Multiorgan transplantation from a deceased donor with intravascular diffuse large B-cell lymphoma: transmission of the disease and results of treatment.

This report presents the transplantation of two kidneys and the liver from a deceased donor with suspected autoimmune encephalomeningitis (ADEM). Due to an atypical post-transplantation clinical course, the transplanted kidneys were biopsied and this disclosed diffuse large B-cell (DLBC) lymphoma of the intravascular type in each kidney. The same malignancy was found in the postmortem donor brain examination. The renal allografts from the two recipients were removed: despite every effort, one patient died, while chemotherapy was successful in the second. No malignancy was observed in the liver transplant recipient, who received prophylactic chemotherapy. These cases highlight the occasional failure of organ donor disease screening and the consequent unforeseen complications.

Polymorphism of genes involved in purine metabolism (XDH, AOX1, MOCOS) in kidney transplant recipients receiving azathioprine.

BACKGROUND: Xanthine dehydrogenase (XDH), aldehyde oxidase1 (AOX1), and molybdenum cofactor sulfurase (MOCOS) are enzymes involved in purine metabolism. The aim of this study was to investigate single nucleotide polymorphisms (SNPs) in XDH, AOX1, and MOCOS genes in relation to clinical parameters and risk of drug side effects in a cohort of kidney transplant recipients treated with azathioprine (AZA) as a part of standard immunosuppressive regimen. METHODS: One hundred fifty-six patients receiving AZA for the first year from the surgery were genotyped for the presence of common SNPs in the coding regions of XDH, AOX1, and MOCOS genes using TaqMan assays. RESULTS: AOX1 rs55754655 variant allele carriers received a higher mean AZA dose 3, 6, and 12 months after transplantation (P < 0.05). The patients inheriting rs594445 MOCOS minor allele required significantly lower doses of AZA for efficient treatment compared with wild-type heterozygotes at 3, 6, and 12 months from the transplantation (mean values: 1.39 versus 1.59, 1.38 versus 1.58, and 1.33 versus 1.53 mg·kg·24 h) and displayed lower mean RBC count at the time points evaluated. Multivariate analysis has shown that the effect of MOCOS rs594445 polymorphism is independent of other investigated gene variations and might influence AZA dosage, similarly to TPMT heterozygosity. The authors have not observed an association between any of the studied XDH SNPs and clinical parameters of AZA-treated patients. CONCLUSIONS: The results of this study should be regarded as preliminary. However, if the observed association between SNPs: AOX1 rs55754655, MOCOS rs594445, and AZA dose requirements would be positively confirmed in further independent studies, it could be introduced into clinical practice to individualize thiopurine treatment.

Laparoscopic live-donor nephrectomy with retroperitoneoscopic access - first case experience.

BACKGROUND: Despite observed huge progress in understanding the immunological basis of transplantation and the development of new immunosuppressive agents that have significantly improved both -- the patient and graft survival, still the kidney donation from live volunteers remains the most consistent factor which affects the long-term survival. The conventional, open method of donor nephrectomy is associated with significant surgical trauma. The laparoscopic live-donor nephrectomy (LDN) is the alternative for open approach. CASE REPORT: We present our experience of the case of laparoscopic removal of the kidney from a living donor. We applied retroperitoneoscopic access, the operation time was 210 minutes. Kidney was implanted shortly after LDN and its immediate function was observed. We have observed no serious postoperative complications either in donor or recipient. CONCLUSIONS: We hope that this successful initial case of LDN will have a positive effect on cooperation between transplantologists and urologists, and on rate of kidney donation in Poland.

The impact of thiopurine s-methyltransferase polymorphism on azathioprine-induced myelotoxicity in renal transplant recipients.

Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathioprine. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TMPT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. It has previously been reported that 3 variant alleles: TPMT*2, *3A, and *3C are responsible for over 95% cases of low enzyme activity. The purpose of this study was to explore the association between these polymorphisms and the occurrence of azathioprine adverse effects in 112 renal transplant recipients undergoing triple immunosuppressive therapy including azathioprine, cyclosporine, and prednisone. TPMT genetic polymorphism was determined using PCR-RFLP and allele-specific PCR methods. Azathioprine dose, leukocyte, erythrocyte, and platelet counts, graft rejection episodes, as well as cyclosporine levels were analyzed throughout the first year after organ transplantation. We found the frequency of leukopenia episodes (WBC < 4.0 x 10(9)/L) significantly higher in heterozygous patients (53.8%) compared with those with TPMT wild-type genotype (23.5%). One patient, who was a compound homozygote (3A/*3C), experienced severe azathioprine-related myelotoxicity each time after receiving the standard drug dose. Our results suggest that polymorphisms in TPMT gene may be responsible for approximately 12.5% of all leukopenia episodes in renal transplant recipients treated with azathioprine. Genotyping for the major TPMT variant alleles may be a valuable tool in preventing AZA toxicity and optimization of immunosuppressive therapy.