Long-Term Preoperative Atorvastatin or Rosuvastatin Use in Adult Patients before CABG Does Not Increase Incidence of Postoperative Acute Kidney Injury: A Propensity Score-Matched Analysis

Shvartz, Vladimir A.; Khugaeva, Eleonora; Kryukov, Yu.Yu.; Sokolskaya, Maria; Ispiryan, Artak; Shvartz, Elena; Petrosyan, Andrey; Dorokhina, Elizaveta; Bockeriа, L.A.; Bockeria, O.L.

doi:10.3390/pathophysiology29030027

Cited by 3 publications

(1 citation statement)

References 56 publications

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“…As a result, statins have been proposed as a potential modulator of clinical outcomes after surgery 8 . In particular, some observational studies suggested that statins may be associated with a reduced risk of acute kidney injury (AKI) after cardiac surgery 9 , although this has not been a consistent finding 10,11 . Any effect on postoperative AKI is relevant as this complication affects as many as 25-30% of patients after cardiac surgery 12,13 and is associated with longer hospital stay and increased risk of mortality [14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

Mechanisms and Predictors of Acute Kidney Injury with Perioperative Rosuvastatin in Patients Undergoing Cardiac Surgery

Wijesurendra

Sardell

Jayaram

et al. 2023

Preprint

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Background In patients undergoing cardiac surgery perioperative statin therapy has been associated with an unexpected increase in postoperative plasma creatinine. Here we investigated mechanisms and predictors of acute kidney injury (AKI) in 1922 patients enrolled in the Statin Therapy in Cardiac Surgery (STICS) randomized placebo-controlled trial of perioperative rosuvastatin (20 mg once daily). Methods AKI was defined according to international guidelines (KDIGO) using plasma creatinine, and also by cystatin C. Potentially mechanistically relevant plasma/serum biomarkers of muscle injury, inflammation, and kidney injury were investigated, including total creatine kinase (CK), growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), procalcitonin (PCT), placental growth factor (PLGF), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL). Results At 48 hours post-surgery, the incidence of AKI was greater in the rosuvastatin group than in the placebo group when defined by a rise in creatinine (24.7% vs 19.3%, p=0.005) or cystatin C (9.2% vs 5.1%, p<0.001); the majority of AKI was stage 1 in severity (87% when defined by creatinine, and 80% when defined by cystatin C). Compared with placebo, rosuvastatin led to higher postoperative serum levels of KIM-1 (278+/-5 pg/ml versus 259+/-5 pg/ml, P=0.01), and to more frequent elevations in CK to >10x and >40x the baseline level (30.9% versus 26.5%, p=0.032, and 2.1% versus 0.7%, p=0.016, respectively), whereas postoperative concentrations of GDF-15, IL-6, PCT, PLGF, and NGAL were similar between groups. In multivariable analyses, insulin treatment, baseline KIM-1, combined coronary artery bypass grafting (CABG) and aortic valve replacement (AVR) surgery, and allocation to rosuvastatin were all independently associated with AKI as defined by creatinine or cystatin C. Odds ratios for rosuvastatin compared to placebo for both creatinine- and cystatin C-defined AKI were not materially altered by further adjustment for post-randomization increases in CK. Conclusions Perioperative rosuvastatin initiation increased the absolute risk of AKI after cardiac surgery by 4-5%, whether defined by creatinine or cystatin C, and led to higher post-operative KIM-1, suggesting a deleterious effect on renal function, possibly mediated by proximal tubular injury. Insulin treatment, baseline KIM-1, combined CABG/AVR surgery, and allocation to rosuvastatin were all independently associated with AKI by any definition.

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Section: Introductionmentioning

confidence: 99%

Mechanisms and Predictors of Acute Kidney Injury with Perioperative Rosuvastatin in Patients Undergoing Cardiac Surgery

Wijesurendra

Sardell

Jayaram

et al. 2023

Preprint

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Effect of preoperative moderate-dose statin and duration on acute kidney injury after cardiac surgery: a retrospective cohort study

Jiang,

Liu,

Cheng

et al. 2023

Current Medical Research and Opinion

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High-Density Lipoprotein Anti-Inflammatory Capacity and Acute Kidney Injury After Cardiac and Vascular Surgery: A Prospective Observational Study

Perkins,

Smith,

Yancey

et al. 2024

Critical Care Medicine

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Objectives: Acute kidney injury (AKI) predicts death after cardiac and vascular surgery. Higher preoperative high-density lipoprotein (HDL) concentrations are associated with less postoperative AKI. In animals, HDL's anti-inflammatory capacity to suppress endothelial cell adhesion molecule expression reduces kidney damage due to ischemia and hemorrhagic shock. The objective of this study is to evaluate the statistical relationship between HDL anti-inflammatory capacity and AKI after major cardiac and vascular surgery. Design: Prospective observational study. Setting: Quaternary medical center. Patients: One hundred adults with chronic kidney disease on long-term statin therapy undergoing major elective cardiac and vascular surgery. Interventions: None. Measurements and Main results: Apolipoprotein B-depleted serum collected at anesthetic induction was incubated with tumor necrosis factor alpha stimulated human endothelial cells. Reverse transcriptase-polymerase chain reaction was used to measure intercellular adhesion molecule-1 (ICAM-1) messenger RNA. Enzyme-linked immunosorbent assay assays were used to measure apolipoprotein A-I and postoperative soluble ICAM-1 concentrations in patient plasma. HDL concentration did not correlate with HDL ICAM-1 suppression capacity (Spearman R = 0.05; p = 0.64). Twelve patients (12%) were found to have dysfunctional, pro-inflammatory HDL. Patients with pro-inflammatory HDL had a higher rate of postoperative AKI than patients with anti-inflammatory HDL (p = 0.046). After adjustment for AKI risk factors, a higher preoperative HDL capacity to suppress endothelial ICAM-1 was independently associated with lower odds of AKI (odds ratio, 0.88; 95% CI, 0.80–0.98; p = 0.016). The association between HDL anti-inflammatory capacity and postoperative AKI was independent of HDL concentration (p = 0.018). Further, a higher long-term statin dose was associated with higher HDL capacity to suppress endothelial ICAM-1 (p = 0.045). Conclusions: Patients with chronic kidney disease undergoing cardiac and vascular surgery who have dysfunctional, pro-inflammatory HDL have a higher risk of postoperative AKI compared with patients with anti-inflammatory HDL. Conversely, a higher HDL anti-inflammatory capacity is associated with a lower risk of postoperative AKI, independent of HDL concentration. Higher long-term statin dose is associated with higher HDL anti-inflammatory capacity.

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Long-Term Preoperative Atorvastatin or Rosuvastatin Use in Adult Patients before CABG Does Not Increase Incidence of Postoperative Acute Kidney Injury: A Propensity Score-Matched Analysis

Cited by 3 publications

References 56 publications

Mechanisms and Predictors of Acute Kidney Injury with Perioperative Rosuvastatin in Patients Undergoing Cardiac Surgery

Mechanisms and Predictors of Acute Kidney Injury with Perioperative Rosuvastatin in Patients Undergoing Cardiac Surgery

Effect of preoperative moderate-dose statin and duration on acute kidney injury after cardiac surgery: a retrospective cohort study

High-Density Lipoprotein Anti-Inflammatory Capacity and Acute Kidney Injury After Cardiac and Vascular Surgery: A Prospective Observational Study

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