ENDOTHELIAL MICROPARTICLES IN MALARIA ASSOCIATED ACUTE KIDNEY INJURY

Introduction:

In regions where malaria is endemic, such as Odisha state in India, acute kidney injury (AKI) can affect over 4% of malaria cases. Endothelial microparticles (MPs) serve as indicators of endothelial dysfunction and play diverse roles in thrombosis, inflammation, and angiogenesis. These circulating MPs may contribute to the widespread endothelial dysfunction observed in patients with malaria-associated AKI by interfering with endothelial nitric oxide (NO) release. Our study aims to measure and compare the levels of endothelial microparticles in patients suffering from malaria-associated acute kidney injury versus those with uncomplicated malaria.

Methods:

The research was conducted from October 2018 to September 2019, enrolling consecutive patients with acute kidney injury. Suspected malaria cases were screened for Plasmodium falciparum using rapid diagnostic tests, microscopy (thick and thin film methods), and confirmed by species-specific PCR. Venous blood samples were collected in trisodium citrate for endothelial microparticle analysis via flow cytometry.

Acute kidney injury (AKI) cases were categorized into three stages of severity according to KDIGO criteria. The study measured endothelial microparticles in patients with malaria-associated AKI (MAKI) and compared these levels to control subjects with uncomplicated malaria.

Patients were monitored monthly to track disease progression and the development of renal failure. This approach allowed for a comprehensive assessment of the relationship between malaria infection, kidney injury, and endothelial dysfunction as indicated by microparticle levels.

Results:

During the study period, 200 patients with acute febrile illness and AKI were screened. From this group, 55 patients with malaria-associated acute kidney injury were identified. The study included 30 patients with KDIGO stage 3 malaria-associated AKI (MAKI) as cases and 60 patients with uncomplicated malaria as controls. Endothelial microparticle levels were compared between these two groups.

Among the 23 stage 3 MAKI patients requiring renal replacement therapy, 22 underwent hemodialysis, while one patient received peritoneal dialysis due to hemodynamic instability. Thirteen patients needed alternate day dialysis for over two weeks. Tragically, three stage 3 MAKI patients with multiple organ dysfunction syndrome died during the study. In contrast, all patients in the uncomplicated malaria control group survived.

Of the 30 stage 3 MAKI patients, 20 were monitored for a 3-month follow-up period. Notably, none of these patients showed evidence of chronic kidney disease during follow-up evaluations.

The study revealed significant differences in microparticle levels between severe stage 3 malaria-associated acute kidney injury (MAKI) patients and those with uncomplicated malaria.

Mean endothelial microparticle levels in severe stage 3 MAKI were substantially higher at 3778.63 ± 777.33 per µL of plasma, compared to 1910.98 ± 395.73 per µL in uncomplicated malaria cases. This difference was statistically significant when analyzed using a student t-test.

Similarly, total microparticle levels showed a marked increase in stage 3 MAKI patients. The mean total microparticle level in these patients was 7188.80 ± 868.91 per µL of plasma, significantly higher than the 2969 ± 613.54 per µL observed in uncomplicated malaria cases.

Conclusions:

The study revealed significantly elevated levels of both mean endothelial microparticles and mean total microparticles in the malaria-associated acute kidney injury (AKI) group compared to the uncomplicated malaria group. This finding highlights the potential of these microparticles as a novel biomarker for assessing endothelial dysfunction in malarial AKI. Moreover, these biomarkers could prove instrumental in identifying therapeutic targets for malarial AKI treatment. Further studies with larger sample size comparing these parameters with other groups of acute febrile illness associated acute kidney injury are needed.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.