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Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) family and may play an important role in the regulation of malignant cells in bladder cancer. The aim of the present study was to investigate BMP expression in non-muscle invasive bladder cancer. Tumor tissue samples from 71 patients treated with transurethral resection and 10 samples of normal bladder tissue were stained using immunohistochemistry for BMP-2, -4, -6 and -7. The levels of BMP were correlated with the number and size of tumors in the bladder, the pathohistological findings as well as with tumor recurrence and progression. The results of the present study demonstrated that BMP-2 and -7 are highly expressed in normal bladder tissue, but significantly downregulated in cancer samples. This reduction correlates with a faster rate of tumor recurrence as well as with an increase in the number of recurrent tumors. There was no evident interrelation between BMP-2 and -7 reduction and changes in tumor grade and stage. In conclusion, BMP-2 and -7 are potential prognostic factors for tumor recurrence and further studies on BMP and bladder cancer are needed to confirm these results., (Copyright: © Hudolin et al.)

Background: Administration of an anticoagulant during therapeutic plasma exchange (TPE) is necessary to avoid circuit clotting and impaired treatment effectiveness. Citrate is the preferred anticoagulant for apheresis worldwide, and unfractionated heparin (UH) is the second most preferred, yet there are only a few published studies regarding the use of UH during TPE. There are even fewer studies regarding the use of low-molecular-weight heparin (LMWH) and TPE performed without anticoagulation., Materials and Methods: We retrospectively analyzed the database of the Department of Nephrology at Zagreb University Hospital Center from 1982 to 2014 to test the safety of various heparin anticoagulation in TPE. We grouped procedures according to anticoagulation type (UH, LMWH, and no anticoagulation) and compared differences in the use of anticoagulants during our study period, patient populations, replacement fluids, and complications., Results: Complications were recorded during 11.1% of the 9,501 procedures. The incidence of any recorded complication was significantly higher in the LMWH group (21.2%) compared to the group with no anticoagulation (16.3%) and the UH group (9.5%) (P < 0.001). Similarly, the blood clotting in the extracorporeal circuit was most common in the LMWH group (LMWH, 12.0%; no anticoagulation, 6.3%; UH, 2.4%; P < 0.001). Incidents of bleeding complications were very low and occurred during or after 13 TPE sessions (0.1% of all procedures)., Conclusions: Our findings indicate that TPE procedures can be conducted safely with UH and, when necessary, without anticoagulation. The use of LMWH was associated with more complications when compared with use of UH and to TPE done without anticoagulation. Further studies are necessary to study its use during TPE procedures., (© 2017 Wiley Periodicals, Inc.)

We hypothesized that patients with sepsis and AKI, especially patients without preserved renal function, and treated with continuous veno-venous hemodiafiltration (CVVHDF), have lower risk for mortality than patients treated with continuous veno-venous hemofiltration (CVVH). Patients were included if they fulfilled the diagnosis of severe sepsis or septic shock, suffered AKI and received continuous renal replacement therapy (CRRT) in intensive care unit. There were 62 patients treated by CVVH and 75 treated by CVVHDF. Mean survival time was longer in CVVHDF group with oliguric/anuric patients than in CVVH group. CVVH, and not classic risk factors, was associated with higher overall mortality in oliguric/anuric patients. In the linear regression model, hourly urine output was the strongest and positive predictor of longer survival. CVVHDF is according to our results a CRRT modality of choice for the treatment and lower mortality of septic patients with AKI where renal function is no longer preserved. CRRT has been associated with improved renal recovery, but it should be started earlier in AKI evolution with still preserved hourly urine output which is the most sensitive and prognostic marker of survival in septic patients with AKI.

Continuous veno-venous hemofiltration (CVVH) could modulate the inflammatory response by removal of circulating cytokines and therefore improve cardiac function in patients with heart failure (HF). We hypothesized that patients with developed cardiorenal syndrome and treated with CVVH have lower risk for mortality than other patients treated with slow continuous ultrafiltration (SCUF). This was a prospective, longitudinal follow-up study for 24 months duration. In total, 120 patients were recruited from the intensive care units. Only patients with cardiorenal syndrome type 1 and 2 were enrolled. 54 CVVH and 23 SCUF patients survived. Mean survival time was longer in CVVH group with cardiomyopathy than in the SCUF group. When we compared patients with cardiomyopathy and hourly urine output <10 mL/h, mean survival time was significantly longer in patients treated with CVVH. This is the first study to analyze the impact of different CRRT modalities (CVVH vs. SCUF) on survival of patients with HF and who developed cardiorenal syndrome. Better survival in patients treated with CVVH, which is mostly pronounced in patients with cardiomyopathy, is a consequence of a better preserved hourly urine output. Longer survival in patients with cardiomyopathy is most probably related to cytokine removal by CVVH with smaller UF rates and longer duration of each treatment. Slow continuous ultrafiltration remains the method of choice in patients with HF and preserved renal function but in cases of developed cardiorenal syndrome is much inferior to CVVH., (© 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: Therapeutic plasma exchange (TPE) can be performed either on a membrane-based system (mTPE) or on a device that separates blood components by centrifugation (cTPE). The number of studies in this field is limited. This randomized study is the first that offers data on the membrane-based Diapact device (B. Braun Medical, Inc.) for TPE procedures and compares it to the centrifuge-based Spectra Optia (Terumo BCT, Inc.)., Study Design and Methods: Twenty-seven patients were enrolled in this randomized prospective head-to-head study comparing the mTPE and cTPE systems. Procedures on both devices were standardized and the plasma removal efficiency (PRE); total procedure time (including setup and priming time); and removal efficiencies of blood cells, immunoglobulin (Ig)G, and fibrinogen for all procedures were analyzed., Results: While both systems removed similar amounts of plasma, it took the cTPE device a mean of 101.5 ± 24.6 minutes to finalize a procedure that was one-third less than procedures on the mTPE device (157 ± 26.2 min; p < 0.0001), due to a difference in PRE between the Spectra Optia (83.0% ± 4.9%) and the Diapact (53.2% ± 6.6%; p < 0.0001). The difference in removal efficiencies of IgG and blood cells were not significantly different but the Spectra Optia was more efficient in removing the larger fibrinogen protein than the Diapact (72.3% ± 8.5% vs. 62.9% ± 16.1%, respectively; p < 0.02)., Conclusion: This study shows that, although both systems perform adequate and safe TPE procedures, those on the Spectra Optia in comparison to the Diapact are more efficient in terms of plasma removal and significantly shorter., (© 2016 AABB.)

Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique designed for the removal of substances with large molecular weight from the plasma. However, it is not commonly performed in children and the elderly because of concern of potential complications. The Department of Nephrology at Zagreb University Hospital Centre's database (8335 procedures, 981 patients) was retrospectively analyzed from 1982 to 2011 to record indications, applications, and safety of TPE use in children (≤18 years), adults (>18 and <65 years), and elderly patients (≥65 years). Indications, blood access, replacement fluid, and anticoagulation during TPE differed among age groups. Significantly more complications were recorded in the youngest and eldest patients compared with the adults (12.2% and 12.7% vs. 9.9%, respectively), while the severity of complications did not differ significantly among the age groups. Our results indicate that TPE may be performed relatively safely in all age groups when the patients' differences are acknowledged prior to prescribing the procedure., (Copyright © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Chronic kidney disease (CKD) is a systemic disease with numerous complications associated with increased morbidity and mortality. Chronic kidney disease-metabolic bone disease (CKD-MBD) starts at early stages of CKD with phosphorus accumulation and consequent initiation of numerous events that result with the development of secondary hyperparathyroidism with changes on bones and extraskeletal tissues. The most important and clinically most relevant consequences of CKD-MBD are vascular calcifications which contribute to cardiovascular mortality. Patients with the increased risk for the development of CKD-MBD should be recognized and treated. Prevention is the most important therapeutic option. The first step should be nutritional counseling with vitamin supplementation if necessary and correction of mineral status. Progression of CKD requires more intensive medicamentous treatment with the additional correction of metabolic acidosis and anemia. Renal replacement therapy should be timely initiated, with the adequate dose of dislaysis. Ideally, preemptive renal transplantion should be offered in individuals without contraindication for immunosuppressive therapy.

Background/aims: Delayed graft function (DGF) is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2) is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF) and DGF., Methods: 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients) and DGF group (15 patients). BMP-2 expression in intima media (BMP2m) and endothelium (BMP2e) of epigastric artery was assessed by immunohistochemistry., Results: Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001) (P<0.001 for no expression and P = 0.015 for 1st grade expression). Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477]) and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492])., Conclusions: Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Despite prolonged survival and better quality of life as compared to dialysis, kidney transplantation frequently presents with a complex set of medical issues that require intensive management to protect graft function. Metabolic acidosis has an impact on several metabolic complications such as mineral and muscle metabolism, nutritional status and anemia. It may also have an effect on graft function, possibly through the stimulation of adaptive mechanisms aimed at maintaining acid-base homeostasis. We investigated current practice in the evaluation of metabolic acidosis at one of the largest transplant centers in the Eurotransplant region. Adult renal transplant recipients having received allograft from January 2011 to August 2012 were included in the investigation. We recorded the frequency of measuring the parameters of venous blood gas analysis, as well as creatinine and urea levels, creatinine clearance, proteinuria, calcium, phosphate and potassium blood levels, body mass index and the time spent on dialysis prior to kidney transplantation. Out of 203 patients who had received renal allograft at our institution during the observed period, 191 (124 males and 67 females, age range from 18 to 77 years) were enrolled in the study. Of these, only 92 (48.167%) patients had parameters of venous blood gas analysis measured at some time after kidney transplantation. Acid-base status was determined more often in males (77 males vs. 22 females, p = 0.001). Patients with pH/blood gas analysis performed were found to have significantly higher creatinine and urea levels and significantly lower creatinine clearance (p < 0.001 both). Serum calcium levels were also significantly lower in this group of patients (p < 0.001). Metabolic acidosis is a very important clinical issue that needs to be monitored in every transplant recipient. Its effects on graft function, nutritional status, anemia and bone mass are complex but can be successfully managed. Our study showed metabolic acidosis to be linked with significantly higher creatinine and urea levels, decreased creatinine clearance and lower calcium levels. Nevertheless, metabolic acidosis still stays a highly underestimated problem among nephrologists dealing with transplant recipients. We suggest regular determination of the acid-base status in renal transplant recipients.

Acute kidney injury is a clinical syndrome associated with increased patient morbidity and mortality, as well as serious short-term and long-term consequences, especially in the perioperative period. Yet, patients having suffering from temporary acute kidney injury and achieving full recovery of kidney function usually complain of poor quality of life associated with loss of energy and limited physical activity. Therefore, there is a necessity for a novel biomarker of acute kidney injury with better features than currently used serum creatinine and urine output. So far, several investigations have demonstrated that the fibroblast growth factor 23 could be that desperately searched novel biomarker of acute kidney injury. It cannot only detect kidney dysfunction at the time but also before the injury process begins. Moreover, serum levels of the fibroblast growth factor 23 can predict adverse progression of the kidney injury. However, the role of the fibroblast growth factor 23 in the acute but also in chronic kidney dysfunction is still a riddle that requires additional research to clarify it.

Unlabelled: Cardiovascular diseases are the major cause of morbidity and mortality in renal transplant recipients. We report our experience in the treatment of patients with renal allograft who required cardiovascular surgery., Methods: Indications for cardiovascular surgery, postoperative complications, and outcome were recorded in a cohort of renal transplant recipients., Results: Thirteen patients, five female and eight male, aged from 46 to 75 years underwent cardiac surgery after renal transplantation at University Hospital Centre Zagreb. Isolated coronary artery bypass grafting (CABG) was performed in five patients, valve replacement in six patients, reconstruction of ascending aorta, and aortic arch in one patient as well as the extraction of tumor formation from the heart. Three patients had simultaneous CABG and valve replacement. Four patients (31%) required acute hemodialysis after the surgery and two of them continued with dialysis after discharge. Postoperative course was complicated with infections of the lower respiratory tract in two patients, pericardial tamponade, unstable sternum with bleeding from the wound, increased drainage from the chest demanding additional hemostasis, and in-stent restenosis in the previously placed stents, in one patient each. Fatal outcome occurred in two patients who underwent simultaneous valvular replacement and CABG within one month from the surgery., Conclusion: In patients with functional renal allograft cardiovascular, surgery procedures are safe, but associated with increased incidence of perioperative complications, with majority of patients maintaining their graft function.

Purpose: Bone morphogenetic proteins (BMPs) are pleiotropic growth factors. This paper investigates the connection between the expression pattern of BMPs in kidney allograft tissue versus the cause of allograft dysfunction., Methods: The expression pattern of BMP2, BMP4, BMP6 and BMP7 in 50 kidney allografts obtained by transplant nephrectomy is investigated. Immunohistochemical staining is semiquantitatively evaluated for intensity to identify the expression pattern of BMPs in normal and allograft kidney tissues., Results: The expression of BMP4 is unique between different tubular cell types in grafts without signs of fibrosis. This effect is not found in specimens with high grades of interstitial fibrosis and tubular atrophy (IFTA). In samples with IFTA grades II and III, the BMP7 expression is reduced in a significant fraction of specimens relative to those without signs of IFTA. The expression pattern of BMP6 indicates that its activation may be triggered by the act of transplantation and subsequent reperfusion injury. The expression of BMP2 is strong in all types of tubular epithelial cells and does not differ between the compared allografts and control kidney specimens., Conclusion: The intensity and expression pattern of BMP4, BMP6 and BMP7 in transplanted kidney tissue are found to be dependent upon the length of the transplanted period, the clinical indication for transplant nephrectomy and signs of IFTA in kidney tissue.

Bone morphogenetic protein-7 (BMP-7) is expressed in all parts of the normal kidney parenchyma, being highest in the epithelium of proximal tubules. It protects kidney against acute and chronic injury, inflammation and fibrosis. Diabetic nephropathy is the leading cause of chronic kidney disease, and is characterized by decreased expression of BMP-7. The aim of our study was to analyze whether the expression of BMP-7 is significantly changed in advanced stages of human diabetic nephropathy. Immunohistochemical analysis of the expression of BMP-7 was performed on archival material of 30 patients that underwent renal biopsy and had confirmed diagnosis of diabetic nephropathy. Results showed that BMP-7 was differently expressed in the cytoplasm of epithelial cells of proximal tubules and podocytes among all stages of diabetic nephropathy. At early stages of diabetic nephropathy, BMP-7 was strongly positive in proximal tubules and podocytes, while low expression was recorded in the majority of samples at advanced stages. In conclusion, increased expression of BMP-7 at initial stages of diabetic nephropathy with subsequent decrease at advanced stage highlights the role of BMP-7 in the protection of kidney structure and function. Further investigations should be focused on disturbances of BMP-7 receptors and signaling pathways in patients with diabetic nephropathy.

Sarcomatoid carcinomas (SC) are rare malignancies with concomitant occurrence of both carcinomatous and sarcomatous components. Although it may occur throughout the body, lungs are only very rarely involved. We present the first documented case of pulmonary SC (PSC) in a renal transplant recipient, and discuss clinical presentation, diagnostic procedures, treatment, and outcome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Diabetic nephropathy is a common complication in patients with diabetes mellitus and one of the major reasons for renal replacement therapy in Croatia, Europe and the United States. It is characterized by proteinuria, decline in glomerular filtration, hypertension, and high risk of cardiovascular morbidity and mortality. Deterioration of renal function in diabetic nephropathy develops through five clinical stages characterized by the respective histologic description. Genetic susceptibility, hyperglycemia, high blood pressure and duration of diabetes mellitus definitely play a role in the pathogenetic sequence. Early diagnosis, appropriate patient follow up and treatment are essential to improve the outcomes. Interdisciplinary approach and close collaboration of nephrologists and diabetologists are essential for timely detection of disease progression. Tight glycemic control under the supervision of diabetologists, screening of patients, and once a year report of albuminuria and glomerular filtration allow for detection of renal damage in the early stages and timely referral to a nephrologist. The points of interest given in this overview are description of clinical staging in relation to pathologic classification, repetition of basic causal features, and brief analysis of treatment.

There is a high incidence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) and malnutrition is a powerful predictor of cardiovascular morbidity and mortality in this population of patients. A multitude of factors related to CKD and renal replacement therapy can affect the nutritional status of CKD patients and lead to the development of malnutrition. In patients with CKD, protein energy wasting (PEW) is a condition that is distinct from undernutrition and is associated with inflammation, increased resting energy expenditure, low serum levels of albumin and prealbumin, sarcopenia, weight loss and poor clinical outcomes. Nutritional and metabolic derangements are implicated for the development of PEW in CKD and leading to the development of chronic catabolic state with muscle and fat loss. Prevention is the best way in treating PEW. Appropriate management of CKD patients at risk for PEW requires a comprehensive combination of strategies to diminish protein and energy depletion, and to institute therapies that will avoid further losses. The mainstay of nutritional treatment in MHD patients is nutritional counselling and provision of an adequate amount of protein and energy, using oral supplementation as needed. Intradialytic parenteral nutrition and total enteral nutrition should be attempted in CKD patients who cannot use the gastrointestinal tract efficiently. Other strategies such as anemia correction, treatment of secondary hyperparathyroidism and acidosis, delivering adequate dialysis dose can be considered as complementary therapies in CKD patients. Multidisciplinary work of nephrologists, gastroenterologist and dietician is needed to achieve best therapeutic goals in treating CKD patients with PEW.

Background/aims: Residual renal function (RRF) has been shown to influence survival of peritoneal dialysis (PD) patients. This study examined the relations between RRF and left ventricular hypertrophy (LVH) before switching on dialysis treatment and observed during 18 months on PD treatment., Methods: A prospective longitudinal study was performed in 50 non-anuric (defined as >200 mL urine output in a 24-hour period) PD patients. Echocardiography, RRF and other known risk factors for the increase of LV mass index (LVMi) were determined at study baseline and the end of follow-up., Results: There was 78% patients with LVH in end-stage renal disease (ESRD) baseline and 60% at the end of follow-up. RRF at the start of the study showed no significant difference between patients with normal and increased LVMi, as well as in daily collection of urine. After 18 months, patients with decreased LVMi had better RRF, lower CRP and better Kt/V compared to patients with increased LVMi (p < 0.001). Patients with better preserved RRF not only had significantly higher total Kt/V, but were less anemic and hypoproteinemic and lesser presence of LVH., Conclusions: PD in non-anuric ESRD patients the first 18 months has a positive effect on the preservation of RRF and partial regression of left ventricular remodeling., (© 2015 S. Karger AG, Basel.)

Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers., (© The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), associated with high morbidity and mortality. Up to 60% of SLE patients develop LN, and despite novel and potent therapeutic regimens, 5 to 22% develop end-stage renal disease within 15 years of diagnosis. While LN primarily affects younger individuals, it is important to choose optimal method of renal replacement therapy for those who develop end-stage renal disease. Numerous studies were carried out trying to solve problems of treatment of patients with LN. Increased risk of infections, disease recurrence in renal allograft, undefined criteria for follow-up of disease activity after transplantation, as well as higher inci- dence of rejection episodes and thrombotic events are well known risks which have postponed and restricted access to transplantation for patients with LN for long-time. However, numerous studies have demonstrated similar long-term survival in patients treated with haemodialysis or peritoneal dialysis, with clear superiority of renal transplantation regarding the prolonged survival and better quality of life for SLE patients. Many questions are still waiting for answers. Close cooperation between nephrologists and immunologists provides the best treatment for SLE patients with end-stage renal disease.

Although glucocorticoid therapy is considered to be the main pathogenic factor, a consistent body of evidence suggests that other immunosuppressants might also play an important role in the development of the post-transplant renal osteopathy (PRO) through their pleiotropic pharmacological effects. Glucocorticoids seem to induce osteoclasts' activity suppressing the osteoblasts while data regarding other immunosuppressive drugs are still controversial. Mycophenolate mofetil and azathioprine appear to be neutral regarding the bone metabolism. However, the study analyzing any independent effect of antimetabolites on bone turnover has not been conducted yet. Calcineurin inhibitors (CNIs) induce trabecular bone loss in rodent, with contradictory results in renal transplant recipients. Suppression of vitamin D receptor is probably the underlying mechanism of renal calcium wasting in renal transplant recipients receiving CNI. In spite of an increased 1,25(OH)2 vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss. More efforts should be invested to determine the role of CNI in PRO. In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Rapamycin markedly decreases bone longitudinal growth as well as callus formation in experimental models, but also lowers the rate of bone resorption markers and glomerular filtration in clinical studies. Everolimus potently inhibits primary mouse and human osteoclast activity as well as the osteoclast differentiation. It also prevents the ovariectomy-induced loss of cancellous bone by 60 %, an effect predominantly associated with a decreased osteoclast-mediated bone resorption, resulting in a partial preservation of the cancellous bone. At present, there is no clinical study analyzing the effect of everolimus on bone turnover in renal transplant recipients or comparing sirolimus versus everolimus impact on bone, so only general conclusions could be drawn. Hence, the use of mTORi might be useful in patients with PRO due to their possible potential to inhibit osteoclast activity which might lead to a decreased rate of bone resorption. In addition, it should be also emphasized that they might inhibit osteoblast activity which may lead to a decreased bone formation and adynamic bone disease. Further studies are urgently needed to solve these important clinical dilemmas.

The use of generic immunosuppressive drugs may decrease the cost of immunosuppressive medication, although total cost sav- ings are still a matter of debate since patients need close monitoring after conversion from original to the generic formulation. A working group of the Croatian Society of Transplantation was established to develop recommendations on the use of generic immunosuppression in renal transplant recipients based on a review of the available data. Immunosuppressive drugs belong to the 'narrow therapeutic index' drugs, with huge pharmacokinetic variations secondary to the impact of food, other drugs, as well as of kidney and liver function. Failure to maintain an appropriate balance of immunosuppression seriously influences graft and patient survival. Published evidence supporting therapeutic equivalence of generic formulations is scarce or completely lacking. Different generic formulations may expose patients to uncontrolled product switching by pharmacists or general practitioners, which is very dangerous for patients, since generic preparations are not required to demonstrate bioequivalence with each other. The Croatian Society for Nephrology, Dialysis and Transplantation is not against the use of generic immunosuppressive drugs, but it requires close supervision of nephrologists and respecting the strict rules of their use. More efforts should be invested in education of primary care physicians as well as of patients to be aware of differences between the original and generic, as well as between different generic formulations.

The usage of temporary and permanent dialysis catheters for hemodialysis vascular access has been on continual increase. The reason for this increase is aging population on hemodialysis with blood vessels inappropriate for arteriovenous fistula creation. Complications may occur during catheter insertion as well as in the already inserted catheters, e.g., thrombosis and infections. The severity of complications is determined by experience of the operator as well as the quality and localization of blood vessels. Monitoring of dialysis catheter function, choice of the site of catheter insertion and methods of salvaging catheters from thrombosis and treating catheter-related local and systemic infections are described in this paper. Constant evaluation, proper care and hygiene of dialysis catheters are highly recommended.

Renal anemia is the result of chronic kidney disease (CKD) and deteriorates with disease progression. Anemia may be the first sign of kidney disease. In all patients with anemia and CKD, diagnostic evaluation is required. Prior to diagnosing renal anemia, it is necessary to eliminate the other possible causes. Direct correlation between the concentration of hemoglobin and the stage of renal failure is well known. Early development of anemia is common in diabetic patients. Correction of anemia may slow the progression of CKD. Anemia is an independent risk factor for developing cardiovascular disease in patients with CKD. Treatment of anemia in patients with CKD is based on current guidelines. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anemia in CKD patients and ERBP (European Renal Best Practice) group its position statement and comments on the KDIGO guidelines. The Croatian Society of Nephrology, Dialysis and Transplantation (HDNDT) has already published its own guidelines based on the recommendations and positive experience of European and international professional societies, as well as on own experience. The latest version of Croatian guidelines was published in 2008. Since then, on the basis of research and clinical practice, there have been numerous changes in the modern understanding of the treatment of anemia in CKD. Consequently, HDNDT hereby publishes a review of the recent recommendations of international professional societies, expressing the attitude about treating anemia in CKD as a basis for new guidelines tailored to the present time.

Protein-energy wasting (PEW) is a frequent problem in patients with end-stage renal disease, which is associated with adverse outcome. Risk factors for development of PEW in dialysis patients include anorexia, limitations in food intake due to problems with mineral metabolism (hyperphosphatemia, hyperkalemia). Prevention of PEW in dialysis population demands different therapeutic measures to correct abnormalities and to prevent loss of energy and proteins. Therapeutic approach should be individualized based on the specific problems of each patient in order to correct metabolic problems and to optimize food intake. In patients with inability to maintain nutritional status with standard oral feeding, other measures which include oral nutrition supplements and intradialytic parenteral feeding should be applied. Anabolic steroids, growth hormone and adequate oral nutritional supplements, together with physical activity may prevent further catabolism and correct abnormalities. Appetite stimulators, antiinflammatory interventions and anabolic drugs seem promising; however, their efficacy should be investigated in future clinical trials.

When compared to hemodialysis, peritoneal dialysis is very simple yet low cost method of renal replacement therapy. Series of studies have shown its superiority in preserving residual renal function, postponing uremic complications, maintaining the acid-base balance and achieving better post-transplant outcome in patients treated with this method. Despite obvious advantages, its role in the treatment of chronic kidney disease is still not as important as it should be. Metabolic acidosis is an inevitable complication associated with progressive loss of kidney function. Its impact on mineral and muscle metabolism, residual renal function, allograft function and anemia is very complex but can be successfully managed. The aim of our study was to evaluate the efficiency in preserving the acid-base balance in patients undergoing peritoneal dialysis at Zagreb University Hospital Center. Twenty-eight patients were enrolled in the study. The mean time spent on the treatment was 32.39 ± 43.43 months. Only lactate-buffered peritoneal dialysis fluids were used in the treatment. Acid-base balance was completely maintained in 73.07% of patients; 11.54% of patients were found in the state of mild metabolic acidosis, and the same percentage of patients were in the state of mild metabolic alkalosis. In one patient, mixed alkalosis with respiratory and metabolic component was present. The results of this study showed that acid-base balance could be maintained successfully in patients undergoing peritoneal dialysis, even only with lactate-buffered solutions included in the treatment, although they were continuously proclaimed as inferior in comparison with bicarbonate-buffered ones. In well educated and informed patients who carefully use this method, accompanied by the attentive and thorough care of their physicians, this method can provide quality continuous replacement of lost renal function as well as better quality of life.

Biological drug is a drug containing one or more active substances produced or secreted from a biological source. Some of them may be previously present in the human body, and examples include proteins such as insulin, growth hormone or erythropoetin. Biosimilar drug is a medical product that is a copy of the original approved drug whose patent has expired. Strict rules apply to similar biological medicines: 1) it is unable to support extrapolation of data on safety and efficacy between individual indications, except in the case of appropriate, science-based evidence; 2) biosimilar drugs must meet the requirements associated with testing the immunogenicity and safety monitoring afterthe introduction of the drug in clinical practice, including the risk management program; 3) each biosimilar drug has to be labeled under its own name in order to allow clear traceability of all medications; and 4) the principle of automatic substitution cannot apply to biosimilar drugs because they are not interchangeable.

Altered lipid and lipoprotein metabolism occurs in patients with chronic kidney disease (CKD). Dyslipidemia persists in patients on chronic hemodialysis orperitoneal dialysis and even in renal transplant recipients, and contributes to accelerated atherosclerosis but may also contribute to the progression of kidney disease as well. The etiologies of altered lipid profile in patients with CKD, dialysis, and renal transplant recipients are complex because there are profound changes in the structure and function of lipoprotein and lipid molecules, which lead to accelerated atherosclerosis, cardiovascular disease and stroke. Cardiovascular disease and stroke are the major cause of morbidity and mortality in patients with impaired renal function. In this review, the pathogenesis and treatment of CKD-induced dyslipidemia are discussed. Studies on lipid abnormalities in predialysis, hemodialysis and peritoneal dialysis patients are analyzed. In addition, results of the studies that tested the effects of hypolipidemic drugs on stroke morbidity and mortality in patients with CKD are reported.

Fabry disease (Anderson-Fabry disease) is one of the most common lysosomal storage diseases (after Gaucher disease) caused by deficient activity of the α-galactosidase A (α-Gal A) enzyme, which leads to progressive accumulation of globotriaosylceramide in various cells, predominantly in endothelium and vascular smooth muscles, with multisystem clinical manifestations. Estimates of the incidence range from one per 40,000 to 60,000 in males, and 1:117,000 in the general population. Pain is usually the first symptom and is present in 60%-80% of affected children, as well as gastrointestinal disturbances, ophthalmologic abnormalities and hearing loss. Renal failure, hypertrophic cardiomyopathy, or stroke as the presenting symptom may also be found even as isolated symptoms of the disease. Life expectancy is reduced by approximately 20 years in males and 10-15 years in females, therefore enzyme replacement therapy should be introduced in patients of any age and either sex, who meet treatment criteria for Anderson-Fabry disease.

Chest pain is the main presenting symptom in patients with acute myocardial infarction. However, many patients present with atypical symptoms, which may delay proper diagnosis and treatment. We present the first documented case of pain in the left ear as an atypical presentation of acute myocardial infarction 5 days after renal transplantation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The exact etiology of the conflicting hemostatic disorder in the advanced stage of chronic renal disease, i.e. prothrombotic versus bleeding tendency, is not completely understood. Abnormal platelet function in patients with renal failure is not caused by high concentrations of urea, although the presence of fibrinogen fragments may prevent binding of normal fibrinogen and formation of platelet aggregates. Hemostatic abnormalities in end-stage kidney disease may be affected, to some extent, by the choice of renal replacement therapy. Patients on hemodialysis have an increased risk of thrombotic events, primarily due to the release of thromboxane A2 and adenosine diphosphate into the circulation, as well as platelet degranulation. Some activation of platelets occurs due to the exposure of blood to the roller pump segment, but microbubbles may also play a role. Renal transplantation is the treatment of choice for patients with end-stage renal disease. Immunosuppressive therapy is associated with an increased risk of thromboembolic complications. Additional research is required to identify the potential benefits of different immunosuppressive therapies in relation to platelet aggregation, keeping in mind the long- term need for immunosuppression in renal transplant patients.

Racial and ethnic disparities exist in access to kidney transplantation worldwide. The Roma people are often socially deprived, uneducated, and unemployed. We investigated all dialysis centers in Croatia to determine number of Roma people on dialysis as well as their access and reasons for eventual failure to enter the waiting list. There are 9463 registered Roma people in Croatia, however, the estimated number reaches 40,000. Twenty-five Roma patients required renal replacement therapy, giving a prevalence of 830 per million people (pmp), compared with 959 pmp among the general population. Average age at the start of dialysis was 29 vs 67 years; waiting time to kidney transplantation was 48.9 vs 53.5 months; mean age at the time of transplantation was 33.18 vs 48.01 years in Roma versus the general population respectively. One patient received a kidney allograft from a living unrelated spousal donor, and all others from deceased individuals. Patients were followed for 51.5 months (range, 6-240). The most frequent post-transplant complications were urinary tract infections. One patient lost a graft due to severe acute rejection caused by noncompliance. Two young patients were also noncompliant with immunosuppressive medications. One patient died with a functioning graft at 20 years after transplantation due to cardiovascular disease. Among 14 Roma patients currently been treated with hemodialysis in Croatia, 10 are old with clinical contraindications for transplantation; 1 is on the waiting list; 1 left hospitalization for pretransplant evaluation twice; 1 refused evaluation; and 1 is currently being evaluated for the waiting list. The Roma people have excellent access to renal transplantation in Croatia. Many of them refuse evaluation. More efforts should be invested in their education to improve compliance and their post-transplant outcomes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Croatian Consensus Conferences on Viral Hepatitis took place in 2005 and 2009. Considering the numerous novel concepts on the epidemiology, diagnosis and management of viral hepatitis (chronic hepatitis C genotype 1 in particular) that have emerged in the past four years, a new Croatian Consensus Conference on Viral Hepatitis was held in Zagreb on February 28, 2013. The abridged text of the Croatian Consensus Conference on Viral Hepatitis 2013 presents the new concepts on the epidemiology of viral hepatitis, serologic and molecular diagnosis of viral hepatitis, determination of the IL-28 gene promoter polymorphism, fibrosis grading, algorithm for patient diagnostic follow up, treatment of chronic hepatitis C (genotypes 1-6) and hepatitis B, treatment of special populations (children, dialysis patients, transplanted patients, individuals with HIV/HCV co-infection), and therapy side effects.

Hepatitis C virus (HCV) infection is a relatively frequent complication among long-term dialysis patients. The paper presents guidelines for serologic and molecular diagnosis of hepatitis C in patients with chronic kidney disease, recommendations for the treatment of HCV infection in these patients and the prevention of transmission of HCV in hemodialysis units. A separate chapter provides guidance on the management of patients who are infected with HCV before and after kidney transplantation, and guidelines for the treatment of renal disease resulting from HCV infection.

There is a widening gap between the needs and possibilities of kidney transplantation. In order to solve the problem of organ shortage, the selection criteria for kidney donors have been less stringent over the last years. Favorable outcome of renal transplantation from deceased donors with acute renal failure requiring dialysis may have an important role in expanding the pool of donors. We present the case of two renal transplantations from a polytraumatized 20-years old donor with acute renal failure requiring dialysis. One recipient established good diuresis from the first post-transplant day and did not require hemodialysis. The second recipient had delayed graft function and was treated with 8 hemodialysis sessions. The patient was discharged with good diuresis and normal serum creatinine. After two years of follow-up, both recipients have normal graft function. According to our experience, kidneys from deceased young donors with acute renal failure requiring dialysis may be transplanted, in order to decrease the number of patients on transplantation waiting lists.

Fabry disease (Anderson-Fabry disease) is one of the most common lysosomal storage diseases (after Gaucher disease) caused by deficient activity of the alpha-galactosidase A (alpha-Gal A) enzyme, which leads to progressive accumulation of globotriaosylceramide in various cells, predominantly in endothelium and vascular smooth muscles, with multisystem clinical manifestations. Estimates of the incidence range from one per 40,000 to 60,000 in males, and 1:117,000 in the general population. Pain is usually the first symptom and is present in 60%-80% of affected children, as well as gastrointestinal disturbances, ophthalmologic abnormalities and hearing loss. Renal failure, hypertrophic cardiomyopathy, or stroke as the presenting symptom may also be found even as isolated symptoms of the disease. Life expectancy is reduced by approximately 20 years in males and 10-15 years in females, therefore enzyme replacement therapy should be introduced in patients of any age and either sex, who meet treatment criteria for Anderson-Fabry disease.

The increasing number of possible recipients for kidney transplantation and relatively unchanged number of organ donors has led to consideration of alternative strategies and expansion of deceased donor criteria in order to expand donor pool. Previously, kidneys from expanded criteria donors (ECD) were strongly underestimated because of the conventional opinion suggesting these kidneys to have a higher rate of preservation injury, delayed graft function, rejection and nonfunction. Reducing the difference between graft outcome in patients transplanted from ECD and standard criteria donor (SCD) is one of the goals of many respectable kidney transplantation centers. This assignment includes major concern about reduction of cold ischemia time, recipient selection, novel and adapted immunosuppressive regimens, increased nephron mass by dual kidney transplantation, and using histologic criteria for marginal donor graft selection. There are not many reports on the outcome of kidneys transplanted from donors with acute renal failure and high terminal creatinine. This review presents the exact definition of marginal donor, especially donor with acute renal failure. The management of such grafts during preimplantation and implantation period, outcomes and post-transplantation care are the main assignments for transplantation teams. Recipients of such grafts should be well informed about the possibilities and potential complications and sign their informed consent thereafter. Some respectable studies have shown that under certain, highly controlled conditions, these kidneys can be used safely, with excellent short- and long-term outcomes.

Muon-spin rotation measurements, performed on the mixed state of the classic anisotropic superconductor Bi(2.15)Sr(1.85)CaCu(2)O(8+δ), obtain quantities directly related to two- and three-body correlations of vortices in space. A novel phase diagram emerges from such local probe measurements of the bulk, revealing an unusual glassy state at intermediate fields which appears to freeze continuously from the equilibrium vortex liquid but differs both from the lattice and the conventional high-field vortex glass state in its structure.

Fabry disease is a progressive devastating disease caused by absent or deficient activity of lysosomal enzyme alpha-galactosidase A, with progressive accumulation of globotriaosylceramide (GL-3) within lysosomes in a different cell types. Accumulation of GL-3 and related glycosphingolipids in different cell types may create diverse clinical picture depending on the organ which is dominantly affected. Renal pathology progresses in severity with aging. Globotryaosil ceramide deposits may be found in different cell types within the kidney. Deposition within the glomeruli may be found in endothelial cells, mesangial cells, interstitial cells, with the highest level found within the podocytes. Although Fabry disease is not curable at the moment, availability of enzyme replacement therapy made it possible to treat this group of patients. Two formulations of recombinant human alpha-galactosidase A are present on the market: agalsidase alfa and agalsidase beta. Longer follow-up period is necessary to estimate the impact of ERT on mortality. Patients with end-stage renal disease caused by Fabry disease could be safely treated with enzyme replacement therapy regardless of the method of renal replacement therapy.

Epidermolysis bullosa is a rare genetic hereditary disease characterized with mechanobullous dermatosis. Except cutaneous, these patients have various extracutaneous manifestations and some types of epidermolysis bullosa comprise almost all organ systems. Because of prolonged life span, chronic renal insufficiency has become an important cause of morbidity and death in these patients. Establishment of functional vascular dialysis access is a great challenge for both the doctors and the patients. Multidisciplinary approach is essential. We present a case of successful establishment of dialysis access via Tesio catheter in a young woman suffering from epidermolysis bullosa dystrophica Hallopeau-Siemens and end-stage renal disease. Since then, the Tesio catheter inserted via the right internal jugular vein has been the functional mean of dialysis. The patient was given the opportunity to lead a quality and active life in spite of disabling disease. Several cases of successful dialysis access establishment with dialysis catheters via central veins have been reported. We report the successful establishment of long-term dialysis access via Tesio catheter and suggest this approach as ideal for these patients. This is the first report dealing with vascular access in this group of patients., (© 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.)

Primary cardiac hemangioma is a very rare benign vascular tumor, with valvular hemangiomas being even less frequent as valves are generally avascular structures. We present the first case of mitral valve hemangioma in a renal transplant recipient. Patient presented with progressive dyspnea. Transesophageal echocardiogram (TEE) demonstrated a 0.8x0.9-cm pedunculated tumor mass on the posterior leaflet of the mitral valve. Coronary angiography identified a small artery which filled from the circumflex artery and fed the tumor. The tumor was surgically removed. Histopathological examination revealed a hemangioma. The postoperative course was uneventful with stable graft function., (Copyright © 2013 S. Karger AG, Basel.)

Calcineurin inhibitors at elevated serum concentrations frequently cause mild elevation of the liver chemistries. Although rare, severe hepatotoxicity is their serious complication. A 54-year-old man with end-stage renal disease due to chronic glomerulonephritis without biopsy received a renal allograft from the deceased donor. Eleven days after transplantation severe liver injury (AST up to 421 IU/L, ALT 1242  IU/L, and GGT 212 IU/L) with the serum bilirubin within the normal range was recorded. Tacrolimus trough level was 5.5 ng/mL. Liver ultrasound and color-Doppler of the portal system were normal. Liver failure completely resolved after withdrawal of the calcineurin inhibitor and switch to sirolimus. After 9 months of follow-up our patient has excellent graft and liver function. Awareness of the possible association of tacrolimus use with hepatotoxicity is important to timely discontinuation of the causative agent, and to introduce sirolimus as the rescue therapy.

The use of intravenous immunoglobulin (IVIg) in the management of patients with neuroimmune disorders has shown a progressive trend over the last few years. Despite the wide use of IVIg, consensus on its optimal use is deficient. The European Federation of Neurological Societies (EFNS) guidance regulations offer consensus recommendations for optimal use of IVIg. The effectiveness of IVIg has been proven in Guillain-Barré syndrome (level A), chronic inflammatory demyelinating polyradiculoneuropathy (level A), multifocal mononeuropathy (level A), acute exacerbations of myasthenia gravis and short-term treatment of severe myasthenia gravis (level A). As a second-line treatment, the use of IVIg is recommended in dermatomyositis in combination with prednisone (level B) and is considered as a treatment option in polymyositis (level C). As a second- or even third-line therapy, the use of IVIg should be considered in patients with relapsing-remitting multiple sclerosis if conventional immunomodulatory therapies are not tolerated (level B) and in relapses during pregnancy or post-partum period (good clinical practice point). Finally, it appears that the use of IVIg has a beneficial effect also in stiff-person syndrome (level A), some paraneoplastic neuropathies (level B), and some acute-demyelinating diseases and childhood refractory epilepsy (good practice point).

WNT 4 is a secreted glycoprotein that is critical for nephrogenesis during mesenchymal to epithelial transformation. Lately there are some experimental modles witch confirm a role of Wnt 4 during regeneration process in acute renal failure. On the other hand there are some evidence that Wnt 4 plays important role in renal fibrosis during experimental renal injury in rats that provide tubuloinerstitial fibrosis. When will Wnt 4 have a protective role or when will induce fibrosis still is not known and therefore futher studies will be necessary to gain a more precise understanding.

Heparin-induced thrombocytopenia type II (HIT) is a clinicopathologic syndrome in which one or more clinical events are temporally related to heparin administration and caused by HIT antibodies. There are at least five different types of clinical events that are associated with HIT: thrombocytopenia; thrombosis; skin necrosis at heparin injection site, venous limb gangrene; and an acute systemic reaction that occurs 5-30 min after intravenous bolus of heparin. HIT typically presents 5-14 days after initiation of heparin therapy, later onset is unusual. Heparin is a routine anticoagulant in hemodialysis but administration is different than in surgical and other medical population. Doses are lower and administered every other day, yet hemodialysis patients receive heparin for years. Relationship between dialysis vintage and HIT-antibody positivity has been analyzed in two studies. In national survey of HIT in hemodialysis population of the United Kingdom mean time between starting hemodialysis and development of HIT was 61 days (5-390 days). Japanese authors also found greatest incidence of HIT antibody positivity in patients who were on hemodialysis for less than 1 year, none of patients on hemodialysis for more than 10 years was HIT-antibody positive. We present a case of 70-years old female who developed HIT after 24 years of hemodialysis and exposure to heparin. First 22 years she was receiving unfractionated heparin for anticoagulation during hemodialysis sessions. Afterwards her therapy was changed to low molecular weight heparin. Last 12 years she has tunneled cuffed catheter which was also filled with unfractionated heparin. She had a history of severe renal osteodistrophy and severe aortal valve stenosis, hypothyreosis, thrombosis of both subclavian veins and partial colon resection due to mesenterial artery thrombosis. Her thrombocyte count was low, but despite extensive work-up which included HIT antibody detection, no cause could be identified. She started complaining of flushing, dyspnea and chest pain that developed several minutes after start of hemodialysis and stopped spontaneously during or after hemodialysis. Symptoms were attributed to her heart disease and she was hospitalized for cardiac reevaluation. Thrombosis of right superficial and commune femoral vein was diagnosed as well as further worsening of thrombocytopenia. HIT antibodies were assessed again and they were positive. Anticoagulation during hemodialysis was changed to fondaparinux and catheter filling to citrate. Afterwards symptoms during hemodialysis disappeared and thrombocyte count recovered. HIT type II is a rare but potentially fatal syndrome that can develop years after start of heparin therapy. To our knowledge, this is the patient with longest hemodialysis vintage and newly diagnosed HIT. This is also the first case of patient on hemodialysis that developed HIT in Croatia published to date.

The balance and quality of different renal replacement treatment modalities used in the elderly with end-stage renal disease vary between countries depending on economic resources, distribution of renal units, number of specialists, and patterns of reimbursement of both hospitals and physicians. Elderly patients with end-stage renal disease need detailed assessment of medical, psychological, motor, and social factors in order to choose an appropriate renal replacement treatment option. Presence or absence of significant comorbidity is much more important than the chronological age. The choice between hemodialysis and continuous ambulatory peritoneal dialysis is largely dependant on preferences of the local team and the patient. Patients with adequate cardiovascular systems are generally considered to be more suitable for hemodialysis. Hemoglobin should be optimized (Hb between 100 and 120 g/L) in all patients. Poor cardiac status and/or angina will require assessment, medical treatment, and, if necessary, surgical treatment or angioplasty. Transplantation should be considered in all reasonably fit and carefully selected patients older than 65 or even 70 years. Only the permanent shortage of suitable kidneys limits our ability to treat all those who could benefit from this type of treatment. Renal transplant recipients may benefit in terms of both survival and quality of life even if older than 70 years and beyond. Immunosuppressive therapy in elderly patients should be moderate.