first 15 minutes of hemodialysis the leukocyte number was decreased by 12.57 ± 9.35% in the group I, 13.61 ± 9.64% in the group II, 18.3 ± 13.24 in the group III and 62.3 ± 15.4 in the group IV, on average. The mean serum level of CRP was 9.4 ± 6.47 mg/l in the group IV, and less than 3.5 mg/l in the group I of the patients (p = 0.001). Conclusion. Postdilution on-line hemodiafiltration in comparison with standard hemodialysis provided the more effective elimination of small and middle uremic toxins molecules and a significantly higher degree of biocompatibility. The patients treated with standard hemodialysis frequently do not achieve the minimal value of urea Kt/V index prescribed by National Kidney Foundation -- Dialysis Outcomes Quality Inatiatives standards. These patients also have significantly higher serum CRP values which suggest the state of chronic microinflammation. [ABSTRACT FROM AUTHOR]

Background/Aim. Hypervolemia is an important risk factor for the development of cardiovascular morbidity and mortality in patients treated with regular hemodialysis. There is still no reliable method for assessing the status of volemia in these patients. The aim of the study was to assess the status of volemia in patients treated with regular hemodialysis by measuring the parameters of the inferior vena cava (IVC) and bioimpedance. Methods. The effect of hemodialysis treatment on ultrasound parameters of the IVC, as well as on the parameters measured by bioimpedance, was examined before and after hemodialysis. The values of the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were measured both before and after hemodialysis. Forty-five patients were involved in this non-interventional cross-section study, including the patients treated with standard bicarbonate dialysis. According to the interdialytic yield, the patients were divided into three groups: I (up to 2,000 mL), II (2,000-3,000 mL), and III (over 3,000 mL). Results. The values of the IVC parameters and the parameters measured with bioimpedance were significantly lower after treatment with hemodialysis (p < 0.005). The third group of patients had a significantly higher total fluid volume in the body compared to the group I, as well as a significantly greater volume of extracellular fluid (p < 0.005). The significantly lower values of NT-proBNP in all groups (p < 0.005) were detected after hemodialysis. After treatment with hemodialysis, a positive correlation was observed between the concentration of NT-proBNP in the serum and the extracellular/intracellular water ratio. However, the correlation between NT-proBNP concentration and total fluid measured by bioimpedance spectroscopy did not reach statistical significance. Conclusion. Measurement of the IVC ultrasound parameters and volemia parameters using bioimpedance significantly contributes to the assessment of the status of volemia. Nevertheless, it cannot be used as a separate parameter, only in combination with all other methods. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is one of the most significant manifestations in systemic lupus erythematosus (SLE), although in some cases there is no direct correlation among clinical, serologic and histologic findings. Therefore, renal biopsy and histopathologic classification by the activity and chronicity assessment of LN are considered necessary before the initiation of the treatment. In this paper 311 renal biopsies in patients with LN were analyzed and classified according to the WHO Classification published in 1974. Renal biopsy specimens were routinely processed for standard analysis by light microscopy (LM), immunofluorescent (IF), and electron microscopy (EM). Biopsy findings were compared with the common clinical symptoms. It is important to recognize that histopathologic lesions in the analyzed tissue might precede the symptoms and clinical manifestations, and therefore are an important factor in the appropriate therapeutic approach. Histopathological assessment of the class of LN represents an important predictor in most patients because the lesions of LN class I and class II most often have no progression and consequently do not require an aggressive treatment. Diffuse proliferative glomerulonephritis (class IV) as a severe form of renal lesion requires the application of high doses of corticosteroids and cytotoxic medicaments. The established quantitive indexes have significant predictive value. Activity index (AI) evaluates the presence of fresh inflammatory and potentially reversible lesions and chronicity index (CI) evaluate the presence of irreversible glomerular lesions such as sclerosis, tubular atrophy, interstitial fibrosis, etc. High AI and low CI, particularly in the class IV of LN, suggest the necessity of an aggressive treatment of the inflammatory process aiming to preserve the renal function. High CI and low AI characterize irreversible sclerosing lesions, where an aggressive treatment is considered unnecessary. Our experience suggests the necessity of introducing the new morphologic elements into the activity and chronicity scoring system which would correlate better the clinical symptoms. This should provide higher reliability of scoring, since it evaluates important elements in clinical-morphologic diagnosis of LN. [ABSTRACT FROM AUTHOR]

Introduction. Situs inversus totalis (SIT) represents a total vertical transposition of the thoracic and abdominal organs which are arranged in a mirror image reversal of the normal positioning 1. We presented a successful pre-dialysis kidney transplantation from a living sibling donor with SIT and the longest donor follow-up period, along with analysis of the reviewed literature. Case report. The pair for pre-dialysis kidney transplantation included a 68-year-old mother and 34-year-old daughter at low immunological risk. Comorbidities evidenced in kidney donors with previously diagnosed SIT, included moderate arterial hypertension and borderline blood glucose level. Explantation of the left donor kidney and its placement into the right iliac fossa of the recipient were performed in the course of the surgical procedure. A month after nephrectomy, second degree renal failure was noticed in the donor. A 20-month follow-up of the donor's kidney and graft in the recipient proved that their functions were excellent. Conclusion. In donors with previously diagnosed SIT the multidisciplinary approach, preoperative evaluation of the patient and detection of possible vascular anomalies are required to provide maximum safety for the donor. [ABSTRACT FROM AUTHOR]

Background/Aim. Tremendous breakthrough in solid organ transplantation was made with the introduction of calcineurin inhibitors (CNI). At the same time, they are potentially nephrotoxic drugs with influence on onset and progression of renal graft failure. The aim of this study was to evaluate the outcome of a conversion from CNI-based immunosuppressive protocol to sirolimus (SRL) in recipients with graft in chronic kidney disease (CKD) grade III and proteinuria below 500 mg/day. Methods. In the period 2003-2011 24 patients (6 famale and 18 male), mean age 41 ± 12.2 years, on triple immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate mofetil (MMF) or azathiopirine (AZA)] and CNI were switched from CNI to SRL and follow-up for 76 ± 13 months. Nine patients (the group I) had early postransplant conversion after 4 ± 3 months and 15 patients (the group II) late conversion after 46 ± 29 months. During the regular outpatient controls we followed graft function through the serum creatinine and glomerular filtration rate (GFR), proteinuria, lipidemia and side effects. Results. Thirty days after conversion, in all the patients GFR, proteinuria and lipidemia were insignificantly increased. In the first two post-conversion months all the patients had at least one urinary or respiratory infection, and 10 patients reactivated cytomegalovirus (CMV) infection or disease, and they were successfully treated with standard therapy. After 21 ± 11 months 15 patients from both groups discontinued SRL therapy due to reconversion to CNI (10 patients) and double immunosuppressive therapy (3 patients), return to hemodialysis (1 patient) and death (1 patient). Nine patients were still on SRL therapy. By the end of the follow-up they significantly improved GFR (from 53.2 ± 12.7 to 69 ± 15 mL/min), while the increase in proteinuria (from 265 ± 239 to 530.6 ± 416.7 mg/day) and lipidemia (cholesterol from 4.71 ± 0.98 to 5.61 ± 1.6 mmol/L and triglycerides from 2.04 ± 1.18 to 2.1 ± 0.72 mmol/L) were not significant. They were stable during the whole follow-up period. Ten patients were reconverted from SRL to CNI due to the abrupt increase of proteinuria (from 298 ± 232 to 1639 ± 1641/mg day in 7 patients), rapid growth of multiple ovarian cysts (2 patients) and operative treatment of persisted hematoma (1 patient). Thirty days after reconversion they were stable with an insignificant decrease in GFR (from 56.10 ± 28.09 to 47 ± 21 mL/min) and significantly improved proteinuria (from 1639 ± 1641 to 529 ± 688 mg/day). By the end of the follow-up these patients showed nonsignificant increase in the serum creatinine (from 172 ± 88 to 202 ± 91 mmol/L), decrease in GFR (from 56.10 ± 28.09 to 47 ± 21 mL/day) and increased proteinuria (from 528.9 ± 688 to 850 ± 1083 mg/min). Conclusion. In this small descriptive study, conversion from CNI to SRL was followed by an increased incidence of infections and consecutive 25-50% dose reduction in the second antiproliferative agent (AZA, MMF), with a possible influence on the development of glomerulopathy in some patients, which was the major reason for discontinuation of SRL therapy in the 7 (29%) patients. Nine (37.5%) of the patients experienced the greatest benefit of CIN to SRL conversion without serious post-conversion complications. [ABSTRACT FROM AUTHOR]

Introduction. Renal artery stenosis (RAS) is narrowing of one or both renal arteries or their branches. Clinically significant stenosis involves narrowing of the lumen, which is approximately 80%. The two most common causes of its occurrence are atherosclerosis and fibromuscular dysplasia. Percutaneous transluminal renal angioplasty (PTRA) with stent implantation is an effective treatment modality that leads to lower blood pressure and improvement of kidney function. Case report. We presented 4 patients with significant stenosis of one or both renal arteries followed by the development of arterial hypertension and renal insufficiency. The causes of RAS were atherosclerosis in two patients and fibromuscular dysplasia in one patient. One of the patients had renal artery stenosis of transplanted kidney that developed 9 month after transplantation. In all the patients, in addition to clinical signs, doppler screening suspected the existence of significant renal artery stenosis. The definitive diagnosis was made by applying computed tomographic angiography (CTA) of renal arteries in 3 of the patients and in 1 patient by percutaneus selective angiography. All the patients were treated by application of PTRA with stent implantation followed by improvement/normalization of blood pressure and kidney function. Conclusion. Application of PTRA with stent implantation is an effective treatment of significant stenosis of one or both renal arteries followed by renal insufficiency. [ABSTRACT FROM AUTHOR]

Background/Aim. Any forms of mercury have toxic action on the majority of organs, especially kidneys. The major source of professional exposure to mercury are departments for the production of chlorine which use mercury as catode. The aim of the study was to prove that chronic exposure to elementary mercury low concentrations could cause asymptomatic damages of the kidneys. Methods. A total of 40 workers from the factory „HIP Petrohemija" Pančevo, of the mean age 45±8 years, who were exposed to the effects of mercury for more than 20 years within the production procedure, and 20 workers from the factory „Panonijaplast" Pančevo, of the mean age 44±7 years, who were not exposed to mercury nor to other nephrotoxic agents, were submitted to laboratory analysis, renal function testing, and determination of mercury concentration in urine. Mercury concentration was also measured in the air of working premises of the factory. Results. The performed measurements confirmed that the concentrations of mercury at any tested working place in the Department of Electrolysis were not more than the maximally permitted concentration for an 8-hour exposition. In the exposed group (40 examinees) 75% of the examinees had mercury in urine in the concentration < 0.1 µmol/l, while in 25% of them it was 0.1-0.75 µmol/l. In the control group (20 examinees) all of the examinees showed to have < 0.1 mol/l mercury in urine. There was determined a positive corelation between the concentration of mercury in urine and the value of β2-microglobulin (p < 0.05), as well as between the corrcentration of mercury in urine and γGT activity (p < 0.05), and between the concentration of mercury in urine and the value of retinol-binding protein (p < 0.01). Conclusion. In 25% of the examinees excretion of mercury was significantly higher than in the control group. The frequency of asymptomatic renal tubular lesions and dysfunction of moderate extent were found to be higher in the exposed group than in the control one. [ABSTRACT FROM AUTHOR]

Background/Aim. Cyclosporine (CyA) therapeutic drug monitoring (TDM) through the measurement of drug concentration in blood two hours after the administration (C2), and/or according to the calculated value of the area under the concentration -- time curve during the first four hours following administration (AUC0-4) shows favourable correlation with clinical manifestations in patients with kidney transplantation (Tx). The aim of this study was to analyze clinical efficiency and usability of TDM CyA through C2 and AUC0-4 in the group of our kidney transplanted patients during the first 24 months following Tx. Methods. The study included 50 patients who had undergone kidney Tx using living donors at the Clinic of Nephrology Military Medical Academy, from 1996 to 2003. The first group (group C2) consisted of 25 patients in whom CyA dose was adjusted according to the target C2 and AUC0-4 (calculated by the regression formula based on C1, C2 and C3), while the second group (group C0) consisted of 25 "historical" patients in whom the dose of this drug was adjusted according to C0. Results. On the 6th day the average daily dose of CyA in the group C2 was 10.1±0.8 mg/kg, while in the group C0 it was 7.6±1.6 (p < 0.05). One month following the Tx, daily drug doses were quite similar in the two observed groups (6.2 mg/kg in C0 and 6.6 mg/kg in group C2, p = NS). In the group C2, target C2/AUC 0-4 (C2 1 700 ng/ml, AUC0-4 4 400 ng·h/ml) on the sixth day was achieved in 36.3%, and on day 14 in 76% of the patients. The target AUC 0-4, in relation with C2, in each observed time interval was reached in the higher number of patients. Maximum CyA concentrations in the group C2 were registered 2 hours following the administration (C2), when compared with the concentrations registered after the first and the third hour (C1 and C3). In relation with C1 and C3, C2 concentration correlated most favorably with AUC 0-4, both on the 6th (r = 0.85) and on the 9th day (r = 0.87). During the first three months following the Tx, in the group C0, 10 episodes (40%) of acute cell rejection (AR) were registered, while in the group C2, two episodes (8%, p = 0.07) were registered; in the observed period covering the first two years, a total of 13 (52%) AR episodes in the group C0 and 5 AR episodes (20%) in the group C2 (p = 0.03) were registered. All of five episodes of steroid resistant AR were registered in the group C0. In the group C2, all five patients with AR had lower C2 during AR: the average C2 at the moment of AR was 933.8 ng/ml, and in the patients without rejections was 1 364.2 ng/ml (p = 0.008). In the same group, the average C0 at the moment of AR was 263.2 ng/ml, and 240.0 ng/ml (p = 0,486) in the patients without AR. In the C0 group, average C0 concentration at the moment of AR was 227.1 ng/ml, while in the patients without AR it was 227.7 ng/ml (p = 0.95). Totally 68% of the patients showed signs of acute CyA nephrotoxicity during the first year in the group C2, and 52% in the group C0 (p = 0.38). In seven patients (28%) of the group C2 and six patients of the group C0 (24%, p = 0.96) in the first two years following Tx, administration of CyA was interrupted due to nephrotoxicity. Överall graft function was good in both groups during the period of two years. One graft was lost in the group C0 due to chronic allo-graft nephropathy. The patients in the group C2 had better early and the same late graft function. Five patients in the group C2 who did not reach the target C2/AUC during the first 30 days, did not have more AR or worse graft function, comparing with the patients who reached the target concentrations. Conclusion.… [ABSTRACT FROM AUTHOR]