Successful Treatment of Urinary Tract Infection in Kidney Transplant Recipients Caused by Multiresistant Klebsiella pneumoniae Producing New Delhi Metallo-Beta-Lactamase (NDM-1) With Strains Genotyping.

BACKGROUND: Klebsiella pneumoniae New Delhi metallo-beta-lactamase-1 (NDM-1) strains have recently become a new threat in kidney transplant recipients due to the strains' resistance to almost all antibiotics, including carbapenems. METHODS: We present a case series of 3 patients with urinary tract infections (UTIs) caused by multiresistant K pneumoniae NDM-1 strains who were treated with the same protocol. Genotyping sequencing with pulsed-field gel electrophoresis was performed in all cases. RESULTS: All patients were male and had undergone kidney transplantation 4, 7, and 8 months, respectively, before the admission. Combined antibiotic therapy consisting of imipenem/cilastatin in maximal doses, gentamicin and/or colistin for 21 to 27 days, followed by oral fosfomycin, was used in all cases. There were no further UTI episodes in 2 patients at the 12-month visit. Three months after initial treatment, the third patient presented with leukocyturia with no clinical symptoms and a urine culture positive for K pneumonia NDM-1 strain. Interestingly, the strain was susceptible to trimethoprim/sulfamethoxazole despite resistance in previous urine culture samples. The patient was successfully treated with trimethoprim/sulfamethoxazole 2 × 960 mg/d for 3 weeks followed by 480 mg/d and 3 doses of fosfomycin. Genotyping sequencing revealed identical DNA restriction fragments in bacterial strains from 2 patients. In the third case, although a difference in 2 restriction fragments was observed, the strain was considered related to the others. CONCLUSIONS: In cases of UTI caused by K pneumoniae NDM-1 strains, prolong combined treatment followed by oral fosfomycin prophylaxis can be successful. Strain genotyping should be performed to optimize further treatment protocols in such cases.

The effect of pregnancy on humoral rejection in patients after vascularized organ transplantation.

The aim of the study was to evaluate the effect of pregnancy on the production of donor- and nondonor-specific anti-human leukocyte antigen antibodies (anti-HLA Abs) in organ allograft recipients. The study group included four pregnant kidney (RT) and four liver (LT) transplant recipients. The genotype of HLA class I (A, B) and class II (DR) antigens was assessed. Anti-HLA antibodies class I and II were evaluated between 36 and 40 weeks' gestation. Two different control groups consisted of the following: group I (n=8) with nonpregnant RT (n=6) and LT recipients (n=2), and group II with healthy pregnant women (n=10) with anti-HLA Abs detected between 38 and 41 weeks' gestation. The HLA genotype was determined in fathers of the fetuses from the study group and group II controls. Half of group II controls had donor-specific anti-HLA (A, B, and/or DR) Abs, while nondonor-specific anti-HLA Abs were detected in all subjects from that group. Anti-HLA Abs were found in all group II controls. In the study group, anti-HLA Abs were found in only two LT recipients and one RT recipient, but they were not confirmed as donor-specific. Anti-HLA antibodies were not detected in the study group, whereas six out of ten group II controls had anti-HLA Abs against the HLA of the child's father. Pregnancy in vascularized organ recipients does not trigger the mechanism of humoral rejection involving anti-HLA class I and II antibodies with a potentially adverse impact on graft function.

Kidney transplantation does not increase the level of basic hope or life satisfaction compared with hemodialysis in patients with chronic kidney disease.

INTRODUCTION: Although renal replacement therapy can lead to improved health, it also can cause emotional disturbances in patients. It is believed that the success of renal replacement therapy hinges not only on medical parameters, but also on psychosocial factors, which is why modern medicine provides an ever-increasing role in the improvement of patients' quality of life. PURPOSE: The purpose of this study was to compare the level of life satisfaction, purpose in life, and basic hope in patients who had received renal replacement due to chronic kidney disease. We also tested whether the specific type of renal replacement therapy and kidney function parameters were influential factors on the above variables. PATIENTS AND METHODS: Sixty-one adult patients treated via renal replacement for chronic kidney disease took part in the study. Patients were divided into two groups: 31 hemodialysis patients (15 women and 16 men, ages 23-77 years, mean 51.19 years, SD 14.53 years) and 30 patients who had undergone kidney transplantation (14 women and 16 men, ages 22-69 years, mean 48.40 years, SD 12.64 years). The following research tools were used for analysis: Satisfaction With Life Scale (SWLS), Purpose in Life Test (PIL), and Basic Hope Inventory (BHI-12). RESULTS: There were no statistical differences in the level of satisfaction with life between hemodialysis patients and postkidney transplant patients. The results for the SWLS obtained from both groups fell within the normal range. The average SWLS for hemodialysis patients remained 20.61, SD = 5.79; for postkidney transplant patients, it was 22.57, SD = 5.16. The PIL level in the group of hemodialysis patients (101.5, SD = 15.64) was significantly lower than in the group of postkidney transplant patients (109.7, SD = 15.54). The average BHI-12 level was similar in both groups. The average BHI-12 result for hemodialysis patients was 29.00 (SD = 5.06), and for postkidney transplant patients 29.93 (SD = 3.55). The correlations between the psychological variables and selected biochemical parameters are worthy of particular attention. Among hemodialysis patients, there was an additional correlation between SWLS and hematocrit; whereas for postkidney transplant patients, there was an additional correlation of PIL and eGFR. CONCLUSIONS: Our data show that satisfaction with life and basic hope do not increase in patients after renal replacement therapy. The form of renal replacement therapy (hemodialysis or kidney transplantation) does not change the above variables. Patients treated via renal replacement require specialized psychological support to improve the efficacy of renal replacement therapy.

Anemia treatment with erythropoietin in pregnant renal recipients.

Pregnancies in renal transplant patients are considered to be high risk. Anemia is one of the major complications of pregnancy occurring among 65% to 85% of cases in this setting, especially since these patients carry additional risk factors. Herein we have presented five renal transplant recipients who were women who were treated with human recombinant erythropoietin due to severe anemia that developed during pregnancy. Hemoglobin levels below 9 g/dL after 3 weeks of oral iron administration were assumed to be qualifying criteria for erythropoietin treatment. No complication was observed to be associated with the treatment. Two of the five patients required blood transfusions despite erythropoietin administration. Two cases delivered small for gestational fetus age. Erythropoietin therapy in pregnant kidney transplant recipients should be considered to be a safe method to reduce the need for blood transfusions.

Biliary complications in relation to the technique of biliary reconstruction in adult liver transplant recipients.

UNLABELLED: Biliary complications are known as a weak point of liver transplantation. Their occurrence can be related to the practice of draining the biliary anastomosis performed at the time of transplantation. At our institution, routine of anastomotic biliary drainage was abandoned in June 2004. AIM: We sought to assess the occurrence and character of biliary complications following orthotopic liver transplantation in relation to the technique of anastomosis. MATERIALS AND METHODS: In two groups of transplantees: last 100 transplantations with biliary drainage (48 females and 52 males aged 17 to 64 years) and last 100 transplantations without drainage (52 females and 48 males aged 18 to 67 years). The results of treatment were compared, for biliary complications and their influence on further management. In both groups, the main indications for transplantation were various types of cirrhosis as well as cholestatic diseases. In most cases (167) we performed a cholangiojejunal Roux-en-Y (CBD) end-to-end anastomosis, less commonly (33 cases) hepaticojejunal anastomoses. RESULTS: In the first group, biliary complications (bile leak at the site of drainage, bile leak after T-tube removal, CBD strictures) requiring surgical or endoscopic intervention, occurred in 17% recipients. In one case, the biliary complication resulted in retransplantation. In the second group, biliary complications occurred in 11% patients. None of them caused organ loss. CONCLUSION: Abandoning drainage of the biliary anastomosis has reduced the occurrence of early biliary complications after orthotopic liver transplantation.

Insulin resistance in kidney allograft recipients treated with calcineurin inhibitors.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is one of the main complications observed in patients after organ transplantation. The incidence of PTDM in transplant recipients is about 9 times higher than in general population. The reported incidence of PTDM varied throughout the years due to different diagnostic criteria of diabetes mellitus. Nowadays the rate of PTDM amounts to 3-19%. MATERIALS/METHODS: 1270 patients after kidney transplantation, who remained under medical care in the outpatient service at the Transplantation Institute in Warsaw, were taken into consideration. The investigated group comprised 207 patients. 133 of them developed DM that constitutes the incidence of PTDM at 10.5%. RESULTS: In the present study several risk factors that are important for PTDM development were observed: male gender, HLA A3, family history of DM, increased body weight (rather than BMI only), tacrolimus--based immunosuppressive regimen, early hyperglycemia. Patients with PTDM developed hypertension more frequently, had higher serum triglycerides levels in the period before the onset of diabetes. The rate of acute rejection episodes in this group was higher compared with the nondiabetic transplant controls. The PTDM group presented with worse graft function and higher levels of proteinuria in 1-year observation. Tacrolimus--based therapy led to higher peripheral insulin resistance and hyperinsulinemia in comparison to cyclosporine--based regimen. CONCLUSIONS: The proper management of the above described risk factors and the right treatment of PTDM may considerably influence life expectancy rate and quality of life in transplanted patients.

Therapeutic monitoring of tacrolimus concentrations in blood of renal and liver transplant recipients: comparison of microparticle enzyme immunoassay and enzyme multiplied immunoassay methods.

Monitoring of tacrolimus blood concentrations is of utmost importance in the management of organ transplant recipients due to narrow therapeutic index of the drug and its considerable interpatient variability in pharmacokinetics. Thus therapeutic monitoring of tacrolimus plays a crucial role not only in the evaluation of the drug efficacy but also in the control of possible side effects. We compared immunoassay-based methods, quantitative enzyme multiplied immunoassay (EMIT) with quantitative microparticle enzyme immunoassay (MEIA), using blood samples from renal and liver transplant recipients (n = 40) treated with tacrolimus. Blood samples were obtained for diagnostic routine measurements. The tacrolimus concentrations measured by EMIT for all the transplant patient samples were higher (2.8 to 28.5 ng/mL) than results obtained in MEIA (3.0 to 25.0 ng/mL). The mean difference expressed in percentage was 13.94% and correlation coefficient EMIT versus MEIA was 0.97. The tacrolimus concentrations measured by EMIT for renal graft recipients (n = 8) were higher (6.0 to 13.3 ng/mL) than those measured by MEIA (6.1 to 12.2 ng/mL), mean difference expressed in percentage was 14.1% and correlation coefficient was 0.85. The tacrolimus concentrations for liver transplant recipients (n = 32) measured by EMIT (2.8 to 28.5 ng/mL) were higher than results obtained in MEIA (3.0 to 25.0 ng/mL), the mean difference expressed in percentage was 13.89%, and the correlation coefficient was 0.98. The results obtained in the study show an insignificant difference in specificity of both methods used to determine the concentration of an active drug. Thus both methods, EMIT and MEIA, seem to have similar diagnostic value.

Biliary liver cirrhosis secondary to cystic fibrosis: a rare indication for liver transplantation.

As more effective therapies prolong the lives of patients with cystic fibrosis, there are now more patients in this population diagnosed with liver diseases. Secondary biliary cirrhosis is not a rare complication of mucoviscidosis. It is diagnosed in 20% of patients with mucoviscidosis; in 2% it is accompanied by portal hypertension. On average patients with portal hypertension and its complications are 12 years old. Liver transplantation is an accepted method of treatment for children with cystic fibrosis and portal hypertension. It eliminates the cause of the portal hypertension, decreases life-threatening medical conditions, and improves their nutritional status and quality of life. Despite immunosuppressive treatment they do not seem to beat increased risk of upper respiratory tract infections. On the contrary improved respiratory function and status are generally observed. We present our first case of orthotopic liver transplantation performed in a 29-year-old man with cystic fibrosis. The donor was a 42-year-old woman who died of a ruptured cerebral aneurysm. The surgery was performed in September 2004. The patient received immunosuppression based on steroids, basiliximab, tacrolimus, and mycophenolic acid due to renal insufficiency. Antibiotic (meropenem) and antiviral prophylaxis (gancyclovir) were used. A 6-month period of observation confirmed the clinical data from the pediatric population-a good prognosis with improved nutritional status, respiratory function, and quality of life.

The use Prometheus FPSA system in the treatment of acute liver failure: preliminary results.

UNLABELLED: The preliminary outcomes of patients with acute liver failure treated with the Prometheus Fractionated Plasma Separation and Absorption (FPSA) system are presented herein. PATIENTS AND METHODS: The procedures were performed in 13 patients (4, intoxication by Amanita phalloides; 4, unknown reason; 3, acetaminophen intoxication; 1, Wilson disease, and 1, liver insufficiency after hemihepatectomy owing to metastases of colon adenocarcinoma). The patients were qualified for the procedure according to the King's College Hospital criteria. The patients' general status was assessed on basic of GCS, UNOS, and the 4-grade encephalopathy classifications. The procedures were performed with the Prometheus 4008H Fresenius Medical Care unit. RESULTS: The 29 procedures were of mean duration 6.5 hours. There were statistically significant reductions in total bilirubin, ammonia, and aminotransferase levels. In addition, the procedures corrected water, mineral, and carbohydrate disorders. One patient did not require liver transplantation. Seven patients received liver transplants: three patients with positive outcomes; two died due to septicemia within 30 days perioperatively, one died at 6 months after OLT owing to respiratory failure; and one, owing to hemorrhagic diathesis. Four patients did not receive a liver transplant because of lack of a organ, no consent for the surgery, or neoplastic disease with metastases. CONCLUSIONS: The Prometheus FPSA-System was an effective detoxication method for patients with acute liver failure. The system was useful as a symptomatic treatment before liver transplantation allowing a longer wait for a graft.

Orthotopic liver transplantation for fulminant hepatic failure.

This paper presents the results of liver transplantation for fulminant hepatic failure in 31 patients qualified as UNOS-1 class (extra-urgent indication for transplantation), operated from January 1989 to April 2005. Twenty-one patients (61.8%) survived the 3-month postoperative period. Three-year survival rate with good liver graft function was 52.9% (18 patients). Before the transplantation, eight patients (23.5%) underwent hepatic dialysis using Fractionated Plasma Separation and Adsorption (FPSA) with the use of a Prometheus 4008H System. Liver transplantation remains the only life-saving procedure for the treatment of fulminant liver failure, regardless of its cause.

Assessment of early biliary complications after orthotopic liver transplantation and their relationship to the technique of biliary reconstruction.

INTRODUCTION: Biliary complications are known as the weak point of liver transplantation. Their occurrence can be related to the practice of drainage of the biliary anastomosis, the routine use of which was abandoned in June 2004. The aim of the study was to assess the incidence and type of biliary complications following orthotopic liver transplantation in relation to the technique of biliary anastomosis. MATERIAL AND METHODS: We compared the results of two groups of adult liver transplant recipients: group I, recent 50 transplantations with biliary drainage (25 women: 25 men of age range: 17 to 63 years), and group II, first 50 transplantations without drainage (19 women and 31 men of age range, 20 to 65 years). We examined the problem of biliary complications and their influence on the further management of the patients. In both groups the main indications for transplantation were various types of cirrhosis as well as cholestatic diseases. In the majority of cases (n = 86) an end-to-end common bile duct anastomosis was performed and in 14 cases, hepaticojejunal anastomosis. RESULTS: In group I, biliary complications requiring surgical or endoscopic intervention occurred in 10 (20%) recipients. In one case, biliary complications resulted in the need for retransplantation. In group II, biliary complications occurred in only four (8%) patients, none of which caused organ loss. CONCLUSION: Cessation of biliary anastomosis drainage has reduced the occurrence of early biliary complications following orthotopic liver transplantation.

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.

Biochemical assessment of the early liver graft function in relation to selected donor parameters.

The aim of this study was to assess the usefulness of liver grafts procured from "marginal donors." Among 62 liver transplants in 2002, almost half were harvested from donors who were not deemed acceptable by other transplant units. The authors compared the data concerning the donor's status with the function of the transplanted liver. The relations between individual parameters were estimated, as well as the differences between two groups of recipients: those who received a graft from the "poorer" donors versus those who received "better" grafts. Regardless of the relations between particular parameters a statistical analysis revealed that differences of liver function that were detected during the first 5 days after transplantation disappeared thereafter.

The impact of experience of a transplantation center on the outcomes of orthotopic liver transplantation.

The so-called learning factor has been disregarded for many years in analyzing the causes of surgical complications and post-operative mortality; it is also the case for OLT. In our center until April 2003, 209 OLT were performed in 196 patients. We evaluated the impact of experience of the transplantation team on the outcomes of liver transplantation. Thirty-four patients died (mortality rate, 16%) and 1-year survival rate, 64%. Mortality rates varied during different periods of observation due to increasing experience of the transplantation team. The causes of mortality were assessed for a series of 34 patients: it was 75% at the beginning of transplantation procedures while recent deaths have not recently exceeded 10% of cases.

Renal function after liver transplantation: calcineurin inhibitor nephrotoxicity.

Renal failure, mainly due to calcineurin inhibitor (CNI) nephrotoxicity, is the most common complication following orthotopic liver transplantation (ltx). The aim of this study was to evaluate the incidence and course of renal failure in adult ltx patients. Severe acute renal failure in early postoperative period due to impaired hemodynamics and CNI nephrotoxicity, occurred in 14 patients, 3 of whom required dialysis. The creatinine clearance after ltx showed a tendency to decrease, but there was no statistically significant difference (P >.05) in the change in serum creatinine clearance levels between patients treated with tacrolimus (TAC) versus Cyclosporine (CsA) during the first 2 years of follow-up. Fourteen patients required conversion of their regimen because of CNI nephrotoxicity namely, dose reduction (n = 7) or discontinuation of CNI therapy with the replacement by mycophenolate mofetil (MMF) (n = 5) or SRL (n = 5). Dose reduction or CNI withdrawal significantly improved the creatinine clearance (P <.05) without affecting lives graft function. No episode of acute rejection was observed after conversion. Neither conversion of CsA to TAC nor the reverse maneuver significantly influenced the serum creatinine level (P >.05). Reduction of the CNI dose or CNI discontinuation or replacement with MMF or SRL in patients with stable liver but impaired renal function is safe, resulting in a significant improvement in renal function.