**4. Leishmaniasis**

Leishmaniasis is the tropical disease caused by the parasites from the genus *Leishmania*, transmitted by mosquitoes *Phlebotomus* and *Lutzomyia*, with the majority of cases concentrated in Latin America, South East Asia, East Africa, and, less frequently, Europe [42, 43]. There are 12–15 million infected people in the world, and 350 million are at risk [43]. Approximately, 1.5 –2 million new cases of leishmaniasis are registered in the world each year [43], and 90% of cases are concentrated in India, Ethiopia, Somalia, Sudan, and Brazil [44–46].

The disease can be asymptomatic or manifest as a localized disease in the skin (cutaneous leishmaniasis) or affect different organs (visceral leishmaniasis, also known as kala-azar or black fever). Incubation period can vary from few weeks to years, and the main symptoms and signs include insidious low-grade fever, pallor, splenomegaly, hepatomegaly, fatigue, weakness, hyporexia, and weight loss [42, 47]. In endemic areas, such as northeast of Brazil, the most affected individuals with visceral leishmaniasis are children [28]. Laboratory abnormalities are common and are typically characterized by pancytopenia, associated with hyperglobulinemia and hypoalbuminemia [28].

Kidney involvement in visceral leishmaniasis has been studied in both cutaneous form of leishmaniasis (American cutaneous leishmaniasis), in which tubular dysfunction predominates [48], and visceral leishmaniasis, in which renal lesions seem to be more frequent and severe [49]. Immunological mechanisms seem to be the key components of kidney injury in leishmaniasis, with immune complex deposition, T cell activation, and inflammatory process, leading to glomerulonephritis and interstitial nephritis [49–51]. Clinically, renal involvement in visceral leishmaniasis can manifest with acute kidney injury (AKI), mild-to-moderate proteinuria, hematuria, leukocyturia, hydroelectrolyte disturbances, and tubular defects—urinary concentration and acidification defects, which can persist even after specific treatment [52–54]. Glomerular disease in leishmaniasis is characterized to be mesangial proliferative, with immune complex deposition, and can complicate with rapidly progressive glomerulonephritis [55, 56]. Microalbuminuria is the most frequent renal abnormality found in patients with visceral leishmaniasis (around 40%), evidencing important glomerular filtration barrier defect caused by the infection process [57, 58]. AKI has also been reported in a considerable number of patients (more than 30%); it seems to be more frequent and severe in adults and is associated with hypokalemia, leukopenia, and use of amphotericin B [53, 59]. AKI was also associated with hyponatremia, hypoalbuminemia, hyperglobulinemia, and secondary infections in children with visceral leishmaniasis [60]. New biomarkers are under investigation aiming to detect early kidney injury in tropical diseases, including leishmaniasis. The most studied by now are the neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and monocyte chemotactic protein-1 (MCP-1) [61–63]. NGAL has been associated with AKI in visceral leishmaniasis, presenting good accuracy for the early diagnosis of AKI, and is a promisor tool for the identification of patients at risk of developing severe disease [64].

Treatment consists of anti-Leishmania drugs, and the standard treatment is pentavalent antimonials [42, 43]. The most commonly used drug is meglumine, but the biggest problem is its toxicity (cardiotoxicity). The second choice is amphotericin B, which has nephrotoxicity as the main adverse effect [42, 43].
