Trends in epidemiology and risk factors of opportunistic infections in kidney transplant recipients between 2004 and 2017.

BACKGROUND: While opportunistic infections are a frequent and challenging problem in kidney transplant recipients, their long-term epidemiology remains hardly known. METHODS: Opportunistic infections were recorded in 1144 recipients transplanted in our center between 2004 and 2015. Incidence rates and baseline risk factors were determined using joint frailty models. RESULTS: After a median follow-up of 5.6 years, 544 opportunistic infections occurred in 373/1144 (33%) patients, dominated by viral infections (396/544, 72%), especially cytomegalovirus (CMV) syndromes and diseases (213/544, 39%). One-third of the infected patients experienced at least two opportunistic infections. The incidence of opportunistic infections was 10 times higher during the first year post-transplantation than after that (34.7 infections for 100 patient-years vs 3.64). Opportunistic infections associated with the age of the donor (P = .032), the age of the recipient (P = .049), the CMV serostatus (P < 10-6), a higher class II HLA mismatch (P = .032) and an induction treatment including rabbit anti-thymocyte globulins (P = .026). Repeated opportunistic infections associated with each other (P < 10-6) and with renal death (P < 10-6). CONCLUSION: Opportunistic infections occur with a two-period incidence pattern and many susceptible patients suffer from repeated episodes. This knowledge may help tailor new prevention and follow-up strategies to reduce the burden of opportunistic infections and their impact on transplantation outcome.

Description of a multidisciplinary model of care in a French cohort of adult patients with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Due to the various manifestations of TSC and their potential complications, a multidisciplinary care approach is recommended by consensus guidelines. OBJECTIVES: Our study aimed to give a complete description of our TSC adult cohort and to evaluate the multidisciplinary and interdisciplinary management model. METHODS: Data on each adult patient diagnosed with TSC, including disease manifestations, interventions and outcomes, were collected at baseline and updated annually. A multidisciplinary TSC approach with all the recommended explorations was carried out annually. RESULTS: 90 patients were enrolled in Centre Hospitalier Universitaire de Bordeaux, between January 2000 and September 2018. Median age of patients at inclusion was 37 years (range, 27-47) and 20 years old at diagnosis of TSC. Regarding the occurrence of TSC manifestations, 97% of the patients had cutaneous lesions, 89% had neurological manifestations, 83% had renal manifestations and 100% had dental lesions with pits. More than half the patients had sclerotic bone lesions (68%), TSC-associated neuropsychiatric disorders (64%) and lymphangioleiomyomatosis (59%). A TSC multidisciplinary approach was developed including a global follow-up and an evaluation of TSC targeting organs, according to the recommendations. A satisfaction survey revealed global and entire satisfaction of patients with TSC. CONCLUSION: We obtained an accurate description of a cohort of adult patients with TSC. Our multidisciplinary approach model allowed us to provide optimal management of patients with TSC with a high level of patient satisfaction.

Vascularization of Cell-Laden Microfibres by Femtosecond Laser Processing.

To face the increasing demand for organ transplantation, currently the development of tissue engineering appears as the best opportunity to effectively regenerate functional tissues and organs. However, these approaches still face the lack of an efficient method to produce an efficient vascularization system. To answer these issues, the formation of an intra-volume channel within a three-dimensional, scaffold free, mature, and cell-covered collagen microfibre is here investigated through laser-induced cavitation. An intra-volume channel was formed upon irradiation with a near-infrared, femtosecond laser beam, focused with a high numerical aperture lens. The laser beam directly crossed the surface of a dense and living-cell bilayer and was focused behind the bilayer to induce channel formation in the hydrogel core while preserving the cell bilayer. Channel formation was assessed through confocal microscopy. Channel generation inside the hydrogel core was enhanced by the formation of voluminous cavitation bubbles with a lifetime longer than 30 s, which also improved intra-volume channel durability. Twenty-four hours after laser processing, cellular viability dropped due to a lack of sufficient hydration for processing longer than 10 min. However, the processing automation could drastically reduce the cellular mortality, this way enabling the formation of hollowed microfibres with a high density of living-cell outer bilayer.

Different impact of rATG induction on CMV infection risk in D+R- and R+ KTRs.

BACKGROUND: Rabbit antithymocyte globulin (rATG) induction is associated with profound immunosuppression, leading to a higher risk of cytomegalovirus (CMV) infection compared with anti-interleukin 2 receptor antibody (anti-IL-2RA). However, this risk, depending on the baseline CMV serological recipient/donor status, is still controversial. METHODS: The CMV DNAemia-free survival between rATG- and anti-IL-2RA-treated patients was analyzed in donor-positive/recipient-negative (D+R-) and recipient-positive (R+) patients in 1 discovery cohort of 559 kidney transplant recipients (KTRs) and 2 independent cohorts (351 and 135 kidney KTRs). The CMV-specific cell-mediated immunity (CMI) at baseline and at different time points after transplantation was assessed using an interferon γ enzyme-linked immunosorbent spot assay. RESULTS: rATG increased the risk of CMV DNAemia in R+ but not in D+R- KTRs. In R+ CMI-positive (CMI+) patients, the CMV DNAemia rate was higher in rATG-treated than in anti-IL-2RA-treated patients; no difference was observed among R+ CMI-negative (CMI-) patients. Longitudinal follow-up demonstrated a deeper depletion of preformed CMV CMI in R+ rATG-treated patients. CONCLUSIONS: D+R- KTRs have the highest risk of CMV DNAemia, but rATG adds no further risk. Among R+ KTRs, we described 3 groups, the least prone being R+CMI+ KTRs without rATG, then R+CMI+ KTRs with rATG, and finally R+CMI- KTRs. CMV serostatus, baseline CMV-specific CMI, and induction therapy may lead to personalized preventive therapy in further studies.

Mediterranean Diet for Cardiovascular Risk Reduction in Chronic Kidney Disease.

The Mediterranean diet is a plant-based healthy diet similar to the vegetarian and the Dietary Approaches to Stop Hypertension diets. Unlike vegetarian and Dietary Approaches to Stop Hypertension diets, the Mediterranean diet encourages a lifestyle associated with physical activity, and social connections. In addition, the Mediterranean diet is not based on restriction of nutrients but does limit intake of processed foods. Prospective studies have confirmed that the Mediterranean diet confers primary and secondary cardiovascular disease prevention in the general population. The benefits of the Mediterranean diet lifestyle include reducing the risk of diabetes mellitus, dyslipidemia, and lowers blood pressure. In adults with CKD, adherence to the Mediterranean diet is associated with a lower risk of CKD progression and its complications such as hyperphosphatemia and metabolic acidosis, and reduces production of uremic toxins and inflammatory mediators when compared to omnivore dietary patterns. Nevertheless, prospective studies are needed to confirm the cardiovascular disease prevention with the Mediterranean diet in adults with CKD. Medical nutrition therapy remains a cornerstone of CKD management, and the Mediterranean diet could be utilized to slow CKD progression and complications.

À qui un néphrologue doit-il prescrire un iSGLT2 ? Indications of SGLT2 inhibitors in kidney disease: who, why and when?

Inhibitors of sodium glucose co-transporter type 2 (iSGLT2) constitute a considerable advance in the management of patients with diabetes, heart failure and with chronic kidney disease (CKD). Randomized controlled studies have shown a significant reduction of cardiovascular risk in diabetic type 2 and/or heart failure with reduced ejection fraction patients. These studies observed a risk reduction of worsening nephropathy, leading to randomized controlled studies in CKD patients : CREDENCE, DAPA-CKD and EMPA-KIDNEY. iSGLT2 are associated with a slower progression toward end-stage kidney disease, a lower slope of GFR and a lower rate of albuminuria. In CKD patients with proteinuria either diabetic or not, the DAPA-CKD and the EMPA-KIDNEY studies have demonstrated a nephroprotective effect. This effect has not been found for patients without proteinuria. For the other nephropathies, further studies are required to confirm results obtained in patients without type 2 diabetes and macroalbuminuria. Therefore, the indication of iSGLT2, with appropriate dose of RAS inhibitor, seems undeniable to an optimal nephroprotection in CKD patients with type 2 diabetes and/or albuminuria and/or heart failure. They must be prescribed in addition to conventional nephroprotective and cardioprotective treatments and care. Side effects are limited. However, special education and monitoring concerning risks of genital infection and euglycemic ketoacidosis (diabetic patients) must be taken in mind. The therapeutic arsenal for CKD patients is expanding, leading to consider a personalized care according to the underlying nephropathy. © 2022 Published by Elsevier Masson SAS on behalf of Société francophone de néphrologie, dialyse et transplantation.