| Abstract|| |
Acute renal failure is one of the serious complications of malaria with untoward consequences including increased risk of mortality. This study was conducted to evaluate the incidence, clinical features, course, outcome, and predictors of mortality of acute renal failure (ARF) in children with malaria in the pediatric general wards and intensive care unit of our medical center from 1 January 2009 to 31 December 2009. Data of all children from 1 month to 12 years of age with confirmed malaria either on peripheral smear and/or OptiMal test were reviewed. Those suffering from ARF were selected for further study. Twelve (eight Plasmodium falciparum; three Plasmodium vivax, and one mixed infection) out of 227 (5%) cases of confirmed malaria had ARF. In addition to ARF, most of the patients had at least one other manifestation of severe malaria. Nine (75%) patients recovered completely, while 3 (25%) died. Presence of associated cerebral malaria, hyperbilirubinemia, and disseminated intravascular coagulopathy (DIC) was a poor prognostic factor and predictor of mortality. In conclusion, ARF can complicate both P. falciparum and P. vivax malaria. Malarial ARF as an isolated complication has a good prognosis. The presence of multiorgan involvement and delayed diagnosis increases morbidity and mortality.
|How to cite this article:|
Zaki SA, Shenoy P, Shanbag P, Mauskar A, Patil A, Nagotkar L. Acute renal failure associated with malaria in children. Saudi J Kidney Dis Transpl 2013;24:303-8
|How to cite this URL:|
Zaki SA, Shenoy P, Shanbag P, Mauskar A, Patil A, Nagotkar L. Acute renal failure associated with malaria in children. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Dec 14];24:303-8. Available from: http://www.sjkdt.org/text.asp?2013/24/2/303/109585
| Introduction|| |
Malaria is a major problem in the developing countries, with an estimated 300-500 million cases and more than 1 million deaths each year.  The global prevalence of acute renal failure (ARF) in malaria has been reported as 0.57%-60%. In developing countries such as India, the incidence of ARF varies from 13% to 17.8%.  Renal involvement has been reported commonly with Plasmodium falciparum (Pf) and occasionally with Plasmodium vivax (Pv) and Plasmodium malariae infections.  ARF in malaria is emerging as an important problem in tropical countries and carries a high mortality, especially when there is a delay in the diagnosis and initiation of treatment. Although there are studies describing the association of ARF with malaria in adults, very few have been reported in children. ,, Hence, we aim in this study to analyze the clinical features, course, outcome, and predictors of mortality in children having ARF following malaria.
| Material and Methods|| |
This was a retrospective study done on confirmed cases of malaria admitted in the pediatric general wards and intensive care unit of Lokmanya Tilak Municipal Medical College and General Hospital, a tertiary care hospital in Mumbai, India, from 1 January 2009 to 31 December 2009. The hospital is situated in close proximity to Dharavi, one of the largest slums in Asia. Our hospital has 102 pediatric beds and approximately 6000 pediatric admissions per year. Data of all children from one month to 12 years of age who were admitted with malaria, diagnosed either by positive blood smears for malarial parasites and/or positive rapid antigen test (OptiMAL test), were reviewed. Those suffering from ARF were selected for further study. ARF in malaria was defined as per the revised World Health Organization (WHO) criteria, i.e. serum creatinine >3 mg% and urine output <12 mL/kg/24 h despite adequate volume repletion. ,, The study included patients diagnosed and treated primarily at our hospital as well as patients already diagnosed before presentation. The patients received partial or complete treatment with antimalarial agents before referral to our hospital. As the co-existence of other diseases may influence the clinical presentation and outcome of malaria, children with associated infection such as dengue fever, leptospirosis, enteric fever, urinary tract infection, glucose-6-phosphate dehydrogenase deficiency, and viral hepatitis were excluded.
A case sheet proforma was prepared and data from all the case records were filled up and analyzed. The data included mode of presentation, clinical course, investigations, treatment, response to therapy, and complications. Systemic complications of malaria were defined as per the WHO criteria for severe malaria. ,, All the patients with malarial ARF received intravenous artesunate in recommended doses.  Supportive treatment in the form of intravenous antibiotic as per creatinine clearance, fluid replacement, correction of electrolyte and acid-base imbalance, and furosemide was started as indicated. Dialysis was initiated when conservative management failed.
| Statistical Analysis|| |
Data analysis was performed using software package SPSS version 15.0 by Chi-square test and by Fisher Exact test. To assess the factors adversely affecting the outcome, the patients were divided into those who survived and those who expired during the course of their illness A P value of <0.05 was considered as significant for all statistical analyses.
| Results|| |
A total of 227 cases of confirmed malaria were admitted, out of which 133 were due to Pv (58.59%), 67 (29.51%) were due to Pf, and 27 (11.89%) were mixed infections (i.e. both Pv and Pf). Rapid antigen test, i.e. OptiMal, was positive in all 227 cases and 197 cases had peripheral smear positive for malarial parasite. Twelve (eight Pf; three Pv, and one mixed infection) patients had ARF complicating malarial infection. The male to female ratio was 2:1 and all were above five years of age. The clinical presentation and associated complications are shown in [Table 1], reflecting that a majority of the patients had severe malarial infection. Probable factors contributing to ARF are presented in [Table 2]. Of the three patients who died, one had Pv and two had Pf malaria. Dialysis was initiated in only one patient. Dialysis could not be initiated in the other two patients who died due to their poor general condition and circulatory collapse. All the three patients who expired had multiorgan dysfunction (MOD; ≥2 organ systems), and death occurred within 48 h of admission. They were managed with intravenous fluids, presser treatment, intravenous antibiotic in doses as per creatinine clearance, and antimalarial agents. [Table 3] shows the indicators of mortality in patients with malarial ARF. The presence of cerebral malaria, hyperbilirubinemia, and disseminated intravascular coagulatopathy (DIC) was significantly associated with a poor outcome. ARF completely resolved with conservative treatment within two weeks in the nine patients who survived.
|Table 1: Clinical features and associated complications of patients with ARF in malaria.|
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| Discussion|| |
ARF is a serious complication of malaria in nonimmune adults and older children, which carries a mortality of 15%-45%.  It can occur as an isolated complication or as a component of multiorgan involvement. It occurs commonly in Pf malaria although its occurrence has been reported rarely in Pv malaria.  In a study by Naqvi et al in patients of all age groups with malarial ARF, out of 124 cases, 121 had Pf and three had Pv malaria.  In a study done by Huda et al in children with severe malaria, 8.7% of the cases had renal failure.  Similar results were observed in our study with incidence of ARF in 5.29% of patients with malaria, of which 63.15% had Pf and 26.3% had P. vivax malaria. ARF in malaria is usually oliguric and hypercatabolic, characterized by a rapid rise of plasma urea and creatinine. ,, The duration of the oliguric phase usually lasts from a few days to several weeks. Occasionally, ARF may be non-oliguric, which can make the diagnosis difficult unless serum creatinine is estimated. We observed oliguric ARF in 75% of our patients, with the duration of oliguria being two to nine days. Similar findings have been reported by Prakash et al in their study where they observed oliguric ARF in 69% of patients, with the duration of oligoanuria being five to 33 days.  In contrast, some studies have found a higher proportion (50%-70%) of non-oliguric renal failure.  The high percentage of oliguric renal failure in our study may also be due to higher referrals of patients with decreased urine output to our tertiary care hospital.
Several hypotheses including mechanical obstruction caused by cytoadherence and sequestration of infected erythrocytes, immune-mediated glomerular pathology, release of cytokines, reactive oxygen intermediates, and nitric oxide by activated mononuclear cells, and alterations in the renal and systemic hemodynamics have been proposed as the mechanisms for renal failure in falciparum malaria. ,,,, However, the cause of renal damage in Pv malaria still remains unclear. Descriptions of vivax-associated renal failure associated with thrombotic microangiopathy and hemolytic uremic syndrome indicate that in some circumstances, Pv might cause microvascular thrombosis, endothelial injury, and thrombocytopenia similar to thrombotic-thrombocytopenic purpura. , Another hypothesis states that although of lesser magnitude, the phenomenon of cytoadherence and/or sequestration commonly described with falciparum can also occur in vivax malaria. The phenomenon of rosetting has also been described ex vivo in vivax malaria; however, its role in pathophysiology is unknown.  In addition to the above, restricted blood flow to the kidneys due to low intake of fluids and loss of fluids because of vomiting and pyrexial sweating can cause dehydration and renal ischemia.  In our study, vomiting was present in all the malarial cases with ARF.
Presence of hyperbilirubinemia in malaria can act as a predisposing factor for ARF. Naqvi et al in their study have found that almost all patients of ARF with jaundice had conjugated hyperbilirubinemia with cholestasis.  This well-described association may contribute to the reduction of glomerular filtration rate or development of acute tubular necrosis. , Pati et al and Burchard et al in their studies found that ARF associated with jaundice had high mortality in comparison to nonjaundiced ARF patients. , Similar findings were noted when ARF was associated with cerebral malaria. In a study conducted by Mishra et al in adult patients, 28.9% cases of cerebral malaria had ARF. In our study, hyperbilirubinemia was present in 41.67% of cases with ARF.
Mortality is as high as 39.5% when cerebral malaria is associated with ARF, while it is only 13.9% in cases without ARF.  It was found in studies on children with severe malaria that the presence of associated DIC increased the mortality rate.  All the patients with malarial ARF, who expired in our study, also had associated hyperbilirubinemia, DIC, and cerebral malaria. Thus, the presence of MOD, i.e. involvement of ≥2 organ systems in patients with malarial ARF, was associated with higher mortality. ,
In addition to hyperbilirubinemia and DIC, other associated complications of malarial infection also predispose and contribute to the pathogenesis of ischemic tubular necrosis and ARF. These include hemolysis, sepsis, gastrointestinal bleed, circulatory collapse, volume depletion, rhabdomyolysis, nephrotoxic drugs, and hyperparasitemia. ,,,,,,,, In our present study, hemolysis (83.33%), sepsis (25%), gastrointestinal bleed (58.33%), hyperparasitemia (25%), and circulatory collapse (66.67%) were noted as the probable factors contributing to ARF. All the three patients who expired had MOD and circulatory collapse at presentation. They were receiving treatment from a local practitioner and were referred to us in a moribund state. All of them expired within 48 h of admission. The remaining nine patients (i.e. 75%) who survived presented at an early stage and the renal failure completely resolved with conservative treatment. Availability of renal replacement therapy for malarial ARF has been shown to improve the outcome. , In our study, 5.29% of patients with malaria had ARF, of whom 25% required dialysis. Early referral to a dialysis-equipped center improves the prognosis in patients with malarial ARF. In our present study, mortality was 25%, which is in agreement with the other studies where renal replacement therapy was available. ,
In conclusion, although ARF occurs more commonly in Pf malaria, Pv infection can cause this complication. Prompt diagnosis and treatment can reduce the mortality and enhance recovery of renal function in malarial ARF.
| Acknowledgment|| |
We wish to thank Dr. Sandhya Kamath, Dean of our institution, for permitting us to publish this manuscript.
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Syed Ahmed Zaki
Department of Pediatrics, Lokmanya Tilak Municipal General Hospital and Medical College, Sion, Mumbai 400022
[Table 1], [Table 2], [Table 3]