6 years old male child, who was apparently normal a month back, developed progressive tiredness and breathlessness. He was treated locally and as he did not improve, evaluated and found to be in severe renal failure hence referred to us.
Initial lab parameters revealed severe azotemia (Urea – 326 mg%, creatinine 7.59 mg/dl) with severe anemia (Hb 4.2 g/dl). His platelets were low (49,000 /mm3) and LDH was high 6132 u / l. He was initiated on dialysis immediately and further evaluation was carried on.
DIC evaluation was negative and his kidneys on ultra-sonogram was of normal size. His reticulocyte count was 21, indicating normal bone marrow response. Peripheral smear showed microcytic hypochromic anemia with few shistocytes. The clinical picture was suggestive of Hemolytic Uremic Syndrome (HUS). Without waiting for the reason for further confirmatory evidences, we counselled the family and proceeded with plasm exchange.
He received 5 exchanges of plasma exchange and continued on dialysis. The two questions that remained unanswered at this point of time was
- What is the reason for HUS in this child? With no history of preceding diarrhea , this is not a classical HUS
- What is the renal recovery chances? How long the child left untreated before we received the child in our hospital?
Upon stabilizing the child on dialysis, and correcting his anemia and thrombocytopenia, he underwent renal biopsy.
Fortunately, there were no evidence of chronic changes due to HUS and the micro vascular thrombosis. It showed acute tubular injury and edematous interstitium. There were no evidence of micro vascular thrombosis or chronic changes as the biopsy was done post treatment.
The evaluation of the root cause of HUS revealed he had Anti Factor H antibody and he received rituximab to stop production of these antibodies by B-lymphocytes.
Renal biopsy Glomeruli appeared normal without proliferation of mesangial, endothelial or epithelial cells. There were no crescents or intra vascular thrombosis. There are foci of moderate acute tubular necrosis with interstitial edema and focal lymphocytic infiltrations.
Small artery that was included in the biopsy was normal.
Immuno florescence did not yield any significant deposits
What is Hemolytic Uremic syndrome?
It is a disorder of the microvasculature where there is endothelial damage that results in micro vascular thrombosis. The classical picture includes Coomb’s negative micro-angiopathic hemolytic anemia, thrombocytopenia and renal disease. Corresponding evidences include indirect hyper- bilirubinemia, elevated LDH, shistocytes on peripheral smear .
TTP (Thrombotic Thrombocytopenic Purpura) is also a similar disease where there is predominantly CNS manifestation .
Normally it follows acute gastroenteritis caused by O157:H7 strain of E.Coli. Otherr pathogens like Shigella , Pneumococcus and non infective causes include pregnancy , abnormalities in alternate pathway of complement system, accelerated hypertension, drugs including Calcineurin inhibitors, anti platelets etc.
The disease has good prognosis in children especially if it is associated with diarrhea. Atypical HUS, that is not diarrhea related has poor prognosis. If the treatment is delayed, the patient ends in chronic renal failure needing long-term dialysis and renal transplantation. aHUS due to complement abnormality needs liver transplantation ahead of renal transplantation to prevent recurrence.
Treatment consists of treating the underlying cause, plasmapheresis, correction of anemia and thrombocytopenia. Antibiotics are avoided in diarrhea associated HUS.
Dr. R. Balasubramaniyam
Chief Nephrologist
Kauvery Hospital, Chennai.[1]