Renal Safety of Nonsteroidal Anti-Inflammatory Drugs and Opioids in Hospitalized Patients on Renin-Angiotensin System Inhibitors

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDS) are increasingly important alternatives to opioids for analgesia during hospitalization as health systems implement opioid-minimization initiatives. Increasing NSAID use may increase AKI rates, particularly in patients with predisposing risk factors. Inconclusive data in outpatient populations suggests that NSAID nephrotoxicity is magnified by renin-angiotensin system inhibitors (RAS-I). No studies have tested this in hospitalized patients.MethodsRetrospective, active-comparator cohort study of patients admitted to four hospitals in Philadelphia, Pennsylvania. To minimize confounding by indication, NSAIDs were compared to oxycodone, and RAS-I were compared to amlodipine. We tested synergistic NSAID+RAS-I nephrotoxicity by comparing the difference in AKI rate between NSAID versus oxycodone in patients treated with RAS-I to the difference in AKI rate between NSAID versus oxycodone in patients treated with amlodipine. In a secondary analysis, we restricted the cohort to patients with baseline diuretic treatment. AKI rates were adjusted for 71 baseline characteristics with inverse probability of treatment-weighted Poisson regression.ResultsThe analysis included 25,571 patients who received a median of 2.4 days of analgesia. The overall AKI rate was 23.6 per 1000 days. The rate difference (RD) for NSAID versus oxycodone in patients treated with amlodipine was 4.1 per 1000 days (95% CI, −2.8 to 11.1), and the rate difference for NSAID versus oxycodone in patients treated with RAS-I was 5.9 per 1000 days (95% CI, 1.9 to 10.1), resulting in a nonsignificant interaction estimate: 1.85 excess AKI events per 1000 days (95% CI, −6.23 to 9.92). Analysis in patients treated with diuretics produced a higher, albeit nonsignificant, interaction estimate: 9.89 excess AKI events per 1000 days (95% CI, −5.04 to 24.83).ConclusionsSynergistic nephrotoxicity was not observed with short-term NSAID+RAS-I treatment in the absence of concomitant diuretics, suggesting that RAS-I treatment may not be a reason to choose opioids in lieu of NSAIDs in this population. Synergistic nephrotoxicity cannot be ruled out in patients treated with diuretics.

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Angiotensin-(1-7) Central Mechanisms After ICV Infusion in Hypertensive Transgenic (mRen2)27 Rats

Frontiers in Neuroscience ◽

10.3389/fnins.2021.624249 ◽

2021 ◽

Vol 15 ◽

Author(s):

Lucas M. Kangussu ◽

Marcella Nunes Melo-Braga ◽

Bruna Soares de Souza Lima ◽

Robson A. S. Santos ◽

Hélida Monteiro de Andrade ◽

...

Keyword(s):

Oxidative Stress ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Peroxiredoxin 1 ◽

Renin Angiotensin ◽

Ace Activity ◽

Carboxyl Terminal ◽

Anti Inflammatory ◽

Inflammatory Profile

Graphical AbstractHypothalamic mechanisms induced by ICV infusion of angiotensin-(1-7) in the transgenic (mRen2)27 hypertensive animals. Ang-(1-7) treatment modulated components of the renin-angiotensin system (RAS), attenuating increased levels of AT1 and ACE activity, and negatively modulated inflammatory profile, by increasing anti-inflammatory IL-10 and decreasing TNFα and iNOS in the hypothalamus. Further, altered oxidative stress/inflammation by ROS mediator, decreasing Uchl1 (ubiquitin carboxyl-terminal hydrolase isozyme L1) while increasing antioxidant peroxiredoxin 1 (figure was created with pictures from biorender.com).

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Why Children Are Less Affected by COVID-19 Than Adults: Potential Immunological Factors and the Renin-Angiotensin System Associated Mechanisms

10.20944/preprints202006.0120.v1 ◽

2020 ◽

Author(s):

Olga Krogh-Jensen ◽

Irina Nikitina ◽

Andrew Donnikov ◽

Anna Lenyushkina ◽

Nataliya Degtyareva ◽

...

Keyword(s):

Immune Response ◽

Transmembrane Protein ◽

Age Groups ◽

Renin Angiotensin System ◽

Scientific Data ◽

Th2 Response ◽

Angiotensin System ◽

Inflammatory Reactions ◽

Renin Angiotensin ◽

Anti Inflammatory

The spread of the infection caused by the new coronavirus SARS-CoV-2 (COVID-19) became pandemic on March 11, 2020. From the time of the first cases (in November 2019, Wuhan, China), to date, a large number of COVID-19 observations have been accumulated in different age groups of patients both in China and abroad. Published scientific data allows us to conclude that children suffer from COVID-19 much less often than adults and tolerate the disease in a milder form, often appear to be asymptomatic. There is currently no final answer why children are less susceptible to this virus; however, scientists are increasingly inclined to consider a complex effect of the immune response and components of the renin-angiotensin system (RAS), which according to recent studies affects not only the cardiovascular system, but is also responsible for the activation of inflammatory reactions. A hypothesis of genetic predisposition to the development of severe forms of COVID-19 has recently been made. We conducted a search for publications in the databases and showed current scientific ideas about COVID-19 pathogenesis and factors influencing the disease development in childhood. Childhood immunity may have several protective features against SARS-CoV-2: immaturity of particular elements of the innate immune response, constitutional lymphocytosis with a shift towards anti-inflammatory Th2-response, as well as "trained" immunity. The influence of renin-angiotensin system reactions in this review is shown from two perspectives: expression of ACE2 receptors and polymorphisms of certain genes of this system. It was established that ACE2 transmembrane protein is not only the entry point for the virus but also plays a regulatory role, turning the pro-inflammatory vasoconstrictor angiotensin II into anti-inflammatory angiotensin (1-7), which has vasodilating properties. Higher ACE2 content in children compared with adults helps maintain balance in the renin-angiotensin system and prevents the development of complications. It was also shown that the presence of certain genetic polymorphisms (AGTR1, AGTR2, ACE2, ACE) could determine the imbalance inside the RAS, leading to more pronounced reactions of alveolocytes, vascular endothelium and smooth muscle fibers in response to SARS-CoV-2 infection due to a shift towards vasoconstrictor, proliferative and profibrotic mechanisms.

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