Aristolochic acid nephropathy revisited: a place for innate and adaptive immunity?

Abstract

Aims:The histological features of aristolochic acid nephropathy (AAN) consist of paucicellular interstitial fibrosis, severe tubular atrophy, and almost intact glomeruli with media lesions of interlobular arteries. As an early phase of interstitial inflammation preceded peritubular fibrosis in the rat model of AAN, the aim was to investigate the presence of inflammatory cells in human AAN. Methods and results: Reports of confirmed cases and case series of AAN were reviewed in terms of interstitial inflammation and found to have very conflicting results. This prompted us to search for and characterize inflammatory cells within the native kidneys provided from four end-stage AAN patients. Prior aristolochic acid exposure was attested by the intrarenal presence of the typical aristolactam I-derived DNA adduct. Besides the tubulointerstitial lesions usually seen in the cortex, a massive infiltration of macrophages, T and B lymphocytes was detected by immunohistochemistry in the medullary rays and in the outer medullae with some extension to the upper cortical labyrinth. Conclusions: In parallel with histological findings reported in the rat model, inflammatory cells are present preferentially in the interstitium of the medullary rays and of the outer medulllae in renal interstitium from human AAN cases, even in the terminal stages. Further studies must be undertaken to determine the respective roles of innate and adaptive immunity in the progression of AAN.

A Histopathological Analyses of in vivo Anti-tumor Effect of an Aqueous Extract of Aristolochia longa Used in Cancer Treatment in Traditional Medicine in Morocco

“…AA-I and AA-II, the major components of AL rhizome, were shown to possess immune-stimulatory properties [21].…”

An Integrated View of Aristolochic Acid Nephropathy: Update of the Literature

“…At Day 35 of the protocol, inflammatory infiltrates were still present, suggesting crucial interactions between tubular cells and immune cells. Finally, histological analyses of human AAN cases also revealed that inflammatory cells are preferentially present in the interstitium of the medullary rays and in the outer medulla even in terminal stages [135]. …”

“…It was therefore concluded that vascular lesions observed in AA-intoxicated patients were not induced by AA but were more likely a late consequence of advanced kidney disease. Since then, other investigations have demonstrated a dramatic decrease in peritubular capillaries especially in the fibrotic areas in human renal biopsies as well as in experimental models [30,135,138]. In a rat model of AAN, the reduction of peritubular capillaries network was associated to a decreased expression of vascular endothelial growth factor (VEGF) and to an increased expression of HIF-1α thereby suggesting that ischemia and hypoxia are important factors contributing to AAN progression [138].…”

Urinary Tract

“…334 Chronic potassium deficiency has also been associated with interstitial fibrosis in both rats and humans. 341,343 An unusual form of interstitial fibrosis was reported in dogs treated with high doses of estrogens and attributed to their pharmacological effects. It is characterized by a renal interstitium widened by edema and extensive fibrosis associated with tubular damage and atrophy.…”