Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, related to severe acute respiratory syndrome coronavirus 2 infection. Few data are available in patients with end-stage renal disease (ESRD). METHODS: We conducted an observational cohort study of COVID-19 patients at 11 dialysis centres in two distinct districts of France to examine the epidemiological and clinical characteristics of COVID-19 in this population, and to determine risk factors of disease severity (defined as a composite outcome including intensive care unit admission or death) and mortality. RESULTS: Among the 2336 patients enrolled, 5.5% had confirmed COVID-19 diagnosis. Of the 122 patients with a follow-up superior to 28 days, 37% reached the composite outcome and 28% died. Multivariate analysis showed that oxygen therapy on diagnosis and a decrease in lymphocyte count were independent risk factors associated with disease severity and with mortality. Chronic use of angiotensin II receptor blockers (ARBs) (18% of patients) was associated with a protective effect on mortality. Treatment with azithromycin and hydroxychloroquine (AZT/HCQ) (46% of patients) were not associated with the composite outcome and with death in univariate and multivariate analyses. CONCLUSIONS: COVID-19 is a severe disease with poor prognosis in patients with ESRD. Usual treatment with ARBs seems to be protective of critical evolution and mortality. There is no evidence of clinical benefit with the combination of AZT/HCQ.

Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study.

BACKGROUND: Nicotinamide (NAM) has been proposed as an alternative treatment to phosphate binders for hyperphosphataemia in chronic kidney disease. METHODS: The NICOREN multicentre, open-label and randomized study was designed to examine non-inferiority and safety of NAM when compared with sevelamer (SEV) in chronic haemodialysis patients. One hundred patients were randomized to either NAM or SEV treatment for 24 weeks. Serum biochemistry and NAM's main metabolite, N -methyl-2-pyridone-5-carboxamide (2PY), were measured to assess compliance, efficacy and safety. RESULTS: After 24 weeks, we observed a comparable decrease in serum phosphorus in the NAM and SEV treatment arms, from 2.1 ± 0.4 to 1.8 ± 0.5 and 2.3 ± 0.5 to 1.7 ± 0.5 mM (P = not significant), respectively. The criterion for non-inferiority was, however, not met due to a more limited number of patients being included than planned. Treatment discontinuation due to adverse events was 1.6 times higher in the NAM than in the SEV group with only 55% of study completers in the NAM arm versus 90% in the SEV arm. Thrombocytopenia was observed in four NAM-treated patients. Serum 2PY levels were comparable at baseline, but increased markedly in the NAM group, but not in the SEV group, at 24 weeks (P < 0.0001). CONCLUSIONS: Thus, both drugs are equally effective in lowering serum phosphorus, but patients' tolerance of NAM was largely inferior to that of SEV. Extremely high 2PY levels may contribute to NAM's side effects.

[Diuretic-based therapy]. / Thérapeutique diurétique.

Diuretics are pharmacological agents that increase natriuresis through inhibition of tubular re-absorption of sodium. The mechanisms and site of this inhibition differ with each drug class, accounting for their additive effects on natriuresis increase and their hydroelectrolytic side effects. The response to a given diuretic dose depends on the diuretic concentration on the urine at its action site. This concentration may be decreased by pharmacokinetic factors such as encountered in renal insufficiency or in nephrotic syndrome. These resistance mechanisms of diuretics may be corrected by dose increase, previous diuretic fixation on albumin or warfarin administration. Once these mechanisms are opposed, the diuretic concentration for maximal efficacy is reached at is action site and the natriuresis obtained as the normal maximal plateau. This is not the case when an oedematous systemic disease with effective hypovolemia is present, like in heart failure or cirrhosis, or when chronic use of loop diuretics has induced a hypertrophy of the more distant part of the tubule. In theses cases, a pharmacodynamic resistance exists, resulting in a lower maximal natriuresis plateau in spite of adequate concentration of the diuretic at its action site, even in the absence of pharmacokinetic resistance factors. The main indications of diuretics are systemic oedematous disease and hypertension. In the oedematous diseases, diuretics indication is both straightforward and sufficient only if effective hypervolemia is present. The therapeutic approach is discussed according to the various clinical conditions and pathophysiological background. In uncomplicated hypertension, diuretics are the cornerstone of the therapy. The most suitable diuretic treatment for hypertension is an association of low doses thiazide (12.5-50 mg/day) with potassium sparing diuretics. Rare indications of diuretics are also reviewed.

Is the angiotensin II Type 2 receptor cerebroprotective?

Most of the deleterious effects of angiotensin II (Ang II) on blood pressure (BP), cardiovascular remodeling, and atherosclerosis are mediated by Ang II type 1 (AT1)-receptor activation. This explains why Ang-II-decreasing or blocking drugs have been successful in decreasing global cardiovascular morbimortality in patients with cardiac complications. However, in primary or secondary stroke prevention trials in patients with low cardiac risk, b-blockers and angiotensin-converting enzyme inhibitors (ACEIs), which decrease Ang II formation, seem to be less protective than thiazides and dihydropyridines, which increase Ang II. When compared with a beta-blocker, an Ang II-increasing AT1-receptor blocker better protects against stroke but not against cardiac events, whereas an ACEI gives the same protection against both cardiac and cerebral events. This dissociation between blood-pressure-independent cardiac and cerebral protection between b-blockers or ACEIs versus AT1-blockers in patients with low cardiac risk can be best explained if, besides the beneficial vascular effect of AT1-receptor blunting, there is evidence of a beneficial effect of non-AT1-receptor activation. In this review, we present experimental evidence for AT2- and AT4-receptor-mediated brain-anti-ischemic mechanisms and propose a direct comparison of AT1-blockers with ACEIs to prove the clinical effectiveness of non-AT1-mediated mechanisms in stroke prevention, particularly in patients with a higher risk for stroke than for cardiac complications.