Dr.RR, 50-year old person with diabetes for 5 years presented to the hospital ER with low urine output for 5 days and drowsiness. There was no history of fever, loose stools, vomiting, chest pain, breathlessness or intake of NSAID’s. Clinically he was euvolemic with a stable hemodynamic state. Investigations revealed that he had severe renal failure (urea 200 mg % and creatinine 7.5 mg %) with normal-sized kidneys on ultrasonogram. His blood sugars were marginally high (275 mg / dl), and cardiac evaluation was normal. Urine analysis could not be done as he was anuric; the other investigations including electrolyte profile, CBC, liver function tests, and calcium were normal.

He was anuric and was taken on hemodialysis. His drowsiness reduced. His vasculitis workup – ANA, ANCA, and anti GBM antibodies were negative. Since his anuric AKI was unexplained, he underwent a renal biopsy towards finding out the exact reason for his AKI.

The glomerulus was normal without any evidence of mesangial or endothelial proliferation, sclerosis, or crescents. Tubules were dilated with loss of brush borders. Some of the tubules showed ropy casts; these casts are intensely positive for myoglobin and negative for hemoglobin. Mild lymphocytic infiltration is noted in the interstitium. Staining for immunoglobulins is negative.

Figure 1 – the tubules showing ropy casts (arrows)

Figure 2 – casts that stain positive for MYOGLOBIN.

Myoglobinuric AKI is the result of excessive muscle breakdown that causes renal tubular damage. Myoglobin is an iron containing muscle protein and serves as a carrier and storage of muscle oxygen. Since its affinity to oxygen is higher than hemoglobin, myoglobin serves as an oxygen supplier to the muscles. Muscle damage results in release of this protein that is filtered and causes direct renal tubular damage.

The reasons for muscle damage (rhabdomyolysis) could be physical injury to muscles as in polytrauma, crush injuries, malignant hyperthermia, burns, seizures, hypothermia, etc.

Non-physical injury to the muscles could be of different causes

1. Metabolic abnormalities – hypokalemia, hypocalcemia, hypophosphatemia, hyponatremia, and hypernatremia,
2. Hypoxic muscle injuries – as in vasculitis, arterial obstruction, venous thrombosis, etc.
3. Genetic disorders of carbohydrate (McCardle’s disease, phoshofructokinase deficiency) and lipid metabolism (carnitine deficiency), polymyositis, etc.
4. Infections – like malaria, influenza, herpes, etc.
5. Drugs and toxins – alcohol, statins, fibrates, sedatives, cocaine, etc.

What caused muscle damage to our patient?

He didn’t have metabolic abnormalities, hypoxic insult to muscles, or infections. He was recently started on statin with fibrates. His CPK and LDH were done and were mildly elevated (his potential nephrotoxic medications were stopped at admission, and by the time the biopsy reports came in, these enzymes were normalized)

What are the reasons for AKI in muscle damage situations?

1. Muscle injury causes fluid accumulation inside the muscles, and it could lead to volume depletion, renal vasoconstriction especially to the afferent arteriole causing hypofiltration.
2. Myoglobin is directly toxic to the renal tubules
3. Myoglobin combines with Tamm-Horsfall protein in the distal tubule in an acid environment and can cause tubular obstruction

Treatment Aspects:

1. Initial management consists of adequate hydration and management of hyperkalemia
2. Alkalanizing the urine towards preventing cast formation by IV bicarbonate administration.
3. Hemodialysis – if the patient has gone into AKI

Prognosis

It is generally good. Kidneys recover in the next few weeks and dialysis support is needed till then. Our patient is still on dialysis and has started passing less than 100 ml of urine. He is in his second week of his illness and is expected to improve in the next one to two weeks.

Figure 3:  typical brownish urine in myoglobinuria

Dr. Balasubramaniam Raju
Chief Nephrologist
Kauvery Hospital