Rhabdomyolysis Induced Acute Kidney Injury in Acute Myeloid Leukemia: An Unusual Association

Archana Chiniwalar; M Edwin Fernando; Suren Sujit; ND Srinivasa Prasad; K Thirumal Valavan

doi:10.4103/1319-2442.292326

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CASE REPORT

Year : 2020 | Volume : 31 | Issue : 4 | Page : 877-880

Rhabdomyolysis Induced Acute Kidney Injury in Acute Myeloid Leukemia: An Unusual Association

Archana Chiniwalar, M Edwin Fernando, Suren Sujit, ND Srinivasa Prasad, K Thirumal Valavan
Department of Nephrology, Government Stanley Medical College and Hospital, Chennai, Tamil Nadu, India

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Date of Submission	21-Apr-2019
Date of Decision	12-Jul-2019
Date of Acceptance	14-Jul-2019
Date of Web Publication	15-Aug-2020

Abstract

Rhabdomyolysis is a potentially life-threatening syndrome that causes acute kidney injury. Association of acute myeloid leukemia (AML) and myoglobin induced acute tubular necrosis (ATN) is rarely reported in the literature. Here, we report a young male who was admitted with fever of unknown origin. Diagnosed to have AML with renal failure and subsequently succumbed to illness, whose post mortem renal biopsy confirmed myoglobin induced ATN.

How to cite this article:
Chiniwalar A, Fernando M E, Sujit S, Srinivasa Prasad N D, Valavan K T. Rhabdomyolysis Induced Acute Kidney Injury in Acute Myeloid Leukemia: An Unusual Association. Saudi J Kidney Dis Transpl 2020;31:877-80

How to cite this URL:
Chiniwalar A, Fernando M E, Sujit S, Srinivasa Prasad N D, Valavan K T. Rhabdomyolysis Induced Acute Kidney Injury in Acute Myeloid Leukemia: An Unusual Association. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2022 May 16];31:877-80. Available from: https://www.sjkdt.org/text.asp?2020/31/4/877/292326

Introduction

Acute myeloid leukemia (AML) is characterized by uncontrolled proliferation of immature myeloid cells, often called blasts, which replace normal production of bone marrow.^[1],[2] Patients may present with anemia, infection, and bleeding. Patients may also present with high peripheral blasts, symptoms, and complications of blast crisis. Acute leukemia is fatal if untreated, most people die within several months after diagnosis if not treated. Rhabdo- myolysis is characterized by breakdown of skeletal muscle fibers with release of intra- cellular myoglobin into the extracellular fluid and systemic circulation,^[3],[4],[5] leading on to acute kidney injury (AKI). Association of rhabdo- myolysis with AML is rarely reported, warranting this case report.

Case Report

Informed consent has been obtained from the family members before reporting the case to the journal.

A 24-year-old male with no comorbidities, presented to our emergency department with fever of two weeks duration, altered sensorium, epistaxis, oliguria with macroscopic hema- turia for the past two days. His pulse rate was 146/min, blood pressure of 100/60 mm Hg and was tachypneic with respiratory rate of 30 cycles/min and temperature recorded was 101°F. He was pale and icteric and had sub- conjunctival hemorrhage. He was conscious but irritable, respiratory system examination was apparently normal, while examination of the abdomen revealed hepatosplenomegaly. His initial laboratory investigations revealed: urine 3+ albumin and 6–10 red blood cells/ hpf, hemoglobin of 6.8 g/dL with leukocytosis of 36,800 cells/mm^[3] and thrombocytopenia of 60,000 cells/mm^[3]. His sugars were normal and serum creatinine: 4 mg/dL, serum calcium: 8.1 mg/dL, serum phosphorus: 5.4 mg/dL, and uric acid: 6.8 mg/dL. abdominal ultrasound revealed hepatosplenomegaly with normal- sized kidneys. Liver enzymes were elevated with aspartate transaminase: 255 U/L and alanine aminotransferase: 74.5 U/L, alkaline phosphatase: 121 IU/L. The patient had elevated C-reactive protein of 267 mg/L, indicative of infective etiology.

With the above background, patient was suspected to have infective etiology, and was started on antibiotics and anti-malarial treatment empirically.

During the course of hospitalization, there was an acute drop in patient’s hemoglobin to 3.6 g/dL and platelet count to 34000 cells/ mm^[3], total leukocyte count worsened to 59000 cells/mm^[3]. Renal failure worsened rapidly with serum creatinine of 8.5 mg/dL. Sepsis with AKI, disseminated intravascular coagulation with AKI or thrombotic microangio- pathy (TMA) as a cause of renal failure were considered and the patient was evaluated in those lines. PT, aPTT, and INR were elevated as depicted in the [Table 1], serum lactate dehydrogenase was elevated to 2326 U/L. Peripheral smear was done as a part of workup for TMA, surprisingly revealed AML (M3) Blasts: 35%, promyelocytes: 5%, myelocyte: 31%, metamyelocyte: 12%) with no toxic granules or schistocytes. As the cause of AKI was unclear in this patient, serum creatine phosphokinase level was checked which was elevated to 3485 U/L, suggestive of rhabdo- myolysis.

Table 1: Laboratory investigations.

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Patient was initiated on hemodialysis in view of raised serum creatinine and oliguria, one session of hemodialysis was done. Subsequently, patient developed hypotension and succumbed to illness.

Postmortem renal biopsy was done after obtaining the consent from family members. Light microscopy revealed 11 glomeruli with normal cellularity, there were no fibrin thrombi, epithelial cell necrosis was identified, nuclear details and brush borders were lost and cells were swollen, pigment casts were seen in some of the medullary tubules [Figure 1] and [Figure 2]. Immunofluorescence stain revealed four glomeruli, the section stained for IgM, IgG, IgA, C3, C1q, and light chains was negative.

Figure 1: Jones methenamic silver stain shows pigment casts in some of the tubules.

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Figure 2: Light microscopy - periodic acid-Schiff staining shows glomeruli of normal cellularity, pigment casts in some of the tubules.

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Immunostaining for myoglobin was positive [Figure 3]. Renal biopsy was suggestive of rhabdomyolysis with myoglobin-induced acute tubular necrosis (ATN).

Figure 3: Immunostaining for myoglobin is positive over the tubular casts.

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Discussion

Leukemias are hematologic malignancies derived from bone marrow. Leukemia can involve other organs, including the kidneys. Kidney manifestations encompass a broad spectrum of disease: prerenal AKI, ATN, renovascular Disease, Parenchymal Infiltration, Obstruction, Glomerulopathies, and Electrolyte and Acid-Base Abnormalities. Kidney Injury May Result from the Underlying Malignancy Itself or as a Secondary Complication of Therapy.^[6]

Prerenal AKI is the most common kidney injury in lymphoma or leukemia. Volume depletion from poor oral fluid intake (78%), anorexia (64%), early satiety (50%), emesis (23%), and diarrhea (16%) contribute to prerenal AKI.^[7] ATN is the most common cause of intrinsic AKI in lymphoma and leukemia. In a single-center study of all patients with hematologic malignancy with AKI, 83% had ATN, with 96% of those patients experiencing sepsis and 88% receiving nephrotoxic medi- cations.^[8] And also Lysozyme-induced tubular necrosis is common in patients with hema- tologic malig-nancies.^[9] Lysozyme is a cationic enzyme stored in macrophages and monocytes that may be released to lyse bacterial cell walls. In certain leukemias, clonal expansion increases lysozyme production. Lysozyme is freely filtered by the glomerulus and then reabsorbed by the proximal tubule cells. At high concentrations, as seen in leukemia, lysozyme induces direct tubular damage- causing kaliuresis and proteinuria. The high concentrations of urinary lysozyme, exacerbated by proximal tubule injury, which prevents reabsorption, can present as proteinuria.^[9]

The kidney is the most common extra- reticular endothelial and extra-hematopoietic organ infiltrated by leukemia and lymphoma, with infiltration seen in 60%–90% of patients with hematologic malignancy.^[10]

Rhabdomyolysis associated with leukemia can also cause AKI and is a rare compli- cation.^[11],[12] Rhabdomyolysis is a potentially clinical and laboratory syndrome characterized by the breakdown of skeletal muscle fibers with the release of intracellular products into the extracellular fluid and systemic circulation. Rhabdomyolysis is usually caused by alcohol abuse, muscle overexertion, the use of certain medications or illicit drugs, crush injury and infections, electrolytes abnormalities or rare cause like dermatomyositis.^{[13],[14],[15]} The mecha- nism of rhabdomyolysis in hematologic malignancies is unclear. It is said that rhabdo- myolysis in patients with leukemia is caused by chemotherapy mainly, and also other factors like sepsis, gastrointestinal complications, infection, the use of diverse antibiotics, and dehydration can also contribute for same.

In our patient, it was thought at first that AKI might be due to sepsis or TMA. However, further work-up with peripheral blood smear did not show toxic granules or schistocytes suggestive of sepsis or TMA, respectively but showed features suggestive of AML (M3). Heme cast nephropathy was a likely differential in view of anemia and increased LDH levels. But elevation of serum CPK levels suggested rhabdomyolysis. Electrolytes abnormalities that can contribute to rhabdomyolysis such as hyponatremia, hypernatremia, hypo- kalemia, hyperglycemia, hypercalcemia, and hypophosphatemia were ruled out. However, AKI secondary to rhabdomyolysis was confirmed by post mortem renal biopsy. High- grade fever and the use of various antibiotics in our patients could be the cause of rhabdo- myolysis. However, the possibility of malignant cells infiltration into the muscle tissue as the cause rhabdomyolysis cannot be ruled out as muscle biopsy was not done in our patient.

Conclusion

Rhabdomyolysis with myoglobin-induced ATN in a patient with AML is rare. High index of suspicion is needed for early detection of rhabdomyolysis, as a cause of AKI.

Acknowledgment

We acknowledged the help rendered by Dr. Anila Abraham Kurien, nephropathologist, Center for Renal and Urological Pathology.

Conflict of interest: None declared.

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