Statin-Associated Necrotizing Myopathy Leading to Acute Kidney Injury: A Case Report

Statins or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are a mainstay of cardiovascular disease therapy. In addition to their lipid-lowering capabilities, they exhibit several pleiotropic effects. Their adverse reactions such as myalgias are not uncommon, but in rare cases, the resulting rhabdomyolysis can be fatal. Recently, more insight has been brought into the pathogenesis of statin-induced rhabdomyolysis, and immune-mediated necrotizing myopathies are diagnosed more frequently. We present a case of a female patient who was on chronic rosuvastatin therapy and developed necrotizing myopathy. The disease progressed to acute kidney and liver injury. We discontinued the drug, started supportive measures, and initiated renal replacement therapy with a high cutoff dialysis membrane once. Her recovery was prompt, with a normal control electromyography 2 weeks after discharge.

Download Full-text

Statins and Inflammation in Cardiovascular Disease

Current Pharmaceutical Design ◽

10.2174/1381612823666171009141201 ◽

2018 ◽

Vol 23 (46) ◽

pp. 7027-7039 ◽

Cited By ~ 7

Author(s):

Georgia Vogiatzi ◽

Evangelos Oikonomou ◽

Gerasimos Siasos ◽

Sotiris Tsalamandris ◽

Alexandros Briasoulis ◽

...

Keyword(s):

Cardiovascular Disease ◽

Lipid Lowering ◽

Hmg Coa Reductase ◽

Ample Evidence ◽

Reductase Inhibitors ◽

Immune System Activation ◽

Hmg Coa Reductase Inhibitors ◽

Anti Inflammatory ◽

Artery Disease ◽

Coa Reductase

Background: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. Objective: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. Methods: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. Results: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert antiatherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. Conclusion: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

Download Full-text

Comparison of Effects of Different Statins on Contrast-Induced Acute Kidney Injury in Rats: Histopathological and Biochemical Findings

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/6282486 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Xiao-lei Wang ◽

Tuo Zhang ◽

Liu-hua Hu ◽

Shi-qun Sun ◽

Wei-feng Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Kidney Injury ◽

Lipid Lowering ◽

Control Group ◽

Sprague Dawley ◽

Atorvastatin Group ◽

New Strategy ◽

Ameliorative Effect ◽

Markers Of Oxidative Stress

Statins are a promising new strategy to prevent contrast-induced acute kidney injury (CI-AKI). In this study we compared the ameliorative effect of different statins in a rat model of CI-AKI. Sprague-Dawley rats were divided into five groups: control group; CI-AKI group; CI-AKI + rosuvastatin group (10 mg/kg/day); CI-AKI + simvastatin group (80 mg/kg/day); and CI-AKI + atorvastatin group (20 mg/kg/day). CI-AKI was induced by dehydration for 72 hours, followed by furosemide intramuscular injection 20 minutes before low-osmolar contrast media (CM) intravenous injection. Statins were administered by oral gavage once daily for 3 consecutive days before CM injection and once 4 hours after CM injection. Rats were sacrificed 24 hours after CM injection, and renal function, kidney histopathology, nitric oxide (NO) metabolites, and markers of oxidative stress, inflammation, and apoptosis were evaluated. The results showed that atorvastatin and rosuvastatin but not simvastatin ameliorated CM-induced serum creatinine elevation and histopathological alterations. Atorvastatin and rosuvastatin showed similar effectiveness against CM-induced oxidative stress, but simvastatin was less effective. Atorvastatin was most effective against NO system dysfunction and cell apoptosis, whereas rosuvastatin was most effective against inflammation. Our findings indicate that statins exhibit differential effects in preventing CI-AKI when given at equivalent lipid-lowering doses.

Download Full-text

MO388DEVELOPMENT OF ACUTE KIDNEY INJURY DURING A RHABDOMYOLYSIS EPISODE: DIFFERENCES IN LONG-TERM KIDNEY FUNCTION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab082.0042 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Sara Núñez Delgado ◽

Miren Iriarte-Abril ◽

Júlia Farrera-Núñez ◽

Sergi Pascual-Sánchez ◽

Laia Sans-Atxer ◽

...

Keyword(s):

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Renal Function ◽

Kidney Function ◽

Kidney Injury ◽

Inpatient Mortality ◽

Short Term ◽

Worse Prognosis

Abstract Background and Aims Acute renal failure (AKI) associated to rhabdomyolysis conditions a worse prognosis in short-term, its implication in the long-term renal function has been less evaluated. Method Retrospective analysis of patients diagnosed with rhabdomyolysis defined by creatinine kinase > 5000 IU/L between 2015-2019. Basal and 12-month renal function was evaluated. AKI was classified as either non-severe (AKI-KDIGO 1/2) or severe (AKI-KDIGO 3). Results Eighty-seven patients were included, 25 (28.74%) had some degree of chronic kidney disease (CKD) on admission. 56 (64.37%) had AKI on admission, 17 of which were severe (6 required hemodialysis). The patients with AKI had more cardiovascular disease (CVD) and worse analytical parameters on admission (table). Patients with severe AKI showed no difference in CVD from those with non-severe AKI but were younger and had more hyperkalemia. There were no significant differences between patients with severe AKI who required hemodialysis and those who did not. Inpatient mortality was 8%, higher in patients with AKI but without differences according to severity. In 45 patients kidney function was available 12 months after the episode, loss of eGF was -4.90 ± 14.35 ml/min-1.73m2 (p=0.007). There was no difference between patients who developed AKI and those who did not (-4.10 ± 14.4 vs. -5.39 ± 14.57 ml/min-1.73m2; p=0.67), nor between non-severe and severe AKI (-5.50 ± 14.76 vs. -5.12 ± 15.08ml/min-1.73m2; p=0.98). Of the 33 patients without previous CKD, 5 developed CKD, with greater decrease in eGF than those who did not (-22.69 ± 6.04 vs. -2.63 ± 13.92 ml/min-1.73m2; p=0.003). Female sex (60% vs. 12%; p=0.031) and previous basal eGF (72.22 ± 4.37 vs. 95.6±19.97 ml/min-1.72m2; p=0.016) were related to this deterioration. Conclusion After an episode of rhabdomyolysis, the loss of eGF is similar in patients who develop AKI compared to those who do not.

Download Full-text

Significance of Crescentic Glomeruli in Acute Kidney Injury with Rheumatoid Arthritis

Case Reports in Nephrology and Dialysis ◽

10.1159/000500105 ◽

2019 ◽

Vol 9 (1) ◽

pp. 42-48

Author(s):

Ali Ayaash ◽

Dipesh Maan ◽

Anastasios Kapetanos ◽

Mark Bunker ◽

Mary Chester Wasko ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Acute Kidney Injury ◽

Kidney Injury ◽

Renal Outcome ◽

Primary Role ◽

Tubular Necrosis ◽

Immune Mediated ◽

Autoimmune Conditions ◽

Spontaneous Improvement

Crescentic glomerulonephritis (GN) without immune reactants or deposits (referred to as pauci-immune) is typically characterized by the presence of anti-neutrophilic cytoplasmic antibodies (ANCA). While ANCA-negative patients might be expected to have a more benign course, they often have poor renal outcomes, especially without treatment with steroids and immune-modulating therapy. Pauci-immune crescentic GN can also co-exist with other autoimmune conditions, including rheumatoid arthritis (RA). Here, we describe an ANCA-negative patient with RA who developed dialysis-requiring acute kidney injury (AKI) with findings consistent with focal pauci-immune crescentic GN (i.e., no IgG or immune complex on kidney biopsy). Coexistent conditions included Klebsiella sepsis attributed to pneumonia, rhabdomyolysis, leukocytoclastic immune-mediated skin vasculitis, and positive ANA. He had spontaneous improvement in renal function without immunosuppressive therapy. This crescentic GN was not associated with poor renal outcome as AKI resolved with supportive care and treatment of his infection. The AKI was likely multifactorial with co-existing acute tubular necrosis in the setting of Kebsiella sepsis and rhabdomyolysis, and the crescentic GN was felt more likely to be related to the infection rather than having a primary role. This case highlights the importance of viewing crescentic GN in the context of the clinical picture, as it may not always lead to the need of aggressive immune suppression and is not a universally poor prognostic kidney finding. However, these cases do warrant close follow-up as our patient had recurrent RA disease manifestations over the next 2 years that eventually led to his death from severe pulmonary hypertension.

Download Full-text

Specific diseases: renal disease

ESC CardioMed ◽

10.1093/med/9780198784906.003.0643 ◽

2018 ◽

pp. 2670-2673

Author(s):

Susanna Price

Keyword(s):

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Risk Factor ◽

Kidney Disease ◽

Renal Disease ◽

Independent Risk Factor ◽

Hospital Admissions ◽

Kidney Injury ◽

Potential Methods

Chronic kidney disease is a global health burden, with an estimated prevalence of 11–13%, with the majority of patients diagnosed as stage 3, and is an independent risk factor for cardiovascular disease. The incidence of acute kidney injury is increasing, and estimated to be present in one in five acute hospital admissions, and there is a bidirectional relationship between acute and chronic kidney disease. The relevance to the patient with cardiovascular disease relates to increased perioperative risk, as reduced kidney function is an independent risk factor for adverse postoperative cardiovascular outcomes including myocardial infarction, stroke, and progression of heart failure. Furthermore, patients undergoing cardiovascular investigations are at risk of developing acute kidney injury, in particular where iodinated contrast is administered. This chapter reviews the classification of renal disease and its impact on cardiovascular disease, as well as potential methods for reducing the development of contrast-induced acute kidney injury.

Download Full-text

Acute kidney injury as the presenting complaint of ceftazidime-induced immune-mediated haemolysis

BMJ Case Reports ◽

10.1136/bcr-2019-232884 ◽

2019 ◽

Vol 12 (11) ◽

pp. e232884 ◽

Cited By ~ 2

Author(s):

Ashley Ferro ◽

Meryl Griffiths ◽

Rona Smith ◽

Andrew Fry

Keyword(s):

Cystic Fibrosis ◽

Acute Kidney Injury ◽

Renal Function ◽

Kidney Injury ◽

Generation Cephalosporin ◽

Third Generation ◽

Tubular Necrosis ◽

Immune Mediated ◽

Cystic Fibrosis Centre ◽

Third Generation Cephalosporins

We present the case of ceftazidime-induced immune-mediated haemolysis with associated acute kidney injury in a 43-year-old woman. The patient initially presented to the regional cystic fibrosis centre for treatment of an infective exacerbation of cystic fibrosis. After initiation of ceftazidime (a third-generation cephalosporin), renal function rapidly deteriorated and a fall in haemoglobin was noted. On transfer to our care, a haemolysis screen identified immune-mediated haemolysis, and renal biopsy confirmed the finding of acute tubular necrosis secondary to haem pigment. The patient’s renal function deteriorated such that she required haemodialysis, although she subsequently recovered and is now dialysis-independent. Although acute haemolytic reactions are recognised with third-generation cephalosporins, this is the first reported case of ceftazidime-induced immune-mediated haemolysis with acute kidney injury. Given the increased frequency of cephalosporin usage, it is important for both nephrologists and general physicians to be aware of this rare but very serious complication.

Download Full-text

HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after surgical procedures requiring cardiac bypass

Journal of Perioperative Practice ◽

10.1177/1750458918777457 ◽

2018 ◽

Vol 28 (6) ◽

pp. 142-143 ◽

Cited By ~ 1

Author(s):

Jill Campbell

Keyword(s):

Acute Kidney Injury ◽

Surgical Procedures ◽

Kidney Injury ◽

Hmg Coa Reductase ◽

Reductase Inhibitors ◽

Cardiac Bypass ◽

Hmg Coa Reductase Inhibitors ◽

Coa Reductase

Download Full-text

Acute interstitial nephritis with immunotherapy; a growing entity?

Journal of Renal Injury Prevention ◽

10.34172/jrip.2020.35 ◽

2020 ◽

Vol 9 (4) ◽

pp. e35-e35

Author(s):

John David Chetwood ◽

Lin Lin Myat ◽

Helen Lammi ◽

Mani Panat ◽

James Hughes

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Interstitial Nephritis ◽

Cancer Survival ◽

Kidney Injury ◽

Acute Interstitial Nephritis ◽

Response To Treatment ◽

Immune Mediated ◽

Life Threatening ◽

Potential Impact

We report a case of acute kidney injury (AKI) secondary to immune-mediated acute interstitial nephritis (AIN), with supporting diagnostic results and a successful response to treatment. This entity is gaining increasing recognition with the burgeoning use of immunotherapy agents in oncology. The timeline for the development of AIN from the initiation of immunotherapy varies, and may range in severity from asymptomatic to severe, organ-threatening and with life threatening consequences. Renal biopsy should be performed to confirm the diagnosis due to the potential impact of discontinuation of immunotherapy on cancer survival. Re-challenge with immunotherapy is reasonable once renal function recovers.

Download Full-text

Complement Inhibition in Severe COVID-19 Acute Respiratory Distress Syndrome

Frontiers in Pediatrics ◽

10.3389/fped.2020.616731 ◽

2020 ◽

Vol 8 ◽

Author(s):

Sharmila Raghunandan ◽

Cassandra D. Josephson ◽

Hans Verkerke ◽

W. Matthew Linam ◽

Treva C. Ingram ◽

...

Keyword(s):

Acute Kidney Injury ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Kidney Injury ◽

Complement Inhibition ◽

Immune Mediated ◽

Detailed Evaluation

Most children with COVID-19 have asymptomatic or mild illness. Those who become critically ill suffer from acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). The rapid deterioration of lung function has been linked to microangiopathic and immune-mediated processes seen in the lungs of adult patients with COVID-19. The role of complement-mediated acute lung injury is supported by animal models of SARS-CoV, evaluation of lung tissue in those who died from COVID-19 and response of COVID-19 ARDS to complement inhibition. We present a summary of a child with COVID-19 disease treated with convalescent plasma and eculizumab and provide a detailed evaluation of the inflammatory pathways.

Download Full-text