[Effect of oral adsorbent AST-120 under standard treatment of care in patients with chronic renal failure].

BACKGROUND: Oral adsorbent AST-120 reduces uremic toxins, such as indoxyl sulfate, and retards the progression of chronic kidney disease (CKD). The present study was conducted to elucidate the association between the progression of CKD and the combined effect of AST-120 and standard care based on diet therapy and medications such as ACE inhibitor and ARB. METHOD: Retrospective analysis was performed using forty-four CKD patients (chronic glomerular nephritis 16, diabetic nephropathy 9, nephrosclerosis 13, and others 6) who were treated by AST-120 during the period from October, 2001 through December, 2004 and followed up for more than 6 months. The selection criteria were an estimated creatinine clearance (eCCr) of 30 mL/min or under at the initiation of treatment and a negative change in eCCr over time (DeltaeCCr (mL/min/year)) before AST-120 treatment. The eCCr was calculated using the Cockcroft-Gault equation and the DeltaeCCr was evaluated as a marker for the progression of chronic renal failure. RESULT: Overall DeltaeCCr before and after AST-120 treatment significantly improved from -7.28 +/- 6.33 to -4.29 +/- 5.09 (paired Wilcoxon test, p < 0.05). AST-120 led to greater improvement of DeltaeCCr in patients with an DeltaeCCr of less than -10 mL/min/year before AST-120 treatment and who had higher blood uric acid, urinary protein, and urinary specific gravity valves. CONCLUSION: This finding suggests that AST-120 treatment is effective in slowing the progression of chronic kidney disease, especially, in patients who exhibit a poor response to standard care.

Stimulation of NHE3 in OKP cells by an autocrine mechanism.

BACKGROUND/AIMS: Chronic hypokalemia increases NHE3 activity in OKP cells. The aim of the present study was to determine whether an autocrine mechanism is involved in this activation. METHODS: After incubation of OKP cells in normal-K(+) and low-K(+) media for 24 h, the potassium concentration in the low-K(+) media was adjusted to a normal level. These conditioned media were then used as the normal-K(+) and low-K(+) supernatants. Other OKP cells were incubated in these normal-K(+) and low-K(+) supernatants and the mechanism of Na(+)/H(+) antiporter activation was examined. RESULTS: The EIPA-resistant Na(+)/H(+) antiporter activity of OKP cells increased after 4 h incubation in the low-K(+) supernatant, and the amount of NHE3 protein increased at 24 h. Since both BQ788 and saralasin blocked this antiporter activation, the supernatant concentration of endothelin I (ET-I) and angiotensin II (Ang-II) were measured. The ET-I concentration was reduced, but the Ang-II concentration remained unchanged. There was a significant association between a reduction in the ET-I concentration and an increase in Na(+)/H(+) antiporter activity, but only when Ang-II was present in the supernatant. CONCLUSION: An autocrine mechanism is involved in the activation of NHE3 in OKP cells. Both ET-I and Ang-II play a role in this activation.