کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5688381 1409899 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A Drug Development Tool for Trial Enrichment in Patients With Autosomal Dominant Polycystic Kidney Disease
ترجمه فارسی عنوان
یک ابزار توسعه دارویی برای غنی سازی پروتئین در بیماران مبتلا به بیماری های کلیوی غده تیروئید اتوزومی
کلمات کلیدی
بیماری کلیوی در مرحله پایانی، کاهش عملکرد کلیه، کل حجم کلیه، غنی سازی محاکمه،
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
چکیده انگلیسی

IntroductionTotal kidney volume (TKV) is a promising imaging biomarker for tracking and predicting the natural history of patients with autosomal dominant polycystic kidney disease.MethodsA drug development tool was developed by linking longitudinal TKV measurements to the probability of a 30% decline of estimated glomerular filtration rate (eGFR) or end-stage renal disease. Drug development tools were developed based on observational data collected over multiple decades for an eGFR decline and end-stage renal disease in 641 and 866 patients with autosomal dominant polycystic kidney disease, respectively.ResultsThe statistical association between predicted TKV at the time of a 30% decline of eGFR and that at the time of end-stage renal disease were both highly significant (P < 0.0001). The drug development tool was applied to demonstrate the utility of trial enrichment according to prespecified baseline TKV, age, and eGFR as enrollment criteria in hypothetical clinical trials. Patients with larger TKV (≥1000 ml) displayed steeper slopes of hazard, which translated into a higher risk of a 30% decline of eGFR within each baseline age (< or ≥40 years) or baseline eGFR (< or ≥50 ml/min per 1.73 m2) subgroups.DiscussionThese results suggest that, when eGFR is preserved, patients with larger TKV are more likely to progress to a 30% decline of eGFR within the course of a clinical trial, whereas eGFR and age displayed limited predictive value of disease progression in early disease. Pharmaceutical sponsors and academic investigators are encouraged to prospectively employ the above drug development tool to optimize trial designs in patients with autosomal dominant polycystic kidney disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International Reports - Volume 2, Issue 3, May 2017, Pages 451-460
نویسندگان
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