Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21.

Dietary restriction promotes resistance to surgical stress in multiple organisms. Counterintuitively, current medical protocols recommend short-term carbohydrate-rich drinks (carbohydrate loading) prior to surgery, part of a multimodal perioperative care pathway designed to enhance surgical recovery. Despite widespread clinical use, preclinical and mechanistic studies on carbohydrate loading in surgical contexts are lacking. Here we demonstrate in ad libitum-fed mice that liquid carbohydrate loading for one week drives reductions in solid food intake, while nearly doubling total caloric intake. Similarly, in humans, simple carbohydrate intake is inversely correlated with dietary protein intake. Carbohydrate loading-induced protein dilution increases expression of hepatic fibroblast growth factor 21 (FGF21) independent of caloric intake, resulting in protection in two models of surgical stress: renal and hepatic ischemia-reperfusion injury. The protection is consistent across male, female, and aged mice. In vivo, amino acid add-back or genetic FGF21 deletion blocks carbohydrate loading-mediated protection from ischemia-reperfusion injury. Finally, carbohydrate loading induction of FGF21 is associated with the induction of the canonical integrated stress response (ATF3/4, NF-kB), and oxidative metabolism (PPARγ). Together, these data support carbohydrate loading drinks prior to surgery and reveal an essential role of protein dilution via FGF21.

[Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis: commensals or pathogens?] / Ureaplasma urealyticum, Ureaplasma parvum et Mycoplasma hominis: commensaux ou pathogènes?

Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum are bacteria commonly found in the urogenital tract. However, their pathogenicity in sexually active or obstetrical patients remains controversial. Therefore, determining the significance of screening and treatment for these organisms is challenging, unlike Mycoplasma genitalium which now has well-defined management guidelines. We conducted a review of the literature to clarify the clinical significance of detecting these micro-organisms. It is crucial to carefully select the few cases that warrant further investigations, in order to mitigate the risks of overdiagnosis and overtreatment.

Mycoplasma hominis, Ureaplasma urealyticum et Ureaplasma parvum sont des bactéries couramment retrouvées au niveau de la sphère urogénitale. Toutefois, leur pathogénicité chez le patient sexuellement actif ou la femme enceinte reste encore controversée. Il est dès lors difficile de déterminer l'intérêt du dépistage et du traitement pour ces germes, à l'inverse de Mycoplasma genitalium dont la prise en charge est maintenant très encadrée. Nous avons effectué une revue de la littérature afin de clarifier la pertinence clinique de la recherche de ces microorganismes. Il est impératif de sélectionner précisément les situations nécessitant des investigations plus poussées, afin de modérer le risque de surdiagnostic et de surtraitement.

Pregnancy after kidney transplantation: an observational study on maternal, graft and offspring outcomes in view of current literature.

Introduction: Pregnancy after kidney transplantation (KTx) is considered to have a high risk of non-negligible complications for the mother, the allograft, and the offspring. With an increased incidence of these pregnancies over the past decades, transplant nephrologists and specialized obstetricians face increasing challenges, with scarce literature regarding long-term outcomes. Methods: We retrospectively collected data from all women with at least one live birth pregnancy after KTx who were followed at our tertiary hospital between 2000 and 2021 to study maternal, graft and fetal outcomes. Results: Ten patients underwent 14 live birth pregnancies after KTx. Preponderant maternal complications were stage 1 acute kidney injury (43%), urinary tract infections (UTI, 43%), progression of proteinuria without diagnostic criteria for preeclampsia (29%), and preeclampsia (14%). Median baseline serum creatinine at conception was 126.5 µmol/L [median estimated glomerular filtration rate (eGFR) 49 mL/min/1.73m2], and eGFR tended to be lower than baseline at follow-ups. Overall, there was no increase in preexisting or occurrence of de novo donor-specific antibodies. No graft loss was documented within the 2-year follow-up. There were nine premature births (64%), with a median gestational age of 35.7 weeks. The median birth weight, height, and head circumference were 2,560 g, 45.5 cm, and 32.1 cm, respectively. These measurements tended to improve over time, reaching a higher percentile than at birth, especially in terms of height, but on average remained under the 50th percentile curve. Discussion: Overall, pregnancies after KTx came with a range of risks for the mother, with a high prevalence of cesarean sections, emergency deliveries, UTI, and preeclampsia, and for the child, with a high proportion of prematurity, lower measurements at birth, and a tendency to stay under the 50th percentile in growth charts. The short- and long-term impact on the allograft seemed reassuring; however, there was a trend toward lower eGFR after pregnancy. With these data, we emphasize the need for a careful examination of individual risks via specialized pre-conception consultations and regular monitoring by a transplant nephrologist and a specialist in maternal-fetal medicine during pregnancy. More data about the long-term development of children are required to fully apprehend the impact of KTx on offspring.

Association of Oliguria With Acute Kidney Injury Diagnosis, Severity Assessment, and Mortality Among Patients With Critical Illness.

Importance: The current definition and staging of acute kidney injury (AKI) considers alterations in serum creatinine (sCr) level and urinary output (UO). However, the relevance of oliguria-based criteria is disputed. Objective: To determine the contribution of oliguria, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, to AKI diagnosis, severity assessment, and short- and long-term outcomes. Design, Setting, and Participants: This cohort study included adult patients admitted to a multidisciplinary intensive care unit from January 1, 2010, to June 15, 2020. Patients receiving long-term dialysis and those who declined consent were excluded. Daily sCr level and hourly UO measurements along with sociodemographic characteristics and severity scores were extracted from electronic medical records. Long-term mortality was assessed by cross-referencing the database with the Swiss national death registry. The onset and severity of AKI according to the KDIGO classification was determined using UO and sCr criteria separately, and their agreement was assessed. Main Outcomes and Measures: Using a multivariable model accounting for baseline characteristics, severity scores, and sCr stages, the association of UO criteria with 90-day mortality was evaluated. Sensitivity analyses were conducted to assess how missing sCr, body weight, and UO values, as well as different sCr baseline definitions and imputations methods, would affect the main results. Results: Among the 15 620 patients included in the study (10 330 men [66.1%] with a median age of 65 [IQR, 53-75] years, a median Simplified Acute Physiology Score II score of 40.0 [IQR, 30.0-53.0], and a median follow-up of 67.0 [IQR, 34.0-100.0] months), 12 143 (77.7%) fulfilled AKI criteria. Serum creatinine and UO criteria had poor agreement on AKI diagnosis and staging (Cohen weighted κ, 0.36; 95% CI, 0.35-0.37; P < .001). Compared with the isolated use of sCr criteria, consideration of UO criteria enabled identification of AKI in 5630 patients (36.0%). Those patients had a higher 90-day mortality than patients without AKI (724 of 5608 [12.9%] vs 288 of 3462 [8.3%]; P < .001). On multivariable analysis accounting for sCr stage, comorbidities, and illness severity, UO stages 2 and 3 were associated with a higher 90-day mortality (odds ratios, 2.4 [95% CI, 1.6-3.8; P < .001] and 6.2 [95% CI, 3.7-10.5; P < .001], respectively). These results remained significant in all sensitivity analyses. Conclusions and Relevance: The findings of this cohort study suggest that oliguria lasting more than 12 hours (KDIGO stage 2 or 3) has major AKI diagnostic implications and is associated with outcomes irrespective of sCr elevations.