Objectives: To characterize renin in critically ill patients. Renin is fundamental to circulatory homeostasis and could be a useful marker of tissue-perfusion. However, diurnal variation, continuous renal replacement therapy and drug-interference could confound its use in critical care practice. Design: Prospective observational study. Setting: Single-center, mixed medical-surgical ICU in Europe. Patients: Patients over 18 years old with a baseline estimated glomerular filtration rate greater than 30 mL/min/1.73 m2 and anticipated ICU stay greater than 24 hours. Informed consent was obtained from the patient or next-of-kin. Interventions: Direct plasma renin was measured in samples drawn 6-hourly from arterial catheters in recumbent patients and from extracorporeal continuous renal replacement therapy circuits. Physiologic variables and use of drugs that act on the renin-angiotensin-aldosterone system were recorded prospectively. Routine lactate measurements were used for comparison. Measurements and Main Results: One-hundred twelve arterial samples (n = 112) were drawn from 20 patients (65% male; mean ± sd, 60 ± 14 yr old) with septic shock (30%), hemorrhagic shock (15%), cardiogenic shock (20%), or no circulatory shock (35%). The ICU mortality rate was 30%. Renin correlated significantly with urine output (repeated-measures correlation coefficient = –0.29; p = 0.015) and mean arterial blood pressure (repeated-measures correlation coefficient = –0.35; p < 0.001). There was no diurnal variation of renin or significant interaction of renin-angiotensin-aldosterone system drugs with renin in this population. Continuous renal replacement therapy renin removal was negligible (mass clearance ± sd 4% ± 4.3%). There was a significant difference in the rate of change of renin over time between survivors and nonsurvivors (–32 ± 26 μU/timepoint vs +92 ± 57 μU/timepoint p = 0.03; mean ± sem), but not for lactate (–0.14 ± 0.04 mM/timepoint vs +0.15 ± 0.21 mM/timepoint; p = 0.07). Maximum renin achieved significant prognostic value for ICU mortality (receiver operator curve area under the curve 0.80; p = 0.04), whereas maximum lactate did not (receiver operator curve area under the curve, 0.70; p = 0.17). Conclusions: In an heterogeneous ICU population, renin measurement was not significantly affected by diurnal variation, continuous renal replacement therapy, or drugs. Renin served as a marker of tissue-perfusion and outperformed lactate as a predictor of ICU mortality.

Hypoparathyroidism is a rare endocrine disease with insufficient parathyroid hormone levels. Replacing the missing hormone is not yet a standard therapy. The objective of this retrospective cohort study was to evaluate if the usual therapy regimens of postsurgical hypoparathyroidism with calcitriol have a negative effect on renal function. We performed a chart analysis of patients who were seen in a tertiary care hospital in Brussels, Belgium. A total of 101 subjects were identified as patients with permanent post-surgical hypoparathyroidism, based on the hospital records of patients who underwent a total thyroidectomy between 1996 and 2016, while still being treated with calcitriol. Patients with pre-existing renal insufficiency and/or active malignancy were excluded. The cohort was predominantly female of Caucasian origin. Renal function was evaluated before and after surgery (with a maximum follow-up of 12 years), using the CKD-EPI equation. A multivariate linear regression model was used to correlate renal function decline with the duration of calcitriol therapy, while correcting for the mean calcium phosphate product and age. We found a statistically significant (p=0.027) relationship between the duration of calcitriol treatment and renal function decline at a rate of 1.06 ml/min/1.73 m2 per year of calcitriol therapy. Our study, although being retrospective, is the first one to demonstrate a relationship between the cumulative use of calcitriol therapy and renal function decline.

Background: Nephrotic syndrome (NS) is associated with an increased risk of thromboembolic events (TE), due to hemostatic derangements. The use of direct oral anticoagulants (DOAC) in the prevention of TE hasn’t been studied intensively in patients suffering from NS. Methods: Retrospective analysis of consecutive incident patients with NS due to glomerular disease, receiving apixaban for thrombophylaxis. It is an uncontrolled, single center study. Results: We identified 27 patients treated with apixaban for the prevention of TE, in the context of NS. During follow-up apixaban Cmin and Cmax levels were measured. The mean duration of the anticoagulant treatment was 153 days (± 132). Patients were followed for a mean of 14.7 months (± 8.4) since the introduction of apixaban. Three patients had a TE at the time of NS diagnosis. Two patients had pulmonary embolism (PE) and one patient presented a stroke in lupus membranous nephropathy context. One patient developed PE approximately 2 months after introduction of apixaban treatment. No minor nor major bleeding events were noticed. Conclusion: The present study shows that patients, suffering from severe NS under anticoagulant therapy with apixaban had reduced risk of venous and arterial TE compared to patients previously described in the literature, without increased risk of bleeding.

Activation of CD4 T cells by B cells has been extensively studied, but B cell-regulated priming, proliferation, and survival of CD8 T cells remains controversial. B cells express high levels of MHC class I molecules and can potentially act as antigen-presenting cells (APCs) for CD8 T cells. Several in vivo studies in mice and humans demonstrate the role of B cells as modulators of CD8 T cell function in the context of viral infections, autoimmune diseases, cancer and allograft rejection. In addition, B-cell depletion therapies can lead to impaired CD8 T-cell responses. In this review, we attempt to answer 2 important questions: 1. the role of B cell antigen presentation and cytokine production in the regulation of CD8 T cell survival and cell fate determination, and 2. The role of B cells in the formation and maintenance of CD8 T cell memory.