Pharmacological interventions for the prevention of renal injury in surgical patients: a systematic literature review and meta-analysis

Abstract

Background: The aim of this systematic review was to summarise the results of randomised controlled trials (RCTs) that have evaluated pharmacological interventions for renoprotection in people undergoing surgery. Methods: Searches were conducted to update a previous review using the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to August 23, 2019. RCTs evaluating the use of pharmacological interventions for renal protection in the perioperative period were included. The co-primary outcome measures were 30-day mortality and acute kidney injury (AKI). Pooled effect estimates were expressed as risk ratios (RRs) (95% confidence intervals). Results: We included 228 trials enrolling 56 047 patients. Twenty-three trials were considered to be at low risk of bias across all domains. Atrial natriuretic peptides (14 trials; n¼2207) reduced 30-day mortality (RR: 0.63 [0.41, 0.97]) and AKI events (RR: 0.43 [0.33, 0.56]) without heterogeneity. These effects were consistent across cardiac surgery and vascular surgery subgroups, and in sensitivity analyses restricted to studies at low risk of bias. Inodilators (13 trials; n¼2941) reduced mortality (RR: 0.71 [0.53, 0.94]) and AKI events (RR: 0.65 [0.50, 0.85]) in the primary analysis and in cardiac surgery cohorts. Vasopressors (4 trials; n¼1047) reduced AKI (RR: 0.56 [0.36, 0.86]). Nitric oxide donors, alpha-2-agonists, and calcium channel blockers reduced AKI in primary analyses, but not after exclusion of studies at risk of bias. Overall, assessment of the certainty of the effect estimates was low. Conclusions: There are multiple effective pharmacological renoprotective interventions for people undergoing surgery.

Diagnosis, pathophysiology and preventive strategies for cardiac surgery-associated acute kidney injury: a narrative review

“…Data from animal models suggest that pretreatment with dexmedetomidine before IRI has a nephroprotective effect by reducing the levels of inflammatory cytokines and damage associated molecular patterns (DAMPs), thereby reducing cell death and toll-like receptor 4 expression in renal tubular cells after renal ischaemia [ 106 ]. These results are also reflected in the data from clinical studies: several recent meta-analyses [ 104 , 107 ] show the benefit of perioperative dexmedetomidine in reducing the incidence of CS-AKI, especially in elderly patients who received dexmedetomidine immediately after induction of anaesthesia and maintained intraoperative infusion. However, the subsequent DECADE trial suggested that perioperative use of dexmedetomidine tended to worsen delirium and AKI after cardiac surgery, although not by a significant amount [ 108 ].…”

“…There is no specific pharmacological intervention to prevent CSA-AKI. Many perioperative pharmacologic prophylaxis strategies have been introduced, evaluated, and then abandoned [ 103 , 104 ], such as perioperative use of corticosteroids, albumin, erythropoietin, statins, N–acetylcysteine, and sodium bicarbonate and intraoperative or postoperative use of dopamine, anaesthetics (volatile or intravenous), mannitol, furosemide, and fenoldopam [ 12 , 103 ]. It is worth noting that most studies were small, used different inclusion criteria, administered different doses of drugs at different times, investigated different outcomes, and used different criteria to define AKI [ 105 ].…”

1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic Acid Acetoxymethyl Ester Loaded Reactive Oxygen Species Responsive Hyaluronic Acid–Bilirubin Nanoparticles for Acute Kidney Injury Therapy via Alleviating Calcium Overload Mediated Endoplasmic Reticulum Stress

“…Calcium channel blockers (CCBs) are drugs that block calcium channels at the plasma membrane in order to reduce calcium flux into cells. 21 Unfortunately, current CCBs on the market or in development can only limit Ca 2+ influx, making it difficult to reverse the already existing intracellular Ca 2+ overload. 22 Furthermore, CCB use is frequently associated with a variety of side effects such as (1) headache, flushing, palpitations, peripheral edema, and hypotension due to peripheral vascular dilation, (2) negative inotropic effects and supraventricular tachyarrhythmia, (3) gastrointestinal adverse effects, and so on.…”

“…Calcium channel blockers (CCBs) are drugs that block calcium channels at the plasma membrane in order to reduce calcium flux into cells . Unfortunately, current CCBs on the market or in development can only limit Ca 2+ influx, making it difficult to reverse the already existing intracellular Ca 2+ overload .…”

Commentary: Preventing postoperative acute kidney injury starts with identifying actionable intermediates?

“…10 A recent meta-analysis offers some hope. In a metaanalysis of interventions aimed at limiting renal injury in surgical patients, Pathak and colleagues 11 suggested that no single intervention works. Rather, what works is a comprehensive patient assessment and a broad-based intervention approach with both renoprotective and pharmacologic interventions using agents and interventions with some evidence of efficacy in AKI prevention.…”