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    Collapsing glomerulopathy with hypertrophic and hyperplastic podocytes containing protein resorption droplets (A; periodic acid–Schiff staining; ×400). Immunohistochemistry with a monoclonal antibody against Plasmodium falciparum histidine-rich protein-2 showed the presence of the P. falciparum antigen in the lumen of a tubule (B; x400) but was negative on glomeruli (C; x400).

  • 1.

    Amoura A, et al.. Malaria, collapsing glomerulopathy, and focal and segmental glomerulosclerosis. Clin J Am Soc Nephrol 2020; 15:964972. doi: 10.2215/CJN.00590120

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  • 2.

    Ng JH, et al.. Pathophysiology and pathology of acute kidney injury in patients with COVID-19. Adv Chronic Kidney Dis 2020; 27:365376. doi: 10.1053/j.ackd.2020.09.003

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Malaria and FSGS—Is There a Connection?

Highlights of a recent study in CJASN, “Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis”

  • 1 Vincent Audard, MD, PhD, is with the Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Service de Néphrologie et Transplantation, Centre de Référence Maladie Rare “Syndrome Néphrotique Idiopathique,” Fédération Hospitalo-Universitaire “Innovative Therapy for Immune Disorders,” and the Univ Paris Est Créteil, Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Institut Mondor de Recherche Biomédicale (IMRB), Equipe 21, Créteil, France. Anissa Moktefi, MD, PhD, is with the Univ Paris Est Créteil, Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Institut Mondor de Recherche Biomédicale (IMRB), Equipe 21, and the Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Département de Pathologie, Créteil, France.
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Malaria, a potentially life-threatening disease, is the most prevalent endemic infectious disease worldwide, affecting millions of people in tropical areas. In European and Western countries, malaria is acquired during travel to areas in which the disease is endemic. Kidney involvement, including acute kidney injury, is seen in up to 60% of patients with severe malaria and is frequently observed with Plasmodium falciparum and Plasmodium malariae. However, the modern era has seen the spectrum of glomerular damage associated with malaria infection widened.

In a retrospective study performed in France (1), we identified 23 patients (22 due to P. falciparum infection and all but one patient of African ancestry) with biopsy-proven glomerular disease occurring after acute malaria (kidney biopsy performed during the three months following confirmation of Plasmodium infection).

All patients (12 men and 11 women, mean age 47 years) presented with acute kidney injury (requiring kidney replacement therapy in 12 cases) at the time of kidney biopsy. The kidney pathology findings included focal segmental glomerulosclerosis (FSGS) in 21 cases and minimal change disease in two patients. Collapsing glomerulopathy (CG) was the most common pathology finding (Figure 1A). CG was observed in 18 patients (including nine with HIV infection) and was associated with the presence of two high-risk APOL1 variants in all seven patients tested for APOL1 polymorphism. Immunohistochemistry with an antibody targeting P. falciparum histidine-rich protein-2 (HRP-2), to search for the presence of P. falciparum in the kidney tissues, revealed the presence of the parasite in the lumina of the tubules (Figure 1B) of all patients tested but its absence from the glomeruli (Figure 1C). At the end of follow-up, eight patients required kidney replacement therapy. Overall, these data suggest that, in patients of African ancestry, imported Plasmodium infection promotes CG in particular. In this setting, malaria may act as a “second hit” in patients with genetic (high-risk APOL1 genotype) or viral infection-associated susceptibility factors.

Figure 1.
Figure 1.

Collapsing glomerulopathy with hypertrophic and hyperplastic podocytes containing protein resorption droplets (A; periodic acid–Schiff staining; ×400). Immunohistochemistry with a monoclonal antibody against Plasmodium falciparum histidine-rich protein-2 showed the presence of the P. falciparum antigen in the lumen of a tubule (B; x400) but was negative on glomeruli (C; x400).

Citation: Kidney News 13, 4

In addition to the recent findings showing that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated CG predominantly affects individuals of African ancestry who have high-risk APOL1 alleles (2), our study emphasizes the role of infectious agents as triggers of CG in patients with genetic susceptibility. The accurate pathophysiological processes of these infectious agents (malaria and SARS-CoV-2) in the development of CG remain to be clarified.

Disclosures: Dr. Audard reports receiving personal fees from Addmedica outside of the submitted work. Dr. Moktefi has nothing to disclose.

References

  • 1.

    Amoura A, et al.. Malaria, collapsing glomerulopathy, and focal and segmental glomerulosclerosis. Clin J Am Soc Nephrol 2020; 15:964972. doi: 10.2215/CJN.00590120

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Ng JH, et al.. Pathophysiology and pathology of acute kidney injury in patients with COVID-19. Adv Chronic Kidney Dis 2020; 27:365376. doi: 10.1053/j.ackd.2020.09.003

    • Crossref
    • Search Google Scholar
    • Export Citation
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