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Key Points Radiologic techniques can be used to assess gross renal morphology, but morphological changes at this level show poor correlation with renal function and the changes over time are often nonspecific Dynamic contrast-enhanced CT or MRI can provide haemodynamic information, such as renal blood flow or tissue perfusion, which can facilitate personalized patient management Information obtained from blood oxygen level-dependent MRI could contribute to the understanding of chronic kidney disease pathophysiology, but technical issues remain to be solved before large-scale clinical use MRI and renal scintigraphy can both provide a measure of split renal function in moderately dilated kidneys, but radiological measurement of single kidney glomerular filtration rate requires further development The ability to identify fibrotic changes and inflammatory components in damaged renal tissue by radiologic imaging is a major goal for future research Radiologic techniques are routinely used to assess tissue macrostructure and gross morphology. In this Review, Nicolas Grenier and colleagues discuss how technological advancements in CT, MRI, and ultrasonography have faciliated the assessment of organ microstructure and function, and how these techniques can be applied to the kidney. They outline the benefits of incorporating radiologic data with routine clinical diagnostics, and the technical challenges that remain to be addressed when imaging the kidney. Radiologic imaging has the potential to identify several functional and/or structural biomarkers of acute and chronic kidney diseases that are useful diagnostics to guide patient management. A renal ultrasound examination can provide information regarding the gross anatomy and macrostructure of the renal parenchyma, and ultrasound imaging modalities based on Doppler or elastography techniques can provide haemodynamic and structural information, respectively. CT is also able to combine morphological and functional information, but the use of CT is limited due to the required exposure to X-ray irradiation and a risk of contrast-induced nephropathy following intravenous injection of a radio-contrast agent. MRI can be used to identify a wide range of anatomical and physiological parameters at the tissue and even cellular level, such as tissue perfusion, oxygenation, water diffusion, cellular phagocytic activity, tissue stiffness, and level of renal filtration. The ability of MRI to provide valuable information for most of these parameters within a renal context is still in development and requires more clinical experience, harmonization of technical procedures, and an evaluation of reliability and validity on a large scale.

Evaluation of CMV-specific cell-mediated immunity (CMI) has improved strategies to prevent post-transplant CMV disease. This study assessed the association between CMV disease and absolute count of TEMRA γδ T cells at the end of universal prophylaxis in kidney transplant recipients (KTR). We retrospectively analyzed 262 R⁺ and 82 D⁺/R⁻ KTRs who received antiviral prophylaxis and had TEMRA γδ T cells quantified at the end of prophylaxis. The primary endpoint was CMV disease within two years post-transplant. Post-prophylaxis CMV disease occurred in 43/344 (12.5%) patients. A threshold of 4.65/mm³ for TEMRA γδ T-cell count was identified by ROC analysis; higher counts were associated with reduced CMV disease incidence. While no significant association was found in the overall cohort, in R⁺ patients, a count >4.65/mm³ was associated with a 97.7% positive predictive value for protection against CMV disease. Multivariate analysis confirmed its independent association with disease-free survival [HR: 0.27 (95% CI: 0.09–0.85), p = 0.0252]. Measuring TEMRA γδ T-cell counts at the end of prophylaxis may serve as a useful, accessible immune marker to guide CMV prevention strategies in R⁺ kidney transplant recipients.

Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Defined by the Banff classification, its gold standard diagnosis remains a challenge, with limited inter-observer reproducibility of the histological scores and efficient immunomarker availability. We performed an immunohistochemical analysis of 3 interferon-related proteins, WARS1, TYMP and GBP1 in a cohort of kidney allograft biopsies including 17 ABMR cases and 37 other common graft injuries. Slides were interpreted, for an ABMR diagnosis, by four blinded nephropathologists and by a deep learning framework using convolutional neural networks. Pathologists identified a distinctive microcirculation staining pattern in ABMR with all three antibodies, displaying promising diagnostic performances and a substantial reproducibility. The deep learning analysis supported the microcirculation staining pattern and achieved similar diagnostic performance from internal validation, with a mean area under the receiver operating characteristic curve of 0.89 (± 0.02) for WARS1, 0.80 (± 0.04) for TYMP and 0.89 (± 0.04) for GBP1. The glomerulitis and peritubular capillaritis scores, the hallmarks of histological ABMR, were the most highly correlated Banff scores with the deep learning output, whatever the C4d status. These novel immunomarkers combined with a CNN framework could help mitigate current challenges in ABMR diagnosis and should be assessed in larger cohorts.

The generation of donor-specific antibodies (DSA) requires that alloreactive B cells receive help from follicular helper T (T FH ) cells. Recent works have suggested that γδ T cells could contribute to T cell-dependent humoral responses, leading us to investigate their role in DSA generation. Analysis of a cohort of 331 kidney transplant recipients found no relation between the number of circulating γδ T cells and the risk to develop DSA. Coculture models demonstrated that activated γδ T cells were unable to promote the differentiation of B cells into plasma cells, ruling out that they can be “surrogate” T FH . In line with this, γδ T cells preferentially localized outside the B cell follicles, in the T cell area of lymph nodes, suggesting that they could instead act as “antigen-presenting cell” (APC) to prime αβ T FH . This hypothesis was proven wrong since γδ T cells failed to acquire APC functions in vitro . These findings were validated in vivo by the demonstration that following transplantation with an allogeneic Balb/c (H2 d ) heart, wild-type and TCRδKO C57BL/6 (H2 b ) mice developed similar DSA responses, whereas TCRαKO recipients did not develop DSA. We concluded that the generation of DSA is unfazed by the absence of γδ T cells.

Cytopenias occur frequently after kidney transplantation but posttransplantation thrombocytopenia (PTTCP) frequency has rarely been reported. This monocenter, retrospective study aimed to describe PTTCP frequency, causes, treatments and outcomes. PTTCP was defined as thrombocytopenia with ≥2 platelet counts <100×10 /L after first month posttransplantation. Among 2118 kidney-transplant recipients between 2002 and 2018, 189 (8.9%) developed PTTCP. Their mean platelet-count nadir was 51×10 /L [range 4-96×10 ]; nadir was <50×10 /L for 87 (46.0%) patients. Main identified PTTCP etiologies were drugs (24.3%), or infectious diseases (20.1%; cytomegalovirus causing 79.4% of them), or unknown for 26 (13.7%). Bleeding rate was high (32.7%), with 40 (64.5%) severe episodes. During follow-up, 103 (54.5%) patients suffered graft loss or died at a median of 5.41 years post-PTTCP episode. Multivariate analyses retained a severe bleeding episode as being significantly associated with antiplatelet or anticoagulation therapy and pancytopenia, and age, creatininemia, transplantation-to-PTTCP interval and severe bleeding as significant risk factors for death or graft loss. PTTCP is frequently associated with severe bleeding, which is a risk factor for graft loss and death. Those findings suggest that the risk/benefit ratio of antiplatelet or anticoagulation therapies should be systemically evaluated for PTTCP patients.

Background Preventing ischemia‒reperfusion injury (IRI) is a major issue in kidney transplantation, particularly for transplant recipients receiving a kidney from extended criteria donors (ECD). The main consequence of IRI is delayed graft function (DGF). Hypoxia is one of the key factors in IRI, suggesting that the use of an oxygen carrier as an additive to preservation solution may be useful. In the OxyOp trial, we showed that the organs preserved using the oxygen carrier HEMO2life® displayed significantly less DGF. In the OxyOp2 trial, we aim to definitively test and quantify the efficacy of HEMO2life® for organ preservation in a large population of kidney grafts. Methods OxyOp2 is a prospective, multicenter, randomized, comparative, single-blinded, parallel-group study versus standard of care in renal transplantation. After the selection of a suitable donor according to the inclusion/exclusion criteria, both kidneys will be used in the study. Depending on the characteristics of the donor, both kidneys will be preserved either in static cold storage (standard donors) or on machine perfusion (for ECD and deceased-after-cardiac-death donors (DCD)). The kidneys resulting from one donor will be randomized: one to the standard-of-care arm (organ preserved in preservation solution routinely used according to the local practice) and the other to the active treatment arm (HEMO2life® on top of routinely used preservation solution). HEMO2life® will be used for ex vivo graft preservation at a dose of 1 g/l preservation solution. The primary outcome is the occurrence of DGF, defined as the need for renal replacement therapy during the first week after transplantation. Discussion The use of HEMO2life® in preservation solutions is a novel approach allowing, for the first time, the delivery of oxygen to organs. Improving graft survival by limiting ischemic lesions is a major public-health goal in the field of organ transplantation. Trial registration ClinicalTrials.gov, ID: NCT04181710 . registered on November 29, 2019.

Bariatric surgery is routinely proposed to patients suffering from obesity including kidney transplant recipients. In this specific population, bariatric surgery has a positive impact in long-term outcomes in terms of patient and graft survival. We report here the cases of 4 patients with five post-kidney transplantation bariatric surgeries who experimented acute renal injury early after surgery. Creatinine rising occurred between day 14 and day 20 after surgery. In all cases, it was due to dehydration leading to a pre-renal acute renal failure. The specific care of kidney transplanted patients is discussed: single kidney associated with pre-existing altered kidney function associated with concomitant use of nephrotoxic drugs. Specific education intervention before surgery associated with careful early management of hydration after surgery is mandatory for these patients.

Our objective was to calculate an immunosuppressant possession ratio (IPR) to diagnose non-adherence at the time of antibody-mediated rejection (ABMR). IPR was defined as the ratio of number of pills collected at the pharmacy to the number of pills prescribed over a defined period. In a first cohort of 91 kidney transplant recipients (KTRs), those with an IPR < 90% had more frequently a tacrolimus through level coefficient of variation >30% than patients with an IPR = 100% (66.7% vs. 29.4%, p = 0.05). In a case-control study, 26 KTRs with ABMR had lower 6 months IPRs than 26 controls (76% vs. 99%, p < 0.001). In KTRs with ABMR, non-adherence was more often diagnosed by a 6 months IPR < 90% than by clinical suspicion (73.1% vs 30.8%, p = 0.02). In the multivariable analysis, only de novo DSA and 6 months IPR < 90% were independently associated with ABMR, whereas clinical suspicion was not (odds ratio, 4.73; 95% CI, 1.17–21.88; p = 0.03; and odds ratio, 6.34; 95% CI, 1.73–25.59; p = 0.007, respectively). In summary, IPR < 90% is a quantifiable tool to measure immunosuppressant non-adherence. It is better associated with ABMR than clinical suspicion of non-adherence.

Donor-specific antibodies (DSAs) are the main risk factor for antibody-mediated rejection (ABMR) and graft loss but could have variable pathogenicity according to their IgG subclass composition. Luminex-based test might lack sensitivity for the detection of IgG subclasses and this test does not allow quantifying the relative abundance of each IgG subclass. We investigated the precise repartition of each DSA subclass and their role in ABMR occurrence and severity, using an innovative mass spectrometry-based method. Between 2014 and 2018, we enrolled 69 patients who developed DSA ( = 29 without ABMR, and = 40 with ABMR) in two transplant centers. All IgG subclasses were detected in every samples tested: 62.7% were IgG1, 26.6% were IgG2, 6.6% were IgG3, and 4.2% were IgG4. The IgG3 proportion was significantly higher in the ABMR+ compared to the ABMR- group (8.4% vs. 5.6%, = 0.003). The proportion of IgG1, IgG2, and IgG4 of DSA was similar between the two groups. Higher IgG3 level was associated with higher C4d deposition, higher microvascular inflammation scores, and glomerular filtration rate decline >25%. IgG3 proportion was not correlated with DSA MFI. Multivariate analysis showed that proteinuria and high level of IgG3 DSA were the only two factors independently associated with ABMR. In conclusion, DSA are always composed of the four IgG subclasses, but in different proportions. High IgG3 proportion is associated with ABMR occurrence and severity and with poorer outcome, independently of DSA MFI.

Background Weight gain (mainly gain of fat mass) occurs quickly after successful kidney transplantation and is associated with metabolic complications (alterations of glycaemic control, hyperlipidaemia). Determinants of weight gain are multifactorial and are mainly related to the transplant procedure itself (glucocorticoid use, increased appetite). In the modern era of transplantation, one challenge is to limit these metabolic alterations by promoting gain of muscle mass rather than fat mass. This prospective study was performed to assess determinants of fat mass, fat-free mass and body cell mass changes after kidney transplantation with a focus on physical activity and nutritional behaviour before and after transplantation. Methods Patients were included at the time of listing for deceased donor kidney transplantation. Body composition was determined using dual X-ray absorptiometry and bioimpedance spectroscopy to assess fat mass, fat-free mass and body cell mass (= fat-free mass − extracellular water) at the time of inclusion, 12 months later, and 1, 6, 12 and 24 months after transplantation. Recall dietary data and physical activity level were also collected. Results Eighty patients were included between 2007 and 2010. Sixty-five had a complete 24-month follow-up after kidney transplantation. Fat mass, fat-free mass and body cell mass decreased during the waiting period and early after kidney transplantation. The nadirs of body cell mass and fat-free mass occurred at 1 month and the nadir for fat mass occurred at 6 months. Maximum levels of all parameters of body composition were seen at 12 months, after which body cell mass and fat-free mass decreased, while fat mass remained stable. In multivariate analysis, male recipients, higher physical activity level and lower corticosteroid dose were significantly associated with better body cell mass recovery after kidney transplantation. Conclusions Lifestyle factors, such as physical activity level, together with low dose of corticosteroids seem to influence body composition evolution following kidney transplantation with recovery of body cell mass. Specific strategies to promote physical activity in kidney transplant recipients should be provided before and after kidney transplantation.