Calcium Kinetic in a patient with acute renal failure due to Rhabdomyolysis. A Case Report and Review of Literature

Abstract

Hypercalcemia may follow hypocalcemia in the course of acute renal failure (also named now as acute kidney injury) secondary to rhabdomyolysis. The clinician should be aware of this calcium kinetics to avoid the complications of both hypocalcemia and hypercalcemia that may occur at few days interval during the recovery phase. We present herewith the case of a young gentleman who developed anuric ARF due to a strenuous exercise induced rhabdomyolysis. He was treated with supportive, corrective and dialysis measures. The progress was favourable with a diuretic phase. During the diuretic phase, he developed progressive hypercalcemia that reached up to 3.54 mEq/lwith constipation and drowsiness. Investigations showed besides stigmata of rhabdomyolysis and ARF, low initial levels of vitamin D metabolites. The calcemia eventually normalized with fluids, dialysis and a single dose of Pamidronate Sodium . The patient was discharged 3 weeks after admission with a recovered clinical condition, improved renal functions and normal calcemia. The biphasic kinetics of calcium in this setting is ocumented. We conclude that serum corrected calcium should be monitored in the context of ARF due to rhabdomyolysis.

Introduction

Rhabdomyolysis is a known cause of ARF. It may be due to different causes that have in common muscle injury and necrosis.¹ Calcium kinetics presents a particular pattern in this type of ARF. The clinician should be well aware of this specific entity to give proper care and to avoid the complications associated with hypo and or hypercalcemia. We present a case which illustrates this biphasic pattern of calcium kinetics and the management of the patient.

Case Report

A 28 year old Omani gentleman was admitted to the nephrology department for the management of ARF. He did not have history of particular medical condition. He complained of fever and severe myalgia that followed shortly after a strenuous exercise in the form of prolonged excessive exercise in the gymnasium lasting for about 2 hours.

The next morning he noticed that the urine was dark and decreased in quantity. These symptoms and signs progressed over a period of one week. Initially, he attended private clinics where he was prescribed symptomatic treatment including non-steroidal anti -inflammatory drugs (NSAIDs). On admission, physical examination showed a young gentleman with a good stature. He presented with the symptoms including nausea, constipation and loss of appetite .The vital signs were stable. He was afebrile. The pulse rate was regular at 82/m. The blood pressure was 140/80mmHg. He was anuric. The other elements of physical examination were unremarkable. The Laboratory investigations showed a urea of 35.5 mmol/l(N: 3.3-7.0), a serum creatinine of 1615mmol/l (N: 45-100) and a creatine kinase (CK) of 14424mmol/l (N: 25-70). The serum calcium was 2.02mmol/l (N: 2.1-2.6). The hemoglobin was 14.6 g/dl (N: 14-18.1), white blood cell count was 10.4 x 10 pwr 9 (N: 3.6-11.5). The ultrasound showed normal kidneys without obstruction. In view of these elements, the clinical diagnosis was acute renal failure (acute kidney injury) due to rhabdomyolysis secondary to strenuous exercise.

Treatment and management consisted of vital signs monitoring, urine output and input charting, calcium and intravenous fluids. Hemodialysis through a temporary vascular access was instituted. On day 2 the urine output was nil. He received dialysis and other supportive measures for 2 weeks. During this period, he improved clinically and started to produce urine. The last dialysis was performed at day 15. Calcium monitoring during the diuretic phase showed that it had increased to a peak value of 3.54mmol/l at day 5 (Figure 1). He complained of vague abdominal pain, constipation and fatigue that could be attributed to the hypercalcemia. Hypercalcemia during the recovery phase of ARF due to rhabdomyolysis was suspected. Further investigations showed the following:

Figure 1.

kinetics of the calcemia during the recovery of the ARF.

1. 25 (OH) Vitamin D3 36nmol/l (N: 53-150);

2. 1,25 (OH)2 vitamin D3 11pmol/l (N: 43-148)

3. Parathormone (PTH) 0.8pmol/l (N: 0.8-8.5).

After 3 weeks of treatment the patient’s

1. serum creatinine 288 mmol/l (N: 45-100)

2. Serum calcemia 2.63 mmol/l.

He was discharged on day 21 in a very good general condition with improved renal functions. He was advised follow up at the nephrology out-patient clinic.

Discussion

The terminology of ARF (Acute Renal Failure) is getting replaced now by the term Acute Kidney injury.^1,2 It is defined as either an abrupt increase in the serum creatinine level of more than 0.3mg/dl (26.5 mmol/l) or a percentage increase of more than 50% (by a factor of 1.5 from baseline) or a reduction in documented urinary output (<0.5 ml/kg body weight /hour for more than 6 hrs). Causes of Acute Kidney Injury are divided into pre-renal, intra-renal and post-renal. Pre-renal factors range from obvious renal hypoperfusion in patients with hypotension or hemorrhage to more subtle hypoperfusion such as that seen in patients with heart failure or cirrhosis. Post-renal acute kidney injury is caused by the blockade of the urinary flow. Intra-renal causes of acute kidney injury can be divided into diseases of the vasculature, tubulo-interstitial compartment or the glomeruli.^1,2 Rhabdomyolysis may lead to myoglobinuric acute renal failure and is the etiology of 5-25% of cases of acute renal failure.^1,2 The first documented case of rhabdomyolysis causing acute renal failure was described by Bywaters and Beall in1941.³ The most common etiological factors are traumatic, crush injuries during wars and natural disasters especially earthquakes, electric shock, pressure necrosis, central occlusion, and surgery.^4,5 Other reported etiologies in order of apparent prevalence include alcoholism, muscle compression, seizures, metabolic derangements, drugs, infection, muscular dystrophies and Strenuous exercise has been reported to cause rhabdomyolysis with ARF in some cases.^1,2,4,5 Abnormal calcium metabolism is a specific complication of rhabdomyolysis induced acute renal failure.⁶ During the initial and oliguric phase, patients are frequently hypocalcemic. The hypocalcemia can be sometimes extreme.^7,8 Nevertheless, care should be taken in the management of the initial hypocalcemia, as overzealous correction may lead to hypercalcemia. Calcium deposition in the muscles, hyperphosphatemia and skeletal resistance to the action of the parathyroid hormone is believe to be possible underlying mechanisms.⁷ It is possible that the initial calcium intake participated in the genesis of the hypercalcemia. During the recovery phase, hypercalcemia may develop in up to 40% of patients.^7,8 The pathophysiology of the hypercalcemia observed in the recovery phase may be due to several mechanisms including mobilization of calcium from injured muscles, soft tissue deposits, to the secondary hyperparathyroidism that developed during the initial phase and to the elevated levels of 1,25 dihydroxy vitamin D that also developed during the initial phase as a corrective response to the hypocalcemia.⁹

Most cases of hypercalcemia are self-limiting and require no major interventions other than observation and proper hydration. Nevertheless, some cases may require specific measures including dialysis intensification, biphosphonate and diuresis with loop diuretics.

Conclusion

Hypercalcemia (during the diuretic phase) following hypocalcemia (in the initial phase) may occur during the course of ARF associated with rhabdomyolysis. In most instances these conditions are self limited and do not require specific measures other than observation and proper hydration, but may require intervention when severe and symptomatic. The clinician should be aware of the dual kinetics of the calcium in this situation to plan proper monitoring and intervention.