Gábor Telkes

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.

Molecular pathogenesis of post-transplant acute kidney injury: Assessment of whole-genome mRNA and miRNA profiles

Acute kidney injury (AKI) affects roughly 25% of all recipients of deceased donor organs. The prevention of post-transplant AKI is still an unmet clinical need. We prospectively collected zero-hour, indication as well as protocol kidney biopsies from 166 allografts between 2011 and 2013. In this cohort eight cases with AKI and ten matched allografts without pathology serving as control group were identified with a follow-up biopsy within the first twelve days after engraftment. For this set the zero-hour and follow-up biopsies were subjected to genome wide microRNA and mRNA profiling and analysis, followed by validation in independent expression profiles of 42 AKI and 21 protocol biopsies for strictly controlling the false discovery rate. Follow-up biopsies of AKI allografts compared to time-matched protocol biopsies, further baseline adjustment for zero-hour biopsy expression level and validation in independent datasets, revealed a molecular AKI signature holding 20 mRNAs and two miRNAs (miR-182-5p and miR-21-3p). Next to several established biomarkers such as lipocalin-2 also novel candidates of interest were identified in the signature. In further experimental evaluation the elevated transcript expression level of the secretory leukocyte peptidase inhibitor (SLPI) in AKI allografts was confirmed in plasma and urine on the protein level (p<0.001 and p = 0.003, respectively). miR-182-5p was identified as a molecular regulator of post-transplant AKI, strongly correlated with global gene expression changes during AKI. In summary, we identified an AKI-specific molecular signature providing the ground for novel biomarkers and target candidates such as SLPI and miR-182-5p in addressing AKI.

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+).

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).

A Single-Center Experience with Kidney Transplantation in the Verteberal, Anal, Cardiac, Tracheoesophageal, Renal, and Limb Birth Detects (VACTERL) Association

VACTERL association is a nonrandom association of birth defects in vertebral, anal, cardiac, tracheoesophageal, renal, and limb structures. Renal anomalies are observed in ∼60%-90% of VACTERL patients. We present 3 cases to demonstrate the clinical and surgical challenges that these patients present for renal transplantation. One pediatric and 2 adult patients with the VACTERL association were transplanted at a single center; their follow-up times were 6 years, 4 years, and 3 months. Only 1 of them had a suitable native bladder to receive the kidney graft; the other 2 required bladder augmentation, 1 of which was performed after the loss of the first graft. None of these patients had an uneventful posttransplantation course. Two patients had acute rejection episodes, and 2 had reoperations for urologic complications. One patient needed a surgical intervention owing to a sigmoid prolapse. All 3 grafts worked at last examination. The 2 patients with bladder reconstructions and longer follow-ups suffered recurrent pulmonary and urinary infections and had been hospitalized several times during each posttransplantation year. In conclusion, multiorgan involvement in VACTERL patients greatly complicates medical care after transplantation; urinary tract reconstruction seems to be essential before transplantation.

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.

[Can urinary neutrophil gelatinase-associated lipocalin predict acute rejection following deceased donor kidney transplantation?].

INTRODUCTION Delayed graft function and acute rejection have negative impact on graft survival. AIM To asses the predictive value of urinary neutrophil gelatinase-associated lipocalin, which has been found to be a promising biomarker for the diagnosis of acute kidney injury. METHOD In this prospective study urinary neutrophil gelatinase-associated lipocalin levels of 27 kidney recipients were measured. RESULTS Patients were grouped as follows: group 1, no complication; group 2, rejection; group 3, delayed graft function requiring dialysis; group 4, rejection plus delayed graft function. There were no significant differences between groups 1 and 2, and between groups 3 and 4. Patients in groups 3 and 4 had significantly higher urinary neutrophil gelatinase-associated lipocalin levels as compared to those in groups 3 and 4. There was a paralIel change in urinary neutrophil gelatinase-associated lipocalin levels in groups 1 and 2. CONCLUSIONS In these patients urinary neutrophil gelatinase-associated lipocalin levels failed to provide useful information in both cases of normal and impaired function.Absztrakt Bevezetes: Veseatultetes utan mind a graft kesleltetett műkodese, mind az akut rejekcio negativan befolyasolja a tulelest. Celkitűzes: A neutrofil gelatinaz asszocialta lipokalin igeretes biomarkernek tűnik az akut karosodasok diagnozisaban. Modszer: Prospektiv vizsgalatban 27 felnőtt veserecipiens vizelet neutrofil gelatinaz asszocialta lipokalin erteket mertek es megvizsgaltak prediktiv erteket. Eredmenyek: A betegeket 4 csoportba osztottak (nincs komplikacio, rejekcio, kesői indulas dializisigennyel, rejekcio + kesői indulas). Nem talaltak szignifikans kulonbseget a nincs komplikacio es rejekcio, valamint a kesői indulas dializisigennyel es rejekcio + kesői indulas csoportok kozott. A kesői indulas dializisigennyel es rejekcio + kesői indulas csoportok neutrofil gelatinaz asszocialta lipokalin szintje lenyegesen magasabb volt, mint a nincs komplikacio es rejekcio csoportoke. A nincs komplikacio es rejekcio csoportokban a kreatinin es neutrofil gelatinaz asszocialta lipokalin szintjei parhuzam...