| Background and objective Kidney is an important excrete path of waste products.Renal function failure leads to accumulation of metabolic products which may be toxic to the body.At least 270 of the waste products have been confirmed as "toxins". Indoxyl sulfate (IS) is one of them. IS is metabolized by the liver from indole,which is produced from tryptophan by intestinal flora. IS molecular weight is 251.3 dol,the main excrete path of IS is through kidney. IS can accelerate the tendancy of glomerular sclerosis and promote renal tubular interstitial fibrosis while there have existed renal function decreased . So, how about the level is of IS in normal ,in patients with different kidney function ?Whether there is any change of IS in patients with acute renal function failure ? How about the effect of different blood purification therapies on clearnance of IS in patients with uremia?Methods: 120 volunteers,312 undilyzed patients with chronic renal failure at different renal function stage(The glomerular filtration rate (GFR) was tested by 99Tcm- DTPA renal dynamic imaging method.). 84 stable dialysis patients who were intermittly given other dialysis treatment methods.45 peritoneal dialysis patients,34 hemodialysis (hemodialysis alone) were included in this research. Blood, urine and dialysate samples of patients in different groups were collected respectively for determining IS concentrations with liquid chromatography-tandem mass spectrometry (LC-MS/MS), blood creatinine (SCr), parathyroid hormone (PTH) were determined at the same time. A randomized, double- blind, placebo-controlled study was designed to examine the nephroprotective effects of Kremezin versus placebo in adult patients with CKD.Results: The IS levels in blood and urine were 0.07~1. 11μg/ml and 11. 34— 75.10 μg/ml of volunteers respectively.There was not any discrepance between health people and stage I chronic kidney diseasy patients(p>0.05),then it showed remarkable discrepance between them with the kidney function decrease (p<0.01);There was negative correlation between blood IS concentration andglomerular filtration rate(GFR)(r=-0.58)and urine IS level(r=-0.53). The IS concentrations before and after hemodialysis were 34.97±17.64μg/ml and 24.36±12.95 μg/ml, respectively. The decrease rate after hemodialysis was 28.53±17.41(%),there was statistic significance (p<0.01). SCr decrease rate after dialysis was 62.97+14.95 (%),higher remakerble than IS (p<0.0 l).There was a lower positive correlation between blood IS concentration of dialysis patients and dialysis time (monthes) (r=0.15).Blood IS concentration in patients with acute renal failure can have a transient increase(8.01 +7.52 u g/ml) in oliguria stage.The level of IS almost decreased to normal at the beginning of polyuria stage.The blood IS decrease rate (25.8±17.4)% after HD was lower than after HDF(53.1±6.3)% (p<0.01 ).The blood IS concentration of patients which were only given HD treatment remarkably higher than that of whom were given different dialysis methods treatment(p<0.01).The IS concentration showed decreased tendancy when dialysate were kept four hours in peritoneal dialysis(PD)patients, but the IS concentration had a remarkable increase when dialysate were kept 12 hours compared with 2hr or 4hr(p<0.01).The IS concentration in dialysate showed an increase tendancy with time of dialysate kept;The blood IS concentration in PD patients remarkably was lower than HD patients before-dialysis and close to the level of after-HD. seventy-four point two percent of patients(23) comepleted the trial(ll in Group Kremezin and 12 in Group placebo).The baseline value of indoxyl sulfate respectively were 7.0 + 4.5ug/ml and 6.0 + 6.2ug/ml in group Kremezin and placebo,and the changes after 12 weeks trial respectively were -3.98 + 5.09ug/ml and3.03 + 7.26ug/ml. During the 12-week treatment period, Kremezin did not affect serum creatinine level. Kremezin was well tolerated and did not adversely affect the general health status of patients. Conclusion: There was no difference of IS level between different aged groups in volunteers.The blood IS level increased and urine IS level decreased with the renal function decreasing. Routine HD therapy can clean part of IS but the effect did not satisfy the clinical need. Blood IS had a transient slightly increase only in oliguria stage in patients with ARF. CAPD,HDF therapies have a better effect on clearning IS than HD. Kremezin may be useful in the treatment of patients with CKD. Kremezin did not directly affect serum creatininelevels.
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