We report the case of a sensitized woman who underwent successful transplantation after a desensitization protocol, with an optically normal 8-day biopsy. At 3 months, she developed active antibody-mediated rejection (AMR) due to preformed donor-specific antibodies. It was decided to treat the patient with daratumumab, an anti-CD38 monoclonal antibody. The mean fluorescence intensity of donor-specific antibodies decreased, pathologic signs of AMR regressed, and kidney function returned to normal. A molecular assessment of biopsies was retrospectively performed. By doing so, regression of the molecular signature of AMR was evidenced between the second and third biopsies. Interestingly, the first biopsy revealed a gene expression profile of AMR, which helped retrospectively classify this biopsy as AMR, illustrating the relevance of molecular phenotyping of biopsy in high-risk situations such as desensitization.

Background: Immunosuppression in kidney transplant recipients with decreased graft function and histological vascular changes can be particularly challenging. The impact of a late rescue conversion to belatacept on kidney graft survival in this context has never been studied. Methods: We report a bicentric retrospective cohort study comparing a calcineurin inhibitor (CNI) to belatacept switch versus CNI continuation in 139 kidney transplant recipients with histological kidney vascular damage (cv ≥2, g + cpt ≤1, i + t ≤1) and low estimated glomerular filtration rate (≤40 mL/min/1.73 m²). Primary outcome was death-censored graft survival. Results: During the study follow-up, 10 graft losses (14.5%) occurred in the belatacept group (n = 69) versus 26 (37.1%) in the matched CNI group (n = 70) (P = .005). Death-censored graft survival was significantly higher in the belatacept group (P = .001). At 3 years, graft survival was 84.0% in the belatacept group compared with 65.1% in the control group. Continuing CNI was an independent risk factor for graft loss [hazard ratio (HR) 3.46; P < .005]. The incidence of cellular rejection after the conversion was low (4.3% in both groups) and not significantly different between groups (P = .84). Patients switched to belatacept developed significantly less donor-specific antibodies de novo. Belatacept was an independent risk factor for the occurrence of opportunistic infections (HR 4.84; P < .005). Conclusion: The replacement of CNI with belatacept in patients with decreased allograft function and vascular lesions is associated with an improvement in graft survival and represents a valuable option in a context of organ shortage. Caution should be exercised regarding the increased risk of opportunistic infection.

Background: Chronic subclinical hemolysis is frequent in patients implanted with Left Ventricular Assist Device (LVAD) and is associated with adverse outcomes. Consequences of LVADs-induced subclinical hemolysis on kidney structure and function is currently unknown.Methods: Thirty-three patients implanted with aHeartmate IILVAD (Abbott, Inc, Chicago IL) were retrospectively studied. Hemolysis, Acute Kidney Injury (AKI) and the evolution of estimated Glomerular Filtration Rate were analyzed. Proximal Tubulopathy (PT) groups were defined according to proteinuria, normoglycemic glycosuria, and electrolytic disorders. The Receiver Operating Characteristic (ROC) curve was used to analyze threshold of LDH values associated with PT.Results: Median LDH between PT groups were statistically different, 688 IU/L [642–703] and 356 IU/L [320–494] in the “PT” and “no PT” groups, respectively p = 0.006. To determine PT group, LDH threshold > 600 IU/L was associated with a sensitivity of 85.7% (95% CI, 42.1–99.6) and a specificity of 84.6% (95% CI, 65.1–95.6). The ROC's Area Under Curve was 0.83 (95% CI, 0.68–0.98). In the “PT” group, patients had 4.2 [2.5–5.0] AKI episodes per year of exposure, versus 1.6 [0.4–3.7] in the “no PT” group, p = 0.03. A higher occurrence of AKI was associated with subsequent development of Chronic Kidney Disease (CKD) (p = 0.02) and death (p = 0.05).Conclusions: LVADs-induced subclinical hemolysis is associated with proximal tubular functional alterations, which in turn contribute to the occurrence of AKI and subsequent CKD. Owing to renal toxicity of hemolysis, measures to reduce subclinical hemolysis intensity as canula position or pump parameters should be systematically considered, as well as specific nephroprotective therapies.

Background: The Banff Classification for Allograft Pathology recommendations for the diagnosis of kidney transplant rejection includes molecular assessment of the transplant biopsy. However, implementation of molecular tools in clinical practice is still limited, partly due to the required expertise and financial investment. The reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) assay is a simple, rapid, and inexpensive assay that permits simultaneous evaluation of a restricted gene panel using paraffin-embedded tissue blocks. The aim of this study was to develop and validate a RT-MLPA assay for diagnosis and classification of rejection. Methods: A retrospective cohort of 220 kidney transplant biopsies from two centers, which included 52 antibody-mediated rejection, 51 T-cell–mediated rejection, and 117 no-rejection controls, was assessed. A 17-gene panel was identified on the basis of relevant pathophysiological pathways. A support vector machine classifier was developed. A subset of 109 biopsies was also assessed using the Nanostring Banff Human Organ Transplant panel to compare the two assays. Results: The support vector machine classifier train and test accuracy scores were 0.84 and 0.83, respectively. In the test cohort, the F1 score for antibody-mediated rejection, T-cell–mediated rejection, and control were 0.88, 0.86, and 0.69, respectively. Using receiver-operating characteristic curves, the area under the curve for class predictions was 0.96, 0.89, and 0.91, respectively, with a weighted average at 0.94. Classifiers' performances were highest for antibody-mediated rejection diagnosis with 94% correct predictions, compared with 88% correct predictions for control biopsies and 60% for T-cell–mediated rejection biopsies. Gene expression levels assessed by RT-MLPA and Nanostring were correlated: r = 0.68, P < 0.001. Equivalent gene expression profiles were obtained with both assays in 81% of the samples. Conclusions: The 17-gene panel RT-MLPA assay, developed here for formalin-fixed paraffin-embedded kidney transplant biopsies, classified kidney transplant rejection with an overall accurate prediction ratio of 0.83. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_04_10_CJN0000000000000100.mp3 and https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_02_Interview-with-Tris.mp3 (CJASN Trainee of the Year interview)

Antithymocyte globulin is the most widely used lymphocyte-depleting treatment in kidney transplantation. In spite of the frequency of side effects, including anemia and thrombocytopenia, their pathophysiological mechanisms are not clearly established. Here, we report the case of a 21-year-old patient who had a first kidney transplantation and received induction immunosuppressive therapy by thymoglobulin. Immediately after kidney transplantation, he developed a severe hemolytic anemia and thrombocytopenia with a subsequent perirenal hematoma, which lead to a second surgical procedure and a transfer to the intensive care unit. Our patients’ anemia and thrombocytopenia had heteroimmune characteristics, and thymoglobulin therapy was suspected to be the cause, via an interaction with a common Fc-receptor epitope in the different cell lines.