Marie-Noelle Peraldi

Background.: Kidney transplant recipients with preformed donor-specific antibodies (DSAs) are at higher risk for antibody-mediated rejection (AMR) and graft failure. This study assesses outcomes during a 15-y period, comparing patients with high levels of preformed DSAs to a matched cohort of recipients without DSA. Methods.: This retrospective study includes 95 patients with high levels of preformed DSAs, defined by DSA levels (mean fluorescence intensity > 3000). Using propensity score matching, 88 of these patients were matched to 154 recipients without DSA based on age, sex, transplant year, cold ischemia time, and other clinical factors. Outcomes included occurrence of AMR, T cell–mediated rejection, and long-term allograft and patient survival. Results.: The mean follow-up after transplantation was 11.9 ± 5.6 y. Among the matched patients, kidney allograft survival rates after transplantation at 5, 10, and 15 y were 90.5%, 79.5%, and 72.8% for the patients without preformed DSA and 86.7%, 60.2%, and 47.6% for the patients with high levels of preformed DSAs ( P = 0.002). The patient survival rates after transplantation at 5, 10, and 15 y were 91.3%, 72.3%, and 57.9% for the patients without preformed DSA and 86.4%, 71.2%, and 49.0% for the patients with high levels of preformed DSAs ( P = 0.206). More AMR occurred in the patients with high levels of preformed DSAs ( P < 0.001) without significant difference in T cell–mediated rejection ( P = 0.203). Conclusions.: Although patients with high levels of preformed DSAs have a higher risk of graft loss, their long-term survival did not differ significantly from recipients without DSA, supporting the use of intensive immunosuppression in this population.

Background.: Efficacy and safety of belatacept have not been specifically reported for kidney transplantations from donors after circulatory death. Methods.: In this retrospective multicenter paired kidney study, we compared the outcome of kidney transplantations with a belatacept-based to a calcineurin inhibitor (CNI)-based immunosuppression. We included all kidney transplant recipients from donors after uncontrolled or controlled circulatory death performed in our center between February 2015 and October 2020 and treated with belatacept (n = 31). The control group included the recipients of the contralateral kidney that were treated with CNI in 8 other centers (tacrolimus n = 29, cyclosporine n = 2). Results.: There was no difference in the rate of delayed graft function. A higher incidence of biopsy-proven rejections was noted in the belatacept group (24 versus 6 episodes). Estimated glomerular filtration rate (eGFR) was significantly higher in the belatacept group at 3-, 12-, and 36-mo posttransplant, but the slope of eGFR was similar in the 2 groups. During a mean follow-up of 4.1 y, 12 patients discontinued belatacept and 2 patients were switched from CNI to belatacept. For patients who remained on belatacept, eGFR mean value and slope were significantly higher during the whole follow-up. At 5 y, eGFR was 80.7 ± 18.5 with belatacept versus 56.3 ± 22.0 mL/min/1.73 m² with CNI (P = 0.003). No significant difference in graft and patient survival was observed. Conclusions.: The use of belatacept for kidney transplants from either uncontrolled or controlled donors after circulatory death resulted in a better medium-term renal function for patients remaining on belatacept despite similar rates of delayed graft function and higher rates of cellular rejection.

Cutaneous squamous cell carcinomas in kidney-transplant recipients are frequent, with an increasing incidence linked to long immunosuppression durations and exposure to ultraviolet radiation. p53 is at the cornerstone of ultraviolet-induced DNA damage, but the role of p53 post-translational modifications in this context is not yet deciphered. Here, we investigated the phosphorylation status of p53 at Serine 392 in 25 cutaneous squamous cell carcinomas in kidney-transplant recipients, compared with 22 non-transplanted patients. Cutaneous squamous cell carcinomas in transplanted patients occurred after a median period of 19 years of immunosuppression, with a median number of 15 cutaneous squamous cell carcinomas and more aggressive histological and clinical characteristics. There was no significant difference between Ki67, p53, and pSer392p53 expression in the two groups. Using principal component analysis, we identified a cluster of exclusively transplanted patients with a median of 23 years of immunosuppression duration, significantly more aggressive biological characteristics, and higher pSer392p53 expression. pSer392p53 was expressed in the whole tumor, suggesting an early carcinogenic event in the course of prolonged immunosuppression. This high, diffuse pSer392p53 expression, corresponding to a high level of DNA damage, might be useful to identify aggressive cutaneous squamous cell carcinomas in kidney-transplant recipients to treat them more aggressively.

Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.

In patients presenting with anti-glomerular basement membrane (GBM) disease with advanced isolated kidney involvement, the benefit of intensive therapy remains controversial due to adverse events, particularly infection. We aim to describe the burden of severe infections (SI) (requiring hospitalization or intravenous antibiotics) and identify predictive factors of SI in a large cohort of patients with anti-GBM disease. Among the 201 patients (median [IQR] age, 53 [30–71] years) included, 74 had pulmonary involvement and 127 isolated glomerulonephritis. A total of 161 SI occurred in 116 patients during the first year after diagnosis. These infections occurred during the early stage of care (median [IQR] time, 13 [8–19] days after diagnosis) with mainly pulmonary (45%), catheter-associated bacteremia (22%) and urinary tract (21%) infections. In multivariable analysis, positive ANCA (HR [95% CI] 1.62 [1.07−2.44]; p = 0.02) and age at diagnosis (HR [95% CI] 1.10 [1.00–1.21]; p = 0.047) remained independently associated with SI. Age-adjusted severe infection during the first three months was associated with an increased three-year mortality rate (HR [95% CI] 3.13 [1.24–7.88]; p = 0.01). Thus, SI is a common early complication in anti-GBM disease, particularly in the elderly and those with positive anti-neutrophil cytoplasmic antibodies (ANCA). No significant association was observed between immunosuppressive strategy and occurrence of SI.