Sodium artesunate-induced diuresis in a patient with malaria.

Sodium artesunate is used in the treatment of malaria. We report a case of sodium artesunate induced diuresis and natriuresis in a patient with malaria. Following artesunate administration there was polyuria accompanied by natriuresis that was reversed after discontinuation of artesunate treatment. The diuretic effect of artesunate can modify the course of renal failure in severe malaria. Prescribers should be aware of this effect of artesunate, so that it can be used judiciously and to the advantage of patients with severe malaria.

Introduction

Malaria is a major health problem in the developing world today, with an estimated 300-500 million cases and more than one million deaths each year.[1] Artemisinin and its derivatives are rapidly acting antimalarial compounds effective against resistant strains of Plasmodium falciparum malaria.[2] This has lead to its increased use in public hospitals in developing countries. We herein report a case of sodium artesunate-induced diuresis in a patient with malaria.

Case Report

A 6-year-old boy presented with fever for five days and vomiting for two days. Fever was high grade and associated with chills and rigors. Vomiting was 2–3 times per day and non-projectile, non-bilious, and contained ingested food particles. There was no dysuria, oliguria, abdominal pain, or bleeding manifestations. On examination, the patient was afebrile with a heart rate of 104/min, respiratory rate of 24/min, and blood pressure of 100/60 mm of Hg. There was no pallor, icterus, edema, or significant lymphadenopathy. Liver was soft and non-tender with a span of 6.5 cm in the midclavicular line. Spleen was palpable 3 cms below the costal margin. Other systems were normal. Investigations revealed: hemoglobin 8.2 gm/dL, total leucocyte count 11,300 /mm3 (60% polymorphs, 40% lymphocytes) and platelet count 53000 /mm3. Liver function tests, renal function tests, serum calcium, and phosphorous were normal throughout the hospital stay. The arterial blood gas, urine microscopy, and chest X-ray were normal. Peripheral smear examination showed ring forms of P. vivax. OptiMAL test was positive for P. vivax and negative for P. falciparum. Widal test, dri-dot test for leptospira and dengue IgM antibody test were negative. Ultrasonography of the abdomen showed mild splenomegaly and normal kidneys. Intravenous sodium artesunate (2.4 mg/kg), i.e., 38.4 mg was given at 0, 12, 24, and then once a day for 7 days. The patient did not receive intravenous fluids, diuretics, or vasodilators and continued normal diet and fluid intake. The serum electrolytes, urine output, and urinary electrolytes during the course of hospital admission are shown in Table 1. On day 3 of artesunate treatment, the patient developed increased urine output along with increased excretion of sodium, potassium, and chloride. The urine output and urinary excretion of electrolytes gradually increased till day seven. Two days after stopping artesunate the urine output and urinary excretion of electrolytes started decreasing. Patient became afebrile on day three and was discharged from the hospital on day 11 of admission. He was asymptomatic without any urinary complaints on follow-up after three months.

Table 1

Serial values of serum electrolytes, urine output, and urinary electrolytes in patient on artesunate treatment

Discussion

The artemisinin derivatives artemether, artesunate, and dihydroartemisinin are derived from the chinese medicinal herb, qinghao.[2] Sodium artesunate is a new antimalarial water soluble drug, which can be administered either by intravenous or intramuscular injection.[3] It is more potent than quinine and rapidly reduces parasitemia and resolves clinical symptoms in resistant parasites strains.[34] Sodium artesunate has been found to have a diuretic and natriuretic effect.[45] It causes renal vasodilatation and increase in renal blood flow leading to natriuresis. This action is due to increased nitric oxide synthesis and inhibitory effect on chloride transport across the cortical thick ascending loop of Henle (TALH) that suppresses tubuloglomerular feedback.[45] Nitric oxide causes diuresis and natriuresis by inhibiting the activity of the Na, K-ATPase and tubular sodium transport.[4] The principal site of action of artesunate in kidneys is supposed to be TALH, which has the highest concentration of the enzyme Na, K-ATPase per tubular length. The increase in the urinary excretion of sodium, chloride and potassium also suggests that this drug has a predominant effect on the proximal segments of the nephron i.e. proximal tubule and the TALH.[4] Reduction in the reabsorption of sodium and an increase in the distal sodium delivery occurs with a consequent greater sodium reabsorption and potassium secretion in the collecting tubule.[4]

The diuretic effect of artesunate is a double-edged weapon that can modify the course of the acute renal failure in malaria. The increase urinary loss of water and electrolytes can worsen the renal failure in hypovolemic patients with pyrexia and tachypnea. However, the administration of artesunate can also be useful in the conversion of an oliguric renal failure to nonoliguric in patients with volume overload. In addition, rapid improvement in pulmonary function has been observed in a patient with respiratory distress syndrome due to the diuretic effect of artesunate.[5] In conclusion, the diuretic effect of artesunate can modify the course of renal failure and respiratory distress syndrome, both of which complicate severe malaria. Physicians should be aware of this effect of artesunate, so that it can be used judiciously and to the advantage of patients with severe malaria.