Rhabdomyolysis and Acute Kidney Injury
August 09 07:18 2022 Print This Article

Rhabdomyolysis and Acute Kidney Injury

Rhabdomyolysis is the breakdown of skeletal muscles and release of its contents like myoglobin, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase. Historically, this entity was discovered during the World War II, when large-scale crush injuries were reported.

Etiology of Rhabdomyolysis

Common causes are crush injury, viral infections like coxsackie, parvovirus, drugs like statins, toxins like alcohol, cocaine and artificial creatine supplements (used for body-building), seizures, prolonged immobilisation and limb compartment syndrome. Rare causes include congenital myopathies involving glycogen storage disorders, malignant hyperthermia and neuroleptic malignant syndrome.

Pathogenesis of Acute Kidney Injury

Massive release of myoglobin from the muscles causes direct toxicity to the proximal tubular cells. Entry of extracellular fluid into the injured muscles causes intravascular volume depletion, activation of the renin-angiotensin system and sympathetic nervous system resulting in renal vasoconstriction, hypoperfusion and additional ischemic injury to the tubules. The filtered myoglobin combines with Tamm-Horsfall protein forming intratubular casts and obstruction of distal tubules. The free iron in the heme pigment also induces oxidative injury and depletion of nitric oxide, which is a free radical scavenger.

Clinical Manifestations of Rhabdomyolysis

Muscle weakness, soreness and swelling with brownish discolouration of urine are characteristic features on physical examination. Laboratory investigations show hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia with or without elevation of blood urea and serum creatinine levels. Elevated serum creatine phosphokinase is the most sensitive test and its level correlates with the severity of rhabdomyolysis. Serum myoglobin level can be measured by radioimmunoassay. Myoglobinuria may or may not be present and is confirmed by positive dipstick test for blood without RBC under microscopy.

Prevention of Acute Kidney Injury

Treatment of the underlying cause is imperative to prevent further renal injury. Prompt and aggressive fluid resuscitation is the key to prevent renal shutdown in myoglobinuric acute kidney injury. In the initial non-oliguric phase, the fluid protocol is isotonic saline 10-20 ml/kg/hr for 6 hours (with careful monitoring of hourly urine output) followed by maintenance fluid infusion to maintain urine flow rate of 1-2 ml/kg/hr. Urinary alkanisation is achieved by infusion of 1L of 5% dextrose with 100 mEq/L of sodium bicarbonate (isotonic sodabicarb) to maintain urinary pH >6.5 and to reduce tubular cast formation. Once volume repletion is achieved, 20% mannitol (100ml) iv bolus followed by 10ml/hr infusion is given for its osmotic diuretic (improves renal perfusion by diverting the oedema fluid from inside the muscles into the systemic circulation) and free radical scavenging effects.

Treatment of Acute Kidney Injury

Once oliguria sets in, renal replacement therapy in the form of intermittent hemodialysis is needed till recovery of tubular function, which usually takes 2-4 weeks. There is no role for extracorporeal removal of myoglobin due its high molecular weight of 17kDa.

Hypercalcemia should be watched out for during recovery of kidney function, due to release of the calcium phosphate precipitates deposited in the damaged muscles.

References

  1. Petejova N, Martinek A. Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review. Crit Care. 2014 May28;18(3):224. doi: 10.1186/cc13897. PMID: 25043142; PMCID:PMC4056317.
  2. Lima RS, da Silva Junior GB, Liborio AB, Daher Ede F. Acute kidney injury due to rhabdomyolysis. Saudi J Kidney Dis Transpl.2008 Sep;19(5):721-9. PMID: 18711286.
  3. Xavier Bosch, Esteban Poch, Josep M. Grau, M.D. Rhabdomyolysis and Acute Kidney Injury. N Engl J Med 2009; 361:62-72. DOI:10.1056/NEJMra0801327.

 


Dr. M. Aarthi
Associate Consultant Nephrologist
Kauvery Hospital Chennai