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Pharmacological interventions for the prevention of renal injury in surgical patients: a systematic literature review and meta-analysis.
Pathak, S, Olivieri, G, Mohamed, W, Abbasciano, R, Roman, M, Tomassini, S, Lai, F, Wozniak, M, Murphy, GJ
British journal of anaesthesia. 2021;(1):131-138
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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; n=2207) 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; n=2941) 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; n=1047) 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.
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Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury.
Zhao, M, Sun, S, Huang, Z, Wang, T, Tang, H
Clinical journal of the American Society of Nephrology : CJASN. 2020;(1):70-78
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Abstract
BACKGROUND AND OBJECTIVES Little is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials. RESULTS In the 18 trials with a total of 2051 AKI events (range: 1-300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis. CONCLUSIONS Current evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.
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Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis.
Manohar, S, Kompotiatis, P, Thongprayoon, C, Cheungpasitporn, W, Herrmann, J, Herrmann, SM
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;(1):108-117
Abstract
BACKGROUND The aim of this meta-analysis was to assess the risks and incidence of nephrotoxicity and electrolyte abnormalities in patients receiving programmed cell death protein 1 (PD-1) inhibitors. METHODS We conducted a meta-analysis of clinical trials that monitored electrolyte levels and kidney functions during treatment with nivolumab or pembrolizumab by searching MEDLINE, EMBASE and the Cochrane Database from inception through April 2017. Our protocol is registered with International Prospective Register of Systematic Reviews; no.CRD42017060579. RESULTS A total of 48 clinical trials with a total of 11 482 patients were included. The overall pooled risk ratios (RR) of all acute kidney injury (AKI) and all electrolyte abnormalities in patients treated with PD-1 inhibitors were 1.86 [95% confidence interval (CI) 0.95-3.64] and 1.67 (95% CI 0.89-3.12), respectively. Compared with non-nephrotoxic controls, the pooled RR of AKI in patients treated with PD-1 inhibitors was 4.19 (95% CI 1.57-11.18). Prespecified subgroup analyses demonstrated a significant association between PD-1 inhibitors and hypocalcemia with a pooled RR of 10.87 (95% CI 1.40-84.16). The pooled estimated incidence rates of AKI and hypocalcemia in patients treated with PD-1 inhibitors were 2.2% (95% CI 1.5-3.0%) and 1.0% (95% CI 0.6-1.8%), respectively. Among patients who developed AKI with PD-1 inhibitors, the pooled estimated rate of interstitial nephritis was 16.6% (95% CI 10.2-26.0%). CONCLUSIONS Treatment with PD-1 inhibitors is associated with a higher risk of AKI compared with non-nephrotoxic agents. It will be important to characterize the AKI patients to better understand the etiology behind the event. In addition, treatment with PD-1 inhibitors is associated with an increased risk of hypocalcemia. This study highlights a rare but serious adverse event of anti-PD-1 antibodies and we recommend, in addition to electrolytes panel, routine calcium monitoring.
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Prevention of Cisplatin-Induced Acute Kidney Injury: A Systematic Review and Meta-Analysis.
Hamroun, A, Lenain, R, Bigna, JJ, Speyer, E, Bui, L, Chamley, P, Pottier, N, Cauffiez, C, Dewaeles, E, Dhalluin, X, et al
Drugs. 2019;(14):1567-1582
Abstract
PURPOSE Cisplatin-induced acute kidney injury (CIA) is a serious adverse event that affects 20-40% of exposed patients, despite any implemented precaution to avoid it. The aim of this work was therefore to identify a relevant nephroprotective method for CIA. METHODS We searched Pubmed, Embase, and Web of Science from 1 January 1978 to 1 June 2018, without language restriction. All studies (observational and interventional) assessing a CIA prevention method for adults receiving at least one course of cisplatin were eligible. The primary outcome was acute nephrotoxicity, as defined by the AKI-KDIGO classification (2012). The odds ratio and corresponding 95% confidence interval were used to assess the associations. We used narrative synthesis in case of heterogeneity regarding intervention, population, or outcome. When possible, a random-effects model was used to pool studies. The heterogeneity between studies was quantified (I2), and multiple meta-regressions were carried out to identify potential confounders. RESULTS Within 4520 eligible studies, 51 articles fulfilling the selection criteria were included in the review, assessing 21 different prevention methods. A meta-analysis could only be performed on the 15 observational studies concerning magnesium supplementation (1841 patients), and showed a significant nephroprotective effect for all combined grades of CIA (OR 0.24, [0.19-0.32], I2 = 0.0%). This significant nephroprotective effect was also observed for grades 2 and 3 CIA (OR 0.22, [0.14-0.33], I2 = 0.0% and OR 0.25, [0.08-0.76], I2 = 0.0%, respectively). CONCLUSION While no method of prevention had so far demonstrated its indisputable efficacy, our results highlight the potential protective effect of magnesium supplementation on cisplatin-induced acute nephrotoxicity. TRIAL REGISTRATION This study is registered in PROSPERO, CRD42018090612.
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Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis.
Donnan, JR, Grandy, CA, Chibrikov, E, Marra, CA, Aubrey-Bassler, K, Johnston, K, Swab, M, Hache, J, Curnew, D, Nguyen, H, et al
BMJ open. 2019;(1):e022577
Abstract
OBJECTIVE To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies. DESIGN We conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs). INTERVENTION SGLT2 inhibitors, compared with placebo or active comparators. PRIMARY OUTCOMES Acute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations. RESULTS We screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I2=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I2=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I2=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I2=1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup analysis did show an increased risk of UTI with dapagliflozin only (RR 1.21; 95% CI 1.02 to 1.43, I2=0.0%), but no other analysis supported an increased risk of AKI, DKA, UTI or fracture. CONCLUSIONS Current evidence from RCTs does not suggest an increased risk of harm with SGLT2 inhibitors as a class over placebo or active comparators with respect to AKI, DKA, UTI or fracture. However, wide CIs for many comparisons suggest limited precision, and therefore clinically important adverse events cannot be ruled out. Dapagliflozin, appears to independently increase the risk of UTI, although the mechanism for this intraclass variation in risk is unclear. PROSPERO REGISTRATION NUMBER CRD42016038715.
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Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis.
Menne, J, Dumann, E, Haller, H, Schmidt, BMW
PLoS medicine. 2019;(12):e1002983
Abstract
BACKGROUND Sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent a new class of oral hypoglycemic agents used in the treatment of type 2 diabetes mellitus. They have a positive effect on the progression of chronic kidney disease, but there is a concern that they might cause acute kidney injury (AKI). METHODS AND FINDINGS We conducted a systematic review and meta-analysis of the effect of SGLT2is on renal adverse events (AEs) in randomized controlled trials and controlled observational studies. PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov were searched without date restriction until 27 September 2019. Data extraction was performed using a standardized data form, and any discrepancies were resolved by consensus. One hundred and twelve randomized trials (n = 96,722) and 4 observational studies with 5 cohorts (n = 83,934) with a minimum follow-up of 12 weeks that provided information on at least 1 adverse renal outcome (AKI, combined renal AE, or hypovolemia-related events) were included. In 30 trials, 410 serious AEs due to AKI were reported. SGLT2is reduced the odds of suffering AKI by 36% (odds ratio [OR] 0.64 [95% confidence interval (CI) 0.53-0.78], p < 0.001). A total of 1,089 AKI events of any severity (AEs and serious AEs [SAEs]) were published in 41 trials (OR 0.75 [95% CI 0.66-0.84], p < 0.001). Empagliflozin, dapagliflozin, and canagliflozin had a comparable benefit on the SAE and AE rate. AEs related to hypovolemia were more commonly reported in SGLT2i-treated patients (OR 1.20 [95% CI 1.10-1.31], p < 0.001). In the observational studies, 777 AKI events were reported. The odds of suffering AKI were reduced in patients receiving SGLT2is (OR 0.40 [95% CI 0.33-0.48], p < 0.001). Limitations of this study are the reliance on nonadjudicated safety endpoints, discrepant inclusion criteria and baseline hypoglycemic therapy between studies, inconsistent definitions of renal AEs and hypovolemia, varying follow-up times in different studies, and a lack of information on the severity of AKI (stages I-III). CONCLUSIONS SGLT2is reduced the odds of suffering AKI with and without hospitalization in randomized trials and the real-world setting, despite the fact that more AEs related to hypovolemia are reported.
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Could platelet-to-lymphocyte ratio be a predictor for contrast-induced nephropathy in patients with acute coronary syndrome?: A systematic review and meta-analysis.
Jiang, J, Ji, HY, Xie, WM, Ran, LS, Chen, YS, Zhang, CT, Quan, XQ
Medicine. 2019;(32):e16801
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Abstract
BACKGROUND Contrast-induced nephropathy (CIN) is acute renal failure observed after administration of iodinated contrast media during angiographic or other medical procedures. In recent years, many studies have focused on biomarkers that recognize CIN and/or predict its development in advance. One of the many biomarkers studied is the platelet-to-lymphocyte ratio (PLR). We performed a systematic review and meta-analysis to evaluate the correlation between PLR level and CIN. METHODS Relevant studies were searched in PUBMED, EMBASE, and Web of Science until September 15, 2018. Case-control studies reporting admission PLR levels in CIN and non-CIN group in patients with acute coronary syndrome (ACS) were included. The pooled weighted mean difference (WMD) and 95% confidence intervals (95%CI) were calculated to assess the association between PLR level and CIN using a random-effect model. RESULTS Six relevant studies involving a total of 10452 ACS patients (9720 non-CIN controls and 732 CIN patients) met our inclusion criteria. A meta-analysis of 6 case-control studies showed that PLR levels were significantly higher in CIN group than those in non-CIN group (WMD = 33.343, 95%CI = 18.863 to 47.823, P < .001, I = 88.0%). CONCLUSION For patients with ACS after contrast administration, our meta-analysis shows that on-admission PLR levels in CIN group are significantly higher than those of non-CIN group. However, large and matched cohort studies are needed to validate these findings and assess whether there is a real connection or just an association.
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N-Acetylcysteine for Preventing of Acute Kidney Injury in Chronic Kidney Disease Patients Undergoing Cardiac Surgery: A Metaanalysis.
He, G, Li, Q, Li, W, Wang, L, Yang, J, Zeng, F
The heart surgery forum. 2018;(6):E513-E521
Abstract
OBJECTIVE The aim of this study was to determine whether N-acetylcysteine (NAC) has an effect on acute kidney injury (AKI) in chronic kidney disease patients undergoing cardiac surgery. METHODS We reviewed literature through PubMed, Medline through PubMed and OVID, The Cochrane Library, Wan Fang Database, China Biology Medicine Database, Chinese Periodical Database, China Knowledge Resource Integrated Database, and Chinese Clinical Trial Registry (1980 to July 10, 2018). Two investigators independently collected the data and assessed the quality of each study. RevMan 5.3 was used for the present metaanalysis. RESULTS A total of 5 RCTs (N = 678 participants) were included in the primary analysis. Pooled analysis showed that intravenous infusion of NAC significantly reduced the incidence of AKI (RR = 0.77, 95% = 0.63 to 0.94, P < .01) and that NAC could decrease the adverse cardiac events (RR = 0.83, 95% = 0.70 to 0.97, P < .05), but that it may increase the length of stay in the ICU (mean difference [MD] = 2.1, 95% CI = 1.61 to 2.60, P < .01). There were no statistically significant differences between the 2 groups in the requirement for renal replacement therapy(RRT) (RR = 1.33, 95% = 0.63 to 2.81, P = .45) and all-cause mortality (RR = 0.51, 95% = 0.25 to 1.06, P = .07). CONCLUSION Our study shows that intravenous infusion of NAC could prevent postoperative AKI in preexisting-renal-failure patients undergoing cardiac surgery.