Marina Varga

Association between the malnutrition-inflammation score and post-transplant anaemia

BACKGROUND Post-transplant anaemia (PTA) is common and is associated with adverse consequences. The protein-energy wasting (PEW) syndrome is associated with erythropoietin resistance in patients on maintenance dialysis. We assessed the association between PEW and PTA in a large prevalent cohort of stable kidney-transplanted patients. METHODS Data from 942 prevalent kidney-transplanted patients were analysed. Socio-demographic parameters, laboratory results, transplantation-related data and medication were obtained from the charts. Biomarkers reflecting nutritional status and inflammation [serum leptin, albumin, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and C-reactive protein] were measured. Anthropometric measures and the malnutrition-inflammation score (MIS) were also tabulated. Anaemia was defined according to the guidelines of the American Society of Transplantation. RESULTS Mean age was 51 ± 13 years, 57% were males and 22% had diabetes. The prevalence of PTA was 33%. The haemoglobin (Hb) level significantly and negatively correlated with the MIS (rho = - 0.316), marginally with serum TNF-α (rho = - 0.079) and serum IL-6 (rho = - 0.075) and positively with serum transferrin (r = 0.298), serum albumin (r = 0.274), abdominal circumference (r = 0.254) and serum leptin (rho = - 0.152), P < 0.05 for all. In a multivariable linear regression model, MIS was independently associated with Hb (beta = - 0.118, P = 0.004) in patients with estimated glomerular filtration rate (eGFR) lower than or equal to 60 mL/min/1.73 m(2), but not in patients with higher eGFR. CONCLUSIONS The MIS is independently associated with PTA in the kidney-transplanted population with eGFR lower than or equal to 60 mL/min/1.73 m(2).

Endoscopic diagnosis of cytomegalovirus infection of upper gastrointestinal tract in solid organ transplant recipients: Hungarian single-center experience

Abstract:  Background:  Cytomegalovirus (CMV) is considered to be the major cause of upper gastrointestinal (GI) symptoms in organ transplant recipients. In the diagnosis of GI CMV infection the detection of the virus in the mucosa is essential. The aim of the study was to evaluate the significance of CMV, detected in biopsy specimens from stomach and duodenum of solid organ transplant recipients.

Comparing cytomegalovirus prophylaxis in renal transplantation: single center experience

Abstract: Background: Cytomegalovirus (CMV) presents a serious threat to CMV‐seronegative recipients (R−), who have received an organ from a seropositive donor (D+).

H1N1 Vaccination in Pediatric Renal Transplant Patients

BACKGROUND Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk of serious infectious complications. In 2009, a new influenza pandemic caused serious infections and deaths, especially among children and immunocompromised patients. Herein we have reported the safety and efficacy of a single-shot monovalent whole-virus vaccine against H1N1 infection in the pediatric renal transplant population. METHODS In November and December 2009, we vaccinated 37 renal transplant children and adolescents and measured their antibody responses. Seroprotection, seroconversion, and seroconversion factors were analyzed at 21 days after vaccination. RESULTS None of the vaccinated patients experienced vaccine-related side effects. None of the patients had an H1N1 influenza infection after vaccination. All of the patients showed elevations in antibody titer at 21 days after vaccination. In contrast, only 29.72% of the patients achieved a safe seroprotection level and only 18.75% a safe seroconversion rate. More intense immunosuppressive treatment displayed negative effect on seroprotection and seroconversion, and antibody production significantly increased with age. No other factor was observed to influence seroprotection. CONCLUSIONS We recommend vaccination of children and adolescent renal transplant recipients against H1N1 virus. However, a single shot of vaccine may not be sufficient; to achieve seroprotection, a booster vaccination and measurement of the antibody response are needed to assure protection of our patients.

HLA-DQ3 is a probable risk factor for CMV infection in high-risk kidney transplant patients

BACKGROUND Cytomegalovirus (CMV) infection in transplant patients with special risk factors remains a major hazard. CMV-seronegative recipients with seropositive donors have the highest risk of developing acute CMV disease. We suggest that the HLA-type may influence the occurrence and the severity of primary CMV infection of these recipients and the measurement of the special HLA-types may be useful in the prediction of acute infection. METHODS Since 1999 1213 cadaver kidney transplantations have been performed in our clinic. 163 of 1213 recipients were CMV-seronegative (13%) and 129 of them received the kidney from seropositive donors. All 129 patients received CMV infection prophylaxis. Of 129 CMV-seronegative patients 49 developed acute CMV infection (38%) during the first posttransplant year. CMV infection was diagnosed by CMV antigenemia test and serologic measurements (ELISA). The particular HLA-genotypes of the recipients were studied before the transplantation. The occurrence and the severity of CMV infection was investigated in association with HLA-types. RESULTS We found different acute CMV infection distribution in the careers and non-careers of investigated HLA-types: HLA-A2, HLA-B12, HLA-Cw7, HLA-DR6 and HLA-DR11, but the differences were not significant in these HLA-types (P = 0.26, P = 0.37, P = 0.83, P = 0.07 and P = 0.37). While investigating HLA-DQ3, we found that of 68 DQ3-positive patients 32 (47%), of 61 DQ3-negative patients 17 (28%) had acute CMV infection and this difference was found to be significant. This result was confirmed by univariate and multivariate Cox Regression (P = 0.001) and the appropriate significance level was considered by Bonferroni correction. CONCLUSIONS HLA-DQ3 was found to be an independent predictor of CMV infection. Our data suggest that patients positive for HLA-DQ3 are more susceptible to CMV infection than a comparable group of patients negative for HLA-DQ3. This result was not due to rejection and/or treatment for rejection and was not influenced by induction therapy. Although we found more symptomatic infections among DQ3+ patients the difference was not significant (P = 0.19). Comparing the gender proportion among all 1213 kidney recipients and among CMV-seronegative recipients we found that the proportion of males is significantly higher among CMV-seronegative recipients (P < 0.001).

Prediction of early renal graft function by the measurement of donor urinary glutathione S-transferases.

BACKGROUND We have investigated the possibility of urinary alpha- and pi class glutathione S-transferases (GST-a; GST-pi) serving as a valuable parameter to predict early graft function after transplantation. METHOD Urinary GST concentrations of 61 donors (DON) and recipients (REC) were analyzed at preoperative, intraoperative, and postoperative periods. We grouped recipients according to the early postoperative graft recovery days. RESULTS The donor graft function, represented by the donor urinary GST concentration (GST-pi:17,1+/-12 microg/l mmol creatinine (crea); GST-a:14,3+/-10 microg/mmol crea), sustained a loss in comparison to the healthy controls (GST-a; pi< or =1 microg/mmol crea). According to statistical analysis, the donor GST-pi level showed a strong correlation with graft recovery days-pi (r = 0.84; P<0.001). The early graft function cannot be predicted by means of cold ischemia time (22.8+/-3.4 hr), nor handling time (42.4+/-11.1 min), nor even the intraoperative enzyme concentrations. The GST-pi cut off level (12.55 microg/mmol crea) might predict the possible posttransplant graft dysfunction. The discriminative analysis showed that using only DON GST-pi alone could discriminate well between the groups among all grafts in 68%. CONCLUSION Prognosis is poorer if the donor GST-pi concentration is above 12.55 microg/mmol crea. On the basis of the determination of GST-pi concentration in the donor urine, we can predict graft viability before the surgical procedure with a reliability of 68%.

Hepatitis B and liver transplantation

The authors overview the results of liver transplantations of HBV patients in Hungary. The special needs of pre- and postoperative period of HBV infected patients in the treatment are discussed. 4 patients were transplanted because of HBV cirrhosis. 1 patient died in the early postoperative period, 3 patients are well and active. The authors also overview the de novo HBV infections in transplanted patients, found in 6 cases.

Pulmonary infections after lung transplantation

Lung transplantation has become an accepted therapeutic modality for end-stage diseases of the lungs and the pulmonary circulation. In the past two decades more than 20,000 lung transplantations were performed all over the world. Due to improvements in immunosuppressive regimens the mortality rate of severe acute rejections has decreased up to 2% in the first post-transplant year. By contrast, infections became the most common cause of morbidity and mortality after lung transplantation. It was reported that 21.2 and 40% of annual deaths are due to infections in the first 30 days and one year, respectively. In the first month 35-70% of transplant recipients develop bacterial pneumonia caused often by Gram-negative organisms especially by Pseudomonas species. All patients should receive prophylactic antibiotics after the operation, which are to be modified according to the resistance patterns of pathogens isolated from the donor lungs. In the early post-operative period, the frequency of invasive fungal (Aspergillus and Candida) and cytomegalovirus (CMV) infections appears to be less then 10% due to prophylactic amphotericin inhalation and systemic valganciclovir administration for 100 days. After withdrawing these drugs, these infections became more common. In the late post-transplant period, the development of bronchiolitis obliterans syndrome (BOS) may predispose to infections. BOS may be manifested in approximately 50% of patients 5 years post-transplant. Routinely or urgently performed screening tests (laboratory and radiological investigations, lung function tests, sputum culture, bronchoscopy) and specific treatments are of central importance in the management of infections. In this review we discuss the clinical manifestation, the diagnosis and the treatment possibilities of the most common pulmonary infections in lung transplant recipients.

Seroprevalence of Helicobacter pylori in Central-European uraemic patients and its possible association with presence of HLA-DR12 allele.

Objectives Renal disease at any stage is often accompanied by significant gastrointestinal symptoms, and Helicobacter pylori (H. pylori) is closely related to these disorders. A debate is still ongoing on the clinical significance of coexisting uraemia and H. pylori. HLA-class II genes have been repeatedly investigated for predisposition to H. pylori infection. The aim of our work was to evaluate the infection rate among uraemic patients, and study the relationship between HLA antigens and H. pylori serologic status in the same cohort. Materials and methods Data of 709 uraemic patients were collected and analyzed from 2001–2006. 58.7% of patients were male, 41.3% were female, mean age was 45.1 years (SD: ±14.65). Microlymphocytotoxicity assay was used for typing of HLA class I, PCR-SSP for typing HLA class II alleles and enzyme immunofluorescency for specific H. pylori IgG. Results Of 709 patients, 49.37% were seropositive for H. pylori. Age of H. pylori positive patients was 48.9 versus 41 years of negatives (P<0.0001). Prevalence of H. pylori decreased strongly with year of birth. Significant difference was observed in the occurrence of HLA-DR12 according to H. pylori serology. Of patients carrying DR12, 27 (73%) were H. pylori positive and 10 (27%) were negative [P=0.0037; risk ratios (RR): 2.76]. Conclusion H. pylori infection rate and its decrease with year of birth was the same in the uraemic patients and in the normal population, according to specific prevalence figures. Frequency of HLA-DR12 was the same as in the general population; consequently, it might be a possible risk factor for H. pylori seropositivity, at least in a Central-European population.

Shear-wave elastography for the assessment of liver fibrosis in liver transplant recipients treated for hepatitis C virus recurrence

Objectives Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE. Patients and methods A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment. Results All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P<0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and &ggr;-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline. Conclusion In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.