THU0302 Hepcidin, Interleukin-6 and Anemia of Chronic Inflammation in Systemic Lupus Erythematosus (SLE)

Abstract

Objectives:To study the effect of renal disease on standardized mortality ratio (SMR) and life expectancy (LE) of patients with systemic lupus erythematosus (SLE). Methods: Patients who fulfilled ³4 ACR criteria for SLE who were prospectively followed in our unit from 1995 to 2011 were studied. The cumulative survival rate (by Kaplan Meier's method), and age and sex adjusted standardized mortality ratio (SMR) was calculated. Life expectancy (LE) was studied by single decrement life table analysis. The effect of renal involvement, histological classes, renal damage and end stage renal disease (ESRD) on these parameters was evaluated. Results: 694 patients were studied (92%). The mean age of onset of SLE was 32.9±13.4 years (range 6-78). 368 (53%) had evidence of renal disease according to the ACR definition of renal involvement (persistent proteinuria of >0.5g/day; cellular casts or histological evidence). 285 (77%) patients had undergone renal biopsy for at least once. The distribution of histological classes (ISN/RPS) was as follows: class I (1%), class II (6%), class III (19%), class III+V (10%), class IV (47%), class V (16%) and others (1%). At the time of analysis, the mean observation of our patients since SLEonset was 9.6±7.3 years. Thirty-four (4.9%) patients were lost to follow-up. Among patients with lupus renal disease, 79 (11%) patients had renal damage as assessed by the SLE damage index (SDI) and 24 (3%) patients developed ESRD. The cumulative 5, 10 and 15 year survival of patients with renal involvement was 92.3%, 88.8% and 84.3%, respectively, which was significantly lower than that of patients without renal involvement (97.0%, 93.7% and 91.6%, respectively; p=0.004). Cox regression demonstrated that the age and sex adjusted hazard ratio (HR) of mortality in patients with renal disease and renal damage compared with those without renal involvement was 2.23 [1.29-3.85] (p=0.004) and 3.59 [2.20-5.87] (p<0.001), respectively ( Table 1). The corresponding hazard ratio for mortality in patients who developed ESRD was 9.20 [4.92-17.2] (p<0.001). Patients with proliferative types of lupus nephritis (class III, IV and III/IV+V) had significantly increased mortality compared to those without renal disease ]; p=0.01). In contrast, pure membranous lupus nephropathy was not associated with increased mortality (adjusted HR 1.09 [0.38-3.14]; p=0.88). Adjustment for the use of immunosuppressive regimens in the Cox regression models did not materially affect the overall hazard ratios for mortality. The age and sex adjusted SMRs of all SLE patients, SLE patients without renal disease, SLE patients with renal disease, proliferative nephritis, pure membranous nephropathy, renal damage and renal failure compared to the general population were 7.3 (95% confidence interval [CI] 5.

Hepcidin and Ferritin: Important Mediators in Inflammation Associated Anemia in Systemic Lupus Erythematosus Patients

“…Lee and his co-workers have noted that hepcidin transcription was stimulated not only by IL-6 but also by IL-1a and IL-1b in murine hepatocytes [19]. In human hepatocyte culture, hepcidin is induced by IL-6, but not IL-1 or TNF-a, indicating that hepcidin induction by inflammation is a type II acute phase response [20,21]. The increase in TNF-a and IL-6 increases the hepatic secretion of hepcidin which represses the ferroportin expression and this situation stimulates iron retention in macrophages and prevents direct absorption of iron into circulation [22].…”

Serum hepcidin and interleukin-6 in systemic lupus erythematosus patients: crucial factors for correction of anemia

“…Mok et al reported that serum hepcidin and IL-6 are correlated with disease activity in SLE patients, and are associated with ACD [26].…”