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Aim. To investigate morphological findings of zero-time biopsies analyzed at the Department of Nephropathology and Electron Microscopy, Dubrava University Hospital, Zagreb. Materials and methods. The retrospective search of data was performed for the period from 2006 to 2018. A total of 316 zero-time renal biopsies were analyzed. Glomerular basement membrane (GBM) thickness was remeasured in 84 zero-time biopsies and 80 protocol biopsies of the same patients 12 months after transplantation. Results and conclusion. The acute tubular injury was present in 90% and glomerular pathology in 17% of zero-time biopsies, with thin basement membranes (TBM ) being the most common entity (13%). Chronic graft changes were evaluated according to Banff classification. Most cases showed Banff scores ci0 (82.6%) and ct0 (65.1%). Banff scores cv2 and cv3 were present in 13% and ah2 and ah3 in 36.4% of specimens. Among 84 remeasured zero-time samples, TBM was present in 26 patients (31%). There were no differences between Banff scores and clinical parameters 12 months after transplantation between recipients with TBM and recipients with normal GBM thickness. Zero-time renal biopsy is of great importance for allograft assessment and comparison with consecutive biopsies. Further investigation is needed to determine the long-term significance of TBM on graft survival.

Previous studies have demonstrated cardiovascular causes to be among the leading causes of death after liver (LT) and kidney transplantation (KT). Although both recipient populations have unique pre-transplant cardiovascular burdens, they share similarities in post-transplant exposure to cardiovascular risk factors. The aim of this study was to compare cardiovascular mortality after LT and KT.We analyzed causes of death in 370 consecutive LT and 207 KT recipients from in-hospital records at a single tertiary transplant center. Cardiovascular causes of death were defined as cardiac arrest, heart failure, pulmonary embolism, or myocardial infarction.After a median follow-up of 36.5 months, infection was the most common cause of death in both cohorts, followed by cardiovascular causes in KT recipients and graft-related causes in LT recipients in whom cardiovascular causes were the third most common. Cumulative incidence curves for cardiovascular mortality computed with death from other causes as the competing risk were not significantly different (P = .36). While 1-year cumulative cardiovascular mortality was similar (1.6% after LT and 1.5% after KT), the estimated 4-year probability was higher post-KT (3.8% vs. 1.6%). Significant pre-transplant risk factors for overall mortality after KT in multivariable analysis were age at transplantation, left ventricular ejection fraction

This report describes data collected by the Croatian Registry of Renal Biopsies (CRRB) for the year 2019. Patients and methods: nine centers (82%) provided data for 255 native kidney biopsies. We assessed the anthropometric data, data on serum creatinine concentration (sCr), 24 h proteinuria, haematuria, serum albumin level, arterial hypertension, histological diagnosis, and complications after renal biopsy. Results: examined group consisted of 58% males, median age 58 y (18-80 y) and 42% women, median age 57 y (20- 86 y). Males had a more impaired renal function at the time of renal biopsy, nephrotic syndrome, and hypertension. The most prevalent clinical presenta tion were urinary abnormalities (34.9%). Among all biopsy cases, primary glomerular diseases were the most often found histology group (41.5%), and IgA nephropathy was the most frequent diagno sis(47.1%). Among secondary glomerular diseases, pauci-immune glomerulonephritis (PIGN) was most often found (30.9%). The highest proteinuria was observed in minimal change disease and dia betic nephropathy (DN). The highest sCR values were found in membranoproliferative glomerulone phritis (MPGN) and necrotizing vasculitis. Patients with MPGN and DN had the highest blood pressure levels. Conclusion: CRRB provides important data on the epidemiology of biopsy-proven kidney diseases from the whole territory of Croatia.

Introduction: primary membranous nephropathy (pMN) is glomerulopathy caused in the majority of cases by autoantibodies to Phospholipase-A2 receptors (PLA2R-AB). This study aimed to evaluate the clinical course and outcomes of the patients with pMN regarding PLA2R-AB status. Patients and methods: 32 patients (21 males, 11 females) with renal biopsy-proven pMN were included in the study. PLA2R-AB (ELI SA method) and outcomes (defined according to KDIGO) were evaluated after 21 and 64 months of follow-up in 28 patients. Results: 19 patients had positive PLA2R-AB (>20 RU /ml) (59.3%), with median titer of 97 (21-1418 RU /ml). The rate of remission in low PLA2R-AB titer group (< 200 RU /ml) after 21 months was significantly higher than in high PLA2R-AB group (> 200 RU /ml) (90% vs. 50%, p=0.045), and after 64 months the difference was not significant (80% vs. 50%, p=0.210). The relapse rate after 64 months was higher in the high PLA2R-AB group (87% vs. 63%). Multivariant linear regression found serum creatinine (ß=0.682, p, Uvod: primarna membranska nefropatija (pMN) je glomerulopatija, koja je u većini slučajeva uzrokovana autoprotutijelima na receptor za fosfolipazu A2 (PLA2R-PT). Cilj ovog istraživanja bio je analizirati povezanost PLA2R-PT s kliničkim tijekom i ishodima bolesti. Ispitanici i metode: 32 bolesnika (21 muškaraca, 11 žena), s biopsijom bubrega dijagnosticiranim pMN, bilo je uključeno u istraživanje. PLA2R-PT (ELI SA metoda) i ishodi (definirani u skladu s KDIGO) određeni su nakon 21 i 64 mjeseca praćenja u 28 bolesnika. Rezultati: 19 bolesnika imalo je pozitivna PLA2R-PT (>20 RU /ml) (59.3%), s medijanom titra 97 (21-1418 RU /ml). Stopa remisije u skupini s niskim titrom PLA2R-PT (< 200 RU /ml) nakon 21 mjeseca bila je značajno viša u odnosu na skupinu s visokim titrom PLA2R-PT (> 200 RU /ml) (90% vs. 50%, p=0.045), a nakon 64 mjeseca razlika nije bila značajna (80% vs 50%, p=0.210). Stopa relapsa nakon 64 mjeseca bila je viša u skupini s visokim titrom PLA2R-PT (87% vs. 63%). Multivarijatnom linearnom regresijom su kao značajni neovisni prediktori za bubrežnu funkciju na kraju praćenja nađeni serumski kreatinin (ß=0.682, p

Introduction: primary membranous nephropathy (pMN) is glomerulopathy caused in the majority of cases by autoantibodies to Phospholipase-A2 receptors (PLA2R-AB). This study aimed to evaluate the clinical course and outcomes of the patients with pMN regarding PLA2R-AB status. Patients and methods: 32 patients (21 males, 11 females) with renal biopsy-proven pMN were included in the study. PLA2R-AB (ELISA method) and outcomes (defined according to KDIGO) were evaluated after 21 and 64 months of follow-up in 28 patients. Results: 19 patients had positive PLA2R-AB (>20 RU/ml) (59.3%), with median titer of 97 (21-1418 RU/ml). The rate of remission in low PLA2R-AB titer group (< 200 RU/ml) after 21 months was significantly higher than in high PLA2R-AB group (> 200 RU/ml) (90% vs. 50%, p=0.045), and after 64 months the difference was not significant (80% vs. 50%, p=0.210). The relapse rate after 64 months was higher in the high PLA2R- AB group (87% vs. 63%). Multivariant linear regression found serum creatinine (ß=0.682, p

The aim was to determine the cost of hospitalization for a transplant procedure and identify the independent variables associated with the cost of transplantation. The investigation was designed as a retrospective single-center cohort study conducted at a tertiary university hospital transplant center in Zagreb, Croatia. The study included 219 consecutive kidney recipients transplanted during the 2007-2013 period at the Merkur University Hospital. There were 141 male and 78 female patients having undergone kidney transplantation during the study period. The majority of kidney transplants were from a deceased donor (n=179), while 40 were from a living donor. The mean cost of a transplantation was 86,140±42,240 HRK (11,460±5,600 €), ranging from 29,000 HRK (3,860 €) to 408,000 HRK (54,000 €). In the bivariate analysis, the variables associated with the cost of transplantation were the length of hospital stay, delayed graft function, death of the patient, graft loss, use of steroids, and death-censored graft loss. In the multivariate analysis, delayed graft function was the only statistically significant variable for the cost of transplantation. Since only delayed graft function had an impact on the cost of transplantation in this study, certain steps such as shortening of the cold ischemia time (better organization of organ transport), better education of family members for living donors, and higher percentage of patients on peritoneal dialysis should be taken to lower the percentage of delayed graft function., Cilj istraživanja bio je odrediti troškove hospitalizacije za postupak presađivanja bubrega i identificirati nezavisne varijable povezane s troškovima transplantacije. Istraživanje je provedeno kao retrospektivna kohortna studija u jednom kliničkom centru. Studija je obuhvatila 219 uzastopnih transplantacija bubrega u razdoblju od 2007. do 2013. godine u Kliničkoj bolnici Merkur, odnosno 219 bolesnika (141 muškaraca i 78 žena). Većina transplantiranih bubrega je bila od preminulog (n=179) donora, dok ih je 40 bilo od živog davatelja. Prosječni trošak transplantacije iznosio je 86.140±42.240 HRK (11.460±5.600 €). U bivarijatnoj analizi varijable povezane s cijenom transplantacije bile su trajanje hospitalizacije, odgođena funkcija presatka, smrt bolesnika, gubitak presatka, upotreba steroida i cenzurirani gubitak presatka. U multivarijatnoj analizi samo je odgođena funkcija presatka bila statistički značajna varijabla za troškove transplantacije. Budući da je samo odgođena funkcija presatka u ovom istraživanju utjecala na troškove transplantacije, potrebno je poduzeti određene korake kao što su skraćivanje vremena hladne ishemije (bolja organizacija transporta organa), bolje obrazovanje članova obitelji za žive donore i veći postotak bolesnika na peritonejskoj dijalizi kako bi se smanjila incidencija odgođene funkcije presatka.

Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, -1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, -1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was non-inferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.

Objective Determining the cost of hospitalization for a transplant procedure and identifying the independent variables associated with the cost of transplantation. Design Retrospective single-center cohort study. Setting Tertiary university hospital transplant center in Zagreb, Croatia. Participants 219 consecutive kidney recipients, transplanted in the 2007– 2013 period, in the Merkur University Hospital. Results This study included 219 patients (141 males and 78 females) who received the KT between 2007 and 2013 in our center. The majority of kidney transplants were from a deceased donor (179), while 40 were from a living donor. The average cost of a transplantation was HRK 86140± 42240, with 29000 being the minimum and 408000 being the maximum. In the bivariate analysis, the variables associated with the cost of transplantation were the duration of hospitalization, DGF, death of the patient, graft loss, use of steroids, and death-censored graft loss. In the multivariate analysis, DGF was the only statistically significant variable for the cost of transplantation. Conclusions Since only DGF had an impact on the cost of transplantation in this study, certain steps, such as shortening of the cold ischemia time (better organization of organ transport), better education of family members for living donors, and higher percentage of patients on PD, should be taken to lower the percentage of DGF.

Background: Hepatitis E virus (HEV) infection is an emerging infectious disease in many European countries. Previous studies in Europe indicate that HEV seroprevalence among patients on maintenance haemodialysis (HD) ranges from 1% to 37%. Risk factors for HEV infection among HD recipients are not fully understood. The aim of this study was to determine the prevalence and risk factors for HEV infection among HD recipients in Croatia, to propose recommendations for preventive measures. Methods: We implemented a cross-sectional study, inviting 515 individuals on HD from 6 medical facilities in 5 Croatian cities.Three facilities are in the continental region (Zagreb sites 1 and 2, and Osijek) and 3 in the coastal region (Sibenik, Dubrovnik and Pula). A self-administered questionnaire elicited risk factors for HEV infection: age, gender, food and water consumption, travel, household composition, animal contact, transfusion history and hemodialysis duration. Blood samples were tested for IgG HEV antibody using an enzyme immunoassay. Results: A total of 392 HD recipients (76%) participated ; their median age was 70.5 years (range 21-92 years) and 145 (37%) were female. IgG HEV antibodies were detected in 125 (32%) of participants. Multiple logistic regression indicated that age (OR=1.03 ; 95%CI=1.01-1.05) and living in the continental region (OR=3.55 ; 95%CI=2.12-5.96) were risk factors for HEV seropositivity. Conclusions: Almost 1/3 of HD recipients in Croatia had been exposed to HEV, which is among the highest seroprevalence rates reported in Europe. As HEV infection has been documented among pigs in the continental region of Croatia, we hypothesize that traditional pork- based food consumption could be an important risk factor, and should be investigated further. Routine HEV screening among HD recipients is recommended in this part of Croatia.

INTRODUCTION: Histologic changes of kidney vessels are common finding on kidney graft biopsies at the time of kidney transplantation (Tx). There are two types of vascular changes: fibrointimal thickening of vessel wall (cv) affecting bigger vessels and arteriolar hyalinosis (ah) affecting afferent arterioles. We aimed to investigate prevalence, type and grade of graft vessel changes at time of Tx and their relation on graft function after Tx. METHODS: We retrospectively examined patients with kidney or simultaneous kidney and pancreas transplantation in University Hospital Merkur from 2008 until 2016. Eligible patients had to have protocol kidney biopsy at the time of implantation and 1 year after Tx. Kidney biopsies were analysed by light, immunoflorescence and electron microcopy. Graft vessel changes were scored in accordance with the Banff 97 classification and its updates. Progression of cv (∆cv) and ah (∆ah) score was calculated by subtracting implantation scores from scores 1 year post-transplant. In assesment of graft function we used eGFR based on MDRD formula and PCR (protein/creatinine ratio) in single urine sample. All statistical analyses were performed using “Statistica 17“ program and statistical significance was considered at p

Considering the reported cases of invasive pneumococcal disease in advanced chronic kidney disease patients, in May 2017 the Steering Board of the Croatian Society of Nephrology, Dialysis and Transplantation (CSNDT) of the Croatian Medical Association issued a decision on the preparation of Guidelines for the prevention of pneumococcal diseases in patients with chronic kidney disease. The Guidelines are based on relevant medical literature, Guidelines of the European Society of Clinical Microbiology and Infectious Diseases, the World Association for Infectious Diseases and Immunological Disorders, and the Program for immunization, seroprophylaxis and chemoprophylaxis for special population groups of the Croatian Institute of Public Health. Nephrologists, infectologists and epidemiologists were involved in their development. There are two types of pneumococcal vaccine available in Croatia that can be used for adults, conjugated vaccine PCV13 and polysaccharide vaccine PPSV23. The Guidelines include planning and implementation of vaccination in chronic kidney disease patients who replace kidney function with hemodialysis, peritoneal dialysis, renal transplant, or are candidates for treatment by transplantation, having one or more comorbidities: diabetes mellitus, chronic pulmonary disease, chronic cardiovascular disease, chronic advanced liver disease, chronic kidney disease with solid or hematological tumors, and splenectomy.

Background: After the introduction of MELD score in liver allocation, the number of simultaneous liver- kidney transplantations (SLKT) significantly increased therefore contributing to the shortage of allografts for patients waitlisted for kidney transplantation. We analyzed the data in our high- volume transplant center with a stable number of SLKT and reviewed our biopsy-guided kidney allocation policy in pts with renal dysfunction undergoing liver transplantation (LT). Methods: We analyzed LT and SLKT performed in UH Merkur, Croatia from April 2007 to April 2018. As significant renal impairment at time of enlisting we defined serum creatinine higher or equal to 2 mg/dL, renal replacement therapy (RRT) or pathologic proteinuria higher than p/c 1 g/g. Results: In total 1056 LT and 19 SLKT were identified. 129 pts fulfilled the criteria for renal impairment given above. There were 95 male pts (73, 6%). 13 patients had ESRD receiving RRT prior to referral for LT and were automatically enlisted for SLKT. From those 13, in 2 pts SLKT was performed because of primary hyperoxaluria. In evaluation of other pts with renal dysfunction 22 renal biopsies were performed under US guidance after correction of coagulation parameters. There were no major complications of biopsies. Other 94 pts were diagnosed with acute kidney injury/hepatorenal syndrome (AKI/HRS). The most common pathohistological diagnosis was IgA nephropathy (63, 6%), followed by ATN (18, 2%) and diabetic nephropathy (9, 1%). The cut-off for SLKT was more than 40% interstitial fibrosis and tubule atrophy (IFTA), or more than 30% of globally sclerosed glomeruli (GS) on biopsy. Based on biopsy results additional 6 pts were enlisted for SLKT. None of the patients with presumed AKI/HRS who received only LT and survived for more than one- month post-LT required RRT at one-month post-LT. Conclusions: We believe that kidney biopsy is a useful and safe tool to avoid kidney graft wasting when evaluating enlistment for SLKT. We enlist a patient for SLKT if IFTA is higher than 40% or GS more than 30%. A separate indication for SLKT are metabolic diseases. In decompensated liver cirrhosis HRS develops and makes evaluation of kidney recovery potential speculative. In our experience, percutaneous kidney biopsy in pts with advanced liver disease was not linked to adverse events and is a safe procedure in experienced centers.

HLA mismatches between donor and recipient frequently lead to production of HLA-specific antibodies. The HLAMatchmaker is a computer algorithm that compares HLA compatibility at the structural level and considers each HLA specificity as multiple linear triplet-defined epitopes to identify the number of shared and nonshared epitopes between donor and recipient. The PIRCHE-II (predicted indirectly recognizable HLA epitopes) is another algorithm which predicts donor-HLA-derived peptides presented by the recipient’s HLA-DRB1 molecules which may be detected by the patients’ T cells. It has been shown that the result score of both algorithms correlate with the risk of HLA donor-specific antibodies (DSA) development. This case present prediction of immunogenicity and the risk of DSA formation based on the mismatched (MM) HLA antigens between cadaveric donor and patient waiting the third kidney transplantation, using HLAMatchmaker and PIRCHE-II algorithm. The patient is 38 years old male who recieved first kidney graft from living donor in 2007 (ABDR MM 000), and only two months later was re-transplanted with the kidney from the second living donor (ABDR MM 011). At the time of returning to the waiting list in 2017, the antibody profile of the patient, determined by Luminex LSA class I and class II Single Antigens beads (SA1, SA2), was negative for antibodies against HLA class I antigens and positive for the presence of HLA class II antibodies (DR1, DR7, DR9, DR10, DR15, DR16, DR51, DR53, DQ8, DQ9, DQA1*03) among which there were DSAs against the second donor: DR53 (MFI 6100), DQ8 (MFI 2200-3400) and DQA1*03 (MFI 2600-3800 ). In October 2017, the patient received kidney offer from cadaveric donor and the chance for the third transplantation. The donor/patient ABCDRDQ MM was 12200, with Luminex SA1, SA2 testing results negative for all ABCDRDQ MM antigens. Patient's and potential third donor's HLA-A, -B, -C, -DRB1 and DQB1 alleles, determined at low resolution level, were assigned to the most common corresponding four digit HLA allele and were entered into the HLAMatchmaker program (version 02) to determine the number of donor eplets that were absent in the patient as well as in the PIRCHE-II algorithm (version 2.4.21) to predict the presentation of HLA-derived mismatched peptide by the patient’s HLA-DRB1 molecules. The donor and patient were mismatched for HLA-A3, B27, B35, Cw2 and Cw4 antigens. The HLAMatchmaker analysis revealed 12 epitopes in total differing beetwen donor and the patient among which only 5 epitopes were „Antibody-verified Epitopes“ (AbVerEp ; identified experimentally with informative HLA antibodies). The PIRCHE-II score was 29. According to Lachmann et al. patients with a HLAMatchmaker score ≥5 to

Introduction: Screening for hepatitis B (HBV) and hepatitis C (HCV) viruses is a requirement in organ transplantation. The information acquired influences organ allocation and post-transplant management. The goal of this review was to determine HBV and HCV serological profiles of liver and kidney donors and recipients. Methods: HBV and HCV serologies were retrospectively obtained for adult liver and kidney recipients and their donors between 6/2006 and 6/2016 using a hospital transplant database. Results: In total 1308 serological profiles of organ recipients and their donors were analyzed. There were 452 kidney (65% male, mean age 49.5 _12.5 years.) and 856 liver recipients (72% male, mean age 55.1 _ 10.4 years). 1.5% kidney and 5.4% liver recipients were hepatitis B surface antigen (HBsAg) positive. 34.5% of kidney and 69.7% of liver recipients were non-immune to HBV. The prevalence of successful pre-transplant HBV vaccine immunity was greater in kidney than in liver recipients (36.9% vs 5.5%). 2.2% of kidney and 3.4% of liver recipients were only HBcAb positive. HBV vaccine immunity of both organ recipient groups did not change significantly during period of 10 years (p = ns). There were 2.2% kidney and 15.7% liver HCV antibody positive recipients. 1.1% of kidney and 0.2% of liver recipients were both HBsAg and HCVAb positive. From the total number of kidney grafts, 8.85% were HBcAb positive and no kidney grafts were HBsAg or anti-HCV positive. From the total number of liver grafts 7.7% were HBcAb, 0.1% HBsAg and 0.2% HCVAb positive. Conclusion: The prevalence of HBV and HCV HBV co-infection in organ recipients is low, as well as the prevalence of anti-HCV in kidney patients at the time of transplant. HBV immunity in the pre-transplant liver kidney cohort is low and has not changed significantly in the observed period. This analysis indicates that greater efforts should be implemented in the pre-transplant vaccination process.

INTRODUCTION AND AIMS: As natural course of iMN varies it is important to determine clinical and laboratory parameters reliable for prediction of clinical outcome and decision on immunosuppressive treatment. Antibodies against M-type phospolipase A2 receptor ( anti PLA2R) are considered highly specific for iMN. In this first Croatian multicenter retrospective study we evaluate the clinical course and prognosis of patients with iMN regarding anti PLA2R status. METHODS: We included 32 consecutive patients (21 M, 11 F) between 8/2014 and 6/2016, median age 55 (20-81) years with biopsy proven iMN and follow-up of at least 6 months. Anthropometric characteristics, blood pressure (BP), hemoglobin (Hb), serum creatinine (sCr), eGFR, 24 proteinuria, serum albumine (sAlb) and atiPLA2R levels (ELISA) were determined in all patients at the time of renal biopsy and during follow-up. All patients were treated with combinations of corticosteroids, cyclophosphamide, cyclosporine and mycophenolate mophetil according to KDIGO guidelines. We defined complete remission as persistent proteinuria < 0.3 g/du and normal serum creatinine (cCr) and partial remission as persistent proteinuria < 3.5 g/du and decrease > 50% from baseline with stable sCr. RESULTS: 19 patients had positive antiPLA2R (> 20 RU/ml) (59, 3%), median 97 ( 21-1418 ) RU/ml. There were no significant differences in basal values of BP, Hb, sCr, eGFR, proteinuria and sAlb between antiPLA2R positive and negative group as well as according to gender. Median follow- up was 18 (range 6-84) months. When we analyse patients regarding lower (< 200 RU/ml) and higher levels (>200 RU/ml) of antiPLAR significant difeference in remision rate was observed (90 vs 50%, χ2 4.0, p=0.045). Highest antiPLA2R values were found in group without remission (88 vs 265 RU/ml p=0.093). Significant positive correlations were found between antiPLA2R levels and sCr (r=0.401 p=0.023) and proteinuria (r=0.493, p=0.004). Multiple regression analysis indicate basal sCr (ß=0.682, p

Rad opisuje značajke odbacivanja bogatog plazma stanicama u primatelja bubrega i gušterače ili bubrega i jetre

Introduction: Screening for hepatitis B (HBV) and hepatitis C (HCV) viruses is a requirement in organ transplantation. The information acquired influences organ allocation and post- transplant management. The goal of this review was to determine HBV and HCV serological profiles of liver and kidney donors and recipients. Methods: HBV and HCV serologies were retrospectively obtained for adult liver and kidney recipients and their donors between 6/2006 and 6/2016 using a hospital transplant database. Results: In total 1308 serological profiles of organ recipients and their donors were analyzed. There were 452 kidney (65% male, mean age 49.512.5 years.) and 856 liver recipients (72% male, mean age 55.110.4 years).1.5% kidney and 5.4% liver recipients were hepatitis B surface antigen (HBsAg) positive. 34.5% of kidney and 69.7% of liver recipients were non-immune to HBV. The prevalence of successful pre-transplant HBV vaccine immunity was greater in kidney than in liver recipients (36.9% vs 5.5%). 2.2% of kidney and3.4% of liver recipients were only HBcAb positive. HBV vaccine immunity of both organ recipient groups did not change significantly during period of 10 years(p=ns). There were 2.2% kidney and 15.7% liver HCV antibody positive recipients. 1.1% of kidney and 0.2% of liver recipients were both HBsAg and HCV Ab positive. From the total number of kidney grafts, 8.85% were HBcAbpositive and no kidney grafts were HBsAg or anti-HCV positive. From the total number of liver grafts, 7.7% were HBcAb, 0.1% HBsAg and 0.2% HCVAb positive. Conclusion: The prevalence of HBV and HCV HBV co- infection in organ recipients is low, as well as the prevalence of anti-HCV in kidney patients at the time of transplant. HBV immunity in the pre- transplant liver kidney cohort is low and has not changed significantly in the observed period.

A case of TTP after childbirth.

Background: Screening for hepatitis B (HBV) and hepatitis C (HCV) is a requirement in organ transplantation. The information acquired influences organ allocation and further recipient treatment. The goal of this study was to determine the serological profile of kidney graft recipient and donor cohort, as well as the HBV immunity status. Methods: Analysis was conducted using University Hospital Merkur transplant database. HBV and HCV pre- transplantat serology profiles were obtained for kidney transplant donors and recipients from 5/2007 to 6/2016. Results: In the analyzed period there were 452 kidney transplantations (294 male recipients, mean age 49.5 ± 12.5 yrs). 7 (1.5%) recipients were hepatitis B surface antigen (HBsAg) positive. 34.5% of the recipients were HBV non-immune. 37.1% were only HBsAb positive due to vaccination. 10 (2.2%) were only HBcAb positive (Table 1). HBV immunity in the observed period did not change significantly (2007-2011 vs. 2012-2016, p=0, 28) There were 10 (2.2%) HCVAb positive recipients. From the total number of kidney grafts, 40 (8.85%) were HBcAb positive. No grafts were HBsAg or HCVAb positive. Conclusion: HBV immunity in the cohort is low and it has not changed significantly in the observed period. Prevalence of HCVAb in CKD patients undergoing transplantation is low. This analysis shows that greater efforts should be implemented in pre- transplant HBV vaccination.

Introduction: Antineutrophil cytoplasmic antibodies are a major cause of rapidly progressive glomerulonephritis (RPGN). Routinely tested ANCA are MPO and PR3. A number of atypical ANCA is also known, such as anti- bactericidal/permeability-increasing protein(BPI) ANCA, which is a well-described cause of vasculitis. Overlap syndromes of pauci-immune ANCA GN and immune complexes (IC)- mediated GN have been reported. After a review of literature, this is the first reported case of BPI-ANCA associated RPGN with IC. Case Description: A 35- year-old Caucasian male with cryptogenic liver cirrhosis was referred to our hospital with the diagnosis of hepatorenal syndrome. At admission, the pt was dialysis-dependent and oliguric. An active urine sediment (E >50, L 15, casts) was noted with P/C 2.6 (g/g). Kidney biopsy was performed. The finding was diffuse endocapillary proliferative glomerulonephritis, active, without signs of chronicity. Immunoflorescence (IF) was positive for IgG, IgM, C3, k and l chains. ANA, ENA, dsDNA, RF, anti-CCP, LAC, cardiolipin IgG and IgM, beta-2 glycoprotein were negative. Serum C3 was 0.53 g/L (0.90-1.80) and C4 0.15g/l (0.10- 0.40). Testing for HCV, HBV and HIV was negative, as well as bacterial respiratory and urine cultures. ANCA was positive by IF (1:640), with negative ELISA for PR3- and MPO-ANCA. ANCA was specified as BPI-ANCA. The pt was treated with combination of PEX, steroid pulses and iv cyclophosphamide (CYC). After 4 PEX, ANCA declined to 1:160. After 10 days the pt was no longer dialysis-dependent. He received in total 6 CYC pulses. After a follow-up of 6 months, his eGFR is 115ml/ min/1.73m2, without pathological proteinuria. Discussion: This is to our knowledge the first described case of BPI-ANCA-associated RPGN with IC. Pathohistology corresponded to lupus grade IVa nephritis (lupus-like nephritis, as serology was negative). Due to ANCA, PEX was added to steroids and CYC. This is an educational case demonstrating the presence of BPI-ANCA in a pt with IC GN. ANCA testing by IF is important for detection of atypical ANCA.

Calcific uremic arteriolopathy or alciphylaxis is a malignant form of calcification of small arteries and arterioles, usually present in patients with chronic kidney disease and dialysis therapy. It causes high mortality. Histological distinctive feature are calcium deposits lining vascular intima. Calcification of medial muscle layer, inflammation and necrosis of subcutaneous adipose tissue are frequent. The disease begins with painful violaceous mottling, resembling livedo reticularis. Ths skin lesion progresses to ulcers and eschars, sometimes it becomes very vulnerable to secondary infection which can often develop into fatal sepsis. Our first patient with proximal form of calciphylaxis dies in repeated sepsis. The second patient with the distal form of calciphylaxis was treated successfully. The decisive moment was the use of calcimimetic. A multiinterventional strategy is likely to be more effective than any single therapy. It is necessary to regulate metabolism of calcium phosphate and secondary hyperparathyroidism. Effectiveness has been demonstrated using calcimimetics, sodium thiosulfate, oxygen therapy, careful application of biphosphonates and surgical procedures. Warfarin withdrawal is urgently recommended and subsequent vitamin K supplementation is appropriate. The control of infection is critically important and the use of carbonylated hemoglobin in the stage without infections could accelerate the wound healing.

Background: Interstitial fibrosis (ci) is a major histological predictor of long-term graft outcome. This randomized controlled trial (NCT01860183) was designed to evaluate the effect of intensified mycophenolate mofetil (MMF) dosing on progression of ci during the first year post kidney transplant (KT). Methods: Immunologically low-risk KT recipients were randomized on MMF 3g/d, or 2g/d during the first year post KT. Immunosuppression consisted of basiliximab induction, with tacrolimus, MMF ± steroids. Protocol biopsies were performed at implantation, and at 12 months post KT and were scored according to the Banff. Progression of ci (Δci) was calculated as ci12-ci0. MMF dose was calculated as an average dose at 1, 3, 6 and 12 months. Difference in Δci with respect to MMF dose was analyzed in an ITT population using one- way ANOVA. Results: Here we report interim results from patients who completed 12 month follow-up by June 1st 2015. Patient and KT data are were similar in MMF 3g and MMF 2g group, except for average MMF dose, which was higher in the 3g group (2697.1±321.6 vs. 1745.5±359.0 g, p

Background: Intensity of overall immunosuppression is a risk factor for BK virus infection (BKVI). However, the exact impact of exposure to tacrolimus and mycophenolate mofetil (MMF) to BKVI is unclear. The aim of this study was to determine if BKVI in kidney transplant (KT) recipients (KTR) is associated with drug exposure to MMF. Methods: This prospective randomised controlled clinical trial (NCT01860183) included 36 KTR who underwent KT from May 2013 to February 2015 at Clinical Hospital Merkur. Immunosuppression consisted of basiliximab induction, with tacrolimus, MMF ±steroid maintenance. KTR were randomized in two groups, with respect to MMF dose (2g or 3 g daily). Urine cytology for decoy cells was performed at prespecified time-points posttransplant. KTR were followed up to 12 months post KT. Graft biopsy was performed per protocol at 2, 6 and 12 months, or in case of graft dysfunction. Kaplan-Meier analysis with log-rank test was used to assess graft survival. A Cox regression was used to determine variables associated with graft survival. Results: 13 (37.1%) KTR had decoy cells in urine, 4 (11.4%) KTR had biopsy-proven BK virus-associated nephropathy (BKVAN). The mean time-to-occurrence was 4.8 months for decoy cells and 4.3 months for BKVAN. Cumulative one-year overall graft survival was 93.5%. Incidence of decoy cells, BKVAN, or acute rejection was similar in the two MMF groups. Rejection was not a risk factor for decoy cell positivity or for BKVAN. Conclusions: MMF dose may not increase risk for BKVI after kidney transplantation.

Background: We have recently found that higher average mycophenolate mofetil (MMF) dose during fi rst posttransplant year was associated with decreased progression of interstitial fi brosis and tubular atrophy during fi rst posttransplant year in kidney transplant recipients. In the present study we sought to evaluate effect of MMF dose on total interstitial infl ammationscore at one year.Methods: This is a single-center retrospective study in which 67 kidney, or kidneypancreas recipients with 12 month protocol biopsy were included.Patients with recurrence of glomerulonephritis and with BKV nephropathy were excluded from the analysis. Immunosuppression consisted of anti-IL2 induction, with tacrolimus or cyclosporine and MMF ± steroid maintenance.During 2007-2010 MMF was dosed in our center according to C0 monitoring, which led to its dose dispersion (1000-4000 mg/day). Total interstitial infl ammation (ti score) and interstitial fi brosis (ci score) were determined according to Banff classifi cation. Creatinine clearence (eClcr) was estimated by the Cockroft-Gault formula. Results: Recipients, were 44.75 ± 12.34 y/o, 65 percent of them were male. There were 20 living donor transplantations. At 12 months postttransplant mean MMF dose was 2205 ± 627 mg/d, eClcr 62.1 ± 16.4 ml/min, ci score 0.87 ± 0.78 and ti score 0.72 ± 0.88. Average MMF dose during fi rst posttransplant year was 2238 ± 571 mg. There was positive correlation between 12 months ci and ti score (r=0.716, p

Background: Liver transplantation (LT) is an established treatment method in patients with hepatocellular carcinoma (HCC). However, a number of patients experience early recurrence and poor results as a consequence of aggressive tumor biology. Due to the ever increasing organ shortage, new biologic prognostic factors are necessary in order to stratify the patients regarding prognosis. Methods: 44 patients with HCC treated by LT were included in this retrospective study. Analyzed clinical and pathologic data include age, sex, number and size of tumors, tumor differentiation, presence of vascular invasion, adherence to Milan criteria, alpha-fetoprotein level. Immunostaining was used to assess the infiltration of CD3+, CD4+, CD8+ and Foxp3+ cells. Kaplan Meier curves and receiver operator characteristic (ROC) analysis were used to analyze recurrence free and overall survival. Results: Presence of microvascular invasion was found to be associated with HCC recurrence (p=0.035). Analysis of immune parameters showed that the patients with increased total lymphocyte infiltration measured by the number of tumor infiltrating CD3+ cells are less likely to experience recurrence (p=0.05). ROC curve analysis showed that patients with a CD4/CD8 ratio greater than 1 had better chances of recurrence free survival. Also, patients with lower numbers of infiltrating T reg cells were found less likely to experience HCC recurrence (p=0.025). Conclusion: Our results indicate that total lymphocyte infiltration, CD4/CD8 ratio and T reg infiltration have prognostic significance in HCC. These parameters could add valuable information to the presently used morphologic criteria in order to stratify HCC patients who benefit from liver transplantation.

Glomerulonephritis (GN) after renal transplantation can be caused by recurrent disease, development of de novo GN in the transplanted organ, or transplanted GN from a donor with unrecognized disease. It is an underlying cause of end-stage renal failure in 30%-50% of kidney transplant recipients. We analyzed clinical data and histopathologic findings of patients who had biopsy proven glomerulonephritis after renal transplantation diagnosed at Department of Pathology, Dubrava University Hospital. Clinicopathologic data of six patients with biopsy proven GN after renal transplantation were collected to assess the prevalence, clinical course and outcome of the disease. Five males and one female (age range 29- 47, mean 37.6 years) had biopsy proven GN, diagnosed 6-525 days after transplantation. Four patients presented with abnormal and two with normal clinical and laboratory data. Focal segmental glomerulosclerosis (FSGS) was diagnosed in three patients. IgA nephropathy, membranoproliferative GN type I and pauci-immune GN (PI-GN) were diagnosed in one patient each. Five patients had recurrence of primary disease (3 patients with FSGS, one membranoproliferative GN and one PI-GN). IgA nephropathy developed de novo in a patient with autosomal dominant polycystic kidney disease. At the end of follow up (1.5-7 years after transplantation), three patients were on chronic dialysis, two had normal and one abnormal graft function. In conclusion, in our study FSGS was the most common GN after transplantation. The graft loss in our transplant patients with GN was 50%.

Objective: To show the epidemiology of renal diseases. Method: We performed a retrospective statistical analysis of native renal biopsies diagnosed in Dubrava University Hospital Zagreb, during period April 2003–December 2012. Results: During analyzed period a total of 1981 native renal biopsies were found. Patient’s age range 1– 88 years (average 47.1). Biopsies originate from 11 Croatian hospitals and Mostar University Hospital (Bosnia and Herzegovina). Men had 1.3× more biopsies than women (M:F=1, 085:806). Glomerular diseases were the most frequent diagnosis (70.9 %) followed by diseases of the blood vessels (8.8 %) and tubulointerstitium (5.0 %). Primary glomerular diseases were 1, 4× more frequent than secondary. IgA nephropathy was the most common disease diagnosed in 18.9 % biopsies, followed by focal segmental glomerulosclerosis (12.1 %) and membranous glomerulonephritis (8.4 %). Pauci-immune glomerulonephritis was the most common secondary glomerular disease in our sample (6.9 %), followed by lupus nephritis (5.6 %) and diabetic nephropathy (5.5 %). Some diseases were more frequently diagnosed in women than in men and vice versa. Conclusion: At present time, two- thirds of renal biopsies performed in Croatia are processed by our laboratory. We believe that presented data are representative and provide detailed information about incidence, prevalence and trends in epidemiology of renal diseases in Croatia.

Background: Studies have reported signifi cant improvement in kidney function in patients on MMF with lower exposition to calcineurin inhibitors.The optimal long-term MMF dosing in patients maintained on contemporary low-dose calcineurin inhibitors is still undetermined. The aim of our study was to determine effect of MMF dose on kidney function over fi ve years post-transplant. Methods: A cohort of 171 transplant patients with kidney, kidney- pancreas and kidney-liver transplantation was included. Immunosuppression consisted of anti- IL2 or antithymocyte immunoglobulin induction with MMF, calcineurin inhibitors ± steroids. Estimated creatinine clearence (eCrcl) was calculated using Cockroft Gault formula. MMF dose at 1, 2, 3, 4 and 5 years was correlated with eCrcl at respective time point. Univariate and multiple regression analyses were done to test relationship between independent variables and eCrcl. Data are shown as mean±SD, or median with range. Results: 105 patients had kidney transplantation and 58 kidney-pancreas transplantation. Recipients were a mean of 42.3 ± 12.03 years old at the time of transplantation, 63 percent of them were male and all were Caucasians. Donors were a mean of 42.8 ± 16.2 years old. There were 46 living donor transplantations. eCrcl at 1, 2, 3, 4 and 5 years post-transplant positively correlated with average MMF dose (p

The aim of the study was to assess the incidence of native renal diseases diagnosed by biopsy at Department of Pathology, Dubrava University Hospital. Renal biopsy registry kept at the Department was reviewed over a nine-year period (from April 2003 to December 2012), with retrospective statistical analysis of data on native renal diseases. During the study period, a total of 1981 native renal biopsies were performed, with patient age range 1-88 (mean 47.1) years. Biopsies originated from 11 Croatian hospitals and Mostar University Hospital (Bosnia and Herzegovina). Men had 1.3 times more biopsies than women (M:F=1085:806). Glomerular diseases were the most frequent diagnosis (70.9%), followed by diseases of the blood vessels (8.8%) and tubular interstitium (5.0%). Primary glomerular diseases were 1.4 times more frequent than secondary ones. IgA nephropathy was the most common disease diagnosed in 18.9% of biopsies, followed by focal segmental glomerulosclerosis (12.1%) and membranous glomerulonephritis (8.4%). Pauci-immune glomerulonephritis was the most common secondary glomerular disease in our sample (6.9%), followed by lupus nephritis (5.6%) and diabetic nephropathy (5.5%). Normal renal parenchyma was found in 3.7% of biopsies. End stage renal disease of unknown cause was found in 0.8% of biopsies. Some diseases were more frequently diagnosed in women than in men and vice versa. IgA nephropathy was 2.7 times (M:F=263:96), diabetic nephropathy 2.4 times (M:F=73:31) and FSGS 1.9 times more frequently diagnosed in men than in women. Lupus nephritis was 2.8 times more frequently diagnosed in women than in men (F:M=78:28). In conclusion, currently two-thirds of renal biopsies performed in Croatia are processed by our laboratory. We believe that the data presented are representative and provide detailed information on the incidence, prevalence and trends in the epidemiology of renal diseases in Croatia.

Introduction and Aims: Renal biopsy database in the Department of Pathology, Dubrava University Hospital was created in 2003. The aim of the database is to accumulate computer-based pathologic data concerning all renal biopsy samples examined at the Department. With our database we can show the epidemiology of renal diseases diagnosed by kidney biopsy: incidence and trends in epidemiology. The aim of this study is to show incidence of some of the renal diseases that were diagnosed at our Department from 2003.-2010.. Methods: We have reviewed the database over a 7 years period and performed statistical analysis of our data including number of biopsies through years, patients gender, age, number of biopsies per patient, diagnoses and hospitals where the biopsy was performed. Results: During a 7 years period there were 2177 renal biopsies (1279 males ; 883 females, 15 donor kidneys, mean age 51 years). There were 1274 native renal biopsies and 888 renal transplant biopsies. Biopsies originate from 11 croatian hospitals and 1 hospiital from Bosnia and Herzegovina. The number of biopsies increased 15, 9 times in that period (from 34 biopsies in 2003. to 542 in 2010.). Among 1274 native renal biopsies, men were 1, 4 times more biopsied than women (M:F=734:540). Among them, glomerular diseases were the most frequent diagnosis (80%). The most common diagnose was IgA nephropathy, diagnosed in 223 cases followed by focal segmental glomerulosclerosis (FSGS) in 180 cases. Among 888 renal transplant biopsies men had 1, 3 times more biopsies then women, (M:F=546:342), mean age was 47, 4 years. Acute tubular injury was the most common disease diagnosed in 332 samples, followed by acute cellular rejection in 212 renal transplant biopsy samples. Conclusions: Primary glomerular diseases were 1, 6 times more frequent then secondary. Some diseases are more frequent in men then in women and vice versa. To our knowledge around 80% of renal biopsy samples from Croatia are examined in our department. Our results show the epidemiology of the renal diseases requiring biopsy in almost whole Croatia.