Can quinine (Kinin) induce creatinine increase?/nA 48-year-old man has been treated for eight years

Fråga: Can quinine (Kinin) induce creatinine increase? A 48-year-old man has been treated for eight years with quinine 250 mg x1 due to muscle cramps. He now has an unsymptomatic rise of creatinine. Creatinine was 990202: 132 umol/l and 990208: 141 umol/l (reference value 70 umol/l). Blood pressure was normal, no hematuria and no albuminuria were found.

Sammanfattning: Quinine can induce hemolytic-uremic syndrome and there exist two reports of quinine-induced interstitial nephritis.

Svar: Quinine, a drug used in the treatment of malaria, does not have muscle cramps as an indication in FASS (1,2).

A search in pharmacology handbooks and Medline gave that quinine can induce hemolytic-uremic syndrome (3,4). In a review of nine patients (4) with quinine induced hemolytic-uremic syndrome the patients developed chills, diaphoresis, nausea and vomiting, abdominal pain, decreased urine output and petechiae within one to 96 hours of quinine intake. All patients experienced significant anaemia, severe thrombocytopenia, increased lactate dehydrogenase, elevated serum creatinine, and oliguria. Renal biopsy performed in one of the patients demonstrated renal cortical necrosis and fibrin deposition in glomeruli and in the walls of arterioles. Quinine-induced antibodies reactive with endothelial cells and possibly margination of granulocytes in renal glomeruli may be responsible for this syndrome. The patients described with this syndrome range from 18 to 75 years in age.

Two cases of acute allergic interstitial nephritis possibly caused by quinine have also been reported (5).

A search in SWEDIS (Swedish Drug Information System) revealed three cases of acute renal failure. One case was of a 57-year-old woman who after one tablet of quinine (dose unknown) developed within 24 hours a hemolytic-uremic-like syndrome with acute renal failure, anaemia and trombocytopenia. Another case was of a 44-year-old woman who after two quinine tablets (dose unknown) developed, within a couple of hours, haemolytic anaemia and acute renal failure (6,7).

A search in WHO adverse register gave 11 unvalidated reports of uremia, creatinine or urea increase with quinine (one report of creatinine increase, six reports of urea increase and four reports of uremia).

In the present case, the patient has an unsymptomatic rise of creatinine, and this is not a clinical picture similar to those reported in the literature. However, it is recommended that quinine in this case is withdrawn and the creatinine level followed (8). The manufacturer, Pharmacia & Upjohn, is aware of these reported cases and is considering registering renal failure as an adverse effect of quinine in FASS (8). The Department of Nephrology at Huddinge Hospital recommends that they be consulted in further evaluation of the patient´s condition (9).

We recommend this case be reported to SADRAC (Swedish Adverse Drug Reactions Advisory Committee).