Michał Ciszek

Urine cytokines profile in renal transplant patients with asymptomatic bacteriuria.

Background. The role of asymptomatic bacteriuria in kidney transplant recipients is unknown. There is no clear evidence of its effect on transplanted kidney. Methods. We studied urine cytokines profile among kidney transplant recipients with bacteriuria found in screening examination. Urine cultures were collected in 269 patients with stable graft function and serum creatinine level <2 mg/dl, during their routine visits. Interleukin (IL)-6 and IL-8 levels were measured in urine samples from patients with asymptomatic bacteriuria, symptomatic urinary tract infection and patients without bacteriuria (control group). Changes in serum creatinine level in patients with asymptomatic bacteriuria and in the control group were observed during 12 months follow up. Results. Urinary tract infection (UTI) was diagnosed in five patients and asymptomatic bacteriuria in 22 patients. Urine IL-6 level was significantly higher in symptomatic UTI group (median 15.71 pg/mg) but there were no differences between group of patients with asymptomatic bacteriuria (3.92 pg/mg) and control group (2.54 pg/mg). Urine IL-8 level was higher in symptomatic UTI group (median 146.8 pg/mg) and was also significantly higher in asymptomatic bacteriuria group (33.49 pg/mg) in comparison to control group (2.97 pg/mg; P=0,0002). During 1-year follow up, incidence of UTI was higher in the asymptomatic bacteriuria group than in the control group but graft function was not different in both groups. Conclusions. Elevated urine IL-8 level in kidney transplant patients with asymptomatic bacteriuria may reflect impaired immune response to bacterial infection and occult inflammatory process in urinary tract.

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.

Rehabilitation and 6-minute walk test after liver transplantation.

BACKGROUND Measurement of exercise capacity is an integral element to assess patients after surgery. Although the 6-minute walk test (6MWT) provides information regarding functional capacity, response to therapy, and prognosis across a range of conditions, its applicability for liver transplant recipients remains to be established. The aim of our study was to examine whether the 6MWT in combination with a subjective rating of perceived exertion (Borg Scale [BS]) could be used to evaluate exercise capacity among patients after liver transplantation (OLT). METHODS Thirteen consecutive subjects were enrolled in this single-center study during routine rehabilitation of the 6MWT and BS. At days 7 and 14 after OLT seeking to assess objective and subjective exercise capacities, we recorded basic clinical parameters, including body weight, blood pressure, heart rate and temperature. The results as compared between days 7 and 14 were related to the reference values for age-, height- and weight-matched healthy subjects. RESULTS On day 7, normal 6MWT was achieved by one patient and at day 14-, by three patients. At days 7 and 14, the average distances of 6MWT were 326.7 m and 421 m, respectively (P<.05), indicating a significant increase in exercise capacity. The average BS rating did not change significantly between days 7 and 14, indicating, that the increased exercise capacity was achieved without excessive effort. CONCLUSIONS Our study indicated that the 6MWT and BS may represent inexpensive and safe assessment methods for exercise capacity after OLT. This evaluation may be helpful to plan and optimize post-OLT rehabilitation.

Safety and Efficacy of Steroid-Free Immunosuppression with Tacrolimus and Daclizumab in Liver Transplant Recipients: 6-Year Follow-up in a Single Center

BACKGROUND Avoidance of steroid therapy after solid-organ transplantation has become a major challenge. Corticosteroid (CS)-free maintenance immunosuppression not only eliminates the well-known adverse effects but also may improve long-term outcome. OBJECTIVE To investigate whether a CS-free regimen of tacrolimus (Tac) in combination with daclizumab (Dac) induction therapy provides adequate coverage after orthotopic liver transplantation. PATIENTS AND METHODS This 6-year, single-center, retrospective study included 25 liver transplant recipients randomized to a Tac/CS regimen (n = 18) vs a Tac/Dac regimen (n = 7) according to the protocol of the MASTER (Monoclonal Antibodies vs STERoids) Study. RESULTS No significant difference was observed in patient and graft survival between treatment arms: 94.4% in the Tac/CS group vs 71.4% in the Tac/Dac group. The incidence of biopsy-proved acute rejection episodes was 23.5% in the Tac/CS group vs 14.3% in the Tac/Dac group (P = NS). Total duration of hospitalization did not differ significantly between groups: 46.5 days in the Tac/CS group vs 73.9 days in the Tac/Dac group. Liver function as estimated using serum alanine aminotransferase and aspartate aminotransferase activity and bilirubin concentration, was not significantly different between the groups during 5 years posttransplantation. However, after 6 years, alanine aminotransferase activity was significantly greater in the Tac/Dac group compared with the Tac/CS group. CONCLUSIONS A CS-free regimen of Tac/Dac is as effective as Tac/Cs in achieving good patient and graft survival. However, no substantial benefits insofar as the safety of Tac/Dac therapy were evident during long-term follow-up.

Leflunomide as a rescue treatment in ganciclovir-resistant cytomegalovirus infection in a seronegative renal transplant recipient – a case report

BACKGROUND Cytomegalovirus (CMV) infection is a frequent complication of immunosuppressive treatment after solid organ and bone marrow transplantation. Prophylaxis and treatment with ganciclovir is successful in most cases, but frequency of infections with ganciclovir-resistant CMV mutants has grown in recent years. Leflunomide, an immunosuppressive drug used in rheumatic diseases and which also exerts antiviral activity, could be a useful treatment option in such cases. CASE REPORT A 60-year-old, CMV-seronegative patient received a kidney graft from a CMV-seropositive donor. The post-transplant period was complicated by 2 episodes of biopsy-proven graft rejection treated with steroid pulses. CMV viremia was diagnosed 4 weeks after transplantation. The patient received treatment with intravenous ganciclovir and anti-CMV immunoglobulins with consecutive oral valganciclovir therapy. He was admitted to our hospital 6 months after transplantation, with symptoms of CMV infection confirmed by high viral load in his blood. Treatment with double-dose ganciclovir and anti-CMV immunoglobulins did not decrease CMV viremia, so we diagnosed ganciclovir-resistant CMV infection. We decided to discontinue mycophenolic acid treatment and start leflunomide 20 mg BID. This therapy led to rapid decrease and final disappearance of CMV viremia. Kidney graft function remained stable during leflunomide treatment. Seroconversion in both IgM and IgG anti-CMV classes was observed. CONCLUSIONS Treatment with leflunomide is a reasonable option in ganciclovir-resistant infection in kidney transplant recipients, providing effective viral elimination and reconstitution of adaptive anti-CMV immunity without excess risk of graft rejection.

Transplant glomerulopathy: clinical and pathological correlations.

OBJECTIVE Chronic transplant glomerulopathy (TG) is one of the leading causes of severe posttransplantation proteinuria and graft loss. Our current knowledge about risk factors for the development of TG, as well as factors that affect its dynamics and prognosis, is poor. We sought to describe the pathological and clinical risk factors and correlations of TG as well as parameters that influenced the survival of grafts with that pathology. MATERIALS AND METHODS We retrospectively reevaluated 86 kidney transplant cases with TG that have been recognized on the basis of an indication biopsy since 1997. All TG as well as all pre-TG (previous) biopsies were characterized for the presence of C4d deposits in the graft. RESULTS Younger recipient age and minimal immunosuppression due to drug withdrawal or suboptimal drug doses/blood levels within 3 to 6 months preceding the biopsy were associated with C4d deposition in peritubular capillaries (PTC; P = .0053 and P = .0365, respectively). Diffuse PTC-itis (P = .029, RR [95% confidence interval] = 3.349 [1.131-9.919]) and total interstitial inflammation score (P = .015, RR [95% confidence interval] = 9.662 [1.784-52.329]) were observed to show a negative impact on graft survival. C4d deposition in PTC and glomeruli, the level of pretransplantation sensitization, episodes of acute rejection, and C4d in previous (pre-TG) biopsies did not influence the survival of grafts with TG. CONCLUSIONS Younger recipient age and minimal immunosuppression were associated with C4d positivity in grafts with TG. The survival of kidney grafts with TG was significantly affected by the magnitude of inflammation in the interstitium and PTC, but not by C4d positivity in PTC and glomeruli.

Different profile of gene expression of cytokines in peripheral blood mononuclear cells of transplant recipients treated with m-TOR inhibitor and calcineurin inhibitor.

AIMS To determine how sirolimus (SRL), in comparison to calcineurin inhibitors (CNI), influences gene expression of cytokines: interleukin 1beta, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin 10 (IL-10) in peripheral blood mononuclear cells (PBMC) of transplant recipients. MATERIAL AND METHODS Twenty-two patients (13 kidney and 9 liver transplant recipients), in which: CNI was replaced by SRL (n=11); SRL was added to CNI (n=7); or SRL was replaced by CNI (n=4), were recruited. PBMC were obtained before and after modification of immunosuppression. Real-time polymerase chain reaction was used for quantitative assessment of expression of investigated genes. RESULTS During therapy with SRL either with, or without CNI (SRL+/-CNI), the pro-inflammatory genes expression was increased, and IL-10 gene expression was decreased, in comparison to treatment with CNI. In subgroup of patients with malignancy as the reason of liver transplantation, gene expression of TNF-alpha and IFN-gamma was higher when SRL+/-CNI was used in comparison to treatment with CNI. Patients with viral infection receiving SRL+/-CNI had higher expression of pro-inflammatory genes than during therapy with CNI. CONCLUSIONS Transplant recipients during therapy with SRL+/-CNI have increased gene expression of Th1 cytokines, and decreased gene expression of Th2 cytokine, IL-10, in PBMC, compared to treatment with CNI. Our data may influence management of transplant recipients.

Effective optimization of living donor kidney transplantation activity ensuring adequate donor safety

Results of kidney transplantation are excellent, but the number of patients on the waiting lists far exceeds the number of available organs. Living kidney donation must be considered as an important part of organ transplantation programmes. In the European Union countries, nearly 20% of all kidney transplants in 2010 were done with organs from living donors. However, the proportion of live donor kidney transplantation between EU countries varies greatly: from 3% to 54% of all kidney transplantations. Multiple initiatives have been undertaken in most of the European countries to increase the number of living donor kidney transplantations. In some countries widening of the donor pool has nearly reached the limits by accepting altruistic donors, paired and group exchanges, and even by performing live donor kidney transplantation in highly immunized recipients. There is a great need to optimize living donor kidney transplantation programmes by using a new strategy of: a. Detailed and adequate medical and psychosocial evaluation, ensuring that the need to increase programme activity will not overshadow the most important principle--donor safety. b. Total removal of all disincentives and financial obstacles that discourage potential donors, and provision of financial coverage for the follow-up. c. Sufficient detailed information about the option of living donor kidney transplantation, its results, and donor safety, delivered to relatives of patients with end-stage renal disease and to the patients themselves.

The dominant sequence types of vancomycin-resistant Enterococcus faecium among transplantation ward patients.

OBJECTIVES Vancomycin-resistant enterococci (VRE) frequently cause therapeutic problems and provide information about the epidemiological condition of the ward. MATERIALS AND METHODS VRE isolated from patients on transplantation wards in 2007-2008 were compared using 2 molecular methods: RFLP-PFGE (restriction fragment length polymorphism-pulse field gel electrophoresis) and MLST (multilocus sequence typing). RESULTS The analysis covered 29 Enterococcus faecium strains resistant to glycopeptides, each from a different patient. All organisms were typed using 2 molecular methods. MLST results were compared with an international base. The 30 examined strains belonged to 8 different worldwide known sequence types. All could be recognized as representatives of a single clonal complex CC17. CONCLUSION Both methods of typing appeared to be useful to asses the epidemiological condition of the investigated wards.

Strains of Klebsiella pneumoniae Producing Extended Spectrum Beta-Lactamases, Isolated from Organ Recipients

OBJECTIVE The aims of this work were to define the effectiveness of identification of the extended-spectrum beta-lactamases (ESBL) phenotype, and to define the genotype of Klebsiella pneumoniae β-lactamase. MATERIALS AND METHODS We identified ESBL phenotypes in 110 strains of K pneumoniae isolated from samples from patients of transplantation wards, using the double-disk synergy test (DDST). For the chosen strains, polymerase chain reaction (PCR) was applied to detect genes determining SHV, CTX-M, and TEM. RESULTS We showed synergism of clavulanic acid and investigated antibiotics including ceftazidime (89.1%), cefotaxime (80%), and aztreonam (82.7%) against ESBL-positive strains PCR revealed that TEM and CTX-M were present in 88.89% of strains. CONCLUSIONS The ESBL mechanism of resistance is frequent among K pneumoniae strains isolated from transplant recipients. Strains with simultaneous synthesis of more than one beta-lactamase predominated.