Renal arcuate vein thrombosis-induced acute kidney injury: a rare multiple-Hit-mediated disease.

Background: Renal arcuate vein thrombosis (RAVT) is a rare and recently recognized cause of acute kidney injury (AKI) in young adults. However, the precise incidence and underlying pathophysiologic mechanisms leading to AKI in these patients remain elusive. Methods: This study included all patients who underwent a kidney biopsy over a 40-month period sent to the pathology department of Necker-Enfants Malades Hospital, with evidence of RAVT. We performed coagulation tests, genetic testing for thrombophilia, complete urine toxicologic screening and kidney metagenomic sequencing to identify an underlying cause of thrombosis. Results: We report five pediatric cases of RAVT discovered on kidney biopsy performed in the setting of unexplained AKI. Investigations did not reveal an underlying cause of thrombosis but only a significant nonsteroidal anti-inflammatory drugs (NSAIDs) use was reported in 4/5 patients, supporting a potential link between NSAIDs use and RAVT. By performing metagenomic sequencing on kidney biopsy samples, we detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the kidney of one patient. These results suggest that systemic SARS-CoV-2 infection may also be a key contributing factor of renal thrombosis, particularly by inducing potential endothelial disruption. Conclusions: In conclusion, RAVT-induced AKI appears to be a multiple hit-mediated disease in which NSAIDs consumption and viral infection such as SARS-CoV-2 may be crucial contributing factors. These findings may have significant public health implications given the prevalence of NSAIDs use in the general population. Increased awareness and additional study of future cases may lead to a better understanding of this rare cause of AKI in children and young adults.

In obese hypertensives cholecalciferol inhibits circulating TH17 cells but not macrophage infiltration on adipose tissue.

In arterial hypertension, increased Th17 cells and reduced Tregs are the hallmarks of immunological dysfunction and the basis for the investigation of immunomodulatory drugs. Although cholecalciferol is not a primary immunomodulator, it has recognized action on immune cells, leading us to hypothesise if cholecalciferol can induce a more tolerogenic phenotype in obese hypertensives. In a phase-2, single-centre, randomised, open, 24-week trial, we assigned adults with obesity-associated hypertension and vitamin D deficiency to receive usual therapy plus 50,000 IU/week of cholecalciferol or usual therapy alone. The primary endpoint was the percentual variation in T CD4+, T CD8+, Tregs, and Th17 cells. Secondary endpoints included the percentual variation in Th1, Tc1, Tc17, and monocytes and variation in the number of perivascular and non-perivascular macrophages, T CD4+ and T CD8+ lymphocytes in subcutaneous abdominal adipose tissue. A control group of 12 overweight normotensives was also evaluated for peripheral immune cells. A total of 36 obese hypertensives were randomised, 18 in each group. In comparison with normotensive controls, hypertensives presented higher percentages of T lymphocytes (p = 0.016), Tregs (p = 0.014), and non-classical monocytes (p < 0.001). At week 24, Th17 cells increased in control group (p = 0.017) but remained stable in cholecalciferol group. For Tregs, downregulation towards the values of normotensive controls was observed (p = 0.003), and in multivariate analysis, an increased loading in the setting of the cells of adaptive immunity observed (eigenvalue 1.78, p < 0.001). No changes were documented for monocytes. In adipose tissue, a baseline negative correlation between vitamin D and perivascular macrophages was observed (r = -0.387, p = 0.024) that persisted in the control group (r = -0.528, p = 0.024) but not in the cholecalciferol group, which presented an increase in non-perivascular macrophages (p = 0.029) at week 24. No serious adverse events were reported for all the participants. In this trial, we found that supplementation with cholecalciferol interfered with peripheral and adipose tissue immune cell profile, downregulating peripheral Th17 cells, but increasing the number of infiltrating subcutaneous adipose tissue macrophages. (Funded by Núcleo Estudos Hipertensão da Beira Interior; EudraCT number: 2015-003910-26).

Hemodialysis vascular access in elderly patients: A comprehensive review.

The number of elderly patients initiating hemodialysis (HD) increased considerably over the past decade. Arteriovenous fistulas (AVFs) are the preferred vascular access (VA) type in most HD patients. Choice of VA for older hemodialysis patients presents a challenge. The higher incidence of comorbidities, longer AVF maturation times, risk of primary failure, risk of patency loss, and shorter life expectancy are important factors to consider. In this review we provide a comprehensive analysis on maturation rates, primary failure, patency, and mortality regarding vascular access in patients older than 75 years of age.

Renal transplantation in Birt-Hogg-Dubé syndrome: should we?

BACKGROUND: Birt-Hogg-Dubé (BHD) Syndrome is a rare genodermatosis caused by a mutation on folliculin gene, with a strong link to renal cancer. To date few patients with such condition have reached dialysis stage, as nephron-sparing surgery is usually possible at the time of diagnosis. To our best knowledge no patient with BHD syndrome has been submitted to renal transplantation. CASE PRESENTATION: We report the case of a woman diagnosed with multifocal bilateral renal cell carcinoma that underwent bilateral radical nephrectomy and was started on a regular hemodialysis program at the age of 29. While on hemodialysis program she was diagnosed clinically with BHD syndrome and molecular testing confirmed an heterozygous mutation on FLCN gene. The patient has been kept on surveillance program for 2 years with no clinical complications from the genetic syndrome and in complete remission from renal cancer. Though there has not been any report of a patient with BHD being transplanted, risks and benefits for this patient were weighted. She has been considered apt by the transplant team and is currently waitlisted for cadaveric renal transplantation. DISCUSSION: It is a matter of discussion which should be cancer-free period for anephric patients with an inherited cancer syndrome to be candidates for renal transplant. So far BHD syndrome has not been causally associated with any other neoplastic disorder elsewhere. Accepting cancer biology is very complex and knowledge of the behaviour of this genetic syndrome is limited to a few cases reported worldwide, the authors believe that renal transplantation is the best treatment option for this young patient. The choice of post transplantation immunosuppression is debatable, but considering experience in other inherited cancer syndromes a maintenance scheme with mTOR inhibitor will be favoured.

Cognitive Impact and Psychophysiological Effects of Stress Using a Biomonitoring Platform.

Stress can impact multiple psychological and physiological human domains. In order to better understand the effect of stress on cognitive performance, and whether this effect is related to an autonomic response to stress, the Trier Social Stress Test (TSST) was used as a testing platform along with a 2-Choice Reaction Time Task. When considering the nature and importance of Air Traffic Controllers (ATCs) work and the fact that they are subjected to high levels of stress, this study was conducted with a sample of ATCs (n = 11). Linear Heart Rate Variability (HRV) features were extracted from ATCs electrocardiogram (ECG) acquired using a medical-grade wearable ECG device (Vital Jacket® (1-Lead, Biodevices S.A, Matosinhos, Portugal)). Visual Analogue Scales (VAS) were also used to measure perceived stress. TSST produced statistically significant changes in some HRV parameters (Average of normal-to-normal intervals (AVNN), Standard Deviation of all NN (SDNN), root mean square of differences between successive rhythm-to-rhythm (RR) intervals (RMSSD), pNN20, and LF/HF) and subjective measures of stress, which recovered after the stress task. Although these short-term changes in HRV showed a tendency to normalize, an impairment on cognitive performance was evident. Despite that participant's reaction times were lower, the accuracy significantly decreased, presenting more errors after performing the acute stress event. Results can also point to the importance of the development of quantified occupational health (qOHealth) devices to allow for the monitoring of stress responses.