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When renal failure develops in the presence of acute sepsis, rhabdomyolysis has to be considered.
An Indian woman aged 29 sought medical advice soon after arriving in Britain. For two weeks she had been feverish with sweats, anorexia, vomiting, diarrhoea and abdominal discomfort. Her bowels were open twenty times a day, the stools being liquid and yellow. On examination her temperature was 40°C, mucous membranes dry, heart rate 100/min, blood pressure 82/44 mmHg, jugular venous pressure low. The abdomen was tender without peritonism; the spleen was enlarged. Blood results were: haemoglobin 8.2 g/dL; platelets 125, lymphocytes 0.28, neutrophils 1.52 × 109/L; sodium 124, potassium 2.2, urea 28.2, bicarbonate 12, corrected calcium 1.35, phosphate 2.16 mmol/L; creatinine 560, bilirubin 48 μmol/L; albumin 28 g/L; C-reactive protein 120 mg/L. Blood clotting was normal. Radiographs of chest and abdomen showed nothing of note.
The patient was initially treated with oxygen, crystalloid fluids and intravenous cefotaxime and metronidazole. She was catheterized and urine output was recorded hourly. When she remained oliguric after 4 L of crystalloids a central venous pressure (CVP) line was inserted. With further volume replacement a CVP of 8 cm H2O was achieved but the oliguria persisted. The urine was dark brown and tested +++ for blood but microscopy revealed only a few red cells and no casts; the myoglobin concentration exceeded 1000 ng/mL. Serum creatine kinase, requested at this point, was 18 477 iu/L and alanine aminotransferase was 439 iu/L. With a presumed diagnosis of rhabdomyolysis and acute myoglobinuric renal failure, secondary to sepsis, she was treated with furosemide infused at 5 mg/h and the urine output increased to 100 mL/h. This diuresis was sustained, and serial measurements over the next 48 hours showed rapid reduction in serum creatine kinase with improvement in urea, electrolyte and bicarbonate values. A CT scan of the abdomen showed hepatosplenomegaly with oedematous and thickened colon only (Figure 1). Blood cultures and stool culture grew Salmonella typhi phage type E1 sensitive to cefotaxime. The patient was discharged on day 7 fully recovered.
The ultimate diagnosis was acute myoglobinuric renal failure secondary to S. typhi infection. Many of the classic features of S. typhi infection were seen in this case including high fever, diarrhoea, anorexia, hepatitis, splenomegaly, anaemia and leukopenia. The pancytopenia (seen in 75% of cases) is explained by splenic sequestration, bone marrow granulomatous inflammation and haemophagocytosis; the likelihood of complications rises substantially when the total white cell count is below 8 × 109/L.1 One of the most lethal complications of typhoid is small-bowel perforation, occurring in 3% of cases, particularly young men.2
Acute myoglobinuric renal failure, first described in 1941 by Bywaters and Beall,3 is characterized by a raised creatine kinase, hyperphosphataemia, hypocalcaemia and acidosis in a patient with urine dip-stick positive for blood.4 Hyperkalaemia, commonly present, can itself exacerbate muscle injury; the hypokalaemia found in our patient was probably caused by potassium loss from the gut. The nephrotoxic effects of myoglobin are attributed to both renal tubular blockage and a direct effect of haematin. Treatments for this condition, which accounts for up to 10% of cases of acute renal failure,5 have not yet been assessed in randomized controlled trials. In one series of seven patients in whom treatment was delayed, all progressed to acute tubular necrosis;6 thus prompt diagnosis and intervention is desirable. Forced alkaline diuresis has been considered the best way to protect the kidneys, by stabilizing myoglobin to prevent haematin release, but its drawbacks include hypercapnia and intracellular acidosis, a decline in cerebrospinal fluid pH and tissue hypoxia. The volume of bicarbonate-containing crystalloid necessary to raise urinary pH over 7.0 can lead to fluid overload, cardiac failure and even compartment syndrome (due to massive tissue swelling). A widely held view is that aggressive early fluid therapy and diuresis of 1.5-2.0 mL/kg per hour, which can be aided by furosemide, mannitol or acetazolamide, is satisfactory treatment alone.7 If initial therapy fails, haemofiltration or haemodialysis may be required. In experimental models, nephroprotective effects have been obtained with glutathione, methylxanthines and iron chelating agents but these methods are not yet clinically endorsed.8