RISK FACTORS FOR PROGRESSION OF CHRONIC RENAL DISEASE

产品说明： 慢性肾衰竭患者的进展率差异很大。 在大多数系列中，至少有15%的患者多年没有进展; 在另一个极端，一些患者失去肾小球滤过率（GFR） 以3 ml/min/mo的速度进行。 以前的研究，题为“修改 肾脏疾病饮食（MDRD）”将925名患者随机分配到不同的饮食组 和血压目标，并跟踪他们平均两年， 有连续的GFR 该数据集的独特之处在于， 超过6,000 GFR。 影响儿童死亡率的因素的多变量分析 到目前为止，这些患者的进展无法解释更多的 而不是观察到的进展率的一小部分变异。 在另一系列的104名患者中，申请人已经确定了4名 分析其水平与进展率强相关：血清 游离色氨酸，血清硫酸脱氢表雄酮，尿硝酸盐， 尿17-羟皮质类固醇。 他们建议测量这些分析 加血清转化生长因子 可行性和全面MDRD研究，并通过回归确定 观察到的进展率的变异性有多大， 通过这些分析。 这种预测能力 与目前确定的肾脏疾病预测因子无关 将研究进展。 他们还将确定这些 分析被饮食和血压干预所改变， MDRD研究，以及这些分析在多大程度上解释了观察到的 达到的血压和达到的蛋白质摄入量与 进展 申请人表示，结果将具有重要意义。 对于理解疾病进展的发病机制的意义， 指出新的治疗方法来减缓进展。

DESCRIPTION: Rates of progression vary widely among patients with chronic renal failure. In most series, at least 15% of patients do not progress at all for years; at the other extreme, some patients lose glomerular filtration rates (GFR's) as rapidly as three ml/min/mo. Previous studies, entitled "Modification of Diet in Renal Disease (MDRD)," have randomized 925 patients to various diets and blood pressure targets and followed them for an average of two years with sequential GFR's. This data set is unique in having documented greater than 6,000 GFR's. Multivariate analysis of the determinants of rates of progression among these patients has so far been able to account for no more than a small proportion of the variability in observed rates of progression. In another series of 104 patients, the applicant has identified four analyses whose levels correlate strongly with rates of progression: serum free tryptophan, serum dehydroepiandrosterone sulfate, urinary nitrate, and urinary 17-hydroxycorticosteroids. They propose to measure these analyses plus serum transforming growth factors in frozen samples from the feasibility and full-scale MDRD studies, and to determine by regression techniques how much of the observed variability in progression rates can be accounted for by these analyses. The extent to which this predictive power is independent of presently identified predictors of renal disease progression will be studied. They will also determine whether these analyses were altered by the dietary and blood pressure interventions of the MDRD studies, and the extent to which these analyses explain the observed association of achieved blood pressure and achieved protein intake with progression. The applicant indicates that the results will have important implications for the understanding the pathogenesis of progression and may point to new therapeutic approaches to slowing progression.