Acute Kidney Injury due to Rhabdomyolysis in H1N1 Influenza Infection

Abstract

Acute kidney injury (AKI) is rarely reported in the clinical course of H1N1 infection and this condition is strongly related with increasing of mortality risk. However, there are no sufficient data about the development of AKI due to H1N1 infections. The recent reports were documented for elevation of creatinine phosphokinase levels in the course of influenza infection, but rhabdomyolysis was rarely reported. Herein, we present a 28-year-old female patient and a 19-year-old male patient with AKI in the course of H1N1 influenza infection due to rhabdomyolysis.

• H1N1 infection
• acute kidney injury
• rhabdomyolysis
• creatinine phosphokinase
• pneumonia

INTRODUCTION

The common complications of H1N1 infection are lung injury and acute respiratory distress.¹ The incidence of acute kidney injury (AKI) in the course of H1N1 infection was reported notably high in recent studies and this condition is strongly related with increasing risk of mortality.^1–3 However, the etiology of renal failure is not well described. Mild creatinine phosphokinase (CPK) elevation and incidental cases of rhabdomyolysis were reported in the course of H1N1 infection.¹ However, many clinicians and researchers overlook this circumstance in general practice. Herein, we report two consecutive patients with AKI due to rhabdomyolysis.

CASE 1

A 28-year-old female patient was diagnosed with membrane-proliferative glomerulonephritis 2 months ago and subsequently received cyclosporine and steroid therapy. One month after administration of treatment, there were no abnormalities on physical and laboratory examination except proteinuria. After a few days she complained of general fatigue, cough, chest pain, and fever (42°C). Her lung examination revealed a few faint crackles at both lung bases. Mild tachypnea and tachycardia were observed (respiratory rate 40 per min, heart rate 165 beats/min). A chest radiograph showed bilateral pulmonary infiltrates. A nasal swab tested with real-time reverse transcription polymerase chain reaction (rRT-PCR) was positive for H1N1 infection. The second day, severe myalgia and weakness developed. In her laboratory examination, serum creatinine was 4.2 mg/dL (normal: 0.84–1.25), urea 94 mg/dL (normal: 17–43 mg/dL), CPK 1371 U/L (normal: 43–156 U/L), aspartate amino transferase (AST) 86 U/L, and alanine amino transferase (ALT) 38 U/L. There was no definitive etiologic condition to lead to rhabdomyolysis in history or medication of patient. Urine was reddish and reactive strip analysis showed positive for hematuria with no cells on sediment. The patient's respiratory status worsened, and the diagnosis of AKI due to rhabdomyolysis was established. The patient's respiratory status worsened and she required supplemental oxygen for hypoxia. Oseltamivir (75 mg orally, once a day) and ceftriaxone were started. She was treated with intense hydration and urine alkalization for rhabdomyolysis and AKI. The serum CPK level returned to 80 IU/L and she steadily improved clinically and was discharged after 15 days of treatment.

CASE 2

A 19-year-old male patient was hospitalized because of diagnosis of pneumonia. On physical examination, his heart rate was 112 beats/min, respiratory rate 24 per minute, and arterial blood pressure 100/60 mmHg. His body temperature was 38°C. Chest auscultation revealed faint crackles at left bases. Other physical findings were normal. In his laboratory examination, serum creatinine was 1.7 IU/L, urea nitrogen 111 mg/dL, ALT 749 IU/L, AST 611 IU/L, and CPK 1715 IU/L. There was no definitive etiologic condition leading to rhabdomyolysis in history or medication of patient. A chest radiograph showed a left lower lung infiltrate. These findings were thought to be consistent with pneumonia. Thereafter we started ceftriaxone and clarithromycin for empirical treatment of pneumonia, but he rapidly developed a severe respiratory failure and required mechanical ventilation. Laboratory values showed a marked increase of C-reactive protein 23 mg/dL (normal: 0–0.8 mg/dL) and procalcitonin 68.01 ng/mL (normal: 0–5 ng/mL). Arterial blood gas analyses showed severe hypoxemia with partial pressure of oxygen about 40 mmHg. Bacterial cultures of blood, urine, and tracheal aspirate were negative. A nasal swab tested with rRT-PCR was positive for H1N1 infection. High-dose oseltamivir (300 mg/day) was immediately added to the initial empirical antibacterial therapy. The chest X-ray showed diffuse, patchy bilateral infiltrates. The patient also became markedly hypotensive and he died despite all medications.

DISCUSSION

The development of rhabdomyolysis is associated with many diseases, injuries, medications, and toxins. However, there are no sufficient data about coexistence of H1N1 infection and development of rhabdomyolysis. Novel influenza A (H1N1) infection rapidly spread throughout the world and new pandemics may occur at any time. Most symptoms of H1N1 are related with respiratory tract involvement. Pulmonary injury and AKI were accused of increasing rate of mortality in the recent studies.^1–3 The incidence of AKI was reported between 30% and 60% in the course of swine flu.^2,4 However, the etiology of AKI has not yet been well described. The authors speculated that all clinical features of influenza virus infection are caused by a virus-induced cytopathy.⁵ In contrast to elevation of CPK levels in the course of H1N1 infection, only eight cases of rhabdomyolysis were reported since 2009 by Medline research.^1,6–13 Three of these cases were reported from pediatric population and all cases of AKI were improved with supportive treatment. The ages of the other cases were between 17 and 57 years. Only one patient (56-year-old male) was under dexamethasone therapy, because of multiple myeloma.⁹ Additionally, only one patient (57-year-old male) required renal replacement therapy due to rhabdomyolysis.⁶

AKI is an important cause of mortality during H1N1 infection. Our cases highlight the importance of recognizing a significant extrapulmonary complication of H1N1 infection. The recent report showed mild to moderate muscular inflammation in approximately 2/3 of patients with 2009 H1N1 pneumonia and respiratory failure. However, the true incidence of rhabdomyolysis during H1N1 and the pathogenesis of development of muscle injury remain unknown. Rhabdomyolysis should be considered in the evaluation of H1N1 influenza, especially among critically ill patients who present with AKI.

ACKNOWLEDGMENTS

Financial Disclosure. The authors have not received funding for research on this article.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.