There are limited data on the application of the RIFLE criteria among patients with severe malaria. This retrospective study was conducted by reviewing 257 medical records of adult hospitalized patients with severe falciparum malaria at the Mae Sot General Hospital, Tak province in the northern part of Thailand. The aims of this study were to determine the incidence of acute renal failure (ARF) in patients with severe falciparum malaria and its association with RRT as well as in-hospital mortality. Using the WHO 2006 criteria, ARF was the second most common complication with incidence of 44.7% (115 patients). The requirement for RRT was 45.2% (52 patients) and the in-hospital mortality was 31.9% (36 patients). Using the RIFLE criteria, 73.9% (190 patients) had acute kidney injury (AKI). The requirement for RRT was 11.6% (5 patients) in patients with RIFLE-I and 44.9% (48 patients) in patients with RIFLE-F. The in-hospital mortality gradually increased with the severity of AKI. The requirement for RRT (
Malaria is caused by protozoan parasites of the genus
Recently, a few observational studies demonstrated that there was an increased risk for mortality with small increments in serum creatinine; this finding made the case for the adoption of more sensitive creatinine-based criteria for acute kidney injury (AKI) [
This study aimed to determine the incidence of ARF by the WHO 2006 criteria and AKI by the RIFLE criteria as well as their association with requirement for RRT and in-hospital mortality.
This study was approved by the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. A retrospective study was conducted at the Mae Sot General Hospital, Tak province, Thailand. Medical records of hospitalized patients with severe falciparum malaria classified according to WHO 2006 criteria [
Patients’ data comprising demographic, clinical features, laboratory data, and outcomes including death and requirement for RRT were reviewed and extracted from medical records and discharge summaries according to the eligible criteria. These data were then transferred into a predefined case record form for further analysis.
In our study, the WHO 2006 criteria [
Patients with ARF were classified according to the WHO 2006 criteria defined as serum creatinine >3 mg/dL and adequate volume status [
The incidence of ARF in adults with severe malaria was approximately 30% to 50% by the reports from South and Southeast Asia [
The demographic, clinical, and laboratory data collected in this study were analyzed using the Statistical Package for the Social Sciences version 18.0 (SPSS, Chicago, IL, USA). Quantitative data were tested for normality using the Kolmogorov-Smirnov test and summarized as median (interquartile, IQR) for nonnormally distributed data. Qualitative data were summarized as frequency (percentage) and then analysed by Chi square test or Fisher’s exact test as appropriate. The Chi square for linear trend was used to determine a linear trend of in-hospital mortality in relation to severity of AKI. Univariate analysis was performed to determine the possible risk factors for in-hospital mortality among severe falciparum malaria patients with AKI. Any variable with
A total of 373 medical records of hospitalized patients with severe falciparum malaria were reviewed. Of these, 257 medical records fulfilled the eligible criteria and the rest were excluded as 86 patients had insufficient data and 30 patients had mixed infection. The median (IQR) age of patients with severe falciparum malaria was 31.0 (22.0–40.0) years and the majority of the patients were males (191/257, 74.3%). The common clinical presentations on admission were fever (245/247, 99.2%) with the median (IQR) temperature of 38.7 (37.7–39.5)°C and rigors (102/109, 93.6%).
Regarding laboratory parameters on admission, hematological findings were hemoglobin (median (IQR), 10.6 (8.3–12.9) g/dL), white blood cell count (8.3 (5.4–12.3) × 109/L), and platelet count (32.0 (17.0–64.0) × 109/L). Blood chemistries showed blood sugar (median (IQR), 123 (98–146) mg/dL), blood urea nitrogen (44.0 (22.0–72.8) mg/dL), creatinine (1.8 (1.2–4.1) mg/dL), total bilirubin (5.0 (2.2–11.1) mg/dL), direct bilirubin (1.5 (0.7–3.8) mg/dL), aspartate aminotransferase (124 (59–232) U/L), and alanine aminotransferase (60 (32–112) U/L).
According to the WHO 2006 criteria, most of the patients had complications of hyperbilirubinemia (139, 54.1%) followed by ARF (115, 44.7%), impaired consciousness (110, 42.8%), severe metabolic acidosis (109, 42.4%), shock (86, 33.5%), multiple convulsions (30, 11.7%), pulmonary edema or ARDS (23, 8.9%), severe anemia (16, 6.2%), hypoglycemia (13, 5.1%) and spontaneous bleeding (7, 2.7%). The incidence of ARF using the WHO 2006 and RIFLE criteria are shown in Table
Incidence of acute renal failure classified by the WHO 2006 and RIFLE* criteria.
Criteria | No. (%) |
---|---|
(a) WHO criteria ( |
|
No ARF† | 142 (55.3) |
ARF† | 115 (44.7) |
(b) RIFLE* criteria ( |
|
No AKI‡ | 67 (26.1) |
Any RIFLE* | 190 (73.9) |
Risk | 40 (15.6) |
Injury | 43 (16.7) |
Failure | 107 (41.6) |
Regarding the WHO 2006 criteria, 53 of 257 (20.6%) patients underwent dialysis (31 patients by hemodialysis and 22 patients by peritoneal dialysis) with median (IQR) duration for dialysis of 4.5 (2.0–10.0) days. Of 53 patients, 52 patients were classified as a group with ARF and only one patient as a group with no ARF. The requirement for RRT was significantly higher in the group with ARF compared to that with no ARF (
Severe falciparum malaria patients with acute renal failure using the WHO 2006 and RIFLE* criteria in relation to RRT† requirement and in-hospital mortality.
Criteria | RRT† ( |
Death ( | ||||
---|---|---|---|---|---|---|
No | Yes |
|
No | Yes |
| |
WHO 2006 | ||||||
No ARF‡ | 141 (99.3) | 1 (0.7) | 117 (86.0) | 19 (14.0) | ||
ARF‡ | 63 (54.8) | 52 (45.2) | <0.001 | 77 (68.1) | 36 (31.9) | 0.001 |
RIFLE* | ||||||
No AKI# | 67 (100.0) | 0 (0.0) | 56 (90.3) | 6 (9.7) | ||
Any RIFLE* | 137 (72.1) | 53 (27.9) | <0.001 | 138 (73.8) | 49 (26.2) | 0.002 |
Risk | 40 (100.0) | 0 (0.0) | 35 (89.7) | 4 (10.3) | ||
Injury | 38 (88.4) | 5 (11.6) | 30 (69.8) | 13 (30.2) | ||
Failure | 59 (55.1) | 48 (44.9) | 73 (69.5) | 32 (30.5) |
The most common indication for RRT in patients with RIFLE-I was severe metabolic acidosis (4, 80.0%) followed by pulmonary edema (2, 40.0%) and severe hyperkalemia (2, 40.0%). Among patients with RIFLE-F, the most common indication for RRT was severe metabolic acidosis (25, 52.1%) followed by pulmonary edema (9, 18.6%), severe hyperkalemia (6, 12.5%), fluid management for nutrition support (2, 4.2%), and uremia (1, 2.1%).
Using the WHO 2006 criteria, in-hospital mortality of patients with ARF was significantly higher than that with no ARF (36/113 (31.9%) versus 19/136 (14.0%);
The clinical, laboratory parameters and the type of RRT were subsequently analyzed for independent factors associated with in-hospital mortality among severe falciparum malaria patients with AKI (Table
Univariate and multivariate logistic regression analysis of risk factors for in-hospital mortality among severe falciparum malaria patients with acute kidney injury.
Parameters | Univariate analysis | Multivariate analysis* | ||
---|---|---|---|---|
OR† (95% CI‡) |
|
OR† (95% CI‡) |
| |
Glasgow coma scale ≤10 | 8.477 (3.852–18.654) | <0.001 | ||
Number of WHO criteria ≥4 | 22.500 (7.625–66.396) | <0.001 | ||
Inotropic drug | ||||
No | 1.000 | 1.000 | ||
Dopamine | 17.185 (5.945–49.679) | <0.001 | 7.172 (1.827–28.145) | 0.005 |
Adrenaline | 130.500 (34.422–494.744) | <0.001 | 14.502 (2.874–73.166) | 0.001 |
Mechanical ventilator | 37.266 (12.450–111.546) | <0.001 | 10.806 (2.569–45.459) | 0.001 |
WBC# >12.0 × 109/L | 5.286 (2.602–10.736) | <0.001 | 3.982 (1.146–13.836) | 0.030 |
Potassium >5.5 mmol/L | 10.427 (2.731–39.808) | 0.001 | ||
Bicarbonate <15 mmol/L | 6.195 (2.509–15.295) | <0.001 | ||
Blood sugar <60 mg/dL | 12.000 (1.379–104.410) | 0.024 | ||
AST€ >500 U/L | 7.429 (2.646–20.858) | <0.001 | ||
ALT |
13.875 (1.497–128.561) | 0.021 | ||
Albumin ≤2.5 mg/dL | 2.597 (1.205–5.597) | 0.015 |
We conducted a retrospective study by reviewing 257 medical records of patients with severe falciparum malaria at the Mae Sot General Hospital, Tak province, Thailand, in order to determine the incidence of ARF using the WHO 2006 criteria and AKI using the RIFLE criteria as well as their association with RRT requirement and in-hospital mortality. Serum creatinine was used to calculate estimated GFR as serum creatinine criteria seemed to show a worse RIFLE category and provided a better predictor for mortality rate than urine output criteria [
Regarding the WHO 2006 criteria, the incidence of ARF in our study (44.7%) was similar to the reports in previous studies (30–50%) [
Recently, the ADQI group established the RIFLE criteria for diagnosing AKI. These criteria have been shown in hospitalized patients to be quite sensitive in predicting the case fatality rate [
There has been only one report from India showing that AKI diagnosed using the RIFLE criteria was associated with the requirement for RRT and case fatality rate in patients with tropical acute febrile illnesses such as scrub typhus, falciparum malaria, enteric fever, dengue, and leptospirosis [
In our study, there were several limitations due to the study design which was retrospective in nature and some baseline data of the patients were missing. Therefore, further prospective evaluations are needed to properly standardize the RIFLE criteria for diagnosing AKI in malaria patients.
In conclusion, RIFLE criteria could be used in diagnosing AKI and predicting both requirements for RRT and in-hospital mortality in patients with severe falciparum malaria similar to WHO 2006 criteria. Early diagnosis and early management of AKI may help to improve the outcomes of severe malaria patients in future.
This study was supported by the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
All authors declare that they have no conflict of interests.
The authors would like to thank all doctors, nurses, and staff at the Registry Unit of the Mae Sot General Hospital, Tak province, Thailand, for collecting and retrieving patients’ medical records. They are grateful to Associate Professor Yupaporn Wattanagoon, Dr. Karnchana Pornpininworakij, and Dr. Suwimol Jearraksuwan for the valuable suggestions and comments. Special thanks are extended to Associate Professor Pratap Singhasivanon, Dean of the Faculty of Tropical Medicine, and Professor Punnee Pitisuttithum, Head of the Department of Clinical Tropical Medicine, Mahidol University, Bangkok, Thailand, for their support to this paper.