KETOACID THERAPY OF RENAL FAILURE

这个项目的第一个目的是设计一种最佳的饮食 慢性肾功能衰竭患者透析前的营养补充 舞台。要优化的标准(按重要性降序)为 肾功能不全、蛋白质营养、甲状旁腺素水平和 血浆氨基酸和电解质水平。20-25克混合品质 将采用低磷蛋白质饮食，其成分为 含有氨基酸和无氮类似物的补充剂将有所不同。 短期氮平衡加上长期(三个月)门诊研究将 被利用。我们将首先比较到目前为止确定的最好的补充剂， “EE”，另一种含有不同比例的丝氨酸 (“FF”)。第二，我们将确定鸟氨酸是更多还是更少 与等氮甘氨酸和IF相比，对短期氮平衡有效 所以，无论这是因为它抑制了酮亮氨酸的氧化 从体外数据来看。第三，我们将确定 单用酮-亮氨酸(添加到含有35克大部分高的 生物价值蛋白质)，或酮-亮氨酸加少量 酮戊氨酸和酮异亮氨酸，首先保持氮平衡，如果有效， 长期的。在这一点上，我们预计已经设计了一款几乎 最佳补充。然后我们将通过比较将其优势记录在 一种含有任何氨基酸配方的交叉设计 可用。在研究2中，我们将继续进行持续鼻胃 含有这些相同成分的混合物的营养 低聚糖，用于终末期肾功能衰竭患者。我们已经展示了 高效的氮素保护和改善蛋白质营养的结果 从这个养生法中。为了探索原因，我们将(1)改变输液方式 从基本连续到只在夜间活动(12-16小时)(2) 以后用等氮丙氨酸取代鸟氨酸(3)，改变其他 选民。在每种情况下，两种方案之间的比较将是 先给个别病人治疗一次(一周或更长时间) 紧随其后的是另一个(间隔相同)。氮平衡，血浆氨基 酸水平和血清化学将是评估的方法 结果。

The first purpose of this project is to design an optimal dietary supplement for patients with chronic renal failure in the pre-dialysis stage. Criteria to be optimized (in descending order of importance) are progression of renal insufficiency, protein nutrition, PTH levels, and plasma levels of amino acids and electrolytes. A 20-25 gm mixed quality protein diet low in phosphorus will be used, and the composition of a supplement containing amino acids and N-free analogues will be varied. Short-term N balance plus long-term (three months) out-patient studies will be used. We will first compare the "best" supplement identified to date, "EE", with another containing different proportions and including serine ("FF"). Second, we will determine whether ornithine is more or less effective on short-term N balance than in equinitrogenous glycine and if so, whether this is because it inhibits oxidation of ketoleucine as suggested by in vitro data. Third, we will determine the effects of keto-leucine alone (added to a diet containing 35 gm of mostly high biological value protein), or keto-leucine plus smaller amounts of ketovaline and ketoisoleucine, first on N balance and if effective, long-term. At or about this point, we expect to have designed a nearly optimal supplement. We will then document its advantages by comparison in a cross-over desing with whatever amino acid formulation is then available. In study 2 we will continue to pursue continuous nasogastric alimentation with a mixture containing these same constituents plus oligosaccharides, in patients with end-stage renal failure. We have shown that highly efficient N conservation and improved protein nutrition results from this regimen. To explore why, we will (1) change the infusion schedule from essentially continuous to nocturnal only (12-16 hours) (2) replace ornithine with isonitrogenous alanine (3) later, vary other constituents. In each case, the comparison between two regimens will be made by treating individual patients first with one (for one week or more) followed by the other (for the same interval). N balance, plasma amino acid levels and serum chemistries will be the methods for evaluating the results.