A RARE CASE OF RHABDOMYOLYSIS LEADING TO PIGMENT NEPHROPATHY AND ACUTE KIDNEY INJURY REQUIRING HAEMODIALYSIS

Rhabdomyolysis is a condition characterized by the rapid degradation of skeletal muscle fibres, leading to the leakage of intracellular components such as myoglobin, creatinine kinase, aldolase, lactate dehydrogenase (LDH), and electrolytes into the bloodstream.1

It is broadly classified into three categories: traumatic (caused by crush injuries or direct trauma), non-traumatic non-exertional (associated with drugs, toxins, or infections), and non-traumatic exertional (triggered by physical activity). Metabolic myopathies, which account for around 10% of non-traumatic exertional rhabdomyolysis cases, should be considered in individuals who experience repeated episodes following exertion.2

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare inherited disorder that impairs mitochondrial fatty acid metabolism, resulting in decreased muscle energy production.3

This case report presents a 30-year-old male who developed acute kidney injury secondary to rare cause of rhabdomyolysis requiring haemodialysis.

Case Report

A 30-year-old male was admitted with complaints of loose stools, vomiting, dark-coloured urine, and muscle weakness following travel. He denied fever, abdominal discomfort, or urinary symptoms. On admission, his blood pressure was elevated at 180/90 mmHg, with tachycardia, tachypnoea, reduced muscle tone, and low urine output.

His medical history included an episode of post-infectious glomerulonephritis at 13 years old, initially presenting with a serum creatinine of 1.5 mg/dL following a skin infection, which later normalized. In 2012, he experienced an episode of dark-coloured urine after mild exertion, with laboratory findings showing myoglobinuria and an elevated creatine phosphokinase-MB (CPK-MB) level of 15,000 U/L, while kidney function remained normal. A similar episode occurred in 2015 after prolonged standing, with normal renal function but increased CPK-MB levels.

During this admission, laboratory tests showed a serum creatinine of 21 mg/dL, hyperkalaemia (potassium level of 8.3 mmol/L), and urine analysis revealing blood positivity without red blood cells. Suspecting rhabdomyolysis, CPK-MB levels were checked and found to be 7500 U/L. in view of anuric state of patient, haemodialysis was initiated using a right internal jugular vein temporary haemodialysis catheter.

The patient was born to parents in a consanguineous marriage. His elder sister had a history of kidney disease, underwent transplantation, experienced allograft failure within a year, and required dialysis before passing away. Further details of her medical condition were unavailable.

He received four haemodialysis sessions during hospitalization, which led to gradual improvement in urine output. Kidney biopsy was done which showed findings suggestive of pigment nephropathy. Due to the possibility of an underlying metabolic disorder, genetic testing was conducted, confirming VLCAD deficiency (Figure 1). He was discharged with an improving renal profile and was advised to modify his diet and avoid strenuous activity. During his latest follow up (March 2025) his serum creatinine is 1.01mg/dl, maintaining blood pressure and no abnormal urinary findings were detected.

Discussion

Rhabdomyolysis is responsible for a 10-15% of acute kidney injury cases.4 Although metabolic myopathies are uncommon, they can lead to muscle energy deficits due to disruptions in glucose, glycogen, lipid, or nucleoside metabolism.

Fatty acids play a vital role as an energy source, particularly in periods of fasting or extended physical activity. VLCAD, an enzyme critical in mitochondrial beta-oxidation, is involved in dehydrogenation of long-chain fatty acids for energy production.5 A deficiency in this enzyme results in an autosomal recessive disorder caused by mutations in the ACADVL gene, which was first identified in 1992. The ACADVL gene is located on chromosome 17 (17p11.2–p11.13).6 The estimated global incidence of VLCAD deficiency ranges between 1 in 40,000 and 1 in 120,000, with newborn screening suggesting a prevalence of approximately 1 in 31,500 births.(7,8)

VLCAD deficiency presents in three distinct clinical forms:

1. Infantile-onset cardiac type – This severe variant is marked by hypertrophic cardiomyopathy and, in some cases, may result in sudden death during infancy.2. Childhood-onset hypoglycaemia type – A moderate form characterized by hypoketotic hypoglycaemia, hepatomegaly, and metabolic instability, typically triggered by fasting or infections.3. Adolescent/adult-onset myopathic type – A milder form that typically arises in adolescence or adulthood, usually in response to increased energy demands such as physical exertion or fasting. Symptoms include muscle pain, weakness, and rhabdomyolysis, often associated with elevated CPK levels.9

The primary management strategy for VLCAD deficiency involves dietary adjustments, with an emphasis on preventing fasting and reducing long-chain fat intake while supplementing with medium-chain triglycerides. Recent studies have explored the role of triheptanoin, a specialized artificial fat substitute, in managing this disorder. Additionally, experimental pharmacological treatments such as bezafibrate and REN-01 (a PPAR-delta agonist) are being investigated for their potential in enhancing fatty acid oxidation.(10,11)

Recurrent rhabdomyolysis due to adult-onset VLCAD deficiency is uncommon but clinically significant. Identifying characteristic symptoms, particularly those linked to fasting, physical exertion, or infections, is essential for timely diagnosis. Implementing preventive measures, including appropriate lifestyle adaptations and dietary strategies, can help lower the risk of metabolic decompensation and subsequent episodes.