Hemolytic uremic syndrome associated with rhabdomyolysis – Need to look beyond kidneys in hemolytic uremic syndrome

Case report

A 3¹/₂-year-old boy presented with complaints of high-grade fever and loose stools of two days’ duration with decreased urine output for one day. Stools were watery, being passed 8–10 times per day with no blood. The urine colour was dark reddish brown. At admission, he was tachypnoeic with acidotic breathing but was haemodynamically stable. On examination, he was pale, with diminished consciousness (glassgow coma scale – 12/15) but no organomegaly. No other pertinent features were found.

He was started on intravenous fluids, antibiotics and supportive therapy. His admission investigations revealed an anaemia (Hb 77 g/L), thrombocytopenia (platelets 71 × 10⁹/L) and leucocytosis (11.7 × 10⁹/m³). A peripheral smear revealed schistocytes > 1%. The serum lactate dehydrogenase (LDH) was 20.8 ukat/L. Electrolytes were normal with deranged urea – 29.63 mmol/L and creatinine – 200.7 µmol/L. Liver function test (LFT) – aspartate transaminase (AST)/alanine transaminase (ALT) – 0.65/0.21 ukat/L, total bilirubin 50.96 µmol/L with conjugated bilirubin 17.1 µmol/L. His coagulation parameters were normal. His urine showed haematuria (RBCs 30-35/HPF) with albumin 2 + . On the second day, there was a worsening trend: Hb 63 g/L, platelets 11 × 10⁹/L and AST/ALT raised to 11.9/5.68 ukat/L. Serum LDH increased to 143.36 ukat/L in 48 h. A diagnosis of hemolytic uremic syndrome (HUS) was proposed; the stool was negative for Shigella toxin and its culture was sterile. Dengue, malaria, leptospira, rickettsia, and HIV serology were all negative. The H1N1 test was negative. Vitamin B12 level was normal. His C3 and C4 level complements were normal and the antinuclear antibody test was negative. Total Creatine kinase (CK) was grossly elevated to 312.2 ukat/L with urine for myoglobin raised to 8.96 nmol/L. The auto-antibody to factor H was reported negative.

Five cycles of plasmapheresis with two of haemodialysis were carried out, to which the child responded well. After two years of follow-up, no renal dysfunction was found.

Discussion

Total Creatine Kinase (CK) was measured in this HUS case to look for extrarenal involvement as rhabdomyolysis has been previously reported with HUS; myoglobinuria was thought to be a possible cause of discoloration of the urine. Rhabdomyolysis may manifest as progressive muscle weakness and tenderness, but in critically ill children these clinical manifestations may not be apparent. Measuring CK, i.e. actively looking for muscle involvement, is the only reliable way of confirming rhabdomyolysis.

There are only few case reports reporting rhabdomyolysis associated with HUS and ours is the sixth such case. Andreoli and Bergstein for the first time reported this unique association with capillary thrombosis as the cause of muscle necrosis. ¹ Pena et al. reported it along with pancreatic involvement with insulin-dependent diabetes in a 28-month-old girl. ²

Recurrent HUS with rhabdomyolysis is reported with succinate coenzyme Q reductase deficiency and extremely reduced cytochrome c oxidase/succinate cytochrome c reductase ratio.^3,4 Another report with anterior compartment syndrome of the right leg of child requiring fasciotomy is described. ⁵

Thus, rhabdomyolysis in patients with HUS may worsen an existing acute kidney injury with associated myoglobinuria, may exacerbate metabolic abnormalities such as hyperkalaemia or rarely may cause compartment syndrome thereby increasing the disease severity and worsening the prognosis in HUS.

To conclude, paediatric HUS patients should be closely monitored for extrarenal organ involvement and rhabdomyolysis where HUS exists with multiorgan involvement.