SEARCH · Search PubMed
Results for “INDICAN”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis.
To determine the role of indoxyl sulfate in the progression of glomerular sclerosis, the serum level of indoxyl sulfate was measured in patients with uremia, and the effect of oral administration of indoxyl sulfate on renal function and renal histology was studied in subtotally nephrectomized uremic rats. Further, the effects of a low-protein diet and oral sorbent (AST-120) administration on the serum and urine levels of indoxyl sulfate were studied in different groups of subtotally nephrectomized uremic rats. We noted a marked elevation of serum level of indoxyl sulfate in the patients with uremia. The oral administration of indoxyl sulfate to the uremic rats increased the serum creatinine and blood urea nitrogen levels and decreased creatinine clearance, inulin clearance, and p-aminohippuric acid clearance. The glomerular sclerosis index in the indoxyl sulfate-administered uremic rats was higher than in the control uremic rats. A low-protein diet and AST-120 administration decreased the serum and urine levels of indoxyl sulfate, the blood urea nitrogen level, the urinary protein level, and the glomerular sclerosis index in the uremic rats as compared with those on a high-protein diet. Thus, indoxyl sulfate, a circulating uremic toxin, stimulated the progression of glomerular sclerosis in the uremic model. A low-protein diet and AST-120 reduced the serum and urine levels of indoxyl sulfate and suppressed the progression of glomerular sclerosis.
Indoxyl sulfate increases the gene expressions of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in uremic rat kidneys.
We recently reported that the serum levels of indoxyl sulfate, a dietary protein metabolite, are increased in both uremic rats and patients, and that the administration of indoxyl sulfate to uremic rats accelerates the progression of glomerular sclerosis. Thus, we hypothesize that the overload of protein metabolites such as indoxyl sulfate on nephrons promotes the progression of chronic renal failure (CRF). Recent studies revealed that tubulointerstitial injury is of equal or greater importance than glomerular sclerosis in determining whether progressive renal dysfunction will ensue in various renal diseases. In the present study, to clarify the role of indoxyl sulfate in the progression of CRF, the expressions of genes related to tubulointerstitial fibrosis such as transforming growth factor (TGF)-beta 1, tissue inhibitor of metalloproteinases (TIMP-1) and pro-alpha 1(I) collagen were examined in the renal cortex of 5/6-nephrectomized uremic rats given indoxyl sulfate. In the first experiment, the administration of indoxyl sulfate for five weeks significantly increased the mRNA levels of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in the uremic rats given indoxyl sulfate compared with the control uremic rats, accompanied by a significant decline in renal function and worsening of glomerular sclerosis. In the second experiment, the administration of indoxyl sulfate for 2.5 weeks also increased the expression of the mRNA levels with no significant decline in the renal function. In conclusion, these findings indicate that the overload of the protein metabolite indoxyl sulfate on remnant nephrons is involved in the increased bioactivity of TGF-beta 1 in uremic kidneys, which enhances the renal expression of TIMP-1 and type 1 collagen, leading to the progression of CRF.
The protein metabolite hypothesis, a model for the progression of renal failure: an oral adsorbent lowers indoxyl sulfate levels in undialyzed uremic patients.
We have recently demonstrated that indoxyl sulfate promotes the progression of glomerular sclerosis in uremic rats. In the present study, we determined whether an oral adsorbent (AST-120) could reduce the serum and urine levels of indoxyl sulfate and suppress the progression of chronic renal failure (CRF) in undialyzed uremic patients. Twenty-five undialyzed uremic patients were given AST-120 at a dose of 6 g/day for 6 months, while 10 undialyzed uremic patients were not given AST-120. The effects of the oral adsorbent on the slope of the 1/serum creatinine (Scr)-time plot, and the serum and urine levels of indoxyl sulfate were evaluated. Administration of AST-120 significantly decreased the serum and urine levels of indoxyl sulfate, and tended to improve the slope of the 1/SCr-time plot in the CRF patients. Among the patients in whom urinary excretion of indoxyl sulfate was reduced by AST-120, the oral adsorbent significantly improved the slope of the 1/SCr-time plot. The change in the slope of the 1/SCr-time plot showed a significant negative correlation with the change in the urine level of indoxyl sulfate. Thus, patients who showed a greater decrease of urinary indoxyl sulfate also showed more marked suppression of the progression of CRF. These results support the notion that indoxyl sulfate, a protein metabolite, is involved in the progression of CRF, and that an oral adsorbent can delay progression at least partly by reducing the serum and urine levels of indoxyl sulfate.
Indoxyl sulfate and progression of renal failure: effects of a low-protein diet and oral sorbent on indoxyl sulfate production in uremic rats and undialyzed uremic patients.
We have previously demonstrated that indoxyl sulfate is a stimulating factor for the progression of glomerular sclerosis in uremic rats. In this study we determined if a low-protein diet or oral sorbent (AST-120) could reduce the serum and urine levels of indoxyl sulfate in 5/6-nephrectomized uremic rats and undialyzed uremic patients. The uremic rats were treated by fasting or AST-120 for 2 days. The serum and urine levels of indoxyl sulfate dramatically decreased 1-2 days after fasting or AST-120 treatment. We then measured the serum and urine levels of indoxyl sulfate and calculated protein intake from urinary amounts of urea nitrogen using Maroni's equation in 80 undialyzed uremic patients with creatinine clearance less than 30 ml/min. The serum and urine levels of indoxyl sulfate were significantly lower in the patients on a low-protein diet than in those in the normal-protein diet group. Administration of AST-120 significantly decreased serum and urine levels of indoxyl sulfate in 22 undialyzed uremic patients. In conclusion, a low-protein diet or AST-120 reduced the serum and urine levels of indoxyl sulfate, a stimulating factor for glomerular sclerosis, in both uremic rats and undialyzed uremic patients.
Indoxyl sulfate stimulates renal synthesis of transforming growth factor-beta 1 and progression of renal failure.
We recently demonstrated that the administration of indoxyl sulfate (dietary protein metabolite) to 5/6-nephrectomized rats accelerated the progression of chronic renal failure by increasing the transforming growth factor (TGF)-beta 1 synthesis in the kidneys, which enhanced the renal expressions of tissue inhibitor of metalloproteinase (TIMP)-1 and type 1 collagen, leading to renal fibrosis. The aim of the present study was to clarify the mechanism by which the administration of indoxyl sulfate increases TGF-beta 1 in the kidneys of uremic rats. Since infiltrative monocytes are suggested to be an important source of TGF-beta 1 in tubulointerstitial fibrosis, we examined the effect of indoxyl sulfate administration to uremic rats on the renal gene expression of intercellular adhesion molecule (ICAM)-1, which is involved in the infiltration of monocytes to kidneys. Indoxyl sulfate administration was observed to enhance the mRNA levels of ICAM-1 as well as those of TGF-beta 1, TIMP-1 and pro alpha 1 (I) collagen in the renal cortex of 5/6-nephrectomized uremic rats. In addition, we demonstrated in vitro that the addition of indoxyl sulfate significantly increased the synthesis of TGF-beta 1 in cultured proximal tubular cells. Thus, the overload of indoxyl sulfate in uremic kidneys increased the infiltration of monocytes and directly increased the synthesis of TGF-beta 1 in proximal tubular cells.