Mycophenolate mofetil combined with steroids: New experiences in the treatment of idiopathic retroperitoneal fibrosis

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 Creactive 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.

Proteinsko-energetski gubitak kod bolesnika na hroničnoj hemodijalizi - etiologija i dijagnostički kriterijumi

The available evidence suggests that nutritional status in the HD patients is an extremely important predictive and causative factor for the good clinical outcome. Nutritional deficits and PEW are frequent problems in the dialysis population and implies an increased risk of negative health outcomes such as mortality risk and quality of life deterioration. There is no single specific measurement that provides complete assessment of the nutritional status in the HD patients, and the results should be analysed in the clinical context of each individual patients. As malnutrition is potentially reversible with appropriate nutritional support, early identification of patients at high nutritional risk may facilitate effective treatment and improve prognosis in the HD patients.

Serumski C-reaktivni protein i nutritivni parametri kod bolesnika na hemodijalizi

Background/Aim. Inflammation is the most important factor in the genesis of vascular complication in the endstage renal disease. The serum C-reactive protein (CRP) level is a sensitive marker of systemic inflammation as well as a predisposing factor for cardiovascular and all cause mortality in patients on hemodialysis. Albumin is the negative acute phase protein and its synthesis declines during the inflammation. The patients undergoing hemodialysis have a high prevalence of protein-energy malnutrition, due to reduced protein synthesis and increased degradation. The low serum albumin levels in these patients originate from the complex setting of conditions with systemic inflammatory response as a major cause, malnutrition and overhydratation. The aim of this study was to determine the prevalence of elevated CRP levels in the dialysis patients and to analyse its correlation with serum albumin levels and other parameters of nutritional status. Methods. The study included 49 patients on maintenance hemodialysis at the Department of Hemodialysis, Clinic of Nephrology, Military Medical Academy, Belgrade, Serbia. In order to analyse the parameters, the blood samples were taken during the arteriovenous fistula (AVF) puncture and before the second weekly dialyse. The following parameters were determined: serum levels of urea and creatinine before and after the dialysis procedure, CRP, hemoglobin, fasting glycemia, total cholesterol, triglycerides, albumins, iron, glycosylated hemoglobin (HbA1c), fasting insulinemia and C-peptide only before the dialysis. Results. Out of 49 patients on maintenance hemodialysis, 37 (75.5%) were males and 12 (24.5%) females with the average age of 56.04 ± 13.93 years. The average duration of the dialysis treatment was 7.37 ± 5 years. The high serum CRP levels (more than 3 mg/L) was found in 65.3% of patients. Singificantly more diabetic patients were observed in the group with the higher CRP levels (n = 12) compared to the group with the normal CRP levels (n = 3) (p ≤ 0.05). A significant positive correlation was found between the CRP value and urea values after the dialysis procedure. We found negative correlation between the CRP values and serum albumin, HbA1c, total cholesterol and triglyceride levels, with no statistical significance. Conclusion. Our study observed a high rate of inflammation in the dialysis patients presenting as high frequency of the elevated CRP levels in the examined group. Negative correlation between CRP levels and serum albumin as well as with some other parameters of nutritional status, suggests that chronic inflammation may be the missing link that actually connect protein energy malnutrition with high morbiditiy and mortality rate in these patients.Uvod/Cilj. Inflamacija je jedan od glavnih faktora odgovornih za nastanak vaskularnih komplikacija kod bolesnika sa terminalnom bubrežnom insuficijencijom. C reaktivni protein (CRP) se smatra senzitivnim markerom sistemske inflamacije, kao i faktorom koji doprinosi povećanom riziku od opšteg i kardiovaskularnog mortaliteta. Albumin je negativni protein akutne faze zapaljenja i njegova sinteza opada sa napredovanjem sistemske inflamacije. Za bolesnike na hemodijalizi poznato je da pate od visokog stepena proteinske malnutricije usled smanjene sinteze proteina i njihove pojačane razgradnje. Nizak nivo serumskog albumina kod tih bolesnika je posledica kompleksnog stanja koje podrazumeva sistemsku inflamaciju, malnutriciju i prekomernu hidrataciju. Cilj naše studije bio je da se ispita učestalost povišenog serumskog CRP-a u našoj populaciji dijaliznih bolesnika i da se utvrdi stepen njegove korelacije sa serumskim albuminom i drugim parametrima nutritivnog statusa. Metode. Ispitivanjem je obuhvaćeno 49 bolesnika na hroničnom programu hemodijalize u Centru za hemodijalizu Klinike za nefrologiju Vojnomedicinske akademije u Beogradu. Uzorci krvi za analizu uzimani su tokom punkcije arteriovenske fistule, a pre druge nedeljne hemodijalize. Određivanu su sledeći parametri: serumski nivo uree i kreatinina pre i posle procedure, CRP, hemoglobin, glikemija, ukupni holesterol, trigliceridi, glikozilirani hemoglobin (HbA1c), insulinemija i C-peptid pre hemodijalize. Rezultati. Od ukupno 49 dijaliznih bolesnika, bilo je 37 (75,5%) muškaraca i 12 (24,5%) žena, prosečne starosti 56,04 ± 13,93 godine. Dužina lečenja hemodijalizom je prosečno iznosila 7,37 ± 5 godina. Povišene vrednosti serumskog CRP-a (više od 3 mg/L) imalo je 65,3% bolesnika. U grupi bolesnika sa povišenim nivoom CRP-a u serumu, bilo je značajno više dijabetičara (n=12) u odnosu na grupu sa normalnim nivoom CRP-a u serumu (n = 3) (p ≤ 0,05). Uočili smo postojanje značajne pozitivne korelacije između serumskog CRP-a i serumske uree nakon dijaliznog procesa. U ispitivanoj grupi postojala je negativna korelacija između serumskog CRPa i serumskog albumina, HbA1c, ukupnog holesterola i triglicerida. Ta korelacija nije bila statistički značajna. Zaključak. Naša studija je potvrdila visok stepen sistemske inflamacije kod dijaliznih bolesnika izražene kroz visoku učestalost povišenih vrednosti serumskog CRP-a. Negativna korelacija između nivoa serumskog CRP-a i serumskog albumina kao i drugih nutritivnih parametara, sugeriše da hronična inflamacija može biti ključna karika koja povezuje proteinsku malnutriciju sa visokim morbiditetom i mortalitetom ovih bolesnika

Zinc Deficiency, Plasma Fatty Acid Profile and Desaturase Activities in Hemodialysis Patients: Is Supplementation Necessary?

Background: Desaturation and elongation are critical processes in endogenous metabolic fatty acid pathways. Zinc (Zn) is a cofactor for desaturases and elongases enzymes. There is limited evidence regarding the relationships between biomarkers of Zn status, nutritional intake, plasma phospholipid fatty acid profile and clinical outcomes among patients undergoing hemodialysis (HD). Objective: To examine the relationships between dietary and serum levels of Zn and Cu/Zn ratio and to explore associations of these micronutrients with PUFA profile and estimated desaturase and elongase enzyme activities in serum phospholipids among HD patients. Methods: This study included 40 adult patients undergoing hemodialysis treatment. Repeated 24-h recalls were applied for dietary intake assessment. Serum concentration of Zn and Cu were determined using inductively coupled plasma mass spectrometry and fatty acid composition by gas-liquid chromatography. Desaturase and elongase activities were calculated from product-precursor fatty acid ratios. Results: Inadequate dietary Zn intake was found in 55% of HD patients. They all had serum Zn concentration below the reference value of 60 μg/dL (mean 38.8 ± 7.72 μg/dL). Adequate zinc intake was accompanied with significantly higher intake of energy, total fats, SFA, MUFA and proteins. There was no correlation between Zn serum status and Zn intake estimates. Serum Cu/Zn ratio was high, (2.76 ± 0.68), directly and significantly associated with HD period, CRP, BMI, VFA, and inversely with Kt/V, albumin, iron, and iPTH. The n-6/n-3 ratio in plasma phospholipids was elevated (12.25 ± 3.45) and patients with inadequate Zn intake had lower n-3 PUFA intake and status compared to those with adequate intake. Serum Zn concentrations were inversely correlated with linoleic/dihomo-γ-linolenic acid ratio (LA/DGLA) (p = 0.037), related to D6-desaturase activity (p = 0.033) and directly with DGLA relative abundances (p = 0.024). Cu status was inversely associated with EPA level (p = 0.03) and estimates of elongase activity (p = 0.001). Furthermore, positive relationship was found between the Cu/Zn ratio and determined elongase value (p = 0.01). Conclusion: Findings of this study underpin the high prevalence of Zn deficiency and inadequate n-3 PUFA intake and status among subjects undergoing HD. The results obtained indicate that the assessment of Zn status should be a standard parameter of nutritional status screening in HD patients while emphasizing the importance of Cu/Zn determination. Although further research is warranted, Zn and-n-3 PUFA supplementation in HD patients might be beneficial for the prevention and attenuation of adverse health outcomes

High Interleukin 27 Production is Associated with Early Clinical Stage and Localized Disease in Patients with Melanoma

Background: The immune response in patients with melanoma is an important focus of research due to the tumor's resistance and immunotherapy possibilities. IL-27 is one of the cytokines with antitumor properties. The role of IL-27 in the pathogenesis of melanoma is still unclear. The aim of this study was to examine the association between serum IL-27 levels and the clinical parameters of melanoma patients. Methods: The IL-27 concentration was determined by commercial ELISA in serum samples from melanoma patients (n=72) and healthy control subjects (n=44). Patients were classified according to AJCC clinical stage, TNM stage, the length of progression-free interval (PFI) and the extent of the disease (localized or widespread). Results: Average IL-27 values were increased in patients with early stages of melanoma compared to patients with terminal stages and control values. The highest IL-27 concentration was found in stage Ila. Patients in stages III and IV had significantly lower values of IL-27 compared to control. Patients with localized melanoma and shorter PFI had insignificantly increased IL-27 levels compared to patients with widespread disease and longer PFI. Patients with metastatic disease and stage TNM4 had significantly lower average IL-27 values compared to control. Patients with high production of IL-27 (>1000 pg/mL) were most numerous in Ila AJCC stage, with initial tumor size TNM2 and in the group of patients with localized disease. Conclusions: High levels of IL-27 in patients with melanoma are associated with the initial stages and localized disease

Myeloma multiplex with pulmonary dissemination

Introduction. Multiple myeloma is a hemathological malignancy characterized by the clonal proliferation of plasma cells in the bone the marrow. Extramedullary dissemination of multiple myeloma is uncommon. In several cases only, the multiple myeloma malignant plasma cells had diseminated to the lung parenchyma. Case report. We presented a case of multiple myeloma with lung plasmacytoma, in a 79-year-old patient, hospitalized for febrility and infiltrative mass in the right lung. Two months before the patient was admitted, because of developing terminal renal failure, hemodialysis treatment had started three times a week. Since then, the patient was oliguric, but because of febrility and hemoptysis that appeared, at first he was treated with dual antibiotic therapy which resulted in temporary improvement of his general condition, but pleural effusion remained. After thoracocentesis, followed by myelogram, the multiple myeloma diagnosis was established. Conclusion. In patients of middle and older age, with general weakness, exhaustion, loss of weight, renal failure which progresses to the end stage rapidly, if symptoms of respiratory tract occur, consider this uncommon disease - extramedullary dissemination of multiple myeloma

Percutaneous transluminal renal angioplasty application effect on renal function in patients with renal artery stenosis: A case report on 4 patients

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

Molekul oštećenja bubrega-1 (KIM-1) i akvaporin-1 (AQP-1) u urinu kod bolesnika sa karcinomom svetlih ćelija bubrega - potencijalni neiznvazivni biomarkeri

Background/Aim. Kidney injury molecule-1 (KIM-1) and aquaporin-1 (AQP-1) are potential early urinary biomarkers of clear renal cell carcinoma (cRCC). The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy) in patients with cRCC. Methods. Urinary concentrations of urinary KIM-1 (uKIM-1) and urinary AQP-1 (uAQP-1) were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. Results. The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ± 1.120 ng/mg urinary creatinine (Ucr)] were significantly greater compared with controls (healthy volunteers) (0.210 ± 0.082 ng/mgUcr) (p = 0.0227). Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 ± 0.099 ng/mgUcr vs 0.210 ± 0.082 ng/mgUcr, respectively). The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 ± 0.092 ng/mgUcr) compared with the control group (0.202 ± 0.078 ng/mgUcr) (p = 0.0014). Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. Conclusion. uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy.Uvod/Cilj. Molekul oštećenja bubrega-1 (KIM-1) i akvaporin-1 (AQP-1) su potencijalni rani biomarkeri karcinoma svetlih ćelija (cRCC). Cilj ove studije bio je da se utvrdi povezanost između koncentracija KIM-1 i AQP-1 u urinu i veličine, gradusa, stadijuma i vrste operacije (radikalna ili parcijalna nefrektomija) kod bolesnika sa cRCC. Metode. Urinarne koncentracije KIM-1 i AQP-1 određene su primenom komercijalnih ELISA kitova. Analizom je bilo obuhvaćeno 40 bolesnika koji su bili podvrgnuti parcijalnoj ili radikalnoj nefrektomiji zbog tumora bubrega i 40 zdravih odraslih ispitanika. Grupe su bile komparabilne po polu i godinama života. Rezultati. Srednja preoperativna koncentracija urinarnog KIM-1 (uKIM-1) u cRCC grupi [0,724 ± 1,120 ng/mg kreatinia u urinu (Ucr)] bila je statistički značajno viša u poređenju sa koncentracijom u kontrolnoj grupi (0,210 ± 0,082 ng/mgUcr ) (p = 0,0227). Postoperativno, koncentracija uKIM-1 značajno je padala i približavala se vrednosti u kontrolnoj grupi (0,177 ± 0,099 ng/mgUcr nasuprot 0,210 ± 0,082 ng/mgUcr). Veličina, gradus i stadijum tumora bili su u pozitivnoj korelaciji sa preoperativnim koncentracijama uKIM-1. Nasuprot ovim rezultatima, koncentracija urinarnog AQP-1 (uAQP-1) u cRCC grupi bila je značajno niža (0,111 ± 0,092 ng/mgUcr) u poređenju sa kontrolnom grupom zdravih osoba (0,202 ± 0,078 ng/mgUcr) (p = 0,0014). Postoperativno, koncentracija uAQP-1 progresivno se povećavala, približno do vrednosti u kontrolnoj grupi. Nismo našli značajnu korelaciju između preoperativnih koncentracija uAQP-1 i veličine, gradusa i stadijuma tumora. Zaključak. uKIM-1 bi mogao biti dodatni pouzdani dijagnostički marker za cRRC na osnovu njegove značajno više preoperativne koncentracije i sniženja vrednosti nakon nefrektomije

Our first experiences in applying an original method for removal of ABO-isoagglutinins in ABO-incompatible kidney recipients

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

Association between oxidative stress and melanoma progression

Background: Overproduction of free radicals accompanied with their insufficient removal/neutralization by antioxidative defense system impairs redox hemostasis in living organisms. Oxidative stress has been shown to be involved in all the stages of carcinogenesis and malignant melanocyte transformation. The aim of this study was to examine association between oxidative stress development and different stages of melanoma. Methods: The measured oxidative stress parameters included: superoxide anion radical, total and manganese superoxide dismutase, catalase and malondialdehyde. Oxidative stress parameters were measured spectrophotometrically in serum samples from melanoma patients (n=72) and healthy control subjects (n=30). Patients were classified according to AJCC clinical stage. Results: Average superoxide anion and malondialdehyde concentrations were significantly higher in melanoma patients than in control group, with the highest value of superoxide anion in stage III, while malondialdehyde highest value was in stage IV. The activity of total and manganese superoxide dismutase was insignificantly higher in melanoma patients than in control group, while catalase activity was significantly higher. The highest activity of total superoxide dismutase was in stage III, while the highest activity of manganese superoxide dismutase was in stage IV. Catalase activity was increasing with the disease progression achieving the maximum in stage III. Conclusions: Results of our study suggest that melanoma is oxidative stress associated disease, as well as deteriorated cell functioning at mitochondrial level