Molecular Mechanisms and Novel Therapeutic Approaches to Rhabdomyolysis-Induced Acute Kidney Injury

Panizo, Nayara; Rubio‐Navarro, Alfonso; Amaro-Villalobos, Juan Manuel; Egido, Jesús; Moreno, Juan Antonio

doi:10.1159/000368528

Cited by 154 publications

(175 citation statements)

References 86 publications

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“…Myoglobin has been shown to cause oxidative stress, inflammation, endothelial dysfunction, vasoconstriction and apoptosis [8]. While the chronicity of these changes is not well described in the setting of rhabdomyolysis, inflammation and changes to the immune system have been implicated in HTN [9].…”

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confidence: 99%

Rhabdomyolysis among Critically Ill Combat Casualties: Long-Term Outcomes

Faulk

Walker

Howard³

et al. 2018

Am J Nephrol

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Background: Although rhabdomyolysis has been associated with acute kidney injury and mortality in the short term, the long-term consequences of an episode of rhabdomyolysis remain unknown. We sought to identify the long-term outcomes of rhabdomyolysis, including mortality, renal function, and incidence of hypertension (HTN), among service members initially admitted to the intensive care unit after sustaining a combat injury in Iraq or Afghanistan between February 1, 2002 and February 1, 2011. Methods: Information on age, sex, injury severity score, mechanism of injury, serum creatinine, burn injury, presenting mean arterial pressure, and creatine kinase were retrospectively collected and analyzed for 2,208 patients. Standard descriptive tests were used to compare characteristics of patients with and without rhabdomyolysis. Competing risk Cox proportional hazards models were performed to assess the associated risk of rhabdomyolysis with both HTN and poor renal function. Results: While rhabdomyolysis was associated with HTN on univariate analysis (hazard ratio [HR] 1.30, 95% CI 1.03–1.64; p = 0.029), this difference did not persist on multivariable analysis (HR 1.27, 95% CI 0.99–1.62; p = 0.058). The median estimated glomerular filtration rate (eGFR) was 119 (interquartile range [IQR] 103–128) among those with rhabdomyolysis, compared with 108 (IQR 94–121) in the group without rhabdomyolysis (p < 0.001). Conclusion: After adjustment, patients with rhabdomyolysis were not at an increased risk of HTN compared to patients without rhabdomyolysis. eGFR was paradoxically higher in patients with rhabdomyolysis. There was no association found between rhabdomyolysis and mortality.

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confidence: 99%

Rhabdomyolysis among Critically Ill Combat Casualties: Long-Term Outcomes

Faulk

Walker

Howard³

et al. 2018

Am J Nephrol

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“…Mild AKI is a precursor of chronic kidney disease (CKD), and there is an increased risk of end-stage renal disease (ESRD) in patients with severe AKI (8,11,12,15,62,67). Oxidative stress has been implicated as one of the principal drivers of renal injury and pathophysiology in all of the common causes of AKI (4,25,34,44,45,50). It occurs when the intrinsic antioxidant systems are unable to counteract the effects of excessive production of reactive oxygen species (ROS) and reactive carbonyl species (RCS), which can cause cellular damage via chemical modification to proteins, lipids, and nucleic acids (18,49,58).…”

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confidence: 99%

Pyridoxamine reduces postinjury fibrosis and improves functional recovery after acute kidney injury

Skrypnyk

Voziyan

Yang

et al. 2016

American Journal of Physiology-Renal Physiology

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Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that antioxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Because oxidative stress is implicated as one of the main drivers of renal injury after AKI, the ability of PM to interfere with multiple aspects of oxidative damage may be favorable for AKI treatment. In these studies we therefore evaluated PM treatment in a mouse model of AKI. Pretreatment with PM caused a dose-dependent reduction in acute tubular injury, long-term postinjury fibrosis, as well as improved functional recovery after ischemia-reperfusion AKI (IR-AKI). This was associated with a dose-dependent reduction in the oxidative stress marker isofuran-to-F2-isoprostane ratio, indicating that PM reduces renal oxidative damage post-AKI. PM also reduced postinjury fibrosis when administered 24 h after the initiating injury, but this was not associated with improvement in functional recovery after IR-AKI. This is the first report showing that treatment with PM reduces short- and long-term injury, fibrosis, and renal functional recovery after IR-AKI. These preclinical findings suggest that PM, which has a favorable clinical safety profile, holds therapeutic promise for AKI and, most importantly, for prevention of adverse long-term outcomes after AKI.

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“…To avoid volume overload, an alternate 500 ml of sterile saline solution with 500 ml of 5% glucose solution is recommended, adding 50 mmol of sodium bicarbonate for each subsequent 2-3 liter of solution (usually 20-300 mmol on the first day). The goal is to maintain the urine pH above 6.5 and plasma pH below 7.50 [5].If refractory hypercalcemia, metabolic acidosis, or refractory oligoanuria is present, renal replacement therapy is required [10].…”

Section: Discussionmentioning

confidence: 99%