A CT-based pelvic calcification score in kidney transplant patients is a possible predictor of graft and overall survival.

OBJECTIVES: Computerized tomography (CT) is the most accurate method for evaluating pelvic calcifications, which are of utmost importance for planning kidney transplantation (KT). The aim of our study was to evaluate the incidence and distribution of iliac artery calcifications and correlate the novel pelvic calcification score (PCS) with cardiovascular risk factors and graft and overall survival in KT patients. METHODS: We retrospectively included 118 KT patients operated at our institution with pretransplant pelvic CT. Calcification morphology, circumference and length of both common and external iliac arteries were independently scored by two uroradiologists. PCS was calculated as the total score sum of all three calcification features in all vessels. PCS correlation with graft and patient survival was performed. RESULTS: Calcification in at least one vascular segment was found in 79% of patients. PCS was significantly higher in male patients (p = 0.006), patients over 55 years (p < 0.001), and patients on haemodialysis (p = 0.016). Patients with a PCS >3 had significantly shorter graft and overall survival rates (p = 0.041 and p = 0.039, respectively). CONCLUSIONS: The extent of iliac artery calcification in KT recipients quantified by PCS on pretransplant CT correlates with graft and overall patient survival. A PCS over three was associated with worse clinical outcomes and could become a possible prognostic factor. ADVANCES IN KNOWLEDGE: Our novel PCS is a robust method for quantifying iliac artery calcification burden. Since higher a PCS correlates with worse patient and graft survival, PCS has the potential to become a prognostic factor in kidney transplant patients.

Kidney Transplants from Elderly Donors: The Experience of a Reference Center in Croatia.

OBJECTIVES: Our country Croatia is among the global leaders regarding deceased donation rates, yet we are facing organ shortage and concurrently a sharp decline in our acceptance rates for kidney offers. To reevaluate our organ acceptance policy, we retrospectively analyzed the factors that influenced the posttransplant outcomes of kidneys from elderly deceased donors at our center during a 20-year period and the changes to our organ acceptance criteria during Eurotransplant membership. MATERIALS AND METHODS: We studied all kidney transplants from donors ≥60 years old during the two 5-year episodes of Eurotransplant membership from 2007 to 2017 (period II and period III) and compared those data to data from the decade before Eurotransplant membership (period I, 1997-2007). Differences in acceptance rates and reasons for the decline of kidney offers between the two 5-year periods of Eurotransplant membership were analyzed. RESULTS: In period I, 14.1% of all kidney allografts were obtained from donors ≥60 years old; in period II and period III the rates were nearly 2-fold higher (27.0% and 25.7%, respectively; P = .007 and P = .008). During the first 5-year period of Eurotransplant membership (period II), we accepted significantly more grafts from marginal donors with a higher number of human leukocyte antigen mismatches compared with period I. Consequently, the 3-month survival rate of kidneys from donors ≥60 years old dropped from 91.1% to as low as 74.2% (P = .034). After application of morestringent human leukocyte antigen matching, especially in human leukocyte antigen DR, and morestringent donor acceptance criteria in period III, graft survival improved to 91.1%. CONCLUSIONS: Our experience indicates that careful selection of kidneys from elderly deceased donors and allocation to human leukocyte antigen-matched recipients is important to improve transplant outcomes.

Pre-transplant HLA Antibodies and Delayed Graft Function in the Current Era of Kidney Transplantation.

Delayed graft function (DGF) occurs in a significant proportion of deceased donor kidney transplant recipients and was associated with graft injury and inferior clinical outcome. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of human leukocyte antigen (HLA) antibodies. 1,724 patients who received a deceased donor kidney transplant during 2008-2017 and on whom a pre-transplant serum sample was available were studied. Graft survival during the first 3 post-transplant years was analyzed by multivariable Cox regression. Pre-transplant predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections in the first 3 post-transplant months were determined by multivariable logistic regression. Donor age ≥50 years, simultaneous pre-transplant presence of HLA class I and II antibodies, diabetes mellitus as cause of end-stage renal disease, cold ischemia time ≥18 h, and time on dialysis >5 years were associated with increased risk of DGF, while the risk was reduced if gender of donor or recipient was female or the reason for death of donor was trauma. DGF alone doubled the risk for graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (hazard ratio HR=4.75, P < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P < 0.001) were present pre-transplant. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections, including antibody-mediated rejections, increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1, whereas patients with both DGF and rejection showed the lowest rate of good kidney function, especially when organs from ≥65-year-old donors were used. In this new era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Measures to prevent the strong negative impact of DGF on outcome are necessary, especially during organ allocation for presensitized patients.

Are Croatian blood donors obese?

The rising prevalence of overweight and obesity is characterized as a pandemic of the modern era. The purpose of this study was to analyze the prevalence of overweight and obesity in healthy blood donors in Primorje-Gorski Kotar County, Croatia, and the relationship between socio-demographic factors, lifestyle and eating habits, and body mass index (BMI), including the association of these factors with overweight and obesity. This cross-sectional study included 1255 healthy individuals aged between 18 and 70 years who donated blood between January 2015 and October 2016 at the Clinical Institute of Transfusion Medicine. Each participant completed a questionnaire regarding weight, height, blood type, socio-demographic factors, health parameters, physical activity, alcohol consumption, and smoking habits. Overweight was defined as BMI of 25-29.9 kg/m2, and obesity as BMI ≥30 kg/m2. A logistic regression model was used on data assessment. BMI was normal in 33.6% of participants, whereas 44.1% were overweight and 21.8% were obese. Higher BMI was correlated with male sex (odds ratio [OR]=0.21), lower education level (OR=0.77) and unhealthy diet (OR=0.57), whereas lower BMI was correlated with lower age (OR=2.05) and unemployment (OR=1.85). To our knowledge, this is the first study to investigate the prevalence of BMI in a healthy Croatian population; our results confirmed the findings of studies conducted in other European countries. Our results highlighted the importance of improving education levels and raising awareness of healthy dietary habits in high-risk groups, i.e. men and older individuals with lower education levels.

Complement-dependent cytotoxicity and Luminex technology for human leucocyte antigen antibody detection in kidney transplant candidates exposed to different sensitizing events.

BACKGROUND: The aim of this study was to determine the frequency of exposure to different sensitizing events (SEs) and to assess their effects on human leucocyte antigen (HLA) alloimmunization in transplant candidates using two different HLA antibody screening techniques: complement-dependent cytotoxicity (CDC) and Luminex. METHODS: This retrospective study included HLA antibody screening results for 163 patients on the kidney transplant waiting list (WL) tested from March 2012 until the end of December 2015 at the Tissue Typing Laboratory, Rijeka, Croatia. All sera samples were tested using the CDC and Luminex techniques in parallel. RESULTS: Two-thirds of the patients [114 (70%)] on the WL were exposed to transfusions, pregnancies and/or kidney transplant. The pre-transplant sera of 104 (63.80%) patients were negative for antibodies. In the sera of 23 (14.11%) patients, HLA antibodies were detected by CDC and Luminex and in the sera of 36 (22.09%) patients by Luminex only. CONCLUSION: In patients on kidney WL, previous organ transplantation represents the strongest immunogenic stimulus, followed by blood transfusions (the most frequent SE) and pregnancies. Although Luminex is more sensitive than CDC in HLA antibody detection, the decision on unacceptable HLA antigens in WL patients has to be based on the results of both assays and the patient's immunization history.

Pretransplantation monitoring of HLA antibodies by complement dependent cytotoxicity and Luminex-based assays.

BACKGROUND: The introduction of more sensitive techniques, such as Luminex® for HLA antibody screening of patients awaiting organ transplantation has resulted in a better understanding of transplantation immunology and improvements in clinical practice. OBJECTIVE: The interpretation of the results obtained only by Luminex® can lead to inaccurate evaluation of a patient's antibody status and unjustified rejection of a potential organ donor. The aim of this study was to demonstrate the benefits of performing HLA antibody screening in the sera of patients on the waiting list for organ transplantation by two different assays, complement dependent cytotoxicity (CDC) and Luminex®. METHODS: A retrospective analysis was performed on 563 pretransplant serum samples from 141 patients on the kidney transplantation waiting list in Rijeka, tested from March 2012 until March 2015. All samples were tested in parallel by the CDC assay and the Luminex®-based assay. RESULTS: Out of the 563 samples tested 302 (53.7%) tested negative for HLA antibodies and 88 (15.6%) positive by both assays. From 173 (30.7%) samples with discordant results 149 (26.5%) were CDC negative and Luminex® positive, while 24 (4.3%) were CDC positive and Luminex® negative. Among the Luminex positive patients seven did not experience any immunizing events. CONCLUSION: Evaluation of the HLA antibody status in patients on a waiting list for organ transplantation should be based on the results of the both CDC and Luminex® (or other sensitive) assays in accordance to information about patient's clinical status and exposure to immunizing events.

Renoprotective mechanisms of chlorogenic acid in cisplatin-induced kidney injury.

The aim of this study was to investigate the renoprotective activity of chlorogenic acid (CA) in a murine model of cisplatin (CP)-induced kidney injury. Male BALB/cN mice were gavaged daily with CA at 3, 10 and 30mg/kg for two successive days, 48h after intraperitoneal injection of CP (13mg/kg). On the fifth day, serum creatinine and blood urea nitrogen (BUN) levels were significantly increased in CP-intoxicated mice, which was recovered by CA. Renal oxidative stress, evidenced by increased 4-hydroxynonenal (4-HNE) expression, was significantly reduced with CA. Simultaneously, the overexpression of heme oxygenase 1 (HO-1) and cytochrome P450 E1 (CYP2E1) was attenuated. The inhibition of inflammatory response by CA was achieved through the reduction of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expression. Additionally, CA significantly suppressed p53, Bax active caspase-3, cyclin D1 and microtubule-associated protein 1 light chain 3 isoform B (LC3B) expression, suggesting the inhibition of both apoptosis and autophagy. The expression of multidrug resistance-associated proteins (Mrp1 and Mrp2) increased and organic cation transporter 2 (Oct2) decreased by CP, protecting the kidneys from nephrotoxicity by reducing the burden of tubular cells. CA dose-dependently restored Mrp1, Mrp2 and Oct2 expression. The recovery of kidney tissue form CP injury was accompanied by increased proliferating nuclear cell antigen (PCNA) expression. The results of this study suggest that CA attenuates CP-induced kidney injury through suppression of oxidative stress, inflammation, apoptosis and autophagy, with the improvement in kidney regeneration.