PHASE II TRIAL OF KETOCONAZOLE + PREDNISONE ON PROGRESSION OF CHRONIC RENAL F

患有四种不同类型慢性肾功能衰竭的患者 (CRF)(肾小球疾病、间质性肾炎、糖尿病肾病、 或多囊肾病)在序列检查中观察到 肾小球滤过率(GFR)测定。这些人的GFR 病情进展的患者每天给药酮康唑200至600毫克(至 抑制皮质醇产生)加泼尼松2.5毫克/天(以防止 垂体前叶逃逸)，并使用更多的GFR观察，或 在开始之前，观察到了另外四个GFR 使用这些药物进行治疗；一些患者随后被撤回 从这些药物中分离出来，并观察更多的GFR。 通过线性样条法估计进展药物，使用 治疗前、治疗中和治疗后(如果有)的观察。在……里面 20名患者，获得了足够的数据来估计 这种效果。在7名慢性肾小球疾病患者中， 在-0.62±0.12ml/min/mo的速度下，进程减慢了66%~112% (P&lt；0.01)。不同类型间质性肾炎5例 病因，进展速度为-1.19 1 0.34ml/min/mo，进展减慢 增加了55%和127%(p&lt；0.05)。在5名糖尿病患者中，进展速度为-1.22 1 0.14ml/min/mo，病程平均减慢77%±14%(p&lt； 0.01)。相比之下，在四名多囊肾病患者中， 进展加快99%~163%。平均尿类固醇排泄量 血浆促肾上腺皮质激素水平无明显升高。 蛋白尿和血脂水平均无变化。尿硝酸盐 排泄量明显减少，但血清硝酸盐无明显变化。 血压略有下降(4.3毫米汞柱)。三名患者发展为 短暂升高的血清转氨酶水平；另外两人停用 因为有副作用。我们的结论是，在慢性肾小球 疾病，糖尿病肾病，间质性肾炎，这个 在没有肾脏的情况下，联合用药与酮康唑一样安全 疾病，并显示出减缓进展的希望。在多囊肾中 疾病，显然是无效或有害的。

Patients with any one of four different types of chronic renal failure (CRF) (glomerular disease, interstitial nephritis, diabetic nephropathy, or polycystic kidney disease) were observed during sequential determinations of glomerular filtration rate (GFR). Those whose GFR showed progression were either given ketoconazole 200 to 600 mg/day (to suppress cortisol production) plus prednisone 2.5 mg/day (to prevent anterior pituitary escape) and observed with the use of more GFR'S, or were observed while four more GFR's were determined before starting therapy with these drugs; some patients were subsequently withdrawn from these drugs and were observed with more GFR'S. The effect of these drugs on progression was estimated by a linear spline technique, using observations before, during, and (when available) after treatment. In 20 patients, sufficient data were obtained to estimate the magnitude of this effect. In seven patients with chronic glomerular disease, progressing at -0.62 1 0.12 ml/min/mo, progression slowed by 66% 1 12% (p < 0.01). In five patients with interstitial nephritis of various etiologies, progressing at -1.19 1 0.34 ml/min/mo, progression slowed by 55% 1 27% (p < 0.05). In five diabetic patients progressing at -1.22 1 0.14 ml/min/mo, progression slowed by an average of 77% + 14% (p < 0.01). In contrast, in four patients with polycystic kidney disease, progression accelerated by 99% 1 63%. Mean urinary steroid excretion decreased significantly; plasma corticotrophin did not increase. Neither proteinuria nor serum lipid levels changed. Urinary nitrate excretion decreased significantly, but serum nitrate did not change. Blood pressure decreased slightly (4.3 mm Hg). Three patients developed transiently elevated serum transaminase levels; two others withdrew because of side effects. We conclude that in chronic glomerular disease, diabetic nephropathy, and interstitial nephritis, this combination of drugs is as safe as ketoconazole in the absence of renal disease and shows promise of slowing progression. In polycystic kidney disease, it is apparaently ineffective or harmful.