|
 
 |
| ORIGINAL ARTICLE |
|
| Year : 2016 | Volume
: 5
| Issue : 3 | Page : 138-141 |
|
Acute kidney injury in patients with Plasmodium vivax malaria: Clinicohistopathological profile
Piyush Kimmatkar, Rajesh Jhorawat, Kunal Gandhi, Rajesh Kumar, Vinay Malhotra, Dhananjai Agrawal, Pankaj Beniwal
Department of Nephrology, SMS Hospital, Jaipur, Rajasthan, India
| Date of Web Publication | 14-Dec-2016 |
Correspondence Address:
Kunal Gandhi
Department of Nephrology, SMS Hospital, Jaipur, Rajasthan
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2278-0521.195819
Context: There has been an unexplained increase in the number of cases with multiorgan dysfunction including acute kidney injury (AKI), attributed to Plasmodium vivax monoinfection. Only a few case reports in literature have published the renal biopsy findings in these patients. Aims: The aim of this study was to evaluate the clinical and histopathologic profile of patients with P. vivax malaria monoinfection and AKI. Settings and Design: A prospective study was performed in a tertiary care hospital in North-Western India. Subjects and Methods: The study included patients diagnosed with P. vivax monoinfection on peripheral smear blood films and rapid diagnostic test (positive for P. vivax specific lactate dehydrogenase). AKI was defined based on the WHO criteria for complicated malaria, i.e. serum creatinine >265 μmol/l or 3 mg/dl. The patients were initiated on hemodialysis for persistent hyperkalemia, fluid overload, severe metabolic acidosis, or uremic symptoms. Renal biopsy was performed in the presence of active urinary sediments (proteinuria, hematuria) or persistence of renal failure >14 days. Results: A total of thirty patients fulfilled AKI criteria. The patients with AKI were older (mean age 42.1 ± 10.9 years), male, with a longer duration of illness (mean 12.3 ± 10 days) and associated with multisystem dysfunction. The mean serum creatinine was 7.58 ± 3.2 mg/dl, thrombocytopenia was seen in 47%. Thirty percent had severe anemia requiring a blood transfusion. Renal biopsy was performed in six patients for various indications. The most common pattern was acute tubular necrosis (four patients), followed by acute cortical necrosis (1), and thrombotic microangiopathy (one patient). The complete renal recovery was seen in 24 (80%). Two patients became dialysis-dependent. Conclusions: AKI associated with P. vivax monoinfection is not rare as previously thought. Therefore, it should be considered in the differential diagnosis of any patient presenting with AKI. Keywords: Acute kidney injury, malaria, Plasmodium vivax
How to cite this article:
Kimmatkar P, Jhorawat R, Gandhi K, Kumar R, Malhotra V, Agrawal D, Beniwal P. Acute kidney injury in patients with Plasmodium vivax malaria: Clinicohistopathological profile. Saudi J Health Sci 2016;5:138-41 |
How to cite this URL:
Kimmatkar P, Jhorawat R, Gandhi K, Kumar R, Malhotra V, Agrawal D, Beniwal P. Acute kidney injury in patients with Plasmodium vivax malaria: Clinicohistopathological profile. Saudi J Health Sci [serial online] 2016 [cited 2023 Mar 22];5:138-41. Available from: https://www.saudijhealthsci.org/text.asp?2016/5/3/138/195819 |
| Introduction | |  |
Malaria is a major public health problem in India with an estimated 0.88 million cases/year. Severe malaria results in approximately 400-1000 deaths/year. [1] Most of these cases are secondary to Plasmodium falciparum. However, recently, there have been an increased number of observational studies reporting severe manifestation in patients with Plasmodium vivax monoinfection as well. These include cerebral malaria, acute kidney injury (AKI), liver dysfunction, acute respiratory distress syndrome (ARDS), shock, and death. [2] The reason for this increase in severity is unknown.
AKI is a major cause of morbidity and mortality in severe malaria with an incidence of 15%-40% in various reports. [3],[4] As stated previously, falciparum is a major contributor to this. However, AKI has also been reported in 12%-20% patients with vivax malaria. [4],[5] Whether this is solely due to vivax malaria or a mixed infection is still debated. Although, molecular studies have shown that P. vivax monoinfection can lead to severe kidney injury if left untreated. There is a lack of research into the exact pathophysiological mechanism leading to AKI. Data suggest that not all patients with vivax AKI recover their renal function completely and 10%-20% may require renal replacement therapy in the future. The mortality is also between 10% and 15% which is comparable to severe falciparum malaria. [4] Hence, vivax malaria, after all, is not so benign as previously thought.
Renal biopsy findings in malarial AKI include acute tubular necrosis (ATN), acute cortical necrosis (ACN), mesangioproliferative glomerulonephritis, and in chronic antigenemia, it includes membranoproliferative glomerulonephritis. These have been reported in both falciparum and vivax malaria. [5] There is no histopathological pattern specific to any of these infections. Furthermore, there is a lack of data on the correlation of histopathological findings and outcomes in patients with vivax malaria and AKI.
This prompted us to evaluate the clinical and histopathologic profile of patients with P. vivax malaria monoinfection and AKI.
| Subjects and Methods | | |
The study was conducted from May 2013 to May 2015 at a tertiary care government-funded hospital catering to patients predominantly of North-Western India. The patients aged 18 years or above with P. vivax monoinfection and AKI were included in the study. The patients with P. falciparum and/or mixed infection were excluded from the study. Other causes of AKI (dengue infection, viral hepatitis, enteric fever, scrub typhus, and sepsis) were excluded by history and relevant investigations. The patients already suffering from other preexisting diseases such as hypertension, diabetes mellitus, and chronic kidney disease were also excluded from the study.
P. vivax monoinfection was diagnosed by direct visualization of parasite in Giemsa-stained peripheral blood smears (thick and thin) and examined under oil immersion microscopy along with rapid diagnostic test based on detection of P. vivax specific lactate dehydrogenase (LDH). The detailed clinical characteristics and laboratory parameters including complete blood counts (hemoglobin, total and differential leukocyte count, platelet count), renal function test, liver function tests, serum LDH, and urine examination were noted. Renal biopsy was performed in the presence of an active urine sediment (proteinuria >1 g/24 h, red blood cells [RBCs] >5/hpf, RBC cast) or in the absence of renal recovery after 14 days of initial insult. Informed consent was taken after explaining in detail regarding the procedure to the patients and his/her relatives.
The patients were treated as per the WHO guidelines. [1] Indications for dialysis included oliguria in spite of adequate hydration and/or diuretics, severe metabolic acidosis unresponsive to bicarbonate therapy, hyperkalemia unresponsive to conservative management, encephalopathy, and/or worsening serum creatinine values. Hemodialysis was performed via a temporary double-lumen central venous catheter inserted in the internal jugular, subclavian, or femoral veins. Dialysis was withheld in patients with urine output >1 L and stabilization of renal functions. The patients were followed until 6 months after initial hospitalization.
Statistical analysis
Continuous variables were expressed as a mean ± standard deviation. Categorical variables were presented as frequencies and percentages. All the analyses were done using IBM SPSS Statistics (Version 19 for Windows; IBM, Armonk, NY, USA) and MedCalc for Windows, version 12.3 (MedCalc Software, Ostend, Belgium).
| Results | | |
A total of thirty patients diagnosed with P. vivax malaria fulfilled the inclusion criteria. The mean age was 42.1 years, with 21 males and 9 females. Clinical characteristics are depicted in [Table 1]. Fever was present in all patients. Almost 37% of the patients had multiorgan dysfunction. One patient had hemolytic uremic syndrome with microangiopathic hemolytic anemia and was initiated on plasmapheresis. The mean serum creatinine in our population was 7.58 mg/dl [Table 2]. Abnormal urinary sediments were seen in 9 (30%) patients, of whom seven had proteinuria, six had RBCs, and two had RBC cast [Table 3]. Renal biopsy was performed in six patients, of whom four patients had features of ATN, one patient had features of thrombotic microangiopathy, while another one had features of ACN [Table 4]. | Table 1: Clinical profi le of acute kidney injury due to Plasmodium vivax malaria (n=30)
Click here to view |
All patients were initiated on hemodialysis, with an average of 3.5 session per patient. Of these, 24 (80%) recovered their renal functions, with two progressing to chronic kidney disease. Four (13.3%) died within a month of initiation of illness, with ARDS as the most common cause of death, followed by superimposed sepsis and refractory shock. Renal outcome was best in ATN patients with 100% renal recovery while a patient with thrombotic microangiopathy had a partial recovery of the renal function. One patient with ACN continued to remain on dialysis after 6 months.
| Discussion | | |
Traditionally, thought to be a benign agent with a low fatality, P. vivax can also cause severe disease like P. falciparum. Multiple studies have shown that vivax malaria can be complicated by thrombocytopenia, severe anemia, renal involvement, and ARDS. [2],[3] Approximately 10%-20% of malaria-related AKI has been linked to infection with P. vivax. [2],[3],[4]
The spectrum of disease associated with P. vivax infection ranges from asymptomatic parasitemia to uncomplicated febrile illness, to severe and fatal malaria. [5],[6] Severe P. vivax malaria is defined as for falciparum malaria but with no parasite density thresholds. [1] Severe P. vivax malaria is characterized by lower blood-stage parasitemia than is observed in severe cases of falciparum malaria. Unlike P. falciparum infection, P. vivax-associated pathogenesis is not associated with significant microvascular obstruction of vital organs. Nevertheless, low blood-stage parasitemia may mask parasite sequestration outside the vascular system (e.g., in the spleen), which may explain how severe syndromes can develop at relatively low levels of parasitemia. [1]
In our study, hepatic dysfunction was the most common complication, apart from renal failure which is similar to the reported observations in severe P. falciparum malaria and P. vivax malaria in this region. [7],[8],[9],[10] ARDS occurred in two patients, both of whom died. Pulmonary syndromes associated with P. vivax malaria include acute noncardiogenic pulmonary edema, ARDS, acute pulmonary injury, and interstitial pneumonia. [11],[12],[13] In a study conducted in Papua New Guinea, these pulmonary complications were the most commonly observed P. vivax--associated complications. [14] Severe anemia was also commonly seen in our population, which is similar to other reports. [15] Interestingly, coma and other neurological complications are rare as is the case with severe P. falciparum malaria outside of Africa. Even in our population, neurological dysfunction was seen in just two patients. Most of our patients had ATN on renal biopsy, which is the most common cause of infection-related AKI worldwide. The renal outcome of ATN is generally favorable. All the patients in our study with ATN completely recovered their renal function. In comparison, one patient had ACN with persistent anuria (urine <100 ml/24 h) and continued to remain dialysis-dependent at 6 months. Interestingly, 1 patient had clinical evidence of hemolytic uremic syndrome and was empirically initiated on plasmapheresis. The patient partially recovered his renal function after eight continuous sessions of plasmapheresis and was dialysis-independent at the end of the study.
Severe malaria results from a combination of parasite-specific factors, such as adhesion and sequestration in the vasculature and the release of bioactive molecules, together with host inflammatory responses. P. vivax preferentially infects young RBCs, parasitemia rarely exceeds 2% of circulating RBCs, and high parasite burden is not a feature of the severe disease. [16] However, cytokine production during P. vivax infections is higher than P. falciparum infections of similar parasite biomass. Various factors such as heavy parasitemia, volume depletion, hyperbilirubinemia, intravascular hemolysis, renal ischemia, sepsis, disseminated intravascular coagulation, cytoadherence to endothelial cells, and microvascular sequestration are postulated to contribute to AKI. [17],[18],[19],[20]
Our study was possibly limited by the fact that polymerase chain reaction testing for P. vivax monoinfection was not done. Furthermore, our sample size was small, and biopsy was performed in a small number of patients, which may have not given the full spectrum of histopathological manifestations.
The observation that P. vivax is responsible for significant malaria morbidity awaits for a large-scale study to determine the exact pathogenesis, clinical spectrum, and burden of P. vivax malaria so that adequate control measures can be implemented against this emerging but neglected disease.
| Conclusions | | |
AKI which is a frequent complication of P. falciparum malaria is also being increasingly recognized in P. vivax malaria. Hence, our study highlights the importance of considering P. vivax in the differential diagnosis of any infection-related acute kidney.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | |
| 2. | Kochar DK, Das A, Kochar SK, Saxena V, Sirohi P, Garg S, et al. Severe Plasmodium vivax malaria: A report on serial cases from Bikaner in Northwestern India. Am J Trop Med Hyg 2009;80:194-8.  |
| 3. | Srivastava S, Ahmad S, Shirazi N, Kumar Verma S, Puri P. Retrospective analysis of vivax malaria patients presenting to tertiary referral centre of Uttarakhand. Acta Trop 2011;117:82-5. |
| 4. | Kanodia KV, Shah PR, Vanikar AV, Kasat P, Gumber M, Trivedi HL. Malaria induced acute renal failure: A single center experience. Saudi J Kidney Dis Transpl 2010;21:1088-91. [ PUBMED]  |
| 5. | Anstey NM, Douglas NM, Poespoprodjo JR, Price RN. Plasmodium vivax: Clinical spectrum, risk factors and pathogenesis. Adv Parasitol 2012;80:151-201. |
| 6. | Douglas NM, Anstey NM, Angus BJ, Nosten F, Price RN. Artemisinin combination therapy for vivax malaria. Lancet Infect Dis 2010;10:405-16. |
| 7. | Kochar DK, Singh P, Agarwal P, Kochar SK, Pokharna R, Sareen PK. Malarial hepatitis. J Assoc Physicians India 2003;51:1069-72. |
| 8. | Kochar DK, Kaswan K, Kochar SK, Sirohi P, Pal M, Kochar A, et al. A comparative study of regression of jaundice in patients of malaria and acute viral hepatitis. J Vector Borne Dis 2006;43:123-9. |
| 9. | Kumar S, Melzer M, Dodds P, Watson J, Ord R. P. vivax malaria complicated by shock and ARDS. Scand J Infect Dis 2007;39:255-6. |
| 10. | Tanios MA, Kogelman L, McGovern B, Hassoun PM. Acute respiratory distress syndrome complicating Plasmodium vivax malaria. Crit Care Med 2001;29:665-7. |
| 11. | Habib AG, Singh KS. Respiratory distress in nonimmune adults with imported malaria. Infection 2004;32:356-9. |
| 12. | Sarkar S, Saha K, Das CS. Three cases of ARDS: An emerging complication of Plasmodium vivax malaria. Lung India 2010;27:154-7. [ PUBMED] |
| 13. | Taylor WR, Cañon V, White NJ. Pulmonary manifestations of malaria: Recognition and management. Treat Respir Med 2006;5:419-28. |
| 14. | Genton B, D′Acremont V, Rare L, Baea K, Reeder JC, Alpers MP, et al. Plasmodium vivax and mixed infections are associated with severe malaria in children: A prospective cohort study from Papua New Guinea. PLoS Med 2008;5:e127. |
| 15. | Tjitra E, Anstey NM, Sugiarto P, Warikar N, Kenangalem E, Karyana M, et al. Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: A prospective study in Papua, Indonesia. PLoS Med 2008;5:e128. |
| 16. | Mohapatra MK, Padhiary KN, Mishra DP, Sethy G. Atypical manifestations of Plasmodium vivax malaria. Indian J Malariol 2002;39:18-25. |
| 17. | Anstey NM, Russell B, Yeo TW, Price RN. The pathophysiology of vivax malaria. Trends Parasitol 2009;25:220-7. |
| 18. | Prakash J, Singh AK, Kumar NS, Saxena RK. Acute renal failure in Plasmodium vivax malaria. J Assoc Physicians India 2003;51:265-7. |
| 19. | Das BS. Renal failure in malaria. J Vector Borne Dis 2008;45:83-97. |
| 20. | Mishra SK, Das BS. Malaria and acute kidney injury. Semin Nephrol 2008;28:395-408. |
[Table 1], [Table 2], [Table 3], [Table 4]
| This article has been cited by | | 1 |
Renal detection of Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi in malaria associated acute kidney injury: a retrospective case–control study |
|
| Charandeep Kaur,Atreyi Pramanik,Kalpana Kumari,Rajendra Mandage,Amit Kumar Dinda,Jhuma Sankar,Arvind Bagga,Sanjay Kumar Agarwal,Aditi Sinha,Geetika Singh,Pragyan Acharya | | BMC Research Notes. 2020; 13(1) | | [Pubmed] | [DOI] | |
|
 |
|
|
|
Search Pubmed for