Claire Tinel

Long-term outcomes of kidney transplantation in patients with high levels of preformed DSA: the Necker high-risk transplant program.

Background There is an increasing number of anti-HLA sensitized and highly sensitized renal transplant candidates on waiting lists, and the presence of donor-specific alloantibodies (DSAs) at the time of transplantation leads to acute and chronic antibody-mediated rejection (AMR). Acceptable short-term outcomes have been described, notably because of desensitization protocols, but mid- and long-term data are still required. Methods Our high immunologic risk program included 95 patients with high peak or day 0 DSA levels (mean fluorescence intensity [MFI] > 3000) with a complement-dependent cytotoxicity-negative crossmatch, who received a posttransplant desensitization protocol starting at day 0 with high-dose intravenous immunoglobulin, plasma exchanges, and eventually rituximab. Their characteristics were compared with a control group including 39 patients with a lower immunologic risk (MFI between 500 and 3000 at day 0) who received the same posttransplant desensitization. Results The median MFI of the immunodominant class I or II DSA in the peak or day 0 serum was 9421 (interquartile range, 4959-12 610). An AMR occurred during the first posttransplant year in 31 patients (32.6%), and at one year, the rate of chronic AMR was 39.5%. The 1-, 3-, 5- and 7-year death-censored allograft survival rates were 98%, 91%, 86%, and 78%, respectively, with concomitant recipient survival rates of 97%, 93%, 85%, and 79%, respectively. Conclusions These results suggest that DSA-sensitized patients with high MFI levels can receive transplantation across the HLA-barrier, with the use of an intensified posttransplant immunosuppressive therapy starting at day 0 combined with close clinical, immunologic, and histologic monitoring.

Reduction in late onset cytomegalovirus primary disease after discontinuation of antiviral prophylaxis in kidney transplant recipients treated with de novo everolimus

Donor (D)+/recipient (R)− serostatus is closely associated with a higher risk of cytomegalovirus (CMV) infection and disease. Antiviral prophylaxis is conventionally used in such patients, but late onset CMV infection/disease still occurs after the discontinuation of prophylaxis.

A Comparative Study of the Predictive Values of Urinary Acute Kidney Injury Markers Angiogenin and Kidney Injury Molecule 1 for the Outcomes of Kidney Allografts

Background Whether injury-related molecules in urines of individuals with ischemia-reperfusion injury (IRI) are independent predictors of graft outcomes and provide additional information compared with usual risk factors remains to be established. Methods We explored a cohort of 244 kidney transplant recipients who systematically had a urine collection 10 days after transplantation. The injury-related markers kidney injury molecule-1 (KIM-1) and angiogenin (ANG) levels in urines were measured. We determined the prognostic values of these markers on graft outcomes. Results Urinary KIM-1 and ANG concentrations were strongly correlated to each other and were significantly and independently associated with cold ischemia time, delayed graft function, and plasma creatinine 10 days after transplantation, indicating that these markers reflect the severity of IRI. However, urinary ANG and KIM-1 were not predictive of histological changes on protocol biopsies performed 3 and 12 months after transplantation. Finally, urinary ANG and urinary KIM-1 were not associated with graft survival. Conclusions Together, our results indicate that, in a cohort of 244 kidney transplant recipients, urinary ANG and KIM-1 levels in a single measurement 10 days after transplantation reflect the severity of IRI after kidney transplantation, but are neither independent predictors of renal function, histological changes and graft survival.

Paraganglioma of the bladder in a kidney transplant recipient: A case report

Renal transplantation has been associated with a significantly increased risk of developing cancer, including bladder neoplasia, with urothelial carcinoma being the most frequent type of bladder cancer. Bladder paraganglioma, also referred to as extra-adrenal pheochromocytoma, is a rare but severe condition that may cause a severe hypertensive crisis during handling and mobilization of the tumor. We herein present the case of a 67-year-old kidney transplant recipient with a bladder polyp consistent with paraganglioma of the bladder. During bladder polyp resection, the patient developed severe hypertension, which resolved with appropriate treatment. The histological analysis of the resected bladder polyp was consistent with extra-adrenal pheochromocytoma, or paraganglioma, and the patient finally underwent partial cystectomy, with no reported postoperative recurrence. To the best of our knowledge, this is the first report of a case of paraganglioma of the bladder in a kidney tranplant recipient. Total or partial bladder cystectomy is considered to be an effective treatment for this type of bladder tumor. Screening for mutations of the succinate dehydrogenase subunit B gene may also be recommended.

FP7 BIOMARGIN SHOWS THAT A SMALL SET OF BLOOD MICRO-RNAS IS ASSOCIATED WITH ACUTE KIDNEY ALLOGRAFTS REJECTION

The positive development of Transplant International over the last years is reflected in the most recent key performance indicators that we think are of interest to potential authors: • Impact Factor: 3.079 (up from 2.835) • Time to first decision: 28 days (down from 32 days) • Rejection rate: 85% for Original Articles Furthermore, submissions are up by about 5% over the previous year and full-text downloads have jumped up by 30%. By now, Transplant International has >1500 followers on Twitter, half of them under the age of 35. The Wiley’s Transplant Peer Review Network (Tx PRN) offers transfer options which are designed to make reviewing and publishing more efficient and which are increasingly used by authors, with more than 250 papers offered for transfer from the American Journal of Transplantation to Transplant International in 2017, for instance. These numbers demonstrate a strong upward trend for Transplant International. But we are not there yet. Therefore, together with our Associate Editors, Statistical Editor and Social Media Editor, we will continue to focus on continually improving the scientific quality of Transplant International also in 2018. In this ongoing effort, we invite you to contribute to the journal as author, reviewer and reader. You can reach us at transpl-int@meduniwien.ac.at with any comments and suggestions you might have. Yours sincerely, Thomas Wekerle and Rainer Oberbauer

Urinary transcriptomics reveals patterns associated with subclinical injury of the renal allograft

AIM Subclinical pathological features in renal allograft biopsies predict poor outcomes, and noninvasive biomarkers are wanted. RNA quantification in urine predicts overt rejection. We hypothesized that a whole transcriptome analysis would be informative, even for discrete injury. PATIENTS & METHODS We performed an mRNA microarray with an optimized normalization method on 26 urinary cell pellets to study renal partial epithelial to mesenchymal transition (pEMT) in stable kidney allografts. RESULTS & CONCLUSION Unbiased pathway analysis revealed immune response as the main underlying biological process. In a subgroup of pristine biopsies, isolated pEMT was associated with reduced metabolic functions. Thus, pEMT translates into specific urinary mRNA patterns, in other words, increased inflammation and decreased metabolic functions. Deposited in Gene Expression Omnibus (GSE89652).