M. Durlik

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.

Long‐term results of treatment of chronic hepatitis B, C and D with interferon‐α in renal allograft recipients

Abstract The aim of this study was to evaluate the efficacy and safety of interferon‐a (IFN‐α) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN‐α three times weekly for 6 months. After IFN‐α therapy, 18 patients (43 %) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN‐α therapy. Repeated liver biopsy was performed in 16 patients after 6–24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN‐α therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN‐α therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long‐term follow‐up (median 22 months, range 0–84 months). IFN‐α seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.

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.

Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation

Renal transplantation ensures distinct advantages for patients with end-stage kidney disease. However, in some cases early complications can lead to allograft dysfunction and consequently graft loss. One of the most common early complications after kidney transplantation is delayed graft function (DGF). Unfortunately there is no effective treatment for DGF, however early diagnosis of DGF and therapeutic intervention (eg modification of immunosuppression) may improve outcome. Therefore, markers of acute kidney injury are required. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes. Different urinary and serum proteins have been intensively investigated as possible biomarkers in this setting. There are promising candidate biomarkers with the ability to detect DGF. We focused on emerging biomarkers of DGF with NGAL is being the most studied followed by KIM-1, L-FABP, IL-18, and others. However, large randomized studies are needed to establish the value of new, promising biomarkers, in DGF diagnosis, prognosis and its cost-effectiveness.

Hypertension in solid organ transplant recipients

Hypertension (HT) is one of the most frequent complications of solid organ transplantation; about 70-90% of this population have high blood pressure or require antihypertensive therapy. Abnormal blood pressure is a potent non-immunological risk factor directly related to patient and graft survival. The etiology of hypertension after orthotopic heart transplantation is multifactorial and varies depending on the time following transplantation. In the early period after transplantation, hypertension is generally related to intravascular volume expansion and persistently increased systemic vascular resistance. Other factors predominant in kidney allograft recipients include: donor age, donor familial history of hypertension, transplant renal artery stenosis, graft function, the recurrence or de novo appearance of glomerulonephritis in transplanted kidney, and post-biopsy arteriovenous fistula. In liver and heart transplantation, hypertension is mainly due to impaired kidney function, with all its consequences. Another contributing factor is immunosuppressive regimen based on calcineurin inhibitors and steroids. The management of post-transplant hypertension usually requests non-pharmacological and pharmacological treatment. In this review, the pathogenesis and treatment of post-transplant hypertension in solid organ transplantation is presented.

Current approaches in national kidney paired donation programs

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. While living donors provide anywhere from a small to a large fraction of kidneys for transplantation in different countries, at least one-third of these donors are incompatible with their potential recipients. To overcome these challenges, kidney paired donation (KPD) programs have been established that organize donor exchanges to find matches among the pool of incompatible pairs. Each program has developed its own features to accommodate local needs. Reasons for participating in KPD include blood group incompatibility, sensitization of the recipient against the donor, and the potential for improvement in transplant quality (e.g., age difference or graft size), and tissue compatibility. KPD programs use sophisticated algorithms to find matches among the pool of donor-recipient pairs to create simultaneous 2-way, 3-way, or 4-way exchanges or more complex non-simultaneous chains of transplants. These KPD allocation systems should be medically sound and ethically acceptable according to the principles of equity, utility, and justice. The variety of possible exchanges provided by these algorithms allows for maximizing the number of transplants, increasing the quality of transplants, and accommodating patients who are difficult to match. In this review, we describe several examples of successful KPD programs with diverse organizational approaches. By highlighting the strategies used by these programs to meet the needs of their patient populations, we aim to inspire improvements in existing programs and to provide a framework for expanding KPD to better serve international transplant communities.

Posttransplantation diabetus mellitus under calcineurin inhibitor

BACKGROUND The development of postransplantation diabetes mellitus (PTDM) is a serious complication of kidney transplantation. PTDM has a major impact on quality of life decreasing rates of patient and graft survival. It is well known that some currently used immunosuppressants are diabetogenic. Greater diabetogenicity of FK-506 has been reported in multicenter trials. We initiated a study of conversion from tacrolimus (FK-506) to cyclosporine (CsA) among kidney allograft recipients presenting with PTDM to evaluate whether this maneuver would ameliorate a diabetic state. METHODS This analysis of 20 adult, renal allograft recipients presenting with PTDM assumed the need for insulin therapy or oral hypoglycemics before and after conversion of the immunosuppressive regimen. The criteria for evaluating the outcome were as follows: dose reduction of insulin or oral hypoglycemic agents, adequacy of glucose control, C-peptide levels, and insulin concentration. RESULTS During the follow-up, we observed an improvement in the control of blood glucose in the converted group. In 13 patients, satisfactory glucose control was obtained without insulin or any other agent. In 3 patients a significant dose reduction of required insulin was possible. In another 2 patients who were insulin-dependent, the switch to oral hypoglycemic treatment was clinically possible after conversion. After conversion we observed significantly lowered fasting blood glucose levels and increased C-peptide levels. CONCLUSIONS The conversion from a tacrolimus to a CsA-based immunosuppressive regimen resulted in better glucose metabolism. We demonstrated a positive effect of conversion on the diabetic state of patients with PTDM.

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.