OSTEOPROTEGERIN AS AN EARLY SIGN OF CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER.

Chronic kidney disease (CKD) is among the most significant health problems, with the associated cardiovascular disease and bone metabolism disorders being the leading cause of morbidity and mortality in these patients. The aim of the study was to determine markers of bone turnover in patient sera (phosphates, calcium, alkaline phosphatase, parathyroid hormone and osteoprotegerin (OPG)) in all stages of kidney failure including kidney transplant recipients. We also wanted to determine whether dialysis vintage affects recovery of bone markers one year after transplantation. There were 164 study patients, whereas 30 healthy individuals served as a control group. Serum OPG progressively increased with decline of the glomerular filtration rate. The highest OPG concentration was recorded in dialysis group. We observed a statistically significant OPG increase in stage 2 CKD. In kidney transplant group, there was positive correlation between OPG and dialysis vintage. We also found that serum OPG was lower in patients treated with dialysis for less than 4 years prior to transplantation. We confirmed that CKD-mineral and bone disorder began in stage 3 CKD with parathyroid hormone and OPG elevation, and a statistically significant OPG increase in stage 2 CKD might be an early sign of CKD-mineral and bone disorder. Dialysis vintage longer than 4 years is associated with more significant disturbances in mineral and bone metabolism.

Hospitalization and death after recovery from acute COVID-19 among renal transplant recipients.

INTRODUCTION: Data on post-COVID-19 in renal transplant recipients (RTR) is scarce. We investigated the rate of hospitalizations, reasons for hospital admission, and mortality rate among RTR who survived acute COVID-19. METHODS: A multi-center retrospective observational cohort study measured hospital admission and death to 180 days after acute SARS-CoV-2 infection in 308 adult patients. RESULTS: The median age was 57 years, 64.9% were male. All patients had at least one comorbidity, and 26.3% had diabetes. Data on post-COVID-19 course was available for 267 patients, and 49 of them (15.9%) required hospital treatment after recovery from the acute infection. The most common indications included pneumonia (24.5%) and renal allograft dysfunction (22.4%), 7 (14.3%) had sepsis and 5 (10.2%) had thrombotic events. A median duration of the hospital stay was 12 days. Six patients (2.2%) died due to multiorgan failure, respiratory insufficiency or urosepsis. The strongest predictor for hospitalization after acute COVID-19 was hospitalization for acute SARS-CoV-2 infection, while better allograft function decreased the probability of hospitalization. CONCLUSION: Delayed consequences of acute COVID-19 are highly prevalent and the health care systems should be prepared to respond to the needs of RTR suffering from post-COVID-19 complications.

THE BEGINNINGS OF KIDNEY TRANSPLANTATION IN SOUTH-EAST EUROPE.

Organ transplantation is one of the most important medical achievements of the 20th century. Kidney transplantation is the most efficient method of renal replacement therapy. The first successful kidney transplantation in human was performed in 1954 in Boston, USA. In former Yugoslavia, the first kidney transplantation was performed on April 16, 1970 in Ljubljana, Slovenia, and second one on January 30, 1971 in Rijeka, Croatia. In both cases, the mother donated kidney to the son. In the article, we describe the prerequisite conditions for this operation, the characteristics of first patients, and the impact of transplantation program on the development of the hospitals and medical schools.

Comparison of clinical assessment and multifrequency bioimpedance analysis as methods of estimating volume status in peritoneal dialysis patients - A single-center experience
.

INTRODUCTION: Clinical assessment (CA) is frequently used for the evaluation of volume status in peritoneal dialysis (PD) patients despite its subjectivity. Multiple-frequency bioelectrical impedance analysis (MF-BIA) is objective, accurate, and quick, proving to be a promising technique for measuring volume status. The aim of this study was to assess volume status in PD patients using CA and MF-BIA and to compare results. MATERIALS AND METHODS: Incident PD patients were prospectively analyzed between January 1, 2014, and January 1, 2016, at the Clinical Hospital Center of -Rijeka, Croatia. Volume status measurements were performed once a month for 6 consecutive months. The presence of symptoms and signs associated with hyper- or hypovolemia were detected by CA. Euvolemia was defined as a symptom-free state or up to 2 symptoms maximum. Patients lacking up to 1.2 L of volume or with up to 1.2 L in excess were considered euvolemic, as measured by MF-BIA. RESULTS: A total of 45 PD patients were analyzed; 51% were men, 27% were diabetic, the mean age was 52 ± 26 years, and PD duration was 11.5 ± 6.5 months. In comparison to MF-BIA, CA showed a significant difference in detected hypervolemia between baseline and follow-up (p = 0.708 vs. p = 0.01, respectively) and among all measurements (p < 0.01). Contrary to CA, volume status measured by MF-BIA correlated significantly with systolic and diastolic blood pressure (R = 0.29; p ≤ 0.01 and R = 0.26; p ≤ 0.01, respectively). CA showed low sensitivity (0.24) and high specificity (0.92) in detecting hypervolemia. CONCLUSION: MF-BIA is an effective, objective, and safe method for assessing volume status in PD patients. Longitudinal monitoring of body composition changes - including hydration state - leading to adequate therapeutic intervention is a promising and potential application of MF-BIA along with CA.

Kidney transplantation using a colon pouch (Mainz pouch III): a case report.

Kidney transplantation is the most efficient method of renal replacement therapy. When this method is performed, native urinary bladder is the preferred urinary reservoir. However, in some patients with an anatomically and functionally abnormal lower urinary tract, the urinary bladder cannot be used for transplantation. In these patients, urinary diversion should be performed before kidney transplantation. We present a case of a 32-year-old male patient with orthotopic kidney transplantation performed using a colon pouch (Mainz-pouch III). He was born with severe anomalies including sacral agenesis, anorectal atresia, and hypospadias, which were corrected during childhood. Neurogenic bladder with severe vesicoureteral reflux led to end-stage renal disease. This dysfunctional bladder was unsuitable for kidney transplantation, and a staged approach for future transplantation was chosen. The first step was the creation of urinary diversion. Due to a short appendix, we created a continent, colon pouch (Mainz pouch III). Two years later, orthotopic kidney transplantation was performed using a right cadaveric kidney. The renal vessels were anastomosed to the aorta and inferior vena cava and the pyelon to the native ureter. Four years after transplantation, the patient has stable renal function without any complications. This is the first documented case of using Mainz-pouch III as a reliable option for kidney transplantation in selected patients.

Severe bleeding complications and multiple kidney transplants in a patient with tuberous sclerosis complex caused by a novel TSC2 missense variant.

We presented an extremely severe case of tuberous sclerosis complex (TSC) in a female patient with recurring, life-threatening bleeding complications related to renal angiomyolipomas. Massive intratumoral hemorrhage required surgical removal of both angiomyolipomatous kidneys and kidney transplantation. During the follow-up period, the patient developed severe metrorrhagia that eventually led to hysterectomy and salpingo-oophorectomy. Bleeding from the operative sites caused the loss of the first kidney transplant received from the mother, and immediate hemorrhagic shock led to the loss of the second, cadaveric kidney allograft. The third kidney transplant had a successful outcome. Pathological analysis of all tissue specimens showed TSC-associated lesions and deformed blood vessels in the surgically removed organs. Molecular genetic analysis of TSC1 and TSC2 in the DNA of peripheral leukocytes identified a novel TSC2 c.3599G>C (p.R1200P) variant. Functional assessment confirmed the likely pathogenicity of the TSC2 c.3599G>C (p.R1200P) variant. To the best of our knowledge, this is the first report of the c.3599G>C (p.R1200P) variant in exon 29 of the TSC2 gene related to a severe clinical course and multiple kidney transplants in a patient with TSC.

[[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.

Peritoneal Dialysis Catheter Placement Using an Ultrasound-Guided Transversus Abdominis Plane Block.

BACKGROUND: Peritoneal dialysis (PD) catheter placement is usually performed using general or local anesthesia. We present our PD catheter placement experience using an ultrasound-guided transversus abdominis plane (TAP) block, which is a regional anesthesia technique. METHODS: In this study, we analyzed 33 patients from our center with ESRD who underwent PD catheter placement using a TAP block between June 2011 and April 2014. RESULTS: The TAP block was successful for 29/33 (87.9%) patients. Four patients (12.1%) had pain at the incision site and required general anesthesia. There were no anesthesia-, surgery- or catheter-related complications. CONCLUSION: ESRD patients have a substantial number of comorbidities that can be negatively influenced by general anesthesia. Because regional anesthesia has no systemic effect, this procedure could be recommended for this group of patients. A TAP block is an effective, safe method and can be used as the principal anesthesia technique for PD catheter placement.

[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.

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular risk in renal transplant recipients.

BACKGROUND/AIMS: Renal transplant recipients (RTRs) are at high risk for cardiovascular (CVD) mortality. Recently, nonalcoholic fatty liver disease (NAFLD) has been recognized as a new risk factor for adverse CVD events in the general population. We examined whether transient elastography (TE) defined NAFLD was associated with atherosclerosis in RTRs, as measured by ultrasound in the carotid arteries. METHODS: Carotid atherosclerosis was assesses in 71 RTRs with a TE proven NAFLD. With the help of TE liver stiffness was used to assess liver fibrosis and Controlled Attenuation Parameter (CAP) was used to detect and quantify liver steatosis. NAFLD was defined by the presence of steatosis with CAP values ≥238 dB.m(-1). RESULTS: RTRs with NAFLD showed more carotid atherosclerosis than RTRs without NAFLD. RTRs-NAFLD patients had the mean intima-media measurements (ITM) of 1.1±0.1 mm and that was statistically significant higher than the mean ITM founded in RTRs without NAFLD (1.1±0.1 vs. 0.9±0.1 mm; p<0.0001). Furthermore, RTRs-NAFLD patients had statistically significant higher prevalence of plaques in comparison with RTRs without NAFLD (p=0.021). CONCLUSION: We showed for the first time that carotid atherosclerosis is advanced in RTRs with NAFLD. Detection of NAFLD by TE should alert to the existence of an increased cardiovascular risk in RTRs.

Non-alcoholic fatty liver disease proven by transient elastography in hemodialysis patients: is it a new risk factor for adverse cardiovascular events?

BACKGROUND/AIMS: Cardiovascular diseases (CVD) are the leading cause of mortality in hemodialysis (HD) patients. Recently, non-alcoholic fatty liver disease (NAFLD) has been recognized as a new risk factor for adverse CVD events in the general population. Our aim was to analyze the incidence of NAFLD in HD patients by using transient elastography and to analyze whether the presence of NAFLD is associated with a higher CVD risk in HD patients. METHODS: The subjects were 72 HD patients and 50 sex- and age-matched controls. RESULTS: NAFLD was found in 52.8% of HD patients. HD patients with NAFLD showed more carotid atherosclerosis and more adverse CVD events than HD patients without NAFLD and control subjects. CONCLUSION: We showed for the first time that HD patients have a high prevalence of NAFLD. HD patients with NAFLD show an advanced carotid atherosclerosis. Detection of NAFLD by transient elastography should alert to the existence of an increased cardiovascular risk in HD patients.

[Management of hemodialysis patients using simple informatics program]. / Menadzment bolesnika na hemodijalizi koristenjem jednostavnih informatickih programa.

Providing health care and good hospital organization are always based on a well-educated and competent nurse. Nurses can significantly affect the result of overall treatment, which has a professional and financial effect. Nursing Informatics is a specialty that integrates nursing, computer and information science applied to nursing management as well as transfer of data, information and knowledge in nursing practice. This facilitates nurses' integration in supporting decision-making and implementation of health care. Informatics emphasizes overall nursing practice and nurses should have basic computer skills. In this article, we show how the use of simple tables, designed by using Microsoft Office programs (Word and Excel), has been employed for over a decade in facilitating the organization of daily work, monitoring of patients and their prescribed therapy. A trained nurse-manager will be able to evaluate patient care and to organize health care administration using all human and technical resources. The vision of the national health care system is still not achievable due to the lack of infrastructure. Nurses and computer documentation of patients with chronic kidney disease can significantly improve the quality of patient care and treatment.

[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.

[Assessment of nutritional status in patients with chronic kidney disease on maintance hemodialysis]. / Procjena nutricijskog statusa u bolesnika s kronicnom bubreznom bolesti koji se lijece redovitom hemodijalizom.

INTRODUCTION: It is well established that nutritional status is an important factor affecting the outcome and recovery from disease or injury. Assessment of nutritional status is an integral part of care for patients with chronic kidney disease, especially for those treated with dialysis procedures. According to available literature, 18%-80% of patients on dialysis have some form of nutritional deficiency. Furthermore, in patients treated with dialysis procedures there is a rule called 'reverse epidemiology', according which patients with better nutritional status have better survival rate. Therefore, nutritional assessment should detect malnutrition and rate the overall nutritional status of each patient through clinical data categories: medical history, physical examination, nutrition physical examination, psychosocial history, demographics, physical activity, and current medical/surgical issues. Consequently, the main aim of our study was to analyze the nutritional status of our patients treated with hemodialysis procedures. Another aim was to analyze the applicability of measuring skinfold by caliper as a method of nutritional status assessment. SUBJECTS AND METHODS: During a six-month period, we analyzed 129 patients (57.4% of men and 42.6% of women), mean age 68.1 ± 12.4 years, treated with hemodialysis procedures (24.8% of patients were treated with online hemodiafiltration and 75.2% with standard, conventional hemodialysis) as the method of choice of renal replacement therapy (RRT) for more than 6 months. All patients were dialyzed three times a week for four hours on biocompatible synthetic membranes. The patients treated with online hemodiafiltration were dialyzed on high-flux helixone membranes, while those treated with standard, conventional hemodialysis were dialyzed on polysulfone membranes and helixone low-flux membranes. The mean time of RRT was 71.2 ± 56.7 months. During the study period, in each patient we followed medical history, and clinical and laboratory parameters of nutritional status at 3 and 6 months. To assess the nutritional status, we used dry weight (DW), body mass index (BMI), skinfold caliper measurement (result is correlated with total body fat, FAT), and common laboratory indicators of nutritional status (serum albumin and cholesterol). RE- SULTS: Analyzing the efficiency of skinfold thickness measurement with caliper, we found that the FAT obtained by caliper showed a statistically significant positive correlation with clinical indicators of nutritional status, and with BMI (r = 0.364, p < 0.0001), DW (r = 0.206, p = 0.005) and volume of muscle circumference (r = 0.399, p < 0.0001). Also, FAT showed statistically significant positive correlation with laboratory indicators of nutritional status, including serum albumin (r = 0.299, p = 0.01) and cholesterol (r = 0.225, p = 0.002). There was no statistically significant correlation between the duration of RRT and FAT (p = NS). CONCLUSION: In clinical practice, as well as for regular evaluation of nutritional status, it is important that the method we used proved efficient, precise, relatively fast and posing less economic burden. From our experience, the measurement of skinfold with caliper is an applicable, relatively quick and inexpensive method for regular assessment of nutritional status in patients treated with hemodialysis proce- dures. Therefore, all patients treated with RRT should undergo nutritional screening and expert help should be available from dietitians or nutritional support teams in order to identify this problem properly in its early stage and to reduce its high prevalence.

[Analysis of patients with acute renal failure hospitalized at department of nephrology and dialysis, Rijeka University Hospital, during the five-year period]. / Analiza akutnog bubreznog zatajenja tijekom petogodisnjeg razdoblja u zavodu za nefrologiju i dijalizu klinickog bolnickog centra Rijeka.

INTRODUCTION: Acute renal failure (ARF) is a serious complication that occurs in 5%-18% of hospitalized patients and in up to 30% of patients admitted to Intensive Care Unit. The hospital mortality rate of patients with ARF is between 28% and 90%. The incidence of ARF is proportional to patient age. Therefore, despite all improvements in modern medicine, the annual incidence of ARF has not changed over the two past decades. The aim of our study was to analyze the incidence and causes of ARF in our Center during the five-year period, to analyze the characteristics of patients and their comorbid conditions, variations in laboratory parameters during hospitalization, and therapy administered. Also, we analyzed the outcome and length of hospitalization. SUBJECTS AND METHODS: During the five-year period (from January 2008 till December 2012), we analyzed 316 patients treated for ARF at Department of Nephrology and Dialysis, Rijeka University Hospital Center. Data were obtained by searching medical records. ARF was defined according to the KDIGO recommendations: increase in serum creatinine (sCR) > 26 µmol/L within 48 h, or increase in sCR by 1.5 times compared to the reference values, which is known or assumed to have appeared within a week of hospitalization, or diuresis < 0.5 mL/kg/h for ≥ 6 hours. RESULTS: Out of 316 ARF patients analyzed, 57 were hospitalized at our Department in 2008 (50.9% of men and 49.1% of women), 56 in 2009 (39.3% of men and 60.7% of women), 66 in 2010 (55.3% of men and 44.7% of women) and 76 in 2011 (55.3% of men and 44.7% of women). In 2012, we analyzed 61 ARF patients (42.6% of men and 53.4% of women). There were no statistically significant age and gender differences, although we noticed an increasing tendency in the number of elderly patients hospitalized for ARF. Furthermore, analyzing the frequency of patient arrival from home, nursing home or transfer from other departments we recorded an increase in the arrival of patients from nursing homes during the study period. Analysis of the proportion of patients hospitalized for ARF in our Department in relation to the total number of hospitalized patients revealed that ARF was the cause of hospitalization in 8.2%-9.9% of all patients. There was no significant change in the number of patients hospitalized for ARF during the period observed. Analyzing the frequency of hospitalization due to ARF by months, we noticed that the largest number of patients were hospitalized during summer months (from June to September). The most common form of ARF was prerenal (56.1%-67.9%). The largest number of patients were treated by parenteral rehydration and antibiotics (52.6%-71.4%). Renal replacement therapy was performed in 12.5%- 21.1% of all patients. The mortality rate throughout the period of observation ranged from 21.2%-30.4%. Furthermore, complete recovery of renal function was achieved in 30.5%-40.4% of all patients. The mean length of hospital stay ranged from 11.8 to 15.1 days. CONCLUSION: Acute renal failure is a significant cause of hospitalization, especially in elderly patients. Therefore, early identification along with appropriate and early treatment of patients with ARF is needed to improve survival and recovery of renal function in these patients.

[Evaluation of viral hepatitis in solid organ transplantation]. / Evaluacija virusnih hepatitisa u transplantaciji solidnih organa.

Renal transplantation has significantly improved survival of patients with end-stage renal disease (ESRD). Transplantation is the best treatment in this population of patients. Despite the introduction of various preventive measures, viral hepatitis, i.e. hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, are still a major problem because they are common in patients on renal replacement therapy as well as in allograft recipients. They are a significant cause of morbidity and mortality in this patient population. In recent years, hepatitis E virus (HEV) infection has been added as an emergent cause of chronic hepatitis in solid organ transplantation, mainly in renal and liver allograft recipients. Most studies show higher mortality in renal transplant recipients (RTRs) infected with HBV, compared with RTRs without HBV infection, although this topic is still under debate. Furthermore, HCV infection in RTRs is associated with a significant reduction in patient and graft survival due to liver disease and septic complications related to cirrhosis and immunosuppressive therapy. The immunosuppressive therapy prescribed after transplantation modifies the natural history of chronic HCV infection. Given the high prevalence of HCV and HBV infections in RTRs, a growing incidence of hepatocellular carcinoma and the possible contribution of immunosuppression might be expected in these patients. Therefore, after renal transplantation, early screening with abdominal ultrasound (every 3 months in cirrhotic patients and every 6-12 months in non-cirrhotic RTRs) is necessary when the risk factors such as HBV and HCV are present. The European Association for the Study of the Liver (EASL) recommends that all HbsAg-positive patients who are candidates for solid organ transplantation should be treated with nucleoside analogs. The KDIGO guidelines recommend that all HbsAg-positive RTRs receive prophylaxis with tenofovir, entecavir or lamivudine; however, tenofovir and entecavir are preferable to lamivudin. Viral suppression by inhibiting necro-inflammation may result in reduced fibrosis, thereby improving transplant survival. Active HCV infection in a dialysis patient requires evaluation of liver fibrosis. Antiviral therapy should be given to all HCV-infected dialysis patients in order to achieve a sustained virologic response (SVR) not only to avoid subsequent hepatic deterioration but also to limit the risks of HCV-related posttransplant de novo glomerulonephritis. Systematic vaccination of all HbsAg-negative patients is the best preventive treatment of HBV infection. HbsAg positive donors are only used occasionally, whereas the use of hepatitis B core antibody (HbcAb)+, HbsAg negative donors is more common but remains somewhat controversial. The presence of antibody to HCV is indicative of HCV infection because antibody to HCV appears in peripheral blood within two months of HCV exposure. However, it is important to emphasize that detection of antibody to HCV by serologic screening of the donor is not predictive of HCV transmission. Approximately 50% of patients positive for antibody to HCV have detectable hepatitis C viremia by PCR analysis of peripheral blood. Therefore, all organ donors with PCR analysis positive for HCV will transmit HCV to RTRs. On the other hand, the risk of transmission from an organ donor with negative PCR analysis is unclear. Another problem in the evaluation of the potential donors of solid organs is the fact that antibody testing by enzyme-linked immunosorbent assays (ELISAs) will not detect recent infections. The use of nucleid acid testing (NAT) could be useful because it involves amplification of viral gene products and thus is not dependent on antibody formation. Therefore, by using this method the period between the infection and detectability, which is known as the window period, could be reduced. However, this method is expensive and time consuming.

[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.

[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.