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Kidney Week

Abstract: PO1269

Megaloblastic Anemia in a Patient on Peritoneal Dialysis Returning from Kenya

Session Information

Category: Dialysis

  • 703 Dialysis: Peritoneal Dialysis

Authors

  • Cambier, Marie-Laure, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Division of Nephrology and Hypertension, Brussels, Belgium
  • Robberechts, Tom, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Division of Nephrology and Hypertension, Brussels, Belgium
  • Planken, Simon, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Division of Internal Medicine, Brussels, Belgium
  • Mertens, Rembert A., Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Division of Internal Medicine, Brussels, Belgium
  • Beckers, Veerle, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Division of Hematology, Brussels, Belgium
  • Francois, Karlien, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Division of Nephrology and Hypertension, Brussels, Belgium
Introduction

We describe a case of atovaquone-proguanil (A-P)-related toxicity in a patient treated with peritoneal dialysis (PD).

Case Description

A 40-year old man treated with PD presented 48 hours after return from Kenya with a diffuse erythematous rash, dysphagia, fever and weight loss. Clinical evaluation showed a maintained general status, diffuse non-palpable purpura and tonsillopharyngitis. Laboratory testing revealed an elevated c-reactive protein and pancytopenia. Malaria prophylaxis (A-P) had been prescribed by his general practitioner and accurately taken. Malaria infection was ruled out through blood smear analysis. Broad serologic testing was negative. Empiric antibiotics were administered for tonsillopharyngitis. Bone marrow examination showed a megaloblastic anemia. Besides, he developed a diffuse nonscarring hair loss within weeks.

Discussion

DNA synthesis requires the presence of thymidylate, a nucleotide present in cells in rate-limiting amounts. Both folate and vitamin B12 are crucial cofactors in the thymidylate metabolism. Vitamin B12/folate deficiency or drugs affecting the vitamin B12/folate metabolism will slow down DNA synthesis. Proguanil is a folate analogue and its metabolites inhibit dihydrofolate reductase (DHFR), disrupting the thymidylate synthesis. The use of a fixed dose combination of A-P for malaria prophylaxis is contra-indicated in chronic kidney disease (CKD) because of proguanil accumulation in patients with kidney disease. Inhibited DNA synthesis manifests as megaloblastic anemia or as hair loss because of altered regulation of hair follicle growth cycle.
DHFR inhibition was corrected by discontinuing A-P and by stimulating thymidylate synthesis through the administration of folinic acid. Supportive care included administration of Granulocyte–Colony Stimulating Factors, platelet and red blood cells transfusion. PD was continued. There was no indication in switching the patient to hemodialysis since extracorporeal clearance of proguanil is limited due to high protein binding (75%) and very high distribution volume (42L/kg).

Key message: The use of A-P is contra-indicated in CKD, due to the risk of proguanil accumulation and consecutive hematologic toxicity. Treatment is based on discontinuing the drug, administration of folinic acid and supportive care. Data suggest proguanil is poorly dialyzable.