Pathomechanisms in the Kidneys in Selected Protozoan Parasitic Infections

Abstract

Leishmaniasis, malaria, toxoplasmosis, and acanthamoebiasis are protozoan parasitic infections. They remain important contributors to the development of kidney disease, which is associated with increased patients' morbidity and mortality. Kidney injury mechanisms are not fully understood in protozoan parasitic diseases, bringing major difficulties to specific therapeutic interventions. The aim of this review is to present the biochemical and molecular mechanisms in kidneys infected with Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Acanthamoeba spp. We present available mechanisms of an immune response, oxidative stress, apoptosis process, hypoxia, biomarkers of renal injury in the serum or urine, and the histopathological changes of kidneys infected with the selected parasites. Pathomechanisms of Leishmania spp. and Plasmodium spp. infections have been deeply investigated, while Toxoplasma gondii and Acanthamoeba spp. infections in the kidneys are not well known yet. Deeper knowledge of kidney involvement in leishmaniasis and malaria by presenting their mechanisms provides insight into how to create novel and effective treatments. Additionally, the presented work shows gaps in the pathophysiology of renal toxoplasmosis and acanthamoebiasis, which need further research.

Keywords: Acanthamoeba spp.; Leishmania spp.; Plasmodium spp.; Toxoplasma gondii; kidneys.

Figure 1

Mechanisms in Leishmania spp.-infected kidneys. 1. Leishmania spp. increase the expression of Toll-like receptors (TLRs), mainly TLR2 and TLR4, and they also affect the growth of interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). It was found that Leishmania spp. increase SHP-1 activity in the kidneys of hosts. The inflammatory cells, which are observed in the kidneys of hosts infected with Leishmania spp., are CD4+ T cells. 2. Leishmania spp. cause oxidative stress manifested by an increase in malondialdehyde (MDA), H₂O₂, and O₂^–. 3. Leishmania spp. cause an increase in caspase-3 activity, the main enzyme in the process of apoptosis, and an increase in transforming growth factor β (TGF-β) level, an apoptotic inducer. 4. Biomarkers, which increase in nephropathy caused by Leishmania spp., are serum and urine neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL, respectively) and monocyte chemoattractant protein-1 in the urine (uMCP-1). 5. Leishmania spp. cause an increase in creatine (CREA) and urea levels in the serum of hosts. 6. The parasites cause hypercellularity, reduced Bowman’s space, and glomerulonephritis in the kidneys.

Figure 2

Mechanisms in Plasmodium spp.-infected kidneys. 1. Plasmodium spp. increase the expression of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), and they also affect the growth of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon- γ (IFN-γ). It was found that Plasmodium spp. decrease the level of the anti-inflammatory cytokine IL-10. The deposition of immunoglobulin (Ig)A, IgM, and IgG was reported in the glomeruli of mice infected with Plasmodium spp. 2. Malaria causes an increase in matrix metalloproteinase (MMP)-3, MMP-9, and MMP-14 and a decrease in MMP-2, MMP-11, and MMP-15. 3. The Plasmodium spp. infection causes hypoxia in the kidneys by increasing the hypoxia-inducible factor 1 (HIP-1). 4. Plasmodium spp. cause oxidative stress manifested by an increase in malondialdehyde (MDA) and an increase in superoxide dismutase (SOD), as well as reduced glutathione (GSH) and a decrease in catalase (CAT). 5. Plasmodium spp. cause an increase in caspase-3 activity, the main enzyme in the process of apoptosis. 6. Biomarkers, which increase in nephropathy caused by Plasmodium spp., are serum and urine neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL, respectively) and monocyte chemoattractant protein-1 (MCP-1) and kidney injury molecule 1 (KIM-1) in kidneys. 7. Plasmodium spp. cause an increase in creatine (CREA) and blood urea nitrogen (BUN) levels in the blood of hosts. 6. The parasites cause hypercellularity, tubular degeneration, and necrosis and also decreased glomerular area, which may be caused by decreased tight junction-associated protein, zonula occludens-1 (ZO-1) in the kidneys.

Figure 3

Mechanisms in Toxoplasma gondii-infected kidneys. 1. TLR2 has a protective role in kidney function against T. gondii infection. While studies about IFN-γ varied, it is reported that IFN-γ inhibits the replication of T. gondii in the kidneys and that it does not play a role in the protection of the renal function against T. gondii infection. 2. The percentage of apoptotic cells was higher in the kidneys with T. gondii infection. 3. Toxoplasma gondii cause increased expression of transforming growth factor β (TGF-β). 4. Toxoplasma gondii cause no difference in serum creatine (CREA). The urea level may be elevated or in normal ranges. 5. The parasites cause inflammation, tubular degeneration, and necrosis in the kidneys.

Figure 4

Mechanisms in the Acanthamoeba spp.-infected kidneys. 1. Acanthamoeba spp. increase the expression of Toll-like receptor 2 (TLR-2). 2. Acanthamoeba spp. increase selenium (Se) concentration in the kidneys of infected host. 3. Acanthamoeba spp. do not affect the levels of creatine (CREA) and urea in the serum of hosts. 4. The parasites cause inflammation and necrotic changes in the tubules and glomeruli of the kidneys.