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

患有四种不同类型慢性肾衰竭中的任何一种的患者 (CRF)（肾小球疾病，间质性肾炎，糖尿病肾病， 或多囊肾病）， 肾小球滤过率（GFR）的测定。 那些GFR 显示进展的患者给予酮康唑200至600 mg/天（至 抑制皮质醇产生）加泼尼松2.5 mg/天（预防 垂体前叶逃逸），并在使用更多GFR时观察到，或 在开始之前， 这些药物治疗;一些患者随后退出 并观察到更多的GFR。 这些影响 通过线性样条技术，使用 治疗前、治疗期间和治疗后（如可用）的观察结果。 在 20例患者，获得了足够的数据来估计 这种效果。 在7例慢性肾小球疾病患者中， 以-0.62 1 0.12 ml/min/mo进展，进展减慢66% 1 12% （p < 0.01）。 在5例不同类型的间质性肾炎患者中， 病因，进展为-1.19 1 0.34 ml/min/mo，进展减缓 提高55%~ 127%（P < 0.05）。 在5名糖尿病患者中，进展为-1.22 10.14 ml/min/mo，进展平均减慢77% ± 14%（p <0.05）。 0.01）。 相比之下，在四名多囊肾患者中， 进展加快了99% 163%。 平均尿类固醇排泄量 显着下降;血浆促肾上腺皮质激素未增加。 蛋白尿和血脂水平均无变化。 尿硝酸盐 排泄量显著降低，但血清硝酸盐无变化。 血压略有下降（4.3 mm Hg）。 3名患者出现 血清转氨酶水平一过性升高;另外2人退出研究 因为有副作用 我们的结论是，在慢性肾小球疾病中， 糖尿病肾病和间质性肾炎， 在无肾损害的情况下，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。 多囊肾 疾病，它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while four more GFR's were determined before starting therapy with these drugs; some patients were subsequently withdrawn from these drugs and were observed with more GFR'S. The effect of these drugs on progression was estimated by a linear spline technique, using observations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.