Porphyria syndrome associated with diabetic nephrosclerosis and erythropoietin.
The porphyrias are inherited or acquired metabolic disorders caused by a partial deficiency in one of the enzymes of the heme biosynthetic pathway. Eight enzymes are utilized in the synthesis of heme. An enzyme defect in one of the last seven enzymes will result in one of the seven different forms of porphyria, some of which have similar signs and symptoms. This article describes six diabetic, azotemic patients with no prior history of porphyria, who developed a syndrome similar to acute intermittent porphyria after initiation of treatment with erythropoietin. One of the patients developed the syndrome predialysis, whereas the remaining patients were on maintenance hemodialysis. The symptoms varied but all resolved when erythropoietin was discontinued and reappeared in four cases when erythropoietin was restarted. In all of the patients, the enzyme aminolevulinic acid-dehydratase (ALA-D) was low and the uroporphyrinogen synthase was normal. This enzyme abnormality suggests an acquired form of delta-aminolevulinic acid dehydratase porphyria (ADP). Lead toxicity, succinylacetone, and zinc deficiency are known to depress ALA-D, but these conditions were not present. The development of the acute porphyria syndrome while the patients were receiving pharmacological doses of erythropoietin, which resolved when the drug was stopped, suggests that by stimulating heme synthesis, erythropoietin may unmask an enzyme deficiency resulting in the clinical expression of ADP. The patients responded favorably to a regimen that included discontinuation of erythropoietin, tight blood sugar control, maintaining the hematocrit above 30%, and a KT/V, a measure of dialysis adequacy, of 1.5 in the hemodialysis group. Plasmapheresis accelerated the recovery when used in two patients.
Hedger
Robert W
RW
Department of Medicine, Northwestern University Medical School, Chicago, IL, USA.
Wehrmacher
William H
WH
French
Arleen V
AV
D000328:Adult; D000368:Aged; D003928:Diabetic Nephropathies / Q000150:complications / Q000628:therapy*; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009400:Nephrosclerosis / Q000150:complications / Q000628:therapy*; D010956:Plasmapheresis; D000623:Porphobilinogen Synthase / Q000097:blood; D017092:Porphyria, Erythropoietic / Q000139:chemically induced*; D006435:Renal Dialysis
D004921:Erythropoietin; D000623:Porphobilinogen Synthase