Huseyin Bakkaloglu

Association of HLA phenotypes of end-stage renal disease patients preparing for first transplantation with anti-HLA antibody status

Patients with pre-transplantation high levels of panel reactive antibody (PRA) have an increased risk of graft failure, and renal transplantation in sensitized patients remains a highly significant challenge worldwide. The influence of anti-human leukocyte antigen (HLA) antibodies on the development of rejection episodes depends on patient-specific clinical factors and differs from patient to patient. The HLA typing of the recipient might influence the development of anti-HLA antibodies. Some HLA antigens appear to be more immunogenic than others. The aim of this study is to demonstrate the distribution of HLA phenotypes in PRA-positive and PRA-negative end-stage renal disease (ESRD) patients on the basis of having sensitizing events or not. Our study included 642 (mean age: 41.54; female/male: 310/332) ESRD patients preparing for the first transplantation and who are on the cadaveric kidney transplantation waiting list of Istanbul Medical Faculty in 2008–2009. Class I HLA-A,B typing was performed by complement-dependent cytotoxicity (CDC) method, whereas class II HLA-DRB1 typing was performed by low-resolution polymerase chain reaction (PCR)-sequence-specific primer (SSP). All serum samples were screened for the presence of IgG type of anti-HLA class I- and II-specific antibodies by enzyme-linked-immunosorbent assay (ELISA). PRA-negative group consisted of 558 (86.9%) and PRA-positive group included 84 (13.1%) patients. We have found statistically significant frequency of HLA-A3 (p = 0.018), HLA-A66 (p = 0.04), and HLA-B18 (p = 0.006) antigens in PRA-positive patients and DRB1*07 (p = 0.02) having the highest frequency in patients with sensitizing event history but no anti-HLA development suggesting that DRB1*07 might be associated with low risk of anti-HLA antibody formation.

Human leukocyte antigen and major histocompatibility complex class I-related chain A antibodies after kidney transplantation in Turkish renal transplant recipients.

BACKGROUND This study was designed to determine whether human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related A (MICA) antibody (Ab) production during the first 6 months posttransplantation correlated with long-term graft survival and rejection rate. The study group included 147 first transplantations from either living related (LRDs) or deceased donors (DDs) who were divided into two subgroups: rejection (RG, n = 28) and nonrejection (NRG, n = 119). Serum samples (n = 441) collected from each patient on posttransplant days 30, 90, and 180 were tested for HLA and MICA Ab using the Luminex technique. RESULTS Among 82 Ab-positive patients (55.8%), 40 had both HLA and MICA, 33 only HLA, and 9 only MICA Ab in the posttransplant period. The rates of HLA class I, class II, or both Ab positivities were greater in the RG than the NRG (P = .011, .037, and .0275, respectively). At 180 days posttransplant, 64.3% of patients in the RG had Ab and 41.2% in the NRG (P = .0349). The data for the LRD (n = 116) group were similar to those for the entire group; whereas there was no significant difference in Ab positivity between RG and NRG patients who received organs from DDs. There was no significant difference with respect to HLA class II and/or MICA Ab positivity between RG and NRG among patients who lacked HLA class I Ab. DISCUSSION We confirmed that HLA and MICA Ab may be harmful posttransplant, promoting rejection processes and representing an important cause of graft failure. HLA class II and MICA Ab positivities were only important predictors of graft failure when present together with HLA class I positivity. Patients who developed HLA alone or both HLA and MICA Ab rejected their grafts more frequently than Ab-negative recipients.

Is Heparinization Necessary in the Early Postoperative Period of Renal Transplantation from Cadaveric Donors

INTRODUCTION Venous thromboemboli and bleeding are the complications that threaten the graft and patients life in the early postoperative period after cadaveric renal transplantation. For this reason, heparin administration after renal transplantation should be administered carefully. The aim of this study was to evaluate the necessity for heparinization after cadaveric renal transplantation. METHODS Between March 2009 and October 2010, we formed 2 study groups among 50 recipients who underwent either cadaveric (n = 25) or living donor transplantations (n = 25). We did not observe any risk factors for thromboembolism while group 1 did not undergo heparinization, group 2 received a prophylactic dose of low-molecular weight heparin for 1 week. Doppler ultrasonography (USG) was performed between postoperative 24-48 hours to examine the transplanted kidney vessels, and in one group 1 case for a bilateral lower extremity venous system examination. We were also compared postoperative thromboembolic and hemorrhagic complications, lymphorrhagia, and serum creatinine levels. RESULTS The female/male ratios in group 1 and 2 were 14/11 and 8/17 with mean ages of 36.7 (range, 17-51) and 35.9 (range, 17-59) years, respectively. The mean preoperative serum creatinine levels were 7.9 ± 2.9 mg/dL and 6.8 ± 2.4 mg/dL, and at postoperative week 1, they were 5.1 ± 4.3 mg/dL and 1.2 ± 0.5 mg/dL, respectively. We did not encounter any partial or total thrombus upon doppler USG studies for renal and lower extremity venous systems. No clinical symptoms of pulmonary emboli were detected in any patients. Only 1 subject group 2 experienced massive postoperative bleeding. CONCLUSION Herein, we have reported that, except for the patients with risk factors for venous thromboemboli, heparinization was not necessary in the early postoperative period and did not add benefits to outcomes of cadaveric renal transplant recipients.

Anti-HLA antibody profile of Turkish patients with end-stage renal disease.

Exposure to human leukocyte antigens (HLA) via blood transfusions, pregnancies, and previous transplantations can result in anti-HLA antibody production. The presence of anti-HLA antibodies in recipient sera before transplantation is an important risk factor. To demonstrate the anti-HLA antibody status of Turkish end-stage renal disease (ESRD) patients, 674 patients (mean age, 40.35 +/- 13.15 years; female/male, 328/346) were enrolled into the study. Anti-HLA antibody screening and identification tests were performed using an enzyme-linked immunosorbent assay (ELISA) method. The panel-reactive antibody (PRA)-negative group consisted of 564 (83.6%) and the PRA-positive group consisted of 110 (17.3%) patients. Of the 110 (17.3%) PRA-positive patients, 43 (6.4%) were class I (+) and class II (-); 19 (2.8%) were class I (-) and class II (+); 48 (7.1%) were both class I and II (+). The most frequent antibodies were directed against the A2 crossreactive group (CREG) and the A10 CREG with less frequent reactions against the B7 CREG, indicating antibodies to both frequent (members of A2 CREG) and relatively rare (members of A10 CREG and B7 CREG antigens). These data also suggested that some antibodies occur at greater than expected frequency because of shared epitopes. Our findings confirmed the significant correlation between female gender, pregnancy, failed graft history, long dialysis duration, and blood transfusions with PRA positivity (P < .05).

Effect of MDR1 Polymorphisms on the Blood Concentrations of Tacrolimus in Turkish Renal Transplant Patients

BACKGROUND Tacrolimus, a calcineurin inhibitör, is prescribed to prevent allograft rejection in renal transplantation. Tacrolimus not only has a narrow therapeutic index, but also shows significant interindividual differences. The absorption and metabolism of this drug are affected by multidrug resistance (MDR) 1 gene polymorphisms that correlated with single-nucleotide polymorphisms (SNPs) affecting in vivo P-glycoprotein activity. This study investigated associations of MDR1 gene C3435T polymorphism with tacrolimus blood concentrations and dose requirements as well as acute rejection episodes among Turkish renal transplant patients. METHODS One hundred living-donor transplant recipients and 150 healthy control subjects underwent C3435T genotyping using polymerase chain reaction-restriction fragment length polymorphism. Blood concentrations of tacrolimus were determined with the cloned enzyme donor immunoassay. RESULTS The CC, CT, and TT genotype frequencies among patients were, respectively, 44.0%, 33.0%, and 23.0% versus 36.7%, 43.3%, and 20.0% among control subjects. There was no significant difference between (P = .061; P = .102; P = .211; respectively). The ratio of blood concentration to dose of tacrolimus for patients with mutant homozygous 3435 TT genotype was higher than that of wild-type 3435 CC genotype homozygous individuals. The doses for these patients were lower at 1, 3, and 12 months (P = .048; P = .03; P = .041, respectively). There were no significant differences between the groups regarding coprescription of drugs that affect tacrolimus concentrations, such as diltiazem. Acute rejection episodes were not associated with the CC vs CT or TT genotypes: odds ratio (OR), 0.517 (95% confidence interval [CI], 0.190-1.407; P = .192); OR 1.558 (95% CI, 0.587-4.136; P = .372); OR 1.346; (95% CI, 0.456-3.968; P = .590), respectively. CONCLUSIONS Determination of MDR1 polymorphism may help to achieve target of tacrolimus blood concentrations.

A rapidly increasing abdominal girth in a young patient: MDCT findings of Budd-Chiari syndrome.

From the Department of Radiology, Department of Gastroenterohepatology, and Department of General Surgery, Transplant Unit, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey This section features outstanding photographs of clinical materials selected for their educational value or message, or possibly their rarity. The images are accompanied by brief case reports (limit 2 typed pages, 4 references). Our readers are invited to submit items for consideration.

Unexpected colonic perforation in a renal recipient: a case report

Gastrointestinal complications such as gastrointestinal bleeding and perforation due to immunosuppressant use are seen more frequently after solid organ transplantation. A 52-year-old male was admitted on the 7th day of a living donor renal transplantation with serous drainage at the incision site. He had no abdominal complaints. He was on triple immunosuppressant therapy. Abdominal plain X-ray and ultrasonography were normal, but diffuse extraluminal air was detected on the computed tomography scan. There were no pathological laboratory findings regarding the function of the renal allograft. We began the operation laparoscopically and then converted to laparotomy. Sigmoid colonic perforation was detected on the antimesenteric side. Neither diverticulitis nor ischemia was observed, and no evidence of iatrogenic injury was seen. There was no transrectal instrumentation history. Omentoplasty and sigmoid loop colostomy were performed. He was discharged on the 9th day following the operation. His colostomy was closed one year after the operation. Gastrointestinal complications can be fatal, but do not seem to influence the long-term survival or renal allograft function. Most of them are seen after using high doses of immunosuppressants to manage the early postoperative period or episodes of acute rejection. Early diagnosis and aggressive treatment play an important role in survival.

Cutting-Balloon Angioplasty in Transplant Renal Artery Stenosis as First-Line Treatment in the Early Postoperative Period

Percutaneous transluminal angioplasty has been successfully used for the treatment of transplant renal artery stenosis (RAS). Cutting-balloon angioplasty (CBA) is being used as a second option in pressure-resistant stenosis. It is thought that CBA is less traumatic and therefore restenosis occurs less frequently than in conventional angioplasty. This case report describes the unusual use of a cutting balloon in transplant RAS as a first option in the early postoperative period. Long-term follow-up data are also presented.

Acquired Acrodermatitis Enteropathica Syndrome in a Kidney Transplant Recipient: A Case Report

Acrodermatitis enteropathica syndrome (AE) is a clinical entity that results in severe zinc deficiency. It can be genetic or acquired. Acquired AE has been reported in patients with chronic liver disease, malabsorption syndrome, sickle cell anemia, and chronic renal failure. We present a kidney transplant recipient with skin rash and watery diarrhea. The patient had low serum zinc levels, which quickly resolved after zinc supplementation. Skin biopsy showed cytoplasmic pallor and vacuolization and ballooning degeneration of keratinocytes within the superficial epidermis, which may have led to confluent necrosis of keratinocytes. Large amounts of keratinosome-derived lamellae were found in the intercellular spaces in the keratinized area, probably related to disturbance of keratinosome metabolism due to zinc deficiency.

High soluble CD30 levels and associated anti-HLA antibodies in patients with failed renal allografts

Introduction Serum soluble CD30 (sCD30), a 120-kD glycoprotein that belongs to the tumor necrosis factor receptor family, has been suggested as a marker of rejection in kidney transplant patients. The aim of this study was to evaluate the relationship between sCD30 levels and anti-HLA antibodies, and to compare sCD30 levels in patients undergoing hemodialysis (HD) with and without failed renal allografts and transplant recipients with functioning grafts. Methods 100 patients undergoing HD with failed grafts (group 1), 100 patients undergoing HD who had never undergone transplantation (group 2), and 100 kidney transplant recipients (group 3) were included in this study. Associations of serum sCD30 levels and anti-HLA antibody status were analyzed in these groups. Results The sCD30 levels of group 1 and group 2 (154 ± 71 U/mL and 103 ± 55 U/mL, respectively) were significantly higher than those of the transplant recipients (group 3) (39 ± 21 U/mL) (p<0.001 and p<0.001). The serum sCD30 levels in group 1 (154 ± 71 U/mL) were also significantly higher than group 2 (103 ± 55 U/mL) (p<0.001). Anti-HLA antibodies were detected in 81 (81%) and 5 (5%) of patients in groups 1 and 2, respectively (p<0.001). When multiple regression analysis was performed to predict sCD30 levels, the independent variables in group 1 were the presence of class I anti-HLA antibodies (β = 0.295; p = 0.003) and age (β = -0.272; p = 0.005), and serum creatinine (β = 0.218; p = 0.027) and presence of class II anti-HLA antibodies (standardized β = 0.194; p = 0.046) in group 3. Conclusions Higher sCD30 levels and anti-HLA antibodies in patients undergoing HD with failed renal allografts may be related to higher inflammatory status in these patients.