Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin‐6 (IL‐6) release. The IL‐6‐receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID‐19) . In this pandemic, kidney transplant (KT) recipients are a high‐risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID‐19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL‐6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D‐dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C‐reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004‐1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID‐19 but randomized trials are needed.
The two major classes of drugs that target the RAS are the angiotensin-converting enzyme (ACE) inhibitors and the selective AT1 receptor blockers (ARBs). Although both of these drug classes target angiotensin II, the differences in their mechanisms of action have implications for their effects on other pathways and receptors that may have therapeutic implications. Both ACEIs and ARBs are effective antihypertensive agents that have been shown to reduce the risk of cardiovascular and renal events. Direct inhibition of renin -the most proximal aspect of the RAS -became clinically feasible from 2007 with the introduction of aliskiren. This latter drug has been shown to be efficacious for the management of hypertension. Combined therapy of direct renin-inhibitors with ACEIs or ARBs has been tested in some clinical situations as congestive HF and proteinuria with diverse results. This article tries to offer an updated review of current knowledge on the use of RAS blocking drugs in clinical settings.
The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.
Aggressive reduction of blood pressure may increase cardiovascular events (the J-curve phenomenon) in certain populations. In this regard, most studies in patients with chronic kidney disease have shown a J curve for cardiovascular morbidity and mortality, and this phenomenon persists after adjusting for confounding factors. Since there is no evidence that a straighter blood pressure target (<130/70 mm Hg) could improve renal outcomes, the increased cardiovascular risk associated with extreme blood pressure reduction should be seen as undesirable. Moreover, the intensive c ontrol of blood pressure may induce an unintended reduction of renal function and this decrease, in turn, may increase cardiovascular risk.
Although elevated inflammatory markers are associated with a worse outcome in CKD patients, they did not add predictive information of all-cause mortality beyond that provided by age and the comorbid index.
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