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Introduction: Tacrolimus is metabolized mainly in the liver by the CYP3A enzyme family, with a particularly well-documented role of CYP3A5. CYP3A5 is also expressed in the renal tissue and is present in the transplanted kidney. To date, the association between donor CYP3A5 polymorphisms and transplant outcome remains poorly understood. The aim of this study was to assess the effect of donor CYP3A5 expression on early and long-term transplant outcomes. Methods: A retrospective cohort study including 207 patients who received kidney grafts from 110 deceased donors was conducted at a single Central European Center. Tissue samples from all donors were studied for CYP3A5 single-nucleotide polymorphism (rs776746). Death-censored graft loss within 5-year follow-up, acute rejection occurrence, and kidney function, measured using serum creatinine and MDRD eGFR, were compared between groups of patients with allografts from rs776746 carriers (CYP3A5 expressors) and noncarriers (CYP3A5 nonexpressors). Results: Recipients who received kidneys from CYP3A5 expressors (n = 24) were at significantly higher risk of death-censored graft loss within 5-year follow-up (adjusted HR, 95% CI: 6.82, 2.01–23.12; p = 0.002) and acute rejection within the 1st posttransplant year (adjusted OR, 95% CI: 4.62, 1.67–12.77; p = 0.003) than those who did not (n = 183). The median time to loss of function was 1.93 [IQR; 0.77–3.19] years. Conclusions: Donor CYP3A5 expressor status is associated with worse renal graft survival and a higher risk of acute rejection. Determination of donor CYP3A5 genotype is a potentially useful tool that may improve kidney transplant outcomes.

BACKGROUND After renal transplantation, immunosuppressants should be administered to prevent organ rejection and prolong graft survival. One of them is tacrolimus, which is metabolized by the CYP3A enzyme family. The variability of the CYP3A5 gene in renal transplant recipients has been previously studied for its correlation with acute rejection and allogeneic kidney function. CYP3A5 enzyme is also present in the renal tissue, and its relevance has not yet been extensively investigated. This study aimed to evaluate the effect of donor and recipient CYP3A5 expression status on early and long-term transplant outcomes. MATERIAL AND METHODS Single-nucleotide polymorphism in CYP3A5 (rs776746) was analyzed in 95 kidney transplant recipients and their grafts. The effect of donor and recipient genotypes on the primary endpoint, which was the loss of the renal graft over 5-year follow-up, was assessed. The secondary endpoints were biopsy-proven acute rejection, proteinuria, delayed graft function, and renal function. RESULTS Patients who received a CYP3A5*1 allele-carrying kidney (n=16) were at greater risk of graft loss (adjusted hazard ratio, 95% CI: 10.61, 2.28-49.42, P=.003) than those with the CYP3A5*3/*3 genotype (n=79). Renal CYP3A5 expression was also a predictor of acute rejection between the 2nd and 12th post-transplant months (adjusted odds ratio, 95% CI: 4.36; 1.08-17.6, P=.038) and proteinuria at different time intervals. No effect of the recipient CYP3A5 genotype was observed. CONCLUSIONS The donor CYP3A5 genotype is associated with inferior transplantation outcomes. Local renal tacrolimus metabolism is a potential target for improving long-term transplantation outcomes.

Background Obese renal transplant recipients (body mass index [BMI] ≥30 kg/m2) are at risk of delayed graft function and postoperative complications, such as infections or delayed wound healing. There is also a tendency to exclude extremely obese patients from transplantation (KTx). Nonetheless, no association between obesity and increased mortality has been reported. The aim of this study is to evaluate the effect of BMI on the most common surgical and infectious complications after KTx. Materials and methods An observational study in 872 patients transplanted from 2010-2017 was conducted. Median BMI was 24.6 (13.9-34.3), and 8.3% of the group was obese. Patient records were searched for early postoperative complications: lymphocele or hematoma (>33 mL), urinary leakage, or urinary tract infection (UTI). Mann-Whitney U and χ2 or Fisher exact tests were used. P Results Renal primary nonfunction was observed in 1.4% (12/872) of patients. Surgical or infectious complications occurred in 52.7% (453/860) of patients. No correlation between BMI and complication rate was noted. Complications were observed in 56.9% (41/72) of obese vs 52.3% (412/788) of nonobese patients (P = .448), including lymphocele in 15.3% vs 16.4% (P = .810), hematoma in 22.2% vs 19.2% (P = .530), urinary leakage in 1.4% vs 4.6% (P = .203), and UTI in 31.9% vs 32.9% (P = .873), respectively. Conclusions Recipient’s BMI has no significant association with the most common surgical complications after KTx. There is no need to delay KTx in moderately obese patients.

BACKGROUND Urinary tract infection (UTI) occurs in 21% of kidney recipients within the first 3 months after transplantation (KTx). It is associated with impaired graft function. Ureteral stent placement increases the occurrence of UTIs. The aim of this study was to assess the correlation between double-J placement, UTI incidence, and graft function. MATERIAL AND METHODS We conducted an observational study in 753 patients transplanted between 2010 and 2017 in compliance with the Helsinki Congress and the Istanbul Declaration. Recipients with preserved graft function at the 1-year follow-up were included. Medical records were searched for intraoperative double-J placement, UTI incidence, and estimated glomerular filtration rate (eGFR) on the 30th and 360th days post-transplant. Pretransplant hypothetical estimated GFR (heGFR) of each donor was calculated from donors' age and physiological age-dependent loss of functional nephrons. Spearman's correlation and linear regression analyses were applied. P < .05 was considered significant. RESULTS UTIs occurred in 239 (31.8%) patients. On the 30th day after KTx, eGFR was significantly lower in the UTI group (median, 39.5 vs 43.2; P < .01). A similar pattern was seen 1 year after KTx (47.5 vs 54.2; P < .01). Urinary stents were placed in 213 (28.3%) patients. UTIs occurred in 92 (43.2%) of them and in 147 (27.2%) of nonstented patients (odds ratio: 2; 95% confidence interval [CI], 1.5-2.8; P < .01). Median donor heGFR was 105.8 mL/min/1.73 m2, whereas median donor Modification of Diet in Renal Disease (MDRD) GFR was 64.2 mL/min/1.73 m2. A moderate correlation between age-adjusted heGFR and 1-year transplant function (r = .47) was noted. CONCLUSIONS UTIs in the early post-transplant period decreased 1-year eGFR by 4 to 5 mL/min/1.73 m2. UTIs occurred twice as often when a urinary stent was placed.

Introduction The adrenal gland is a frequent site of metastases in different types of cancer. The aim of this study was to assess the results of metastatic adrenalectomy in a single institution and to identify factors for survival. Material and methods A retrospective, single-centre analysis of outcomes of 39 patients (22 male, 17 female) with adrenal metastases who underwent surgery within 14 years (2004-2017) was performed. The median age at the time of adrenal surgery was 64.8 years (range 49-79 years). Results In our study group non-small cell lung cancer (NSCLC) was the most frequent primary tumour type (15 pts), followed by renal cell carcinoma (RCC) (14 pts) and colon cancer (6 pts). Most of the metastases - 36 (92%) - were metachronous (> 6 months). All synchronous metastases were NSCLC. The mean time from primary cancer to adrenalectomy was 42.3 months (range 1-176) and was statistically longer for RCC. In 3 patients (8%) metastases were bilateral and both adrenal glands were removed. In all patients, surgery was limited to the adrenal gland, and no major complications of surgery were observed. The median overall survival after metastasectomy was 18 months (3-81) and was statistically longer for colon cancer - 29.5 months (p = 0.012). In patients who died, tumours were significantly bigger than in survivors, 76.5 mm vs. 52.5 mm (p = 0.026). Conclusions Surgery for adrenal metastasis is safe and indications for this procedure should be individualized. In selected patients, surgical removal of adrenal metastasis was associated with longer survival.

Previous reports have established that patient CYP3A5 allelic variability may be the most important genetic contributor to interindividual variation in tacrolimus exposure in renal transplant recipients. However, CYP3A5 protein is expressed in the allogenic kidney. The aim of this study was to investigate the role of the renal CYP3A5 genotype in tacrolimus concentration-to-dose ratio within 3 years posttransplant.A retrospective cohort study of 90 renal transplant recipients and their donors evaluated the effect of the CYP3A5 single-nucleotide polymorphism (rs776746) on tacrolimus exposure. The area under the curve for tacrolimus concentration-to-dose ratio within 3-year follow-up was calculated and compared in kidneys carrying at least 1 CYP3A5*1 allele and those carrying the CYP3A5*3/*3 genotype.A significant effect of CYP3A5 expression on tacrolimus exposure was observed in both donors (mean ± SD: 23.8 ± 7.9 vs 32.6 ± 7.4 ng/mL/mg, respectively; P.001) and recipients (mean ± SD: 27.1 ± 8.0 vs 32.2 ± 7.9 ng/mL/mg, respectively; P = .034) and was lower when CYP3A5 enzyme occurred. Thus, new groups were formed: the group in which at least 1 of the pairs, donor or recipient, had a CYP3A5 expressing allele (n = 23) had lower exposure to tacrolimus compared with nonexpressors (n = 67; mean ± SD: 26.2 ± 7.6 vs 33.2 ± 7.4 ng/mL/mg, respectively; P.001).Intrarenal metabolism of tacrolimus may affect both local and systemic drug exposure. Nonexpressors receiving kidneys with the CYP3A5*1 allele may benefit from higher tacrolimus doses to hasten achievement of target drug concentrations.

Biliary complications are one of the most serious and dangerous complications following liver transplantation. Factors that may determine their occurrence are still being assessed. The retrospective analysis of 239 consecutive liver transplantations (LT) performed between January 2013 and December 2018 was conducted in compliance with the Helsinki Congress and the Istanbul Declaration. We divided recipients into 2 groups depending on whether biliary complications occurred. The first (biliary complication [BC group]) consisted of patients who developed biliary complications (n = 41) and the second (nonbiliary complications [NBC group]) without them (n = 198). Demographic and statistical data analysis showed no differences between the groups in terms of age, Model for End-Stage Liver Disease with sodium serum concentration (MELD-Na) score, and average cold or warm ischemia time. In comparison, estimated intraoperative blood loss, 1341 mL in the NBC and 1399 mL in the BC, was not significantly different, as were the number of transfused red blood cells (RBC) units, which were respectively 1.7 and 2.1 (P = ns). The recipients’ hemoglobin levels just before surgery were (11.5 g/dL vs 11.6 g/dL; P = ns) and after transplantation (9.8 g/dL vs 9.8 g/dL; P = ns). Eleven patients died within 30 days of transplantation. This group was characterized by a higher MELD-Na score (25 vs 17; P = .01), lower pretransplant hemoglobin level (10 g/dL vs 11.6 g/dL; P = .02), and the number of transfused RBC units (3.3 vs 1.7; P = .01). However, there was no correlation between intraoperative blood loss, the number of transfused RBC units, pre- and postoperative hemoglobin levels, and the incidence of biliary complications after LT. Lower pretransplant hemoglobin levels and a higher amount of intraoperatively transfused blood products were associated with a higher fatality rate after LT.

Hypothermic machine perfusion (HMP) has become a standard method of preservation for kidneys procured from expanded-criteria donors and donors after cardiac death. There are different systems and approaches to the HMP preservation period, with cold storage prior to HMP sometimes taking several hours. This study evaluated whether the time at which kidneys receive HMP had any influence on the outcomes of kidney transplantation.In this analysis, patient and graft survival were evaluated over a 1-year post-transplantation period. Patients who received HMP kidneys (n = 379) were divided into 2 groups: those who received kidneys with a cold ischemia time (CIT) prior to HMP 295 minutes (group G1; n = 254) and those who received kidneys with CIT prior to HMP295 minutes (group G2; n = 125).Delayed graft function was observed in 31.8% (81/254) of patients in group G1 vs 46.4% (58/125) of patients in group G2 (P = .007). One-year graft survival was statistically higher in the group G1 (93.2%; 233/254) vs group G2 (86.5%; 105/125, P = .029). Mean 1-year estimated glomerular filtration rate was significantly better in the group G1.In conclusion, introduction of HMP up to 295 minutes from procurement led to better early and 1-year graft results. Kidneys should receive HMP as soon as possible after retrieval, preferably during procurement.

Background One of the most common infective complications after kidney transplant (KTx) is surgical site infection (SSI). Providing indications of improvement of perioperative antibiotic prophylaxis (PAP) and allowing the characterization of risk factors are critical to reduce SSI. The purpose of this study was to evaluate the SSI risk factors and impact of reoperation in the early post-transplant period on SSI occurrence and assess if standard PAP in those cases is a best consideration. Methods Between April 2014 and October 2015, a total of 236 KTxs were performed in our center. Deceased donor data, recipient data, and data related to surgical procedures were collected. Results Surgical site infections were reported in 5.6% (12/214) of patients. Seven patients were diagnosed as having superficial SSI (7/12; 58.3%), 2 with deep SSI (2/12; 16.6%), and 4 with organ-specific SSI (4/12; 33.3%). Extended criteria donor–related transplant, cold ischemia time > 22 hours, dialysis period > 30 months, recipient age older than 45 years, recipient body mass index > 27, induction therapy prior to transplant, diabetes prior to transplant, and ≥ 1 reoperation during 30 days of observation were independent risk factors of SSI occurrence. A total of 19 reoperations were performed in 17 patients. In 8 of all 12 patients with SSI diagnosis, the reoperation was performed (66.7%). In 202 patients of non-SSI patients, only 9 reoperations were performed (4.5%). Conclusions Early reoperation after Ktx is a strong risk factor of SSI occurrence. There is a probability that > 4 SSI risk factors and reoperation in the early post-transplant period could require different and more aggressive proceeding, as standard PAP in those cases is insufficient.

Background Infections in kidney transplant recipients are particularly challenging owing to the immunosuppressive treatment, usually long history of chronic illness, comorbidities and prior exposures to antibiotics. Among the most common complications early after surgery are surgical site infections. The aim of this study was to identify risk factors and evaluate epidemiological data regarding surgical site infections. Moreover, we were able to compare the current results with historical data from our institution when different perioperative antibiotic prophylaxis was practiced. Methods We conducted a retrospective case–control study in a group of 254 deceased donor renal graft recipients transplanted in a single Central European institution. We evaluated epidemiological findings and resistance patterns of pathogens causing surgical site infections. We used multivariable logistic regression to determine risk factors for surgical site infections. Results We revealed no differences in baseline characteristics between patients with and without surgical site infections. Ten surgical site infections (3.9%) were diagnosed (six superficial incisional, two deep incisional, and two organ/space). Eight species (19 strains) were identified, most of which were multi-drug resistant (63%). The most common was extended-spectrum β-lactamase producing Klebsiella pneumoniae (26%). We showed that statistically significant differences were present between reoperated and non-reoperated patients (adjusted odds ratio: 6.963, 95% confidence interval 1.523–31.842, P = .012). Conclusions Reoperation is an individual risk factor for surgical site infection after kidney transplantation. According to our experience, cefazolin-based prophylaxis can be safe and is associated with relatively low prevalence of surgical site infections.

Background: Infections in kidney transplant recipients are particularly challenging owing to the immunosuppressive treatment, usually long history of chronic illness, comorbidities and prior exposures to antibiotics. Among the most common complications early after surgery are surgical site infections. The aim of this study was to identify risk factors and evaluate epidemiological data regarding surgical site infections. Moreover, we were able to compare the current results with historical data from our institution when different perioperative antibiotic prophylaxis was practiced.Methods: We conducted a retrospective case-control study in a group of 254 deceased donor renal graft recipients transplanted in a single Central European institution. We evaluated epidemiological findings and resistance patterns of pathogens causing surgical site infections. We used multivariable logistic regression to determine risk factors for surgical site infections.Results: We revealed no differences in baseline characteristics between patients with and without surgical site infections. Ten surgical site infections (3.9%) were diagnosed (six superficial incisional, two deep incisional, and two organ/space). Eight species (19 strains) were identified, most of which were multi-drug resistant (63%). The most common was extended-spectrum β-lactamase producing Klebsiella pneumoniae (26%). We showed that statistically significant differences were present between reoperated and non-reoperated patients (adjusted odds ratio: 6.963, 95% confidence interval: 1.523-31.842, P = .012).Conclusions: Reoperation is an individual risk factor for surgical site infection after kidney transplantation. According to our experience, cefazolin-based prophylaxis can be safe and is associated with relatively low prevalence of surgical site infections.

Introduction The approach toward transplanting kidneys from expanded-criteria donors (ECDs) in Poland is largely site-dependent. The Kidney Donor Risk Index (KDRI) allows for obtaining a more precise characteristic of ECDs and further stratification into “better” and “worse” quality grafts. Methods Comparison of the incidence of delayed graft function (DGF) and biopsy-proven acute rejection (BPAR), median of hospitalization time and median of estimated glomerular filtration rate (eGFR) at 1 year after transplantation among kidney graft recipients (n = 468), divided by donor status (ECD/standard-criteria donor [SCD]) and KDRI value (I: 0.67–1.2, II: 1.21–1.6, III: 1.61–2.0, IV: 2.01–3.48). Results ECD kidneys have been transplanted to 32.47% of recipients. There were no ECD recipients in KDRI compartment I, 16.55% in compartment II, 79.22% in compartment III, and 100% in IV. In KDRI compartment II, DGF was diagnosed in 34.9% of SCDs and 56% of ECDs (P = .003), BPAR occurred in 7.8% of SCDs and 16% of ECDs (P = .073), median hospital stay was 12 days for SCDs and ECDs (P = 1), and eGFR was 50.7 mL/min for SCDs and 49.4 mL/min for ECDs (P = .734). In KDRI compartment III, DGF was diagnosed in 43.8% of SCDs and 49.2% of ECDs (P = .139), BPAR occurred in 6.3% of SCDs and 31.7% of ECDs (P = .001), median hospital stay was 10 days for SCDs and 12 days for ECDs (P = .634), and eGFR was 49.5 mL/min for SCDs and 45.2 mL/min for ECDs (P = .382). Among ECD recipients, DGF was diagnosed in 56.0%, 49.2%, and 47.7% of patients for KDRI compartments II, III, and IV respectively (P = .776); BPAR occurred in 16% (compartment II), 31.7% (compartment III), and 23.1% (compartment IV) (P = .273); the median hospital stay was 12 days (compartment II), 12 days (compartment III), and 12.5 days (compartment IV) (P = 1); and eGFR was 49.5 mL/min (compartment II), 45.4 mL/min (compartment III), and 36.1 mL/min (compartment IV) (P = .002). Conclusion Assessment using both the ECD and KDRI systems allows for a more precise evaluation of prognosis and predicting complications among recipients.

Aim A major problem for the transplant society is a shortage of organs for transplantation compared with the number of patients on the waiting list. This study aimed to assess the results of the transplantation of kidneys procured from older donors. Patients and Methods A total of 27 kidneys procured from donors age 70 years or older were transplanted between January 1, 2010, and April 25, 2015. These represented only 4.1% of the 657 kidneys transplanted from deceased donors during this period at the same center. Results Delayed graft function (DGF) in the recipients of kidneys procured from donors age 70 or older occurred in 46.1% of patients, whereas the recipients of kidneys from younger donors showed DGF at a frequency of 32.7% ( P = NS). The annual and 3-year survival rates of kidneys in the study group were 85% and 80%, respectively, and in the control group were 92.5% and 88.6%, respectively ( P = NS). According to the Polish National Organ Procurement Organization (Poltransplant), the annual survival rate of a transplanted kidney in Poland stands at 89%, whereas the 3-year survival rate is 82%. We detected no significant posttransplantation differences in the serum creatinine concentration and in the estimated glomerular filtration rate between the study and control groups. The donor age and donor creatinine were the variables independently associated with DGF. Conclusions The results of transplantation of kidneys from elderly donors were comparable to those of transplantation from younger donors. Kidneys harvested from elderly donors should be used for a transplant after a preliminary assessment.

Use of livers from cadaveric nonstandard donors has become justified, especially for recipients awaiting urgent transplantations. However, it is known that results are superior when organs are obtained from ideal rather than expanded-criteria donors. We designed a study to compare the characteristics of 582 liver donors whose organs were used for elective versus urgent transplantations in 2006-2008 and the recipients' outcomes. Donors and recipients were classified into 2 groups: 1) elective (n = 387); and 2) urgent transplantations (n = 195). We evaluated 12 donor risk factors: age >55 years, alcohol ingestion, intensive care unit stay >4 days, hypotensive episodes ( 10 min), noradrenaline dose >0.1 μg/kg/min, anti-hepatitis B of core (+), Na level >155 mmol/L, international normalized ratio >1.5, aspartate transaminase >140 U/L, alanine transaminase >170 U/L, bilirubin >2.0 mg/dL, and changes in liver sonography. There were no significant differences in the frequency of incidence of 11 donor risk factors in both groups. Only sodium level >155 mEq/L significantly (P = .04) differed. Donors for elective recipients showed this factor more frequently than the urgent cohort. The mean number of risk factors per donor among the elective cases was 2.28 and for the urgent cases 2.3, a difference that was not significant. In almost all cases of liver transplantations (94%), donor-related risk factors were acceptable. The criteria for cadaveric liver donors were not different for elective versus urgent recipients; biologic characteristics of the transplanted organs were similar in both groups. A tendency was not observed to expand donor criteria for urgent recipients.