Parasites and the Kidney — A Very Long and Tumultuous Relationship

The relationship between kidney disease and parasites dates back to ancient times. The Ebers papyrus (1550 BCE) contained the description of a “bloody urine disease” caused by a “worm” that would later be identified as schistosomiasis. Surprisingly, the papyrus also contained recommendations regarding prophylaxis and treatment of this ailment. A recent article published in the American Journal of Kidney Diseases reviews the evolution of the understanding of parasitic kidney disease since the origins of humanity until the latest discoveries in parasite molecular pathogenesis. Author Dr. Rashad S. Barsoum (RB), from Cairo University in Egypt, discusses his recent review with Dr. Helbert Rondon (eAJKD), eAJKD Contributor.

eAJKD: How did you become interested in parasitic kidney disease?

RB: Soon after I began practicing clinical nephrology in 1969, my colleagues and I at Cairo University and the Naval American Research Unit (NAMRU)-3 in Cairo encountered several cases of a full-blown nephrotic syndrome in patients with hepatosplenic schistosomiasis. This disease typically spares the urinary tract. We obtained kidney biopsies from these patients and found histologic lesions similar to those reported by Brazilian investigators. Our group published several papers on glomerulonephritis in hepatosplenic schistosomiasis, particularly when associated with salmonellosis—a well-known co-morbidity. We later identified a pathogenetic link, established a role of impaired hepatic macrophage function, and implicated Th2 cytokines, particularly IL-10, in the disease process. Finally, we put together a histopathologic classification system of the different glomerular lesions in hepatosplenic schistosomiasis, and correlated them with clinical features and prognosis.

eAJKD: Why is this topic important? Can you comment on the importance of these diseases for physicians in Western countries where they are not frequently seen in clinical practice?

RB: According to the World Health Organization (WHO), one in four individuals living on our planet is infected with one or more parasites. Literally, hundreds of millions are infected, and millions die every year as a direct result of those infections. The prevalence of acute kidney injury (AKI) due to malaria is 10 fold that of all other causes of AKI. Eighty percent of chronic kidney disease (CKD) patients in the world live in areas endemic for parasitic disease with these infections the cause of their kidney disease in an appreciable, yet imprecisely identified, frequency. Colleagues in the West are not commonly aware of the magnitude of this health problem, largely because of the containment of parasitic diseases in Africa, India, South-East Asia, and Central and South America. However, more and more parasitic diseases are being seen in the industrialized world owing to immigration of infected patients and vectors and exposure of Western populations through tourism and ex-partite appointments. Furthermore, the impact of parasitic infection has been seriously magnified by the growing immunocompromised populations including those with HIV infection, malignancy, and immunosuppression for organ transplantation. While many parasites share this scenario, my article is focused only on those which seem to cause the highest morbidity, both in endemic areas and in Western communities.

eAJKD: Can you briefly describe the milestones in our understanding of parasitic kidney disease?

RB: I have conventionally classified the evolution of our knowledge in this area into 4 stages: a) Ancient scripts, drawings, and embossments dating to about 2500 BCE in Egyptian, Sumerian, Assyrian, Indian, Nok, and other civilizations, followed many centuries later by documentation of the clinical syndromes associated with relevant parasitic diseases by Greek, Roman, and Byzantine philosophers; b) discovery of the causative agents and life cycles during the 19th century; c) discovery of the kidney manifestations of such infections during the 20th century; and d) appreciation of the impact of co-infection with multiple parasites, bacteria, and viruses around the turn of the millennium. 

eAJKD: Can you comment on the epidemiology of parasitic kidney disease in Africa and Asia? Is parasitic kidney disease identified as an important cause of CKD or end-stage renal disease in these geographical areas?

RB: There are no statistics to respond to this question with reasonable accuracy. However, there is some relevant data that can assist us. It has been estimated that 1% of patients with falciparum malaria develop AKI. Taking the WHO data on the incidence of this type of malaria, the parasite would account for 1200 cases per million population, mostly in Africa, India, China, and South East Asia. Registry data of the Egyptian Society of Nephrology 4 decades ago blamed schistosomiasis as the cause of CKD in 29% of patients treated with regular dialysis. With the implementation of mass treatment programs, this proportion fell to 8% according to the latest (2010) review of the same registry. Data on leishmaniasis are even less precise. According to the WHO, only one third of cases are officially reported, with less documentation of association with CKD. The data on filarial nephropathy are still weaker.

eAJKD: How do we establish causality between a parasitic infection and a specific pattern of kidney disease (i.e., glomerulonephritis) beyond a simple temporal relationship?

RB: There are three sets of data that establish this relationship: a) animal models where particular glomerular lesions can be induced by experimental infection in a dose-dependent manner (e.g., schistosomiasis); b) demonstration of parasitic antigens in early glomerular deposits by immunofluorescence or in-situ hybridization (all 4 parasites addressed in the article); c) parallel clustering of CKD in regions with highest prevalence of respective parasitic infection, with significant reduction in kidney disease paralleling parasite eradication programs (e.g., malaria, schistosomiasis).

To view the article (freely available), please visit AJKD.org.

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