Effect of Granulocyte and Monocyte Adsorption Apheresis on Urinary Albumin Excretion and Plasma Endothelin-1 Concentration in Patients with Active Ulcerative Colitis

Abstract

Background/Aim: Increases in microalbuminuria and endothelin (ET-1) are involved in the development of ulcerative colitis (UC) and in its progress. Because granulocyte and monocyte adsorption apheresis has proven to be useful in the treatment of UC, we examined whether urinary albumin excretion and plasma ET-1 concentrations are altered and whether granulocyte and monocyte adsorption apheresis affects the concentrations of these two factors in patients with active UC. Methods: Twenty patients with active UC and 20 age-matched healthy volunteers (our hospital staffs) were included in this study. UC patients were randomly divided into two treatment groups: a granulocyte and monocyte adsorption treatment group (n = 10) and a conventional treatment group (n = 10). The urine albumin/creatinine ratio, plasma ET-1 concentration and tumor necrosis factor (TNF)-α were determined before and after treatment and compared between 2 treatment groups. The 10 adsorption treatment patients underwent 5 consecutive weekly apheresis sessions, each of 60 min duration at a flow rate of 30 ml/min. Results: The urine albumin/creatinine ratio in UC patients (6.4 ± 2.2 mg/mmol) were higher than that in healthy subjects (1.0 ± 0.7 mg/mmol, p < 0.01). In addition, the plasma ET-1 level in UC patients (3.5 ±1.5 pg/ml) was higher than that in healthy subjects (0.8 ± 0.4 pg/ml, p < 0.01). Plasma TNF-α was detected in UC patients (18.8 ± 8.4 pg/ml), but not in healthy subjects. The urine albumin/creatinine ratio was highly correlated with the plasma ET-1 level (r = 0.62; p < 0.01) and plasma TNF-a level (r = 0.66, p < 0.01). Granulocyte and monocyte adsorption apheresis reduced the urine albumin/ creatinine ratio from 6.6 ± 2.4 to 1.8 ± 0.6 mg/mmol (p < 0.01), reduced the plasma ET-1 level from 3.7 ± 1.6 to 1.4 ± 0.6 pg/ml (p < 0.05) and reduced the plasma TNF-α from 19.2 ± 8.6 to 3.8 ± 1.2 pg/ml (p < 0.01). Conventional treatment did not affect these factors. Conclusion: Our data suggest that increases in the urine albumin/creatinine ratio, ET-1 and TNF-α play an important role in active UC and that granulocyte and monocyte adsorption apheresis is effective in ameliorating such increases.

Clinical Effectiveness of Selective Granulocyte, Monocyte Adsorptive Apheresis with the Adacolumn® Device in Ulcerative Colitis

“…The results after 6 weeks show moderate heterogeneity (I 2 = 63%), but sensitivity analyses do not provide an explanation for this heterogeneity. There was some nonsignificant evidence of publication bias, but this finding was mainly due to the extremely positive results in one trial [17].…”

“…In three other trials, the protocol dictated that medications administered concurrently were to remain unchanged [15,17,21]. Only in the two trials by Hanai et al [19] was concurrent steroid medication increased or decreased in line with the clinical course of the disease.…”

Systematic review: granulocyte/monocyte adsorptive apheresis for ulcerative colitis

“…Individual trial characteristics are provided in Table 1. Four trials compared GMAA with conventional medical therapy, 24, 25, 31, 32 two separate trials (reported in a single article) compared GMAA with sham apheresis 26 and four trials compared ‘intensive’ vs. ‘conventional’ GMAA regimens 27–30 . Only two trials were at low risk of bias according to our assessment 26 .…”

“…The search strategy identified a total of 1729 citations, 16 of which appeared to be relevant to the study question, and were therefore retrieved and evaluated in more detail (Figure 1). Nine articles, 24–32 reporting the results of ten separate RCTs, were eligible for inclusion in the systematic review. We did not perform a formal meta‐analysis due to concerns about the high risk of bias among the RCTs we identified.…”

Therapeutic landscape for ulcerative colitis: where is the Adacolumn&reg; system and where should it be?

“…Extremely positive results have been reported using this method for the treatment of ulcerative colitis in Japan,6–13 but results obtained in Europe and the US have been more contradictory 14–19. Nevertheless, a recent meta-analysis20 pooling data from seven randomized controlled trials 6,9,17,21–24 clearly demonstrated the benefits of this method with respect to control treatments for the induction of remission or response at week 12. On the other hand, the only sham-controlled randomized controlled trial, in a slightly to moderately ill population, did not show a statistically significant difference between sham and active treatment 24…”