Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis

Abstract

Background and objectivesMalaria, a potentially life-threatening disease, is the most prevalent endemic infectious disease worldwide. In the modern era, the spectrum of glomerular involvement observed in patients after malarial infections remains poorly described.Design, setting, participants, & measurementsWe therefore performed a retrospective multicenter study to assess the clinical, biologic, pathologic, and therapeutic characteristics of patients with glomerular disease demonstrated by kidney biopsy in France within 3 months of an acute malaria episode.ResultsWe identified 23 patients (12 men), all but 1 of African ancestry and including 10 patients with concomitant HIV infection. All of the imported cases were in French citizens living in France who had recently traveled back to France from an endemic area and developed malaria after their return to France. Eleven patients had to be admitted to an intensive care unit at presentation. Plasmodium falciparum was detected in 22 patients, and Plasmodium malariae was detected in 1 patient. Kidney biopsy was performed after the successful treatment of malaria, a mean of 24 days after initial presentation. At this time, all patients displayed AKI, requiring KRT in 12 patients. Nephrotic syndrome was diagnosed in 17 patients. Pathologic findings included FSGS in 21 patients and minimal change nephrotic syndrome in 2 patients. Among patients with FSGS, 18 had collapsing glomerulopathy (including 9 patients with HIV-associated nephropathy). In four patients, immunohistochemistry with an antibody targeting P. falciparum histidine-rich protein-2 demonstrated the presence of the malaria antigen in tubular cells but not in podocytes or parietal epithelial cells. An analysis of the apoL1 risk genotype showed that high-risk variants were present in all seven patients tested. After a mean follow-up of 23 months, eight patients required KRT (kidney transplantation in two patients), and mean eGFR for the other patients was 51 ml/min per 1.73 m2.ConclusionsIn patients of African ancestry, imported Plasmodium infection may be a new causal factor for secondary FSGS, particularly for collapsing glomerulopathy variants in an APOL1 high-risk variant background.

Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

“…Infection with the parasite Plasmodium is responsible for extensive hemolysis with hemoglobin and free heme release. Acute kidney injury is a clinical hallmark of disease severity and malaria is also associated with collapsing glomerulopathy [ 143 ]. Labile heme concentrations are increased in the plasma of patients and in mouse models; interestingly, labile heme levels in the latter increased more strongly in urine compared to plasma [ 144 ].…”

Renal Diseases Associated with Hematologic Malignancies and Thymoma in the Absence of Renal Monoclonal Immunoglobulin Deposits

“…A significant increase in the levels of proinflammatory cytokines (such as TNF-α) was observed in three of the cases studied by Thaunat et al [ 27 ]. Unfortunately, in this cohort, including 63.6% Afro-Caribbean individuals, APOL1 risk alleles, a recently identified major risk factor associated with the occurrence of collapsing glomerulopathy, were not investigated [ 93 , 94 ]. Another glomerular disease has been described as a specific pattern of HPS, defined as “histiocytosis glomerulopathy”.…”

Heme Burden and Ensuing Mechanisms That Protect the Kidney: Insights from Bench and Bedside

“…Classical indicators of renal involvement that include elevation of serum creatinine and blood urea nitrogen, proteinuria, microalbuminuria and urinary casts are often seen [ 49 ]. Although rare, cases of nephrotic syndrome have also been reported [ 52 ]. Overall, AKI, likely resulting from overt acute tubular necrosis, is the predominant finding when kidneys are affected [ 48 , 53 , 54 ].…”