THE COST OF KIDNEY TRANSPLANTATION AT THE MERKUR UNIVERSITY HOSPITAL, ZAGREB, CROATIA.

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.

Periodontal inflamed surface area in patients on haemodialysis and peritoneal dialysis: a Croatian cross-sectional study.

BACKGROUND: The decision to initiate dialysis treatment via haemodialysis (HD) or peritoneal dialysis (PD) often involves the consideration of complex factors and remains a matter of debate. The purpose of this study was to quantify the inflammatory burden that periodontitis causes in dialysis patients and to examine whether patients on PD and HD differ in terms of the periodontal inflamed surface area (PISA), which can be helpful for selecting the most appropriate dialysis modality. METHODS: A cross-sectional study was performed on 58 consecutive patients on HD and 31 consecutive patients on PD. PISA was calculated using measurements of the clinical attachment level, recession and bleeding on probing. We performed the primary analysis using multivariable robust regression. RESULTS: Patients on PD had a 746 mm2 (93%) lower mean PISA than patients on HD after adjustment for 20 possible confounders, including the duration of dialysis. The type of dialysis was independently correlated with the PISA (semipartial correlation: - 0.50; p = 0.017; false discovery rate < 5%). After adjusting for confounding factors, the correlation between the duration and type of dialysis was not significant (F (2,44) = 0.01; p = 0.994; η2 = 0.00). Differences in the PISA between patients who had undergone dialysis for less than a year, 2-3 years or ≥ 3 years were not significantly different in either of the two dialysis groups. CONCLUSIONS: PISA levels in Croatian patients on dialysis indicate a high need for periodontal treatment. PD is associated with a smaller PISA independent of many sociodemographic, lifestyle, laboratory and clinical factors. The duration of dialysis does not influence PISA levels. TRIAL REGISTRATION: ISRCTN17887630. A clinical study to investigate gum infection in patients undergoing kidney dialysis.

IgM as a novel predictor of disease progression in secondary focal segmental glomerulosclerosis.

AIM: To determine the role of immunoglobulin M (IgM) deposits in clinical manifestations, disease outcome, and treatment response of idiopathic and secondary focal segmental glomerulosclerosis (FSGS). METHODS: Kidney biopsy specimens of 171 patients diagnosed with FSGS (primary and secondary) and 50 control patients were retrospectively included in the study. For each patient, clinical and outcome data were obtained and compared to morphological parameters, including immunofluorescence analysis of mesangial IgM and complement 3 (C3) deposits analyzed on kidney biopsy samples. RESULTS: There were significant positive correlations between IgM and C3 deposition in secondary FSGS (P<0.001) and between IgM and mesangial deposits detected by electron microscopy in secondary FSGS (P=0.015), which indicated that higher IgM deposition correlated with higher C3 deposition and mesangial deposits only in secondary FSGS. Patients with secondary FSGS and the deposition of IgM showed inferior renal outcomes at earlier time points in comparison with patients with negative IgM expression (P=0.022). CONCLUSIONS: We detected a positive correlation between IgM and C3 in secondary FSGS. The association between IgM deposition and worse renal outcome in secondary FSGS indicates that IgM may play a role in the progression of this disease.

[Calcific uremic arteriolopathy: clinical features and treatment]. / Kalcificirajuca uremijska arteriolopatija: klinicka slika i lijecenje.

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.

[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.

Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: Fractionated plasma separation and adsorption (FPSA) is an extracorporeal procedure that supports liver function by removing endogenous toxins that cause complications from acute-on-chronic liver failure (AOCLF). We performed a randomized trial to investigate survival of patients with AOCLF treated with FPSA. METHODS: Patients with AOCLF were randomly assigned to groups given a combination of FPSA and standard medical therapy (SMT) (FPSA group, n = 77) or only SMT (SMT group, n = 68). The Prometheus liver support system was used to provide 8 to 11 rounds of FPSA (minimum of 4 hours each) for 3 weeks. Primary end points were survival probabilities at days 28 and 90, irrespective of liver transplantation. RESULTS: Baseline clinical parameters and number of transplant patients were similar between study arms. Serum bilirubin level decreased significantly in the FPSA group but not in the SMT group. In an intention-to-treat analysis, the probabilities of survival on day 28 were 66% in the FPSA group and 63% in the SMT group (P = .70); on day 90, they were 47% and 38%, respectively (P = .35). Baseline factors independently associated with poor prognosis were high SOFA score, bleeding, female sex, spontaneous bacterial peritonitis, intermediate increases in serum creatinine concentration, and combination of alcoholic and viral etiology of liver disease. There were no differences between the 2 groups in the incidence of side effects. CONCLUSIONS: Among all patients with AOCLF, extracorporeal liver support with FPSA does not increase the probability of survival. Further studies are needed to assess whether therapy might be beneficial in specific subsets of patients.

Successful pregnancy and delivery after kidney transplantation.

The kidney transplantation is considered to be the best therapy for terminal kidney disease, nowadays. Numerous studies have shown that pregnancy may be successful and may result in a delivery of a healthy baby after the kidney transplantation. Pregnant women who are the recipients of a kidney transplant have increased chances of developing hypertension, preeclampsia, as well as going into premature labour and frequently giving birth to newborns of low birth weight. We present a case of a successful pregnancy and delivery in a 32-year-old kidney transplant recipient who conceived spontaneously four years posttransplantation. The kidney transplantation has been done due to the chronic hypertension and the consequential kidney atrophy. During the pregnancy, the patient underwent antihypertension and immunosupressive drugs therapy. She was also being monitored by the gynaecologist and the nephrologist. The pregnancy was terminated in the 40th week by an urgent Caesarean section due to the fetal bradycardia. The patient gave birth to the healthy baby girl.

Safe administration of celecoxib to a patient with repeated episodes of nephrotic syndrome induced by NSAIDs.

Nephrotic syndrome, with or without concomitant tubulointerstitial nephritis, is a rare renal adverse effect of NSAIDs. In the present report we describe a case of a 60-year-old Caucasian man who was admitted because of nephrotic syndrome following several days of use of meloxicam for hip osteoarthritis. Renal histopathology revealed minimal change disease, one of the commonest causes of nephrotic syndrome. The patient's condition resolved rapidly upon discontinuation of meloxicam. Because he had already experienced two episodes of nephrotic syndrome after administration of diclofenac several years previously, it was concluded that the patient had renal hypersensitivity to both diclofenac and meloxicam. While waiting for the hip arthroplasty, he was prescribed celecoxib for pain control. After 1 month of regular celecoxib use the patient remained in remission with respect to nephrotic syndrome and had normal renal function. We conclude that challenge with a structurally distinct NSAID (such as celecoxib in this case) may be an option, under close surveillance, in a patient with a history of nephrotic syndrome associated with use of an NSAID when continued treatment with an NSAID is indicated.

[Tunneled dialysis catheters placement program in Clinical Hospital Merkur]. / Program postavljanja trajnih dijaliznih katetera u KB "Merkur".

INTRODUCTION: Tunneled dialysis catheters are one of the methods for vascular access in hemodialysis patients. In the Clinical Hospital Merkur placement of tunneled dialysis catheters was started in 2007. The aim of this study was to analyze results of that program. METHODS: We analyzed survival of tunneled dialysis catheters placed in our Division of nephrology from January 2009. to April 2011. First site of choice for placement of catheter was right jugular vein. Catheters were placed de novo or as over the wire exchange of a previous catheter. Catheters were placed under fluoroscopy guidance. Survival was analyzed using Kaplan-Meier analysis. Difference between survivals was tested by the log-rank test. RESULTS: 88 catheters have been placed in 70 patients. Cumulative 1- year catheter survival, censored for patient death was 58%. 1-year catheter survival analyzed by the location of placement was as follows: jugular veins 70%. right subclavian vein 58%, left subclavian vein 43% and femoral veins 33%. Left jugular vein and femoral veins had lower survival rate in comparison with jugular veins (p=0.057). There was no statistical difference in catheter survival with respect to placement de novo or after over the wire exchange (p=0,516). CONCLUSION: Jugular veins are best location for placement of tunneled dialysis catheter. There is no statistical difference of catheter survival after placement de novo or after over the wire exchange in the presence of previous catheter.

[Effect of pretransplant dialysis modality on incidence of early posttransplant infections in kidney recipients]. / Utjecaj tipa dijalize na pojavnost ranih infekcija nakon transplantacije bubrega.

INTRODUCTION: Infection is one of the main causes of patient death and graft failure early after kidney transplantation. Effect of pretransplant dialysis modality on incidence of infections after kidney transplantation still remains controversial. The aim of the present study was to determine the impact of pre-transplant dialysis modality on incidence urinary tract infections (UTI) and sepsis in early posttransplant period in kidney transplant recipients. MATERIALS AND METHODS: In this case-control retrospective study a cohort of 72 kidney, kidney- pancreas or kidney-liver transplant recipients was included. Infection was defined by either clinical presentation or microbiological finding. Infections were categorized by localization and cause of infection. In patients on peritoneal dialysis peritoneal catheter was removed intraoperatively during transplantation. Infection rate during first three months posttransplant was analyzed. Difference in frequencies was calculated using nonparametric tests. Proportions were calculated using chi2 test. Time to first infection was analyzed using Kaplan-Meier survival analysis, p value < 0.05 criterion was used to decide statistical significance. RESULTS: The total number of infections per patient per day was not significantly different in peritoneal vs. hemodialysis modality (0,029 +/- 0.019 to 0,029 +/- 0,031, p=ns). Also, there was no significant difference in peritoneal vs. hemodialysis modality in the number of UTI (0.0156 +/- 0.0144 to 0,0165 +/- 0,0125, p=ns) and sepsis (0.0018 +/- 0.0044 to 0.0026 +/- 0.0019, p=ns) during first three months posttransplant. Similarly, no difference was noted between the groups in the location or cause of infection. Peritonitis prior to transplantation was not an independent risk factor for infections (p=0.37). In Cox regression PD was not an independent risk factor for either total infections, UTI, or sepsis. CONCLUSION: This study showed that there was not statistically significant difference in the risk for infection in first three months after kidney transplantation with respect to pretransplant dialysis modality. PD should be the first choice for renal replacement therapy in patients with end stage renal disease.

[Flow cytometry and acute renal rejection confirmed by histopathologic analysis]. / Protocna citometrija i akutno odbacivanje bubrega dokazano patohistoloskim nalazom.

Transplantation of solid organs, tissues or hematopoietic cells is now standard in the treatment of patients with terminal stage disease in order to cure and improve the recipients' quality of life. The study included 54 patients having undergone single or multiple organ transplantation. All patients received a combination of immunosuppressant therapy consisting of corticosteroids, calcineurin inhibitor (cyclosporine; tacrolimus), anti-CD25 (daclizumab) and mycophenolate-mofetil. In 24 patients, acute rejection was stratified by histopathologic analysis of renal biopsy. Fifteen highly sensitized patients were administered antithymocyte globulin (ATG) therapy. Absolute count and percentage of B/T lymphocyte subsets, NK cells and CD25+ or CD69+ activated T cells were measured on a flow cytometer (EPICS XL, Coulter) using single platform standardized protocol. Upon ATG therapy, rapid decline to a very low level of T and NK cell lymphocyte count was observed, as well of B lymphocytes, resulting in redistribution of lymphocyte compartment. Between consecutive measurements, kinetic changes of lymphocyte subset numbers (absolute count or percentage) did not differ in a large spectrum of immune parameters between the groups with and without rejection episode and having received quadruple immunosuppressive induction and maintenance therapy. Immunologic monitoring must be initiated prior to transplantation and continued consistently and frequently post-transplantation. Such a program is expensive and time-consuming and stressful for the patient, therefore, prospective studies should identify whether treatment decisions can be based reliably on these immune parameters. Serial measurement of immune cell counts is necessary for maintenance of ATG therapy and could be useful for monitoring patient recovery.

[Disseminated aspergillosis in a patient with simultaneous pancreas and kidney transplant]. / Diseminirana aspergiloza u bolesnice s transplantiranim bubregom i gusteracom.

A 31-year-old woman suffering from diabetes type1 and terminal kidney disease, with simultaneously transplanted kidney and pancreas, developed an episode of acute organ rejection caused by antibodies. The management of organ rejection was complicated by cytomegalovirus viremia, with accompanying leukopenia and neutropenia. The patient also developed invasive aspergillosis of the lungs, which progressed and disseminated hematogenously to the thyroid gland and the skin. Due to resistance to classical antimycotic therapy, the patient was treated with a combination of caspofungin and variconazole. In the beginning of treatment, the effects of this combined therapy were not evident due to strong immunosuppression caused by antimycotic immunoglobulin, which the patient had been administered on her previous hospital stay to treat acute kidney transplant rejection caused by antibodies, as well as due to immunosuppression caused by tacrolimus, mycophenolate mofetil and prednisone. On combined therapy with antimycotic drugs and supportive therapy, the patient was completely cured.

Cardiovascular mortality in liver and kidney transplant recipients: A retrospective analysis from a single institution.

ABSTRACT: 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 <50%, and diastolic dysfunction grade 2 or greater, while significant risk factors for cardiovascular mortality were peripheral artery disease and left ventricular ejection fraction <50%. In the LT group no variables remained significant in a multivariable model for either overall or cardiovascular mortality.The present study found no significant overall difference in cardiovascular mortality after LT and KT. While LT and KT recipients may have similar early cardiovascular mortality, long-term risk is potentially lower after LT. Differing characteristics of cardiovascular death between these two patient populations should be further investigated.

Dual kidney transplantation: case report.

Chronic shortage of kidney transplants worldwide has led to the use of organs from so called marginal or borderline donors, now termed "expanded-criteria donors". There has been an emerging practice of dual kidney transplantation (DKT) to compensate for sub optimal nephron mass of such kidneys. We performed DKT in "Merkur" University Hospital in August 2005. The donor was a 72-year old female with a history of long-term hypertension, aneurysm of the posterior cerebral artery, cerebrovascular insult (CVI), and with normal creatinine values and kidney function at the time of explantation. Initial biopsy of donor kidneys revealed acute tubular damage, with connective changes in 22% and 11% of glomeruli in the left and the right kidney, respectively. The recipient was a 60-year old male diagnosed with the IgA nephropathy on the last biopsy in 1999, and on dialysis since November 2003. Postoperative course was uneventful without any surgical complications. A triple immunosuppressive protocol was used. On follow-up ultrasonography 4 years posttransplantation both kidneys appeared of normal size and parenchymal pattern and with no signs of dilatation of the canal system, and color Doppler examination demonstrated normal flow in both kidneys. In conclusion, the use of DKT ie. donors by the expanded-criteria will continue to increase, and further studies of the results will, with no doubt, support this method.

Polyomavirus associated nephropathy after kidney and pancreas transplantation: case report.

Polyomavirus virus associated nephropathy (PVAN) is an important cause of graft failure in the renal transplant population. The prevalence of PVAN has increased from 1% to 10% in the past decade, leading to loss of transplanted organ in 30% to 80% of cases. In the absence of specific antiviral drugs, early detection of disease and modification/reduction of immunosuppressive regimen is currently the cornerstone of therapy. In the setting of multiorgan transplantation, like simultaneous pancreas and kidney transplantation (SPKT), diagnosis and therapy of PVAN can be even more challenging problem. We report a first described case of PVAN in patient after SPKT in Croatia. Patient is a 32 years old Caucasian male with type 1 diabetes mellitus and end stage renal failure, diagnosed for PVAN 6 month after SPKT. Patient was treated with reduced immunosuppressive regimen. At 32 month follow up, patient has preserved kidney and pancreas function with estimated glomerular filtration (eGFR) rate of 91 mL/min and no signs of PVAN on his 2 year protocol kidney biopsy.

Urine immunocytology as a noninvasive diagnostic tool for acute kidney rejection: a single center experience.

Renal biopsy is a gold standard for establishing diagnosis of acute rejection of the renal allograft. However, being invasive, renal biopsy has potential significant complications and contraindications. Therefore, possibility to noninvasively diagnose acute rejection would improve follow-up of kidney transplant patients. The purpose of this study was to evaluate urine immunocytology for T cells as a method for noninvasive identification of patients with acute renal allograft rejection in comparison to renal biopsy. In this prospective study a cohort of 56 kidney, or kidney-pancreas transplant recipients was included. Patients either received their transplant at the University Hospital "Merkur", or have been followed at the "Merkur" Hospital. Patients were subject to either protocol or indication kidney biopsy (a total of 70 biopsies), with simultaneous urine immunocytology (determination of CD3-positive cells in the urine sediment). Acute rejection was diagnosed in 24 biopsies. 23 episodes were T-cell mediated (6 grade IA, 5 grade IB, 1 grade IIA, 1 grade III and 10 borderline), while in 1 case acute humoral rejection was diagnosed. 46 biopsies did not demonstrate acute rejection. CD3-positive cells were found in 21% of cases with acute rejection and in 13% of cases without rejection (n.s.). A finding of CD3-positive cells in urine had a sensitivity of 21% and specificity of 87% for acute rejection (including borderline), with positive predictive value of 45% and negative predictive value of 68%. Although tubulitis is a hallmark of acute T cell-mediated rejection, detection of T cells in urine sediment was insufficiently sensitive and insufficiently specific for diagnosing acute rejection in our cohort of kidney transplant recipients.

The value of urinary decoy cells finding in patients with kidney transplantation.

Childhood infection with polyomaviruses leads to a life-long latent infection of renal and urinary tract epithelia. Replication in the reno-urinary epithelium is associated with viral cytopathic changes such as nuclear inclusions and decoy cells. During the 2005-2009 period, cytological urine analysis was performed in 154 samples (94 male and 60 female) from patients with kidney transplantation (n = 19), simultaneous pancreas-kidney transplantation (SPKT) (n = 9) and simultaneous kidney and liver transplantation (n = 2). Urine samples were analyzed monthly following transplantation according to the protocol. The period from transplantation to the first occurrence of decoy cells in the urine and the period of decoy cell persistence in the urine were assessed. The presence of decoy cells (< 10 and > 10 decoy cells) and red blood cells (< 20 E, 20-100 E and > 100 E) per cytospin smear was semiquantitatively determined, along with analysis of inflammatory cells (neutrophilic granulocytes) and fungi. In patients with decoy cells detected, their sensitivity, specificity, and negative and positive predictive value for BK virus nephropathy were calculated. Correlation of the study parameters was estimated by use of Kruskal-Wallis test (Statistica 7.1, StatSoft Inc., Tulsa, USA). Decoy cells were found in 30 patients (20 male and 10 female), age median 40 (range 16-69) years, at a mean of day 115 (range day 5-747) post transplantation, whereas their presence was recorded for a mean of 141 (range 77-771) days. Immunohistochemical staining of kidney biopsy sample for polyomavirus (SV40 large T-antigen) yielded positive reaction in 2/30 (7%) patients. Erythrocyturia was present in 29/30 patients with decoy cells. The number of decoy cells per cytospin smear generally ranged less than 10 in 25/30 patients, whereas more than 10 decoy cells per cytospin smear were only recorded in 5/30 patients. Immunohistochemistry produced positive finding for BK virus in one patient with SPKT and simultaneous kidney and liver transplantation each, which was statistically significantly more common as compared with patients with kidney transplantation alone (p = 0.0244). Immunohistochemical positivity for BK virus was more significant in cases with more than 10 decoy cells detected in cytospin smear (p = 0.013). In BK nephropathy, the finding of urinary decoy cells showed a 100% sensitivity, 84% specificity, 100% negative predictive value and 6% positive predictive value. BK virus nephropathy remains a significant post transplantation complication.

First documented case of BK nephropathy in kidney transplant recipient in Croatia: usage of urine cytology in evaluation process.

BK virus associated nephropathy (BKVAN) in transplanted kidney, although recognized as a distinct entity in the 1970-es, continues to represent a challenge in kidney transplantation, mainly because the optimal treatment approach has not been determined yet. The fact that about 10-20% of patients have simultaneously some stage of acute rejection, complicate the treatment even more. Herein we present a case of BK nephropathy in the patient, one year after combined liver and kidney transplantation, complicated by episode of acute T-cell mediated rejection. Identification of decoy cells by cytology urine exam in patient with acute kidney graft function deterioration, raised suspicion of BKVAN. Diagnosis has been made by histological examination and confirmed with immunohistochemical staining for BK virus in kidney graft biopsy. One month after he had been treated for BKVAN with intravenous immunoglobulin, leflunomide and overall immunosuppression therapy reduction, there was further deterioration of graft function due to an episode of acute T-cell mediated rejection (Banff classification IA). He received 500 mg of metilprednisolon intravenously and mycophenolate mofetil had been reintroduced, which resulted in slow partial recovery of the graft function, but never to the baseline values. For the past two years his renal graft function has been stable, maintaining lower levels of immunosuppressive therapy. According to our knowledge this is the first documented case of BK virus associated nephropathy, diagnosed and confirmed with immunohistochemical staining of tissue from kidney biopsy in Croatia.

Combined liver-kidney transplantation for rare diseases.

Combined liver and kidney transplantation (CLKT) is indicated in patients with failure of both organs, or for the treatment of end-stage chronic kidney disease (ESKD) caused by a genetic defect in the liver. The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT. They are major indications for CLKT in children. However, in some of them (e.g., atypical hemolytic uremic syndrome or primary hyperoxaluria), CLKT may be required in adults as well. Primary hyperoxaluria is divided into three types, of which type 1 and 2 lead to ESKD. CLKT has been proven effective in renal function replacement, at the same time preventing recurrence of the disease. Nephronophthisis is associated with liver fibrosis in 5% of cases and these patients are candidates for CLKT. In alpha 1-antitrypsin deficiency, hereditary C3 deficiency, lecithin cholesterol acyltransferase deficiency and glycogen storage diseases, glomerular or tubulointerstitial disease can lead to chronic kidney disease. Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality. In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H, successful CLKT has been reported in a small number of patients. However, for this indication, CLKT has been largely replaced by eculizumab, an anti-C5 antibody. CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA, facilitating transplantation in a highly sensitized recipient.

Evaluation of cell-mediated immune response by QuantiFERON Monitor Assay in kidney transplant recipients presenting with infective complications.

The net level of immunosuppression in kidney transplant recipients is difficult to assess. QuantiFERON Monitor (QFM) is an in vitro diagnostic test that detects interferon-γ (IFN-γ) release in peripheral blood. The aim of our study was to compare QFM testing results in stable kidney transplant recipients and kidney transplant recipients with infection, in a single-centre cohort.We enrolled 71 kidney transplant recipients from our transplantation centre. They were divided into 2 groups according to clinical presentation (Stable kidney transplant recipients or Infection).There were no significant differences in interferon-γ release between the 2 groups (Stable kidney transplant recipients 140.59 ±â€Š215.28 IU/ml, Infection group 78.37 ±â€Š197.03 IU/ml, P = .24). A further analysis revealed that kidney transplant recipients presenting with bacterial infection had significantly lower IFN-γ release when compared to stable kidney transplant recipients (26.52 ±â€Š42.46 IU/ml vs 140.59 ±â€Š215.28 IU/ml, P = .04).Kidney transplant recipients presenting with bacterial infection had lower IFN-γ release when compared to stable kidney transplant recipients. The QFM test may be useful as a tool to help guide immunosuppression dosing in kidney transplant recipients, but further studies are required to confirm its diagnostic value.