Efficacy of CytoSorb®: a systematic review and meta-analysis.

INTRODUCTION: Cytokine adsorption using the CytoSorb® adsorber has been proposed in various clinical settings including sepsis, ARDS, hyperinflammatory syndromes, cardiac surgery or recovery after cardiac arrest. The aim of this analysis is to provide evidence for the efficacy of the CytoSorb® adsorber with regard to mortality in various settings. METHODS: We searched PubMed, Cochrane Library database and the database provided by Cytosorbents™ (01.1.2010-29.5.2022). We considered randomized controlled trials and observational studies with control groups. The longest reported mortality was defined as the primary endpoint. We computed risk ratios and 95%-confidence intervals and used DerSimonian and Lairds random effects model. We analysed all studies combined and divided them into the subgroups: sepsis, cardiopulmonary bypass surgery (CPB), other severe illness, SARS-CoV-2 infection and recovery from cardiac arrest. The meta-analysis was registered in advance (PROSPERO: CRD42022290334). RESULTS: Of an initial 1295 publications, 34 studies were found eligible, including 1297 patients treated with CytoSorb® and 1314 controls. Cytosorb® intervention did not lower mortality (RR [95%-CI]: all studies 1.07 [0.88; 1.31], sepsis 0.98 [0.74; 1.31], CPB surgery 0.91 [0.64; 1.29], severe illness 0.95 [0.59; 1.55], SARS-CoV-2 1.58 [0.50; 4.94]). In patients with cardiac arrest, we found a significant survival advantage of the untreated controls (1.22 [1.02; 1.46]). We did not find significant differences in ICU length of stay, lactate levels, or IL-6 levels after treatment. Of the eligible 34 studies only 12 were randomized controlled trials. All observational studies showed moderate to serious risk of bias. INTERPRETATION: To date, there is no evidence for a positive effect of the CytoSorb® adsorber on mortality across a variety of diagnoses that justifies its widespread use in intensive care medicine.

Renal events in patients receiving neprilysin inhibitors: a systematic review and meta-analysis.

BACKGROUND: While it is well known that angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) increase the risk of acute renal failure, the role of neprilysin inhibition (NEPi) is unclear and some physicians are reluctant to prescribe sacubitril/valsartan because of safety concerns. This meta-analysis aimed to examine the risk for renal events, progression of chronic kidney disease (CKD) or progression to dialysis on combined NEPi and ACEi/ARBs compared with ACEi or ARBs. METHODS: We performed a systematic meta-analysis including 17 randomized controlled trials (study drug sacubitril/valsartan or omapatrilat), involving a total of 23 569 patients, after searching PubMed, Cochrane, ClinicalTrials.org and Embase for eligible studies. From the included trials, all renal endpoints, including long- and short-term outcomes and hyperkalemia, were extracted. Pooled odds ratios (ORs) were calculated using the DerSimonian and Laird method. The study was registered at PROSPERO. RESULTS: Overall, treatment with sacubitril/valsartan or omapatrilat showed a slightly lower risk of any renal event [OR 0.82 (0.7-0.97)] compared with treatment with an ACEi or ARB alone. Also, there was a decreased risk of severe acute renal events [OR 0.8 (0.69-0.93)] and a decrease in estimated glomerular filtration rate decline [mean difference -0.58 mL/min (-0.83 to -0.33 mL/min)]. There was no difference in chronic renal events [OR 0.92 (0.8-1.05)] or hyperkalemia [OR 1.02 (0.84-1.23)]. CONCLUSION: NEPi + ACEi/ARBs are safe in terms of renal adverse events. Longer trials focusing on CKD are needed to evaluate the effect of NEPi on decreasing progression of CKD.

Risk of acute kidney injury after contrast-enhanced computerized tomography: a systematic review and meta-analysis of 21 propensity score-matched cohort studies.

OBJECTIVES: Intravenous application of contrast media is part of a wide spectrum of diagnostic procedures for better imaging quality. Clinical avoidance of contrast-enhanced imaging is an ever-present quandary in patients with impaired kidney function. The objective of this study was to estimate the risk for acute kidney injury (AKI), dialysis and mortality among patients undergoing contrast-enhanced CT compared to propensity score-matched controls (i.e. contrast-unenhanced CT). Selected cohort studies featured high-risk patients with advanced kidney disease and critical illness. METHODS: This review was designed to conform to the Preferred Reporting Items in Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed was searched from August 2021 to November 2021 for all-language articles without date restriction. A random-effects model (DerSimonian and Laird method) was used for meta-analysis. RESULTS: Twenty-one articles were included, comprising data of 169,455 patients. The overall risk of AKI was similar in the contrast-enhanced and unenhanced groups (OR: 0.97 [95% CI: 0.85; 1.11], p = 0.64), regardless of baseline renal function and underlying disease. Substantial heterogeneity was detected (I2 = 90%, p ≤ 0.0001). Multivariable logistic regression identified hypertension (p = 0.03) and estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 (p = 0.0001) as factors associated with greater risk of post-contrast AKI. CONCLUSIONS: Based on propensity score-matched pairs obtained from 21 cohort studies, we found no evidence for increased risk for AKI, dialysis or mortality after contrast-enhanced CT among patients with eGFR ≥ 45 mL/min/1.73 m2. In congruence with the emerging evidence in the literature, caution should be exercised in patients with hypertension and eGFR ≤ 30 mL/min/1.73 m2. KEY POINTS: • The application of contrast media for medical imaging is not associated with higher odds for AKI, induction of renal replacement therapy, or mortality. Many comorbidities traditionally associated with greater risk for acute kidney injury do not appear to predispose for renal decline after contrast media exposure. • Underlying hypertension and eGFR less than or equal to 30 mL/min/1.73 m2 seem to predispose for post-contrast acute kidney injury. • Propensity score matching cannot account for unmeasured influences on AKI incidence, which needs to be addressed in the interpretation of results.

Efficacy of pharmacological and interventional treatment for resistant hypertension: a network meta-analysis.

AIMS: Resistant hypertension is associated with a high risk of cardiovascular disease, chronic kidney disease, and mortality. Yet, its management is challenging. This study aims to establish the comparative effectiveness of pharmacologic and interventional treatments by conducting a network meta-analysis. METHODS AND RESULTS: MEDLINE, Cochrane Register of Controlled Trials, and Web of Science Core Collection were systematically searched in March 2022. Randomized controlled trials comparing treatment options for management of resistant hypertension were included. Outcomes were blood pressure (BP) changes, measured in the office and in 24 h ambulatory BP measurement. We applied a frequentist random effects model to perform a network meta-analysis combining placebo medication and sham procedure as the reference comparator. From 4771 records, 24 studies met the inclusion criteria with 3458 included patients in total. Twelve active treatment alternatives [spironolactone, doxazosin, ß-blocker, clonidine, darusentan, guanfacine, various types of renal sympathetic denervation, lifestyle intervention, continuous positive airway pressure, and baroreflex activation therapy (BAT)] were analysed. Among all comparators, spironolactone had the highest ranking probability and was considered the most effective treatment to reduce office systolic blood pressure (sBP) [-13.30 mmHg (-17.89; -8.72); P < 0.0001] and 24 h sBP [-8.46 mmHg (-12.54; -4.38); P < 0.0001] in patients with resistant hypertension. Lifestyle interventions were the most effective non-pharmacological treatment, lowering office sBP by -7.26 mmHg (-13.73; -0.8), whereas BAT lowered office sBP by -7.0 (-18.59; 4.59). Renal denervation lowered office sBP by -5.64 mmHg (-12.95; 1.66) and -3.79 mmHg (-11.39; 3.8) depending on the type of the procedure. CONCLUSION: Among all pharmacologic and interventional treatments, spironolactone is the most effective treatment in reducing BP in patients with resistant hypertension. More comparative trials and especially trials with long-term follow-up are needed. In the meanwhile, we have to conclude that a combination of spironolactone and lifestyle modification are the most effective treatments in resistant hypertension.