**12. Discussion**

Anemia of CKD/ESRD has multiple etiologies, although the decrease in EPO production by the diseased kidneys is the major contributor. Recently, studies targeting higher Hb levels or using higher EPO dosing regimens in the correction of anemia have shown detrimental effects including increased all cause mortality, cardiac and cerebral vascular events and vascular access thrombosis**8-10,54** It is not clear whether this is due to higher HCT or EPO the molecule itself at higher concentration. This review article focused on adjuvant oral and parenteral agents that have been used along with EPO to reduce its dose and give foundation to research in randomized control trials. There may also be a potential benefit of these agents to use along with EPO in reducing cost and expenditures especially when the bundling method of dialysis payment is in effect.

### **13. References**


placebo and the NAC groups. NAC reduced the baseline acute systemic generation of oxidative stress when compared to placebo, which was statistically significant with MDA (12.76 +/- 4.4% vs 9.7 +/- 4.4%) but not with HsCRP. Pre-treatment with NAC reduced the endothelial dysfunction when compared to placebo, but it was not statistically significant. The author concluded that in those HD patients, NAC reduced the oxidative stress before and after the administration of intravenous iron therapy in addition to the endothelial

Finnigan and Benz reported the results of treating 12 ESRD EPO resistant hemodialysis subjects with oral NAC 600 mg by mouth twice daily for 6 months. In that small pilot study, NAC therapy was associated with a 53% reduction in the EPO Resistance Index (weekly

These preliminary studies suggest the need for a larger, controlled trial with NAC. Until

Anemia of CKD/ESRD has multiple etiologies, although the decrease in EPO production by the diseased kidneys is the major contributor. Recently, studies targeting higher Hb levels or using higher EPO dosing regimens in the correction of anemia have shown detrimental effects including increased all cause mortality, cardiac and cerebral vascular events and vascular access thrombosis**8-10,54** It is not clear whether this is due to higher HCT or EPO the molecule itself at higher concentration. This review article focused on adjuvant oral and parenteral agents that have been used along with EPO to reduce its dose and give foundation to research in randomized control trials. There may also be a potential benefit of these agents to use along with EPO in reducing cost and expenditures especially when the

then, routine use of NAC as an EPO- adjuvant cannot be recommended.

[1] Valderrabano F. EPO in chronic renal failure. Kidney Int. 1996; 50:1373 – 91

[2] Benz RL, Pressman MR, Hovick ET, Peterson DD. A preliminary study of the effects of

[3] Revicki DA , Brown RE, Feeney DH, Henry D, Teehan BP, Rudnick MR, Benz RL: Health

predialysis chronic renal disease patients . Am J Kidney Dis 25:548-554, 1995 [4] Evans RW, Rader B, Manninen DL, and the Cooperative Multicenter EPO Clinical Trial

[5] Barany P, Petterson E, Bergstron J: EPO treatment improves quality of life in hemodialysis patients. Scand J Urol Neprol 131: 55 -60, 1990 (suppl) [6] Auer J, Oliver DO, Winearls CG: The quality of life of dialysis patients treated with recombinant human EPO. Scand J Urol Nephrol 131: 61-65, 1990 ( suppl)

correction of anemia with recombinant human EPO therapy on sleep, sleep disorders, and daytime sleepiness in hemodialysis patients (The SLEEPO study).

– related quality of life associated with recombinant human EPO therapy for

Group: The quality of life of hemodialysis recipients treated with recombinant

dysfunction induced by this treatment.**<sup>52</sup>**

bundling method of dialysis payment is in effect.

Am. J. Kidney Dis*.* 1999; 34: 1089–95

human EPO. JAMA 263: 825-830, 1990

EPO dose/weight in Kg/Hb).**<sup>53</sup>**

**12. Discussion** 

**13. References** 


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**11** 

*China* 

**Molecular Mechanisms of** 

*Traditional Chinese Medicine, Wenzhou* 

*4Zhuhai City NO 5 Hospital, GuangDong* 

Li-qun He1, Dong Feixia2, Qiang Fu3 and Jun Li4

**Nephro-Protective Action of HE-86 Liquid** 

*Research Team in Universities of Shanghai Municipal Education Commission* 

*3Heilongjiang University of Traditional Chinese Medicine, HeiLongJiang* 

**Extract in Experimental Chronic Renal Failure** 

*1Department of Nephrology, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Ministry of Education Key Laboratory of Liver and Kidney Disease Syndrome, E-Institutes of Shanghai Municipal Education Commission, Innovative* 

*2Department of Nephrology, Wenzhou TCM Hospital Affiliated to Zhejiang University of* 

Chronic renal injury can be mediated by angiotensin II (Ang II) through hemodynamic and inflammatory mechanisms and attenuated by individual suppression of these mediators. Hypertension is usually associated with the development of vascular and renal fibrosis [3]. This pathophysiological process is characterized by structural changes in vasculature caused by increased synthesis and rearrangement of extracellular matrix proteins, such as the collagen type I [4]. Several studies support a major role for the renin-angiotensin system in

Hypertension injures blood vessels and thereby causes end-organ damage. The mechanisms are complicated and although they have been studied for decades in experimental animal models [7], they are only currently being elucidated. From the efforts of many investigators, we are now in the position of constructing a chain of events from the endothelium to the underlying matrix, to the vascular smooth muscle cells, and beyond to the adventitia, and surrounding tissues. The endothelial layer acts as a signal transduction interface for hemodynamic forces in the regulation of vascular tone and chronic structural remodeling of arteries [8]. Infiltration of the permeabilized endothelium by leukocytes sets the stage for an inflammatory cascade, involving cytokines, chemokines, growth factors, and matrix metalloproteinases. Altered integrin signaling, the production of tenacin, epidermal growth factor signaling, tyrosine phosphorylation, and activation of downstream pathways culminate in vascular smooth muscle cell proliferation [9]. Evidence is accumulating that matrix molecules provide an environment which decreases the rate of programmed cell

**1. Introduction** 

death [10].

the development of fibrosis [5, 6].

