Single-center experience with perioperative antibiotic prophylaxis and surgical site infections in kidney transplant recipients.

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 ß-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.

Adrenal metastases - long-term results of surgical treatment, single-centre experience.

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.

Effect of the Organ Donation Quality System on Donation Activity of Warsaw Hospitals.

BACKGROUND Like many other countries, Poland faces a shortage of transplantable organs despite implementing strategies to develop donation programs. Increasing the effectiveness of deceased organ donation programs requires the implementation of protocols and quality standards for the entire process. The aim of this study was to assess the organ donation potential in Warsaw hospitals (with and without implemented donation procedures) in the years 2017-2018, before the COVID-19 pandemic affected donation activity. The obtained results were compared with quality indicators established in the ODEQUS project and the European Commission project "Improving Knowledge and Practices in Organ Donation" (DOPKI). MATERIAL AND METHODS Retrospective analysis was performed of hospitalization and death causes (including deaths in the brain death mechanism) in the hospitals and intensive care units in 2017-2018. We divided 15 Warsaw hospitals into 2 groups: those with implemented quality programs for organ donation (n=4) and those without such programs (n=11). RESULTS Hospitals with procedures obtained significantly higher values than hospitals without procedures, but were lower than the values in DOPKI and ODEQUS. The success rate of the organ donation process after brain death recognition was comparable in all groups. The conversion rate to actual donors was 73% in hospitals with procedures compared to 68% in hospitals without procedures, significantly higher than in the 42% reported in the DOPKI project. CONCLUSIONS Low numbers of brain death declarations in Warsaw hospitals result from low recognition of deaths in the brain death mechanism. Implementing procedures at each hospital level will enable identification of critical points and comparison of solution outcomes.

CYP3A5 Expressor Genotype of the Transplanted Kidney Increases the Risk of Preterm Graft Loss and Acute Rejection.

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.

Risk of malignancy in adrenal tumors in patients with a history of cancer.

Purpose: Adrenal gland is a common site of metastasis and on the other hand, metastases are the most frequent malignant adrenal tumors. The aim of this study was to estimate the risk of malignancy in suspicious adrenal mass in patients with a history of cancer. Methods: This is a single-center retrospective analysis of patients with adrenal tumors treated previously for different types of cancers. Between 2004 and 2021 a hundred and six such patients were identified. Mean age of patients was 62.6 years (30-78), and mean time from oncologic treatment was 55.8 months (0-274). The most common primary cancer was kidney (RCC): 29 (27.4%), colon/rectum (CRC): 20 (18.9%) and lung (NSCLC): 20 (18.9%). Results: Of 106 patients, 12 had hormonally active (HA) (11,3%) and 94 (88,7%) non active (HNA) tumors In group of patients with HA tumours 4 had hypercortisolaemia and 8 had elevation of urinary metanephrines. In the first group of HA patients pathology confirmed preoperative diagnosis of adrenocortical cancer and no metastasis was found. In all patients from the second group pheochromocytomas were confirmed. Primary (PM) and secondary (SM) malignancies were found in 50 patients (47.2%). In hormone inactive group only SM - 46/94 (48.9%) were diagnosed. The odds that adrenal lesion was a metastasis were higher if primary cancer was RCC (OR 4.29) and NSCLC (OR 12.3). Metastases were also more likely with high native tumor density, and bigger size in CT. The cut-off values for tumor size and native density calculated from receiver operating characteristic (ROC) curves were 37mm and 24, respectively. Conclusion: Risk of malignancy of adrenal mass in a patient with a history of cancer is high (47,2%), regardless of hormonal status. 47,2% risk of malignancy. In preoperative assessment type of primary cancer, adrenal tumour size and native density on CT should be taken into consideration as predictive factors of malignancy. Native density exceeding 24 HU was the strongest risk factor of adrenal malignancy (RR 3.23), followed by history of lung or renal cancer (RR 2.82) and maximum tumor diameter over 37 mm (RR 2.14).

Donor CYP3A5 Expression Decreases Renal Transplantation Outcomes in White Renal Transplant Recipients.

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.

Renal Cyp3a5-Expressing Genotype Decreases Tacrolimus-to-Dose Ratio in Small Cohort of Renal Transplant Recipients-Preliminary Report.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Organ Donation in Intensive Care Units of Hospitals in Warsaw.

BACKGROUND: In recent years a systematic decrease in donation activity in Poland (15.4 vs 13.0) has been observed. A significant reduction has been noticed in Warsaw (36.2 vs 19.2) as well. METHODS: Data on deaths of patients admitted to intensive care units (ICUs) of Warsaw hospitals in from 2014 to 2018 were analyzed. Analysis was conducted in compliance with the Helsinki Congress and the Istanbul Declaration. Population of the city during this period averaged 1,753,480, although specialized capital hospitals service substantially bigger area than Warsaw alone. There are 18,500 to 18,600 deaths affecting this population every year. A total of 333 patients diagnosed as having brain death were included in analysis. RESULTS: In 42 cases (12.7%) data collection was given up because of lack of authorization. In all donors, death was diagnosed according to neurologic criteria. The most common causes were vascular brain diseases (64.1%) and craniocerebral trauma (21.4%). In 14.5% brain death occurred from other reasons. There are 20 hospitals with ICUs in Warsaw, which totals 318 intensive care beds. Program of identification of deceased organ donors was active in only 14 hospitals. A total of 243 potential donors (73%) were identified in the 3 most active hospitals. CONCLUSION: Analysis of ICU deaths of Warsaw hospitals showed a gradual decrease in the number of reported donors (from 75 in 2014 to 46 in 2018), although the number of all deaths did not decrease (the number of deaths in ICUs was on average 2.571/y).

Impact of Blood Loss and Intraoperative Blood Transfusion During Liver Transplantation on the Incidence of Early Biliary Complications and Mortality.

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.

How Early Postoperative Urinary Tract Infections Affect Renal Graft Function at 1-Year Follow-up.

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.

Early Postoperative Complications and Outcomes of Kidney Transplantation in Moderately Obese Patients.

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 < .05 was considered statistically significant. The study complies with the Helsinki Congress and the Istanbul Declaration. 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.

Time of Cold Storage Prior to Start of Hypothermic Machine Perfusion and Its Influence on Graft Survival.

BACKGROUND: 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. METHODS: 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 HMP >295 minutes (group G2; n = 125). RESULTS: 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. CONCLUSIONS: 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.

Reoperation in Early Kidney Post-transplant Period as a Strong Risk Factor of Surgical Site Infection Occurrence.

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.