Lower urinary-interleukin-1 receptor-antagonist excretion in IgA nephropathy than in Henoch-Schönlein nephritis

Abstract

Background. IgA nephropathy (IgAN) and Henoch-Schönlein nephritis (HSN) share many clinical, histological and immunological features. It has been postulated that these two conditions have a common pathogenesis and that HSN might be a systemic form of IgAN. Activity of interleukin-1β (IL-1β) in urine has been found to be higher in IgAN and HSN patients than in healthy controls. Interaction between IL-1β and interleukin-1 receptor antagonist (IL-1ra) plays a significant role in the regulation of inflammatory responses. We studied levels of urinary excretion of IL-1β and IL-1ra in patients with IgAN and HSN. Methods. Amounts of IL-1β and IL-1ra excreted in 24-h urine samples collected from 241 IgAN, 26 HSN patients and from 33 healthy controls were determined. Results were expressed as cytokine/creatinine (ng/mmol) ratios. Results. Urinary IL-1β excretion by the IgAN and HSN patients was no greater than urinary IL-1β excretion by healthy controls. Urinary IL-1ra excretion by the IgAN patients was lower than urinary IL-1ra excretion by healthy controls (P < 0.05) and by the HSN patients (P < 0.01). In both patients and controls women had significantly higher IL-1ra, IL-1β excretion levels and IL-1ra/IL-1β ratios. The differences in urinary excretions of IL-1ra by the healthy controls and by the IgAN and HSN patients were significant in both sexes. Excretion of IL-1β or IL-1ra did not correlate with excretion of urinary protein, duration of the disease or any histopathological variable. However, histopathological changes in renal biopsy specimens from patients with IL-1ra/IL-1β ratios above normal were significantly milder than in renal biopsy specimens from patients with low or normal IL-1ra/IL-1β ratios. Conclusion. Urinary IL-1ra levels in IgAN patients were lower than urinary IL-1ra levels in healthy controls or HSN patients, a finding which may indicate that the two diseases have a different pathogenesis. Whether the male predominance in IgAN and HSN and the worse outcomes in males that have been reported previously in IgAN and HSN are connected with the lower excretion of IL-1ra and consequently lower IL-1ra/IL-1β ratios in male patients than in female patients needs more thorough investigation.