Renal Failure Affects the Enzymatic Activities of the Three First Steps in Hepatic Heme Biosynthesis in the Acute Intermittent Porphyria Mouse

Chronic kidney disease is a long-term complication in acute intermittent porphyria (AIP). The pathophysiological significance of hepatic overproduction of the porphyrin precursors aminolevulinate acid (ALA) and porphobilinogen (PBG) in chronic kidney disease is unclear. We have investigated the effect of repetitive acute attacks on renal function and the effect of total or five-sixth nephrectomy causing renal insufficiency on hepatic heme synthesis in the porphobilinogen deaminase (PBGD)-deficient (AIP) mouse. Phenobarbital challenge in the AIP-mice increased urinary porphyrin precursor excretion. Successive attacks throughout 14 weeks led to minor renal lesions with no impact on renal function. In the liver of wild type and AIP mice, 5/6 nephrectomy enhanced transcription of the first and rate-limiting ALA synthase. As a consequence, urinary PBG excretion increased in AIP mice. The PBG/ALA ratio increased from 1 in sham operated AIP animals to over 5 (males) and over 13 (females) in the 5/6 nephrectomized mice. Total nephrectomy caused a rapid decrease in PBGD activity without changes in enzyme protein level in the AIP mice but not in the wild type animals. In conclusion, high concentration of porphyrin precursors had little impact on renal function. However, progressive renal insufficiency aggravates porphyria attacks and increases the PBG/ALA ratio, which should be considered a warning sign for potentially life-threatening impairment in AIP patients with signs of renal failure

The major worldwide stress of healthcare professionals during the first wave of the COVID-19 pandemic – the international COVISTRESS survey

International audienceIntroduction The COVID-19 pandemic has initiated an upheaval in society and has been the cause of considerable stress during this period. Healthcare professionals have been on the front line during this health crisis, particularly paramedical staff. The aim of this study was to assess the high level of stress of healthcare workers during the first wave of the pandemic. Materials and methods The COVISTRESS international study is a questionnaire disseminated online collecting demographic and stress-related data over the globe, during the pandemic. Stress levels were evaluated using non-calibrated visual analog scale, from 0 (no stress) to 100 (maximal stress). Results Among the 13,537 individuals from 44 countries who completed the survey from January to June 2020, we included 10,051 workers (including 1379 healthcare workers, 631 medical doctors and 748 paramedical staff). The stress levels during the first wave of the pandemic were 57.8 ± 33 in the whole cohort, 65.3 ± 29.1 in medical doctors, and 73.6 ± 27.7 in paramedical staff. Healthcare professionals and especially paramedical staff had the highest levels of stress (p 80) compared to other workers (OR = 2.13, 95% CI 1.87–2.41). Paramedical staff risk for very-high levels of stress was higher than doctors’ (1.88, 1.50–2.34). The risk of high levels of stress also increased in women (1.83, 1.61–2.09; p 50). Conclusions The first wave of the pandemic was a major stressful event for healthcare workers, especially paramedical staff. Among individuals, women were the most at risk while age was a protective factor