Membrane therapeutic plasma exchange with and without heparin anticoagulation.

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.

Differences in CVVH vs. CVVHDF in the management of sepsis-induced acute kidney injury in critically ill patients.

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.

A randomized crossover study comparing membrane and centrifugal therapeutic plasma exchange procedures.

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.

Expression of BMP-2 in Vascular Endothelial Cells of Recipient May Predict Delayed Graft Function After Renal Transplantation.

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.

Therapeutic Plasma Exchange-Does Age Matter? A Single-Center Study.

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.

[[GUIDELINES FOR THE PREVENTION, MONITORING AND THERAPY OF CHRONIC KIDNEY DISEASE-METABOLIC BONE DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE].]

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.

The Effect of Preserved Residual Renal Function on Left Ventricular Structure in Non-Anuric Peritoneal Dialysis Patients.

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.

Cardiovascular surgery after renal transplantation--indications, complications and outcome.

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.

[Croatian guidelines for screening, prevention and treatment of protein-energy wasting in chronic kidney disease patients]. / Preporuke za pracenje, prevenciju i lijecenje proteinsko-energijske pothranjenosti u bolesnika s kronicnom bubrezom bolesti.

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.

Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy.

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.

[What do we know about chronic kidney disease at the beginning of the 21st century?]. / Sto znamo o kronicnoj bolesti bubrega pocetkom 21. stoljeca?

Data are presented on the number of chronic kidney disease (CKD) patients and on the most common causes of the disease, with special reference to data collected at the Registry of Renal Replacement Therapy by Dialysis and Kidney Transplantation in the Republic of Croatia. Emphasis is put on the very high cost of managing patients with end-stage CKD. As currently there is no drug able to halt progression of kidney damage in CKD, attention is focused on early detection of renal disease, screening of CKD patients, specific therapy, slowing down disease progression, and treatment of complications and comorbidities. The role of general practitioners and compliance of patients who have to decide on the mode of renal replacement therapy, as well as of continuous education of nephrologists and public awareness of renal diseases is underlined.

[What doctors need to know about biosimilar medicinal products?]. / Sto bi lijecnici trebali znati o bioloski slicnim lijekovima?

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.

[Acid-base status in patients treated with peritoneal dialysis]. / Acidobazni status u bolesnika lijecenih metodom peritonejske dijalize.

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.

[Dyslipidemia and stroke in patients with chronic kidney disease]. / Dislipidemija i mozdani udar u kronicnih bubreznih bolesnika.

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.

[Consensus statement of the Croatian Society for Nephrology, Dialysis and Transplantation regarding the use of generic immunosuppressive drugs]. / Stav hrvatskog drustva za nefrologiju, dijalizu i transplantaciju bubrega prema uporabi generickih imunosupresiva u transplantaciji bubrega.

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.

[Temporary and permanent central venous catheters for hemodialysis]. / Primjena trajnih i privremenih centralnih venskih katetera za hemodijalizu.

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.

[How to prevent protein-energy wasting in patients with chronic kidney disease--position statement of the Croatian Society of Nephrology, Dialysis and Transplantation]. / Kako prevenirati i lijeciti proteinsko-energetsku pothranjenost u bolesnika s kronicnom bolescu bubrega--osvrt hrvatskog drustva za nefrologiju, dijalizu i transplantaciju na preporuke medunarodnog drustva za prehranu bubreznih bolesnika.

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.

[Treatment of anemia in chronic kidney disease--position statement of the Croatian Society for Nephrology, Dialysis and Transplantation and review of the KDIGO and ERPB guidelines]. / Lijecenje anemije u kronicnoj bubreznoj bolesti--stav hrvatskog drustva za nefrologiju, dijalizu i transplantaciju i osvrt na preporuke KDIGO i ERBP.

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.

[Guidelines for diagnosis, therapy and follow up of Anderson-Fabry disease]. / Smjernice za dijagnostiku, lijecenje i pracenje Anderson-Fabryjeve bolesti.

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.

[Renal transplantation in patients with lupus nephritis]. / Transplantacija bubrega u bolesnika s lupusnim nefritisom.

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.