Acute kidney injury (AKI) in pregnancy, though uncommon, is responsible for 15-20% of AKI in the developing countries. Infection and sepsis are considered to be the two major causes of AKI particularly in developing countries like India.
Compared to general population, pregnant women are more susceptible to be infected by malaria parasite. In addition, malaria during pregnancy tends to be more severe and fatal (13%). Only a few cases of vivax malaria causing AKI in pregnancy were reported in the literature. Acute renal failure during pregnancy generally occurs either early in the first trimester, when it complicates septic abortion, or late in the third trimester, when it complicates obstetric events such as abruptio placentae, hemorrhage or severe pre-eclampsia. AKI in pregnancy is associated with increased maternal morbidity and mortality.
The abrupt onset of and quick progression to severity of AKI demands the need for recording such cases to study the disease process. Our objective is to report an atypical case of acute renal failure in late pregnancy caused by vivax malaria; its diagnosis, treatment and follow up.
Case History :
Mrs. B.G., a G4 P1+2 lady, with history of caesarean section 7 years back, had booked in our antenatal clinic at 9 weeks of pregnancy with regular antenatal visits until she was admitted with history of fever and mild leg pain at 35 weeks of pregnancy on 23rd September 2016.
Her fever used to come every alternate day. She, however, does not have any significant headache, vomiting, urinary symptoms or typical chill with rigor before the rise of temperature. Except persistent tachycardia (100-110/min), all her examination findings were within normal limits. Her initial investigation reports including the slide for malaria parasites, dual antigen for malaria and Dengue IgM and IgG by ELISA were negative. Her blood and urine culture reports were sent. She was kept on paracetamol on a need basis. Thick and thin slides for MP and dual antigen for malaria were repeated on two more occasions; but without any positive result.
On the night of 27th September 2016, she developed dribbling, for which caesarean section was done on the following morning i.e. on 28th September, 2016. Following an uncomplicated operation, she was shifted to the post operative ward. In the evening she had an episode of fever with profuse sweating. On examination, she was alert, conscious, with a pulse rate of 140-150 bpm, BP of 90/50 mm Hg, SpO2 of 90% in room air and urine output of 40-50 ml per hour. There was no obvious clinical evidence of sepsis, PPH or cardiac cause. She was shifted to ICU for monitoring and evaluation of the unexplained tachycardia including repeat fever screening. ECG showed evidence of sinus tachycardia. On the morning of 29th September, it was observed that during the night her vital parameters remain almost unchanged except gradual reduction in the urine output. Initially there was oliguria (10-15 ml/hour) for 4 hours (from 3 am to 7 am) and finally anuria (5 ml). Considering hypoperfusion as a cause, intravenous fluid and frusemide challenge was done without any positive response. All the investigations (CBC, MP, dual antigen for malaria, LFT, renal function test, coagulation screen, CRP, PROCAL, USG abdomen, ECG and echo and urine) were sent.
In the afternoon, trophozoites for Plasmodium Vivax was detected in the slide. Repeat dual antigen for malaria parasite was also positive for P.vivax. Artisunate by IV was started under supervision of Medicine consultant. As sepsis could not be ruled out conclusively, broad spectrum IV antibiotics with meropenem, tegecycline and levofloxacin were also started. Her blood urea was 46 mg/dl and creatinine 2.9 mg/dl. But she continued to have persistent anuria. Moreover, she developed bilateral leg swelling and facial puffiness. In the evening, her blood urea and creatinine increased to 96 mg/dl and 3.6 mg/dl respectively. Her haematological parameters were indicative of haemolysis and thrombocytopenia (platelet count 30,000) and anaemia (Hb 6.0 g/dl). So, she was transfused with 2 units of packed cell, 2 units of whole blood and 5 units each of single donor platelet on two consecutive days. She also developed deranged liver function with billirubin 6.8 mg%, ALT 263 IU/L and ALT 306 IU/L. USG showed evidence of bilateral renal parenchymal disease. Other supportive managements with oxygen inhalation and CPAP were also maintained. The dosages of all the drugs used were adjusted according to the deranged renal function. On 30th September 2016, haemodialysis was started by the nephrologist. Initially haemodialysis was done daily with adjustable loss; thereafter it was performed on the basis of the alternate day renal function test. Gradually her urine output increased over a period of 7 days thereby reducing the need of and increasing the interval of dialysis. Her general condition also improved gradually with correction of anaemia, thrombocytopenia and haemolytic manifestations. Finally, it was possible to discharge her on 14th October 2016 with advice of OPD based dialysis at twice weekly interval and follow-up. Gradually the interval between dialysis was increased and she had her last dialysis on 28 November 2016 with almost complete reversal of renal function.
The frequency distribution of pregnancy related AKI is bimodal in relation to period of gestation. The first peak is seen between 7-16 weeks, mainly due to septic abortion, while toxemia of pregnancy, haemorrhage and puerperal sepsis account for 2nd peak between 34-36week. Lindheimer and Katz3 have noted that acute renal failure complicating pregnancy generally occurs at 12 to 18 weeks as a complication of septic abortion and at 35 to 40 weeks as a complication of abruption placentae, hemorrhage or PIH.
Soyannwo, Armstrong and McGeown described a patient with acute renal failure following hyperemesis at 30 weeks of pregnancy who recovered without dialysis; the fetus was delivered at 38 weeks' gestation. Kurtz and coworkers1 reported successful labour at term in a patient in whom acute renal failure developed at 22 weeks of pregnancy following hypotension during dialysis therapy for a glutethimide overdose. Farzana rabee Choudhury reported a case of AKI in pregnancy following septic abortion.
In developing countries of tropical region, where malaria is endemic, the malaria parasite infestation along with gram negative septicemia is considered important risk of developing AKI. Haemodynamic changes in pregnancy particularly during the peripartum period add fuel to it.
Till today, only limited numbers of cases of AKI in pregnancy were reported. Our patient presented with alternate day fever and persistent trachycardia, without any other characteristic features of malaria. She was diagnosed to have severe vivax malaria, following development of anuria soon after caesarean section. AKI was diagnosed by anuria and rapid rise of serum creatinine level and USG findings of kidney. The patient responded to antimalarial drugs and renal function improved with repeated haemodialysis.
Even after 4 dialyses, there was no improvement in renal function. She started producing urine with slight declining trend in serum creatinine from 5th dialyses onwards. She was discharged after 10 dialyses for continuing the same as an OPD procedure on a twice weekly basis until her urine output becomes normal and serum creatinine high normal. The entire period of illness was about 2 months.
Malarial related AKI (MAKI) occurs in 1% to 5% of all cases of AKI in endemic areas, whereas the prevalence in immune-compromised individuals is around 25% to 30%. Due to the hormonal, immunological and hematological changes of pregnancy, the parasitemia tends to be 10 times higher and as a result, malaria tends to be more severe as well as fatal in pregnancy compared to the non-pregnant population. Malaria during pregnancy tends to be more severe and atypical in presentation. So, any febrile patient during pregnancy must be investigated for malaria.
In severe malaria there is tubular degeneration associated with distal tubular necrosis. Casts loaded with malarial pigments and haemoglobin granules may be found in the tubular cells. Severe malaria can cause acute kidney injury by several pathologies - inability of parasitise infested RBCs to deform according to the need of microcirculation leading to sluggish blood flow and consequently to renal ischaemia; hypovolumia; non-specific effects of inflammation and increased vascular permeability; intravascular coagulation; increased plasma viscosity due to infection; release of chemical mediators (TNF etc.) that produce vasoconstrictor effect; hyperbilirubinaemia etc. MAKI during pregnancy is diagnosed by elevation of serum creatinine level above 3 mg/dL ( 265 mol/L) and/or when urinary output is less than 400 ml in 24 hours keeping in mind the renal physiological alteration in pregnancy. Treatment efficacy depends on proper fluid balance, electrolyte monitoring along with haemodialysis. Dose adjustment of antimalarial and other antibiotics is vital to avoid further nephrotoxicity. More critical Situation arises when fetus remains in-utero as teratogenic drugs have to be avoided.
Better education, higher standards of living and improvements in obstetric care have drastically brought down the incidence of pregnancy related AKI in the tropics, caused by unsafe home deliveries, illegal septic abortions, renal ischemia due to hemorrhagic shock or hypotension. Maternal mortality from AKI has decreased to great extent by early diagnosis, infection control and appropriate therapy in higher center.
The tragedy of AKI in pregnancy is increased morbidity and many times increased mortality. In tropics malaria, even by Plasmodium vivax, can lead to severe parasite load and sequentially impaired renal microcirculation, renal tubular ischemia and necrosis, haemolysis, thrombocytopenia and multi organ failure. So, any febrile illness in pregnancy should be thoroughly evaluated. Presentation of malaria may not always be typical; so, repeated evaluation of MP slides should be carried out in an otherwise unexplained fever. AKI following even benign malaria is a distinct possibility. So, strict urinary output should be maintained. Early detection of AKI is possible by monitoring vital signs and urine output, and blood urea and creatinine in suspected cases. Prompt antimalarial therapy, along with maintenance of fluid and electrolyte balance and supportive hemodialysis in cases of malaria induced AKI can reduce maternal morbidity and mortality.