A. Chmura

Machine Perfusion Preservation Improves Renal Allograft Survival

Machine perfusion (MP) has been used as the kidney preservation method in our center for over 10 years. The first, small (n = 74) prospective, single‐blinded randomized study comparing MP and Cold Storage (CS) showed that the incidence of delayed graft function was higher after CS. There have been no reports in the literature on the effect of storage modality on long‐term function of renal allografts. This paper presents an analysis of long‐term results of renal transplantation in 415 patients operated on between 1994 and 1999. Of those, 227 kidneys were MP‐stored prior to KTx. The control group consisted of 188 CS kidney transplants. Kidneys were not randomized to MP or to CS. Donor demographics, medical and biochemical data, cold ischemia time, HLA match and recipient data were collected. Standard triple‐drug immunosuppression was administered to both groups. Mortality, graft survival and incidence of return to hemodialysis treatment were analyzed. Despite longer cold ischemia time and poorer donor hemodynamics in MP group, 5‐year Kaplan‐Meier graft survival was better in MP‐stored than in CS‐stored kidneys (68.2% vs. 54.2%, p = 0.02). Conclusion: In this nonrandomized analysis, kidney storage by MP improved graft survival and reduced the number of patients who returned to dialysis.

Urinary tract infections in the early posttransplant period after kidney transplantation: etiologic agents and their susceptibility.

OBJECTIVE Urinary tract infection (UTI) is among the most common infections in solid organ transplantation, especially in kidney transplantation. PATIENTS AND METHODS This study included 295 adult patients undergoing KTx between September 2001 and December 2007. All patients were followed prospectively for UTI during the first 4 weeks after surgery. Samples of urine were investigated by bacteriological cultures to identify microorganisms in accord with standard procedures. Susceptibility testing was performed using Clinical and Laboratory Standards Institute procedures. RESULTS Urine specimens (n=582) were obtained from 84.5% of 245 recipients during the first month after transplantation. Among the isolated bacterial strains (n=291), the most common were Gram-negative bacteria (56.4%) predominantly Serratia marcescens (32.3%) and Enterobacter cloacae (14.6%). Extended- spectrum beta-lactamase (ESBL+) strains were isolated in 52.5% of cases. Gram-positive bacteria comprised 35.7%; most commonly, high-level aminoglycoside resistant (HLAR; 87.8%) and vancomycin-resistant (VRE; 11%) Enterococci. There were fungal strains in 23 cases (7.9%). CONCLUSION Our study showed predominantly Gram-negative rods from the Enterobacteriaceae family comprising (84.8%) of Gram-negative isolates: 52.5% ESBL and resistant enterococci (87.5%) in Gram-positive isolates. The increased proportion of isolates of multi-drug-resistant bacterial agents which can cause severe UTIs may be due to our frequent use of ceftriaxone for perioperative bacterial prophylaxis.

Efficacy of rapamycin in patient with juvenile rheumatoid arthritis

Juvenile rheumatoid arthritis (JRA) is an immune‐mediated disease characterized by articular inflammation and subsequent tissue damage that may result in severe disability. Several combinations of drugs, including immunosuppressive agents have been used to control disease progression. Although there is no information available on rapamycin efficacy in JRA, it has demonstrated a potential to inhibit inflammatory processes observed in adult rheumatoid arthritis (RA). We present a 21 years old renal transplant recipient with JRA, primarily treated with tacrolimus and steroids, who achieved a long‐term disease remission after introduction of rapamycin. As long as pathogenesis of JRA and RA is similar, we conclude that rapamycin could be promising immunosuppressant for patients after renal transplantation suffering from both JRA and RA.

Transplantation of kidneys harvested from non‐heart‐beating donors: early and long‐term results

Abstract  The purpose of this retrospective study was to evaluate results of non‐heart‐beating donor (NHBD) kidney transplantation. Between Jan 1986 and Dec 1994,80 out of 582 cadaveric kidneys were harvested from NHBD (31.9 min ± 24 after cardiac arrest). The results in the NHBD group (76 recipients) were compared with those obtained after transplantation of kidneys harvested from heart‐beating donors (HBD) with respect to early graft function, and the graft and recipients survival. Both groups were matched for sex, age, PRA level, number of HLA mismatches, and cold ischemia time. Triple immunosuppression therapy was used in both groups. Acute tubular necrosis (ATN) was observed significantly more frequently in the NHBD group (50 of 76 recipients vs 33 of 100 in the HBD group). The striking finding of this study was that the occurrence of primary non‐function was the same in both groups and that the main cause of it was acute rejection. The 1‐year patient and graft survival rates were 98.7 % and 81.6 % for the NHBD group and 99 % and 90 % for the HBD group, respectively. There was also no statistical difference in the serum creat‐inine concentration in both groups. We concluded that despite an increased incidence of ATN in the NHBD kidney recipients, the long‐term results are good and comparable with those in the HBD group.

SIRT1 and SIRT7 expression in adipose tissues of obese and normal-weight individuals is regulated by microRNAs but not by methylation status

Background/Objective:Given their importance in the regulation of metabolism, sirtuins (SIRTs) constitute promising subjects of research on the pathogenesis of obesity and the metabolic syndrome. The aim of this study was to assess whether obesity in humans is associated with changes in the expression of SIRT genes in adipose tissue and whether epigenetic mechanisms, DNA methylation and microRNA (miRNA) interference, mediate in this phenomenon.Subjects/Methods:The expression of SIRTs and of SIRT1 and SIRT7 mRNA-interacting miRNAs was evaluated by real-time PCR in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of 58 obese (body mass index (BMI) >40 kg m−2) and 31 normal-weight (BMI 20–24.9 kg m−2) individuals. The methylation status of SIRTs was studied by the methylation-sensitive digestion/real-time PCR method.Results:SIRT1 mRNA levels were lower in adipose tissues of obese patients than of normal-weight controls (VAT: P=0.0002, SAT: P=0.008). In contrast, expression of SIRT7 was higher in adipose tissues of obese patients than in the control group (VAT: P=0.001, SAT: P=0.008). The mean methylation of the SIRT1 and SIRT7 CpG islands was similar in tissues with high and low expression of these genes, and there was no correlation between the level of expression and the level of methylation. On the other hand, expression of SIRT1 in VAT of obese subjects correlated negatively with the expression of miR-22-3p (P<0.0001, rs=−0.514), miR-34a-5p (P=0.01, rs=−0.326) and miR-181a-3p (P<0.0001, rs=−0.536). In turn, expression of SIRT7 in VAT of slim individuals correlated negatively with the expression of miR-125a-5p (P=0.003, rs=−0.562) and miR-125b-5p (P=0.018, rs=−0.460).Conclusions:We observed obesity-associated downregulation of SIRT1 and upregulation of SIRT7 mRNA levels that were not associated with the methylation status of their promoters. We found a negative correlation between mRNA levels of SIRT1 in VAT of obese individuals and SIRT7 in VAT of the normal-weight subjects and expression of the relevant miRNAs.

One-year results of a prospective, randomized trial comparing two machine perfusion devices used for kidney preservation.

Studies have shown beneficial effects of machine perfusion (MP) on early kidney function and long‐term graft survival. The aim of this study was to investigate whether the type of perfusion device could affect outcome of transplantation of deceased donor kidneys. A total of 50 kidneys retrieved from 25 donors were randomized to machine perfusion using a flow‐driven (FD) device (RM3; Waters Medical Inc) or a pressure‐driven (PD) device (LifePort; Organ Recovery Systems), 24 of these kidneys (n = 12 pairs; 48%) were procured from expanded criteria donors (ECD). The primary endpoints were kidney function after transplantation defined using the incidence of delayed graft function (DGF), the number of hemodialysis sessions required, graft function at 12 months, and analyses of biopsy. DGF was similar in both groups (32%; 8/25). Patients with DGF in the FD group required a mean of 4.66 hemodialysis sessions versus 2.65 in the PD group (P = 0.005). Overall, 1‐year graft survival was 80% (20/25) vs. 96% (24/25) in the FD and PD groups. One‐year graft survival of ECD kidneys was 66% (8/12) in the FD group versus 92% (11/12) in the PD group. Interstitial fibrosis and tubular atrophy were significantly more common in the FD group – 45% (5/11) vs. 0% (0/9) (P = 0.03) in PD group. There were no differences in creatinine levels between the groups. Machine perfusion using a pressure‐driven device generating lower pulse stress is superior to a flow‐driven device with higher pulse stress for preserving kidney function.

Electrocardiographic criteria of left ventricular hypertrophy in patients with morbid obesity.

Background: Obesity is frequently accompanied by systemic hypertension complicated by left ventricular hypertrophy (LVH). Standard electrocardiography (ECG) is generally accepted screening tool for LVH in systemic hypertension. The aim was to assess currently used ECG criteria in the diagnosis of LVH in morbidly obese patients.

A Threat of the Klebsiella Pneumoniae Carbapenemase–Producing Strains Among Transplant Recipients

BACKGROUND Infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are associated with increased therapeutic failure and mortality. Our laboratory recognized several strains producing KPC, most of which originated from transplantation ward patients. MATERIALS AND METHODS All strains of K pneumoniae resistant to at least 1 carbapenem isolated in 2010 were examined for KPC production by disc diffusion and then verified by molecular methods. RESULTS All positive strains originated from 7 patients. Six of them were from transplantation wards. None of the KPC-producing strains was isolated from the patients blood. CONCLUSIONS A quick, accurate diagnosis of KPC-producing strains enabled immediate isolation of carriers or infected persons. Isolation prevented spread of dangerous strains among immunocompromised patients and reduced the possibility of serious infections.

Assessment of Kidneys Procured From Expanded Criteria Donors Before Transplantation

BACKGROUND Using expanded criteria donor (ECD) organs is 1 strategy to make more organs available for transplant. To reduce the number of posttransplant complications and failures, there is a need to create a comprehensive system of evaluation before transplantation, especially for kidneys harvested from ECD. The aim of this study was to assess the results of kidneys procured from ECD seeking to discover the most useful factors for kidney evaluation before transplantation. PATIENTS AND METHODS One hundred seventy-two patients received cadaveric renal transplants between January 1, 2006, and August 31, 2008. We collected data on donors, recipients, and perfusion parameters. We analyzed patient and graft survivals, as well as immediate, delayed, and slow graft function. Kidney recipient function was assessed by serum creatinine concentrations and by creatinine clearance calculated according to the Cockroft-Gault formula. Renal biopsy specimens were obtained in the perioperative periods 147 cases. RESULTS The overall 1-year graft survival was 86.9%. More than 25% of transplanted kidneys were harvested from ECD. There were no significant differences in patient survival between recipients of standard criteria donor kidneys (RSCDK) versus of expanded criteria donor kidneys (RECDK). One-year graft survival was higher among the RSCDK group than the RECDK group, namely, 94.4% versus 62.5%, (P = .004). There were no differences in the incidence of primary nonfunction or in delayed graft function between the groups. RECDK were more likely to show slow graft function (69.2% vs 37.8%; P = .033). A lower graft survival at 6 months after transplantation was observed among organs harvested from ECD compared with standard criteria donor (SCD) kidneys who showed histologic lesions or a flow at the fourth hour of machine perfusion below 0.4 mL/g. Using a logistic regression model, chronic histologic changes were shown to influence kidney survival at 6 months after transplantation. CONCLUSION There was no significant difference in patient survival between recipients of kidneys harvested from expanded versus standard criteria donors. ECD kidneys displayed lower graft survival rates. There was no significant difference in the incidence of delayed graft function between recipients of kidneys harvested from expanded versus standard criteria donors. Pretransplant evaluation of ECD kidneys should include 3 variables: donor parameters, histologic findings, and machine perfusion parameters.

Bacterial and fungal infections in the early post-transplantation period after liver transplantation: etiologic agents and their susceptibility.

OBJECTIVE It has been reported in many studies that one of the main factors influencing morbidity and mortality in patients receiving transplants is infection after transplantation. PATIENTS AND METHODS The study included 190 adult patients undergoing orthotopic liver transplantation (OLT) between September 2001 and December 2007. All the patients were followed prospectively for infections from the OLT date and during the first 4 weeks after surgery. Immunosuppression consisted of steroids and tacrolimus. Antimicrobial prophylaxis included piperacillin/tazobactam, fluconazole, and selective bowel decontamination (SBD) was performed. Samples of clinical materials were investigated for microbiological cultures. The micro-organisms were cultured and identified in accordance with standard bacteriological procedures. Susceptibility testing was performed using Clinical and Laboratory Standards Institute procedures. RESULTS From 190 OLT recipients, 2213 clinical samples were obtained for microbiological examination. Positive cultures were found in 27.2% (n = 603) of all samples tested; 1252 strains were collected. Gram-positive bacteria were found in 64.1% (n = 802), Gram-negative bacteria were found in 31.6% (n = 396), and fungal strains were isolated in 4.3% (n = 54). Surgical site specimens (n = 1031) were obtained from 190 recipients during the first month after transplantation. Positive cultures accounted for 29.2% (n = 301) of all samples tested. Among the isolated microbial strains (n = 677), most common were Gram-positive bacteria (73.7%; n = 499). Gram-negative bacteria comprised 25.1% (n = 170). There were fungal strains in 1.2% (n = 8). There were 539 urine specimens. Positive cultures accounted for 16.7% (n = 90) of those. Among the isolated microbial strains (n = 210), most common were Gram-negative bacteria (62.4%; n = 131). Gram-positive bacteria comprised 28.6% (n = 60) and fungi 9% (n = 19). There were 549 blood specimens. Positive cultures were found in 30.6% (n = 168) of all samples tested. Among the isolated microbial strains (n = 263), most common were Gram-positive bacteria in 72.3% (n = 190); Gram-negative bacteria were found in 26.2% (n = 69), and fungal strains were isolated in 1.5% (n = 4). There were 69 respiratory tract specimens. Positive cultures were found in 46.4% (n = 32) of all samples tested. Among the isolated microbial strains (n = 84), most common were Gram-positive bacteria (51.2%; n = 43); Gram-negative bacteria comprised 27.4% (n = 23) and fungi 21.4% (n = 18). CONCLUSIONS (1) Surgical site samples were predominated samples after LTx. (2) Our study showed Gram-positive bacteria were 64.1% (n = 802), Gram-negative bacteria, 31.6% (n = 396) and fungal strains isolated in 4.3% (n = 54). (3) The increased proportion of isolates of multi-drug-resistant bacterial strains (methicillin resistant coagulase negative Staphylococcus, vancomycin-resistant Enterococcus, high-level aminoglycoside resistance, and extended- spectrum β-lactamase). (4) These data indicate strict cooperation infection control procedures in these patients.