RESUMO
Introduction: De novo donor-specific antibody (dnDSA) is a strong biomarker associated with the development of antibody-mediated rejection (AMR) and graft loss after kidney transplantation. This procedure is expensive; however, systematic annual screening was recommended by some national organ transplant agencies or societies even though its clinical utility was not clearly established. Methods: To address this question, we retrospectively assessed the incidence of dnDSA according to the test justification (clinically indicated or systematic) in a cohort of low-immunological risk patients, defined by being nonhuman leukocyte antigen (non-HLA)-sensitized and having no previous kidney transplants. Results: A total of 1072 patients, for whom 4611 anti-HLA tests were performed, were included in the study. During the follow-up period of 8 (interquartile range, IQR: 5-11) years, 77 recipients developed dnDSA (prevalence of 7.2%). Thirty-five of these dnDSAs (45.5%) were detected during the first year posttransplantation. In 95% of patients with dnDSA, an immunizing event was identified in their medical records. dnDSA was detected in 46 of 4267 systematic screening tests (1.08%) performed. Active and chronic AMR were frequently observed in biopsies performed after systematic DSA testing (17.9% and 15.4%, respectively). Conclusion: Our results suggest that the detection by systematic screening of dnDSA in low-immunological risk kidney transplant patients without sensitizing events is a rare event, especially after 1 year. Moreover, in real life, systematic annual screening for dnDSA, seems having a limited impact to detect AMR at an earlier stage compared to patients in whom dnDSA was detected after a clinically indicated test.
RESUMO
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. While biallelic variants affecting IFT140 are responsible for Mainzer-Saldino syndrome (characterized by severe ciliopathy causing skeletal abnormalities, kidney disease, and cysts), monoallelic loss-of-function (LoF) variants have been recently reported as an important cause of ADPKD beyond PKD1/2 genes. Herein, we report 6 non-family-related cases of monoallelic IFT140 LoF variants, identified from 1,340 exomes sequenced for nephrological indications in our local database. Every patient presented with polycystic kidney disease. Furthermore, the mother of a boy diagnosed with Mainzer-Saldino syndrome with a biallelic variant affecting IFT140 presented with several bilateral cysts, revealed after kidney imaging, and was found to carry a pathologic frameshift IFT140 variation. As well as this particular Mainzer-Saldino case, our 6 additional patients confirm that heterozygous IFT140 frameshift variants are responsible for the cystic phenotype and kidney failure. Interestingly, of the 6 patients, 2 also exhibited dilated cardiomyopathy, which was of unknown origin, as no genetic cause was found after exome sequencing analysis, suggesting a potential connection between IFT140 and heart disease.
RESUMO
Whether C5 blocking may improve the outcomes of patients developing chemotherapy-induced thrombotic microangiopathy (TMA) remains elusive. Lung fibrosis is a well-known complication of bleomycin, whereas TMAs are very rare (<20 cases described). Here, we report an exceptional case of a male patient that developed acute respiratory distress syndrome and TMA following administration of bleomycin, cisplatin and etoposide . Refractoriness to plasma exchanges prompted us to use eculizumab as salvage therapy. Eculizumab led to complete remission of the TMA before Day 2. However, the patient progressed towards refractory respiratory failure, suggesting that pathophysiological mechanisms of bleomycin-induced lung fibrosis and TMA differ.