Acute kidney injury (AKI) represents the most frequent complication after cardiac surgery. Macrophage migration inhibitory factor (MIF) is a stress-regulating cytokine that was shown to protect the heart from myocardial ischemia-reperfusion injury, but its role in the pathogenesis of AKI remains unknown. In an observational study, serum and urinary MIF was quantified in 60 patients scheduled for elective conventional cardiac surgery with the use of cardiopulmonary bypass. Cardiac surgery triggered an increase in MIF serum concentrations, and patients with high circulating MIF (>median) 12 hours after surgery had a significantly reduced risk of developing AKI (relative risk reduction, 72.7%; 95% confidence interval, 12 to 91.5%; = 0.03). Experimental AKI was induced in wild-type and mice by 30 min of ischemia followed by 6 or 24 hours of reperfusion, or by rhabdomyolysis. -deficient mice exhibited increased tubular cell injury, increased regulated cell death (necroptosis and ferroptosis), and enhanced oxidative stress. Therapeutic administration of recombinant MIF after ischemia-reperfusion in mice ameliorated AKI. In vitro treatment of tubular epithelial cells with recombinant MIF reduced cell death and oxidative stress as measured by glutathione and thiobarbituric acid reactive substances in the setting of hypoxia. Our data provide evidence of a renoprotective role of MIF in experimental ischemia-reperfusion injury by protecting renal tubular epithelial cells, consistent with our observation that high MIF in cardiac surgery patients is associated with a reduced incidence of AKI.

During the ongoing coronavirus disease 2019 (Covid-19) pandemic, it is critical to ensure the safety of Covid-19 vaccines. We herein report a 51-year-old Japanese woman who developed acute-onset type 1 diabetes with diabetic ketoacidosis six weeks after receiving the first dose of a Covid-19 mRNA vaccine. Laboratory tests indicated exhaustion of endogenous insulin secretion, a positive result for insulin autoantibody, and latent thyroid autoimmunity. Human leukocyte antigen typing was homozygous for DRB1*09:01-DQB1*03: 03 haplotypes. This case suggests that Covid-19 vaccination can induce type 1 diabetes in some individuals with a genetic predisposition.

Background/Aims: Hyperuricemia has been reported to affect renal hemodynamics in rat models. We evaluate the relationship between serum uric acid and intrarenal hemodynamic parameters in humans, utilizing the plasma clearance of para-aminohippurate (C_PAH ) and inulin (C_in). Methods: Renal and glomerular hemodynamics were assessed by simultaneous measurement of C_PAH and C_in in 58 subjects. Of these, 19 subjects were planned to provide a kidney for transplantation; 26 had diabetes without proteinuria; and 13 had mild proteinuria. Renal and glomerular hemodynamics were calculated using Gomez`s formulae. Results: C_in was more than 60 ml/min/1.73m² in all subjects. Serum uric acid levels correlated significantly with vascular resistance at the afferent arteriole (R_a) (r = 0.354, p = 0.006) but not with that of the efferent arteriole (R_e). Serum uric acid levels (β = 0.581, p = <0.001) were significantly and independently associated with R_a after adjustment for several confounders (R² = 0.518, p = <0.001). Conclusions: These findings suggest, for the first time in humans, that higher serum uric acid levels are associated significantly with R_a in subjects with C_in > 60 ml/min/1.73m². The increase in R_a in subjects with higher uric acid levels may be related to dysfunction of glomerular perfusion.

Objective: Low thyroid function may be associated with a reduced glomerular filtration rate (GFR) calculated on the basis of creatinine metabolism. Thyroid hormone directly affects serum creatinine in muscle and low thyroid function might exert a similar direct effect in the kidney. The goal of the study was to evaluate this possibility by assessment of the inulin-based GFR and to examine the mechanism underlying the reduction of GFR. Patients and methods: Renal and glomerular hemodynamics were assessed by simultaneous measurements of plasma clearance of para-aminohippurate (C PAH ) and inulin (C in ) in 26 patients with serum creatinine !1.00 mg/dl and without thyroid disease. All subjects were normotensive with or without antihypertensive treatment and were kept in a sodium-replete state. Renal and glomerular hemodynamics were calculated using Gomez's formulae. Results: Serum TSH, including within the normal range (0.69-4.30 mIU/ml), was positively correlated with vascular resistance at the afferent arteriole (R a ) (rZ0.609, PZ0.0010), but not at the efferent arteriole (R e ). Serum TSH was significantly and negatively correlated with renal plasma flow (RPF), renal blood flow (RBF), and GFR (rZK0.456, PZ0.0192; rZK0.438, PZ0.0252; rZK0.505, PZ0.0086 respectively). In multiple regression analysis, serum TSH was significantly positively associated with R a after adjustment for age and mean blood pressure. Conclusions: These findings suggest that low thyroid function, even within the normal range, is associated with reduced RPF, RBF, and GFR, which might be caused by a preferential increase in R a .