Deceased Donor Kidney Transplantation in a Human Immunodeficiency Virus-Infected Recipient: A Case Report.

Human immunodeficiency virus (HIV) infection has traditionally been considered an absolute contraindication for transplantation because immunosuppression will accelerate the disease progression and increase mortality. New antiretroviral agents have given rise to new perspectives and transplantation practices. Now renal transplantation is the gold standard treatment for end-stage renal disease in HIV-infected patients, but increased rejection and toxicity rates and compliance with treatment are important issues. Therefore, patient selection and follow-up should be done carefully in this patient group. Here we present a 51-year-old, male, HIV-infected patient who was diagnosed with HIV at his routine serologic investigation at 2015. Highly active antiretroviral therapy was initiated. One haplotype-matched kidney transplantation from a deceased donor was performed on October 19, 2016. Induction therapy was not administered, and the immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisolone. After 26 months, serum creatinine was 1.1 mg/dL and proteinuria 0.1 g/day. There was no development of donor-specific antibodies. The patient's current HIV viral load remains undetectable (and had been the entire time post-transplantation) while his CD4+ T-cell count currently is 543/mm3.

Association Between HLA Antibodies and Different Sensitization Events in Renal Transplant Candidates.

BACKGROUND: Human leukocyte antigen (HLA) allo-immunization is caused by various events such as blood transfusions, pregnancies, or organ transplantations, which can lead to sensitization. In this retrospective study, we evaluated different sensitization models and their effects on panel-reactive antibody (PRA) profiles of renal transplantation candidates. METHODS: Anti-HLA class I/II antibody screening tests were performed in 906 renal transplantation candidates with the use of a microbead-based assay (Luminex). RESULTS: Two hundred ninety-seven (32.8%) of the patients were determined as positive in terms of PRA, and 609 (67.2%) were negative. Sensitized and non-sensitized patients were compared separately in terms of each sensitization type. The anti-HLA class I, II, and I+II positivity rates in patients sensitized only by blood transfusion were 13.1%, 6.3%, and 14.1%, the rates with pregnancy sensitization were 35.5%, 29%, and 45.2%, and rates with previous transplantation sensitization were 15.6%, 34.4%, and 38.9%, respectively. Prevalence of PRA positivity was significantly higher in patients with previous pregnancy than with transplantation and transfusion (odds ratio, 1.003; 95% confidence interval, 0.441-2.281; P = .031). The risk of developing HLA class I antibodies was higher in pregnancies (P < .001), and the risk of developing anti-HLA class II antibodies was higher in patients who had undergone a previous transplantation (P < .001). The rate of developing HLA-B antibodies in patients sensitized by pregnancy were significantly higher compared with sensitization after transfusion (P = .015), as was the rate of developing HLA-DQ antibodies in patients sensitized by previous transplantation compared with sensitization through pregnancy (P = .042). CONCLUSIONS: In patients who are waiting for kidney transplantation, sensitization by pregnancy and transplantation have a significant impact on development of HLA class I and class II antibodies.

Corrected Panel-Reactive Antibody Positivity Rates for Hypersensitized Patients in Turkish Population With Calculated Panel-Reactive Antibody Software.

INTRODUCTION: High rates of panel-reactive antibody (PRA) may decrease the chance of kidney transplantation and may result in long waiting periods before transplantation. The calculated PRA (cPRA) is performed based on unacceptable HLA antigens. These antigens are identified by a program that was created based on the antibodies that developed against the HLA antigens circulating in serum and on the risk of binding of these antibodies to antigens. The antigen profile of the population and antigen frequencies can be measured, and more realistic cPRA positivity rates may be obtained using this method. MATERIALS AND METHODS: We developed a program based on the HLA antigens of 494 blood donors in 2 European Federation for Immunogenetics-accredited Tissue Typing Laboratories in Turkey. Next-generation sequencing-based tissue typing (HLA-A, -B, -C, -DR, -DQ, 4 digits) of the samples was performed. The PRA screening test was performed on 380 patients who were waiting for organ transplant from a cadaver in Istanbul Faculty of Medicine. The single antigen bead assay testing was performed to identify the antibody profiles on 48 hypersensitized patients. RESULTS: The PRA testing results using the current methods were 44.6% ± 18.5%, and the cPRA rate was 86.2% ± 5.1%. The mean PRA positivity of the sensitized patients using the current methods was 44.6%; however, the rate was 86.2% using the cPRA. DISCUSSION: cPRA shows the rate of the rejected donors according to all unacceptable antigens. The need for a list of unacceptable antigens in place of the PRA positivity rate is a real change in the sensitization-dependent calculation as cPRA positivity rate. CONCLUSION: In principal, implementation of cPRA will encourage many centers and laboratories to adopt a standard measurement of sensitization in Turkey. It will increase the chances of better donor match, particularly for hypersensitized patients, by the creation of an unacceptable mismatch program using cPRA software.

Acquired Acrodermatitis Enteropathica Syndrome in a Kidney Transplant Receipt: 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.

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.

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 patient's 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).

Outcome of living unrelated (commercial) renal transplantation.

BACKGROUND: Due to inadequate cadaveric and living related organ supply, many end-stage renal disease patients go to Third World countries for commercial transplantation, although the high risk of complications is well established and ethical arguments debate this practice. METHODS: The midterm outcome of 115 patients who had been commercially transplanted in various countries and admitted to our center for post-transplant care and follow-up between 1992 and 1999 was retrospectively analyzed. Data considering the transplantation practice and post-transplant course were collected from the patient files. Outcome of these patients was compared with those with a living related transplant performed at our center. RESULTS: The patients (91 male and 24 female; mean age of 42 +/- 12 years) were transplanted in India (N = 106), Iraq (N = 7), and Iran (N = 2). The mean follow-up period was 64.5 +/- 23.9 months. Post-transplant course was complicated by numerous surgical and/or medical complications, and many of the latter were unconventional infections caused by malaria, invasive fungal infections, and pneumonia due to various opportunistic pathogens. Overall, 52 patients still have functioning allografts, while 22 lost their grafts, 20 died, and 21 were lost to follow-up. Graft survival rates at two, five, and seven years were 84, 66, and 53%, respectively, for the study group, while it was 86, 78, and 73% for living related transplantations performed at our center (P = 0.036). Patient survival rates for the same periods were 90, 80, and 74% for the study group and 90, 85, and 80% for the living related transplantations (P = 0.53). CONCLUSIONS: Besides the ongoing ethical debate, commercial transplantation carries a high risk of unconventional complications, and despite that the patient survival rate is comparable, graft survival is worse than conventional living related transplantations at the midterm.

Successful therapy combined with surgery for severe post-transplant nocardiosis.

We report a case of a 35-year-old man with nocardiosis infection involving soft tissue and the central nervous system who had received a cadaveric donor kidney. The patient was admitted with fever, malaise and right shoulder pain. Soft tissue abscess was seen on ultrasound examination. It was presumed due to gram (+) microorganisms, so 4 g day (IV) ampicillin/sulbactam was started empirically once the abscess was drained. Nocardia asteroides was found in the pus specimen. On the second day in hospital, severe headache, ataxia and signs of meningeal irritation appeared. The cranial CT showed two intracranial abscesses in the frontal lobe and cerebellum. We assumed Nocardia asteroides was the infective agent for the cerebral abscesses, so antibiotic therapy was switched to trimethoprim-sulphamethox-asole (3x160/800 mg/d). Nausea and vomiting occurred on the fifth day of therapy, improving after drainage from the frontal abscess. However, these complaints recurred five days later. CT showed cerebellar abscess had become bigger. The patient's complaints improved after the second surgical drainage. N. asteroides was again grown in the aspiration fluids of both cerebral abscesses. Complete regression of the abscesses was seen in the CT after two months. Co-trimoxazole was continued for six months then withdrawn. Graft dysfunction was not observed. Early medical and surgical interventions may be life-saving in this potentially lethal disease.

Transplantation in renal amyloidosis.

In this report, the results of renal transplantation in patients with renal amyloidosis were retrospectively analysed and compared with the control group. Fifteen (3.04%) of the 493 renal transplant recipients whom were followed up in Istanbul School of Medicine transplant outpatient clinic, between 1983 and 1997, were included in the study. The etiology of amyloidosis was familial Mediterranean fever in all patients. The mean follow-up period was 38.3 +/- 31.8 (range 7-65) months. Twelve of the patients were male and 3 female with the mean age 34.13 +/- 10.87 (range 21-60) years. Seven patients had living related, 4 living-unrelated and 4 cadaveric donors. Five patients were lost because of different complications: Three patients died from cardiac amyloidosis all with well functioning grafts, 2, 3 and 36 months after the operation. Sepsis and cardiovascular failure was the probable cause of death in 1 patient who also had chronic rejection. Another one patient with chronic rejection died from hepatic failure. Acute rejection developed in 2 patients. Renal functions of these patients improved by anti-rejection therapies. Chronic rejection developed in 3 patients. In the control group, acute rejection and chronic rejection were diagnosed in 5 and 1 patients, retrospectively. While 1 patients returned to hemodialysis in control group, the others are alive with satisfactory graft function. There was no death in control group. The 5-yr graft and patient survival rates in amyloidosis and the control groups were 75, 77, 95 and 100%, respectively. It was concluded that although transplantation is not a contraindication for the treatment of end stage renal failure in patients with renal amyloidosis, it carries high risk of cardiac complications in the postoperative period. Detailed preoperative cardiovascular evaluations are mandatory in these patients and this intervention should improve the prognosis by excluding the patients who have already been complicated with this problem.

Posttransplant malaria.

The frequency and clinical characteristics of plasmodium infection were reported in 420 renal transplant recipients who were followed in the Transplantation Unit and Out-Patient Clinic of the Medical School of Istanbul. Plasmodium infection was diagnosed in eleven (9 male, 2 female) of the 420 patients (2.6%). Ten of the patients were transplanted in India, and one in our institution. The mean duration between the transplantation and the diagnosis of malaria was 21.7 + 44.4 days in patients who were transplanted in India. All of the patients were taking triple immunosuppressive drugs (CsA, AZA, PRED). Plasmodium falciparum was diagnosed in 6 patients, P vivax in 1 patient and P malariae in 1 patient. Also mixed infection with P falciparum and P malariae was diagnosed in 3 patients. After definite diagnosis, the patients were hospitalized. Chloroquine phosphate plus primaquine phosphate was administered for P vivax infection, whereas chloroquine phosphate alone was given for P falciparum and P malariae infection as a first line antimalarial therapy. As a result of therapy, infection improved clinically and the plasmodia disappeared rapidly from the thick blood film in 10 of the patients. Severe hemolysis and acute renal failure developed in one patient, who improved after hemodialysis therapy and exchange transfusions. It was concluded that malaria is quite a frequent infection of transplant recipients who get their allografts from donors living in high-risk areas, and all transplant recipients having this kind of transplantations should be suspected and examined for malaria. This may help to diagnose and treat the complication in the early period, thus resulting in an improved prognosis for this potentially life-threatening complication of the posttransplant period.

Evaluation of the frequency of HLA determinants in patients with gingival overgrowth induced by cyclosporine-A.

This study has been designed to investigate the immunogenetic susceptibility of Cyclosporine-A (CsA) immunosuppressed renal transplant patients to development of gingival overgrowth, and the amplifying effect of calcium channel blockers on the severity of this clinical entity. 52 renal transplant recipients were selected and initially grouped as follows: group (Gp)1: CsA (n = 7); Gp 2: CsA + verapamil (n = 26); Gp 3: CsA + diltiazem (n = 6); Gp 4: CsA + nifedipine (n = 13). These groups were not found to be significantly different in age, sex, plaque index (PlI), gingival index (GI), calculus index, periodontal probing depth, serum CsA level, or duration of CsA therapy (p > 0.05). No significant (p > 0.05) additive effect of the calcium channel blockers on the gingival overgrowth (GO) was assessed. The main group (n = 52) was evaluated for the correlations between the clinical and the pharmacological variables and the GO. GI (rs = 0.60) and the periodontal probing depth (rs = 0.71) were found to be moderately correlated with the GO. The patients were regrouped based on the severity of overgrowth and recognized as responders (n = 26) and nonresponders (n = 26). Age, sex, calculus index, serum CsA level, duration of the CsA therapy, were not statistically different among these groups (p > 0.05). PlI, GI, periodontal probing depth, and GO were significantly higher in the responder group (p > 0.05). Analysis of HLA distribution of the responders and the nonresponders and comparison with the controls (n = 3731) revealed that a statistically significant (p < 0.001)% of the nonresponders were positive for HLA-DR1. These data would indicate that an immunogenetic predisposition should be suspected in the pathogenesis of the entity, and that HLA-DR1 would have a protective rôle against gingival overgrowth induced by CsA.

Living unrelated (paid) kidney transplantation in Third-World countries: high risk of complications besides the ethical problem.

Due to inadequate cadaveric and living related organ supply, many end-stage renal disease patients go to third-world countries for living unrelated (paid) kidney transplantation. Thirty-four patients who have had transplantations in two centres in India before coming to our centre for post-transplant care and follow-up are reported in this study. In the post-transplant phase at our centre, the mean follow-up period of the patients was 209.7 +/- 137.3 (range 6-450) days. Fourteen of them, having an uneventful course, were followed on an outpatient clinic basis. The rest of the patients were hospitalized because of the following surgical and/or medical complications, during admission: urinary fistula in two patients; lymphocele in three patients; urinary tract obstruction in two patients; decubitus ulcer in one patient; severe wound infection in one patient; subacute myocardial infarction in one patient; acute irreversible vascular rejection in two patients; urinary tract infection in two patients; pneumonia in two patients; congestive heart failure and severe electrolyte disturbance in two patients; post-transplant diabetes mellitus and ketoacidosis in one patient; cyclosporin nephrotoxicity in two patients; cyclosporin nephro-, hepato-, and neurotoxicity in one patient. Plasmodium falciparum malaria in three patients, generalized mucormycosis infection in one patient, and genitourinary aspergillosis in one patient were seen during the first month. Hepatitis B virus infection followed by chronic active hepatitis was diagnosed in two patients, 2 and 4 months after the operation; and Kaposi's sarcoma was noted in another two patients, 1 and 5 months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum lipids and apolipoprotein concentrations and plasma fibronectin concentrations in renal transplant patients.

In those cases where hypertriglyceridaemia was present before renal transplantation, it persisted after transplantation, and hypercholesterolaemia also developed. We studied serum lipid, lipoprotein, and apolipoprotein concentrations and plasma fibronectin concentrations in 57 renal transplantation patients and 29 healthy controls. We concluded that atherosclerosis in renal transplantation patients might be related to alterations in the constitutions of lipoproteins and apolipoproteins, but fibronectin synthesized by vascular endothelial cells seemed not to be associated with the atherosclerotic process.