Saudi Journal of Kidney Diseases and Transplantation

: 2019  |  Volume : 30  |  Issue : 4  |  Page : 960--963

Acute kidney injury due to acute cortical necrosis following vivax malaria

Ranjith K Nair, Konapur Ananth Rao, D Mukherjee, Bhaskar Datt, Sourabh Sharma, Sudeep Prakash 
 Department of Nephrology, Army Hospital Research and Referral, New Delhi, India

Correspondence Address:
Konapur Ananth Rao
Department of Nephrology, Army Hospital Research and Referral, New Delhi - 110 010


Malaria is a parasitic infection of global importance but has a high prevalence in the developing countries. Renal failure is a common complication of severe Plasmodium falciparum malaria and has been reported in up to 40% of all cases. Acute kidney injury (AKI), however, is not commonly associated with Plasmodium vivax infection. In those patients who develop AKI following P. vivax infection, the cause is commonly attributed to mixed undiagnosed falciparum infection or coexistent sepsis, dehydration, or hypotension. Infrequently, an association of P. vivax infection with thrombotic microangiopathy (TMA) has been reported. The purpose of this report is to describe renal failure due to TMA following malaria caused by P. vivax. A 24-year-old female presented with a history of fever and jaundice of two weeks duration followed by progressive oliguria and swelling of the face and feet five days after the onset of fever. The evaluation revealed normal blood pressure, anemia, thrombocytopenia, azotemia, unconjugated hyperbilirubinemia with mildly elevated transaminases, and elevated lactate dehydrogenase. Peripheral smear was positive for P. vivax, and schistocytes were seen. She was given intravenous artesunate followed by oral primaquine for 14 days. Urine examination showed proteinuria and microscopic hematuria. She remained oliguric and dialysis dependent, and her kidney biopsy revealed patchy cortical necrosis involving 40% of sampled cortex with widespread fibrinoid necrosis of the vessel wall, red blood cell fragmentation, and luminal thrombotic occlusion. Hemodialysis was discontinued after three weeks when there was the improvement of renal function over time, and her serum creatinine decreased to 2.2 mg/dL by six weeks. Patients with P. vivax malaria developing renal failure may have TMA. Renal biopsy, if performed early in the course of the disease, may identify TMA and institution of plasma exchange in such patients could help in early recovery.

How to cite this article:
Nair RK, Rao KA, Mukherjee D, Datt B, Sharma S, Prakash S. Acute kidney injury due to acute cortical necrosis following vivax malaria.Saudi J Kidney Dis Transpl 2019;30:960-963

How to cite this URL:
Nair RK, Rao KA, Mukherjee D, Datt B, Sharma S, Prakash S. Acute kidney injury due to acute cortical necrosis following vivax malaria. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2021 Sep 21 ];30:960-963
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Full Text


Malaria is endemic in the Indian subcontinent and is commonly caused by Plasmodium vivax and Plasmodium falciparum species. Severe thrombocytopenia is a feature of P. falciparum species,[1] while it is rare in vivax malaria.[2]

Acute kidney injury (AKI) due to P. vivax malaria is uncommon.[3]

 Case Report

Informed consent was obtained from the patient before presenting the report.

A 24-year-old female, resident of Mathura, Uttar Pradesh, India, presented to her local clinic with complaints of high-grade intermittent fever associated with chills for 10 days, yellowish discoloration of eyes and urine, generalized pain abdomen, nausea and vomiting for seven days, which was followed by decreased urine output, facial puffiness, and swelling of the feet for five days. There was no history of diarrhea. Her obstetric history was gravida - 5, para - 3, abortion - 2, live -3, and the last childbirth was two years ago. Her last menstrual period occurred just before the onset of fever. On examination, the patient was conscious and cooperative. She was afebrile with a pulse rate of 96/min and blood pressure of 110/60 mm Hg in the right arm in the supine position. There was pallor, icterus, and bilateral pitting pedal edema. There was no petechiae/ecchymosis/skin rash. Her abdomen was distended, with tenderness in all quadrants without any guarding or rigidity. She had mild splenomegaly (tip palpable), the liver was not palpable and had a span of 12 cm on percussion. Her flanks appeared full and were dull on percussion. Respiratory system examination revealed stony dullness in the bilateral infrascapular region.

The investigations on day-3 of her fever showed anemia [hemoglobin (Hb) 10.3 g/dL], which worsened (7.7 g/dL) on day-6, and thrombocytopenia (platelets: 11 × 103/mm3). The total leukocyte count was 7000/mm3 with 75% neutrophils, 21% lymphocytes, 2% monocytes, and 2% eosinophils. By day-7 of fever, the thrombocytopenia had resolved (platelets: 110 × 103/mm3). Peripheral smear showed microcytic normochromic red blood cells (RBCs), reduced platelets, with occasional fragmented RBCs; no schistocytes were seen. Trophozoites and gametocytes of P. vivax were seen. Immunochromatographic test for malaria was negative for P. falciparum. Serology for dengue virus infection (IgM and IgG), enteric fever, and chikungunya were negative, and the blood/urine cultures were sterile. She had azotemia (blood urea of 162 mg/dL and serum creatinine of 6.7 mg/dL), unconjugated hyperbilirubinemia (serum bili-rubin total/direct: 4.9/1.2 mg/dL, respectively), mildly elevated transaminases [aspartate amino-transferase of 150 IU/L, alanine aminotransferase of 103 IU/L, and alkaline phosphatase of 81 U/L), elevated lactate dehydrogenase (LDH) of 2273 U/L and hypoalbuminemia (serum total protein/albumin: 4.1 and 1.8 g/L, respectively). Electrolytes and coagulation parameters were normal. Urine analysis revealed 2+ proteinuria, 8–10 white blood cells, and numerous RBCs/high-power field. There were no casts or Hb in the urine. The serum LDH continued to be elevated, associated with a drop in Hb. In view of ongoing hemolysis, direct and indirect Coomb’s test was performed and found to be negative. Hepatitis B surface antigen, anti-hepatitis C virus antibody, and anti-human immunodeficiency virus antibody were negative. Glucose-6-phosphate dehydrogenase level was normal. Ultrasound of the abdomen showed normal-sized kidneys (10.4 cm bilaterally) with raised echogenicity and maintained corticomedullary differentiation. There were splenomegaly, ascites, and bilateral pleural effusion.

She was managed with injection artesunate followed by tablet artemether + lumefantrine followed by tablet primaquine for 14 days. She was treated with hemodialysis through a double-lumen jugular uncuffed nontunneled catheter on alternate days along with multiple blood transfusions. Nutrition, fluid, and electrolytes were managed appropriately. She was treated with injection piperacillin + tazobactam in renal modified doses for intercurrent infection. A kidney biopsy was performed on day- 14 of her admission due to prolonged anuria and dialysis dependence. It showed features of thrombotic microangiopathy (TMA) with patchy cortical necrosis [Figure 1] and [Figure 2].{Figure 1}{Figure 2}

The patient was a young female with a short febrile episode associated with oliguric AKI, thrombocytopenia, hemolytic anemia, and TMA. As vivax malaria is not a common cause of TMA, autoimmune workup for TMA was performed: anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, and anti-dS DNA were negative; complement C3/C4 levels were normal, and anti-cardiolipin antibody was negative. On the 3rd week of her illness, urine output improved, and she became dialysis independent. At the time of discharge, her serum creatinine was 3.4 mg/dL, Hb was 10 g/dL, platelet count was 2.5 L/mm3, and LDH was 255 U/L. At the end of six months, her serum creatinine was 1.8 mg/dL.


AKI in malaria is of multifactorial etiology in Falciparum malaria. The common mechanisms are: volume depletion, hyperbilirubi- \nemia, intravascular hemolysis, and sepsis.[4] AKI is generally associated with heavy parasitemia. Infected erythrocytes begin to retreat from peripheral to visceral circulation as the knobs appear on the surface. This may explain why, in some patients, parasitemia is not severe despite severe AKI.[5] Peritoneal dialysis is less effective in complicated malaria due to microvascular clogging by infected RBC.[5] Clogging of capillaries causes tissue hypoxia leading to increase in lactate, increase in H+, and decrease in ATP. These factors lead to increased vascular resistance leading to release of hormones causing generalized arterial vasodilation, increased vascular permeability, and increased interstitial volume. As cardio regulatory response, there is increase in sympathetic tone and renin–angiotensin-aldos-terone system activation leading to renal vaso-constriction and AKI. Renal ischemia is the most important pathogenic cause leading to acute tubular necrosis in F. malaria.[6]

Renal cortical necrosis following vivax malaria is being increasingly reported from the Indian subcontinent. P. vivax has been shown to be associated with atypical HUS.[7] Plasma exchange may be helpful in the management of these patients.[7] Vivax malaria can cause TMA with acute cortical necrosis, acute interstitial nephritis, acute tubular necrosis, and severe endothelial injury and subendothelial widening on ultrastructural examination.[8] These features are associated with prolonged oligo-anuria and dialysis dependence. Early recognition and plasma exchange therapy has been reported to be effective in malaria-induced TMA and should be instituted early. The role of complement dysregulation in such cases is yet unclear. Geography, climatic conditions or genetic variation in the local population, can all play a role; although, it is not clear which of them can lead to this condition. Successful renal transplantation in a patient with renal failure due to TMA following vivax malaria has been reported.[9] Biomarkers of endothelial activation (angiopoietin 1 and 2, soluble ang-receptor: Tie-2) are predictors of severe malaria.[10] Endothelial dysfunction and reduction in ADAMTS 13 level associated with large vWF polymers are seen in patients with TMA caused by both P. falciparum and vivax.[11] Inhaled nitric oxide and administration of L-Arginine may improve endothelial function and decrease mortality.[10]


Our patient had complicated malaria as evidenced by severe thrombocytopenia, hemo-lysis and severe oliguric renal failure. Complicated malaria is usually caused by P. falciparum. In case of isolated P. vivax malaria, complications are generally attributed to undetected mixed infection with P. falciparum, dehydration and/or superadded sepsis. Renal failure in malaria is usually multifactorial. TMA is a rare cause of renal failure seen with falciparum malaria and has been increasingly reported following P. vivax infection. Our patient had vivax malaria with TMA leading to cortical necrosis and AKI.

Conflict of interest: None declared.


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