高血壓與糖尿病型腎臟病：罹患率、目前治療與未來展望

本報告已在2011年07月19日停止出版。

簡介

糖尿病型腎臟病已演變為全球性的問題。目前的治療焦點放在以 Renin-angiotensin 降壓劑阻礙，幾乎沒有任何防止腎臟功能降低的方式，因此疾病進行與治癒效果等方面有許多未滿足的需求。

擅長多領域市調分析的英國專業公司 Datamonitor Corporation（總公司：倫敦），調查分析了高血壓與糖尿病型腎臟病的罹患率、目前治療與未來展望後，出版了一本綜合報告書 "Hypertension and Diabetic Kidney Disease - Prevalence, current treatment and future options"。

報告書內容包括：目前治療選項、未來的潛在治療方法、以糖尿病型腎臟病相關流行病學資料為基礎的糖尿病型腎病變（Nephropathy）市場現況與未來分析等等，內容綱要摘記如下：

摘要

流行病學

• 定義
• 糖尿病型腎病變原因
• 糖尿病型腎病變與高血壓的關係
• 患有糖尿病的高血壓患者數
• 2 型糖尿病型腎病變患者數
• 2 型糖尿病患者糖尿病型腎病變的進行
• 醫療體系的 ESRD（末期腎臟不全）的負擔增加
• ESRD 市場的主要影響要素
  • ESRD 患者數增加
  • 隨高齡化而提升的 ESRD 發病率
  • 風險要素增加成為罹患原因：糖尿病與高血壓

糖尿病型腎病變治療

• 糖尿病型腎病變的血糖管理
• 血壓管理的重要性
• 藥理學策略：Renin-angiotensin 系
  • Renin-angiotensin 系的主要要素
  • Renin-angiotensin 系於糖尿病的狀況
• ACE 阻礙的好處
  • ACE 阻礙劑的作用程序
  • ACE 阻礙劑的腎臟保護效果資訊
• ARB 的好處
  • ARB 的作用程序
  • 對糖尿病型腎病變患者的 ARB 投藥
  • 類別效能相關前提條件

糖尿病型腎病變的未來治療

• ACE/ARB 的組合治療可能性
• Renin 阻礙：治療機會為？
• 新化合物應以宿疾患者為標的
• 糖尿病型血管合併症的新做法
• 糖尿病型腎病變的潛在治療藥物
  • ALT-711
  • ALT-946
  • AVE-7688
  • CR002
  • Darusentan
  • FG-3019
  • KRX-101
  • Pratosartan
  • PTR-3173
  • Pyridorin
  • Ruboxistaurin (LY-333531)
  • SPP-100 (aliskiren)
  • SPP-301
• 總論

附錄

目錄

Abstract

Overview

Introduction

The increase in diabetic kidney disease is a worldwide problem. Current treatment centers on antihypertensives inhibitors for the renin-angiotensin system and merely retards the decline of renal function. A large unmet need thus exists for therapies that fully halt disease progression or provide curative benefit

Scope

• The prevalence and progression of diabetic nephropathy in the seven major markets is evaluated
• The foremost pharmacological strategies for the treatment of diabetic nephropathy are reviewed
• The current status of angiotensin II receptor blockade as first line therapy in the treatment of diabetic nephropathy is discussed
• An overview is given of the drugs in development for the treatment of diabetic nephropathy

Report Highlights

The necessity for aggressive blood pressure control is undisputed in the medical community, but the therapeutic focus is now extending to end-organ protection as a treatment goal of equal importance to BP reduction. Thus, commercial performance of both ACE inhibitors and ARBs is dependent on renoprotective benefits beyond blood pressure control

The pipeline for developmental drugs targeting the cause of diabetic kidney disease is dominated by endothelin receptor antagonists and advanced glycosylation end product inhibitors. The commercial potential for successful new agents is substantial as existing therapies do not halt the progression of diabetic nephropathy to end stage renal disease

Proximal blockade of the renin-angiotensin system (RAS) through renin inhibition offers greater treatment opportunities than distal inhibition via angiotensin II receptor blockade. Recent basic and clinical research supports the strong theoretical appeal of renin inhibition as the most promising pharmacological strategy in the short-to-medium term

Reasons to Purchase

• Explore the growing burden of ESRD on healthcare systems through data on the prevalence and progression of diabetic nephropathy
• Assess the potential of current treatment options in the diabetic nephropathy arena
• Identify novel R&D compounds in the diabetic nephropathy pipeline

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the cardiovascular pharmaceutical analysis team
• EXECUTIVE SUMMARY
  • Introduction
  • Scope and coverage of the Brief
  • Methodology
  • Key findings about the the topic
• EPIDEMIOLOGY
  • Definition
  • Etiology of diabetic nephropathy
  • The role of hypertension in diabetic nephropathy
  • Prevalence of hypertensive patients with diabetes
  • Prevalence of hypertensive patients with diabetes
  • Prevalence of nephropathy in type 2 diabetics
  • Progression of diabetic nephropathy in type 2 patients.
  • The growing burden of ESRD on healthcare systems
  • Key factors influencing the ESRD market
    • The increasing prevalence of ESRD
    • ESRD occurrence is increasing in an aging population
    • Increasing causal risk factors - diabetes andhypertension
• TREATMENT OF DIABETIC NEPHROPATHY
  • Glucose control in diabetic nephropathy
  • Importance of blood pressure control
  • Pharmacological strategy: the role of therenin-angiotensin system
    • The key components of the renin-angiotensin system
    • The status of the renin-angiotensin system in diabetics
  • Benefits of ACE inhibition
    • Mechanism of action of ACE inhibitors
    • Data supporting the renoprotective benefits of ACEinhibitors.
      • The MICRO-HOPE study (2000): the benefits of ramipril
      • The AASK study (2001): ramipril vs. metoprolol
      • BENEDICT (2004): trandolapril
      • DETAIL (2004): enalapril is not more efficacious thantelmisartan
  • Benefits of angiotensin II receptor blockade
    • Mechanism of action of angiotensin II receptor blockers
    • Current status of angiotensin II receptor blocker use inpatients with diabetic nephropathy
      • Overview
      • The issue of dose in ARB-based therapy
    • Class effect assumption
• FUTURE TREATMENT OF DIABETIC NEPHROPATHY
  • Potential of the ACE/ARB combination
    • Marketing rationale for the ACE/ARB combination
  • Renin inhibition: what are the therapeuticopportunities?
  • New compounds should target the underlying disease
  • New approaches for diabetic microvascular complications
    • Inhibitors of aldose reductase (ARIs)
    • Protein kinase C-beta (PKC) inhibitors
    • Advanced glycation end product (AGE) inhibitors
    • Endothelin A receptor antagonists (ERAs)
  • Potential treatments for diabetic nephropathy
    • ALT-711
    • ALT-946
    • AVE-7688
    • CR002
    • Darusentan
    • FG-3019
    • KRX-101
    • Pratosartan
    • PTR-3173
    • Pyridorin
    • Ruboxistaurin (LY-333531)
    • SPP-100 (aliskiren)
    • SPP-301
  • Conclusion
• APPENDIX
  • Bibliography
    • Epidemiology
    • Treatment and novel agents
  • Disclaimer
• List of Tables
  • Table 1: Changes in kidney structure and function indiabetic nephropathy
  • Table 2: Prevalence of diabetic hypertension(millions), 2002-15
  • Table 3: Diabetic hypertensive population bysub-population across the seven major markets (millions), 2002-15
  • Table 4: Estimated prevalence of type 2 diabeticnephropathy in the seven major markets
  • Table 5: Number of type 2 patients affected bydiabetic nephropathy and time of progression across the seven majormarkets (millions), 2003
  • Table 6: Renal transplantation, hemodialysis andperitoneal dialysis prevalence rates by country (PMP), 2002
  • Table 7: Hemodialysis population by country (in 000s),2002-12
  • Table 8: The growth and distribution of the riskcausal factors in ESRD in the seven major nations
  • Table 9: The growth and distribution of the riskcausal factors in ESRD in the seven major nations
  • Table 10: Evolution of treatment guidelines withrespect to target blood pressure and therapy options: reducing the riskof nephropathy in patients with diabetes or kidney disease
  • Table 11: JNC7: compelling indications for individualdrug classes
  • Table 12: Pharmacokinetic profiles of commerciallyavailable ARBs
  • Table 13: Current indications for ARBs in addition tohypertension
  • Table 14: Dual RAS blockade in patients with diabeticnephropathy
  • Table 15: Renin inhibition reduces plasma reninactivity
  • Table 16: Nephropathy pipeline, 2005
• List of Figures
  • Figure 1: Prevalence of diabetic hypertension, 2002-15
  • Figure 2: Diabetic hypertensive population bysub-population across the seven major markets, 2002-15
  • Figure 3: Estimated progression of diabeticnephropathy in type 2 diabetes across the seven major markets
  • Figure 4: Increased risk of death and diabeticnephropathy
  • Figure 5: Hemodialysis population by country, 2002-12
  • Figure 6: Increasing prevalence of ESRD in thedeveloped world
  • Figure 7: Hemodialysis is preferred over peritonealdialysis in all markets
  • Figure 8: Age distribution and growth of prevalentESRD patients
  • Figure 9: The increasing prevalence of diabetes andhypertension in the major seven nations
  • Figure 10: Guideline-based treatment tree: use of ACEinhibitors and ARBs in nephropathy patients
  • Figure 11: The renin angiotensin system
  • Figure 12: Angiotensin II is a cardiovascular riskfactor with direct tissue effects
  • Figure 13: Prorenin/renin receptor mediates the directtissue effects of renin and prorenin
  • Figure 14: Pharmacological strategies for theinhibition of the renin-angiotensin system
  • Figure 15: The AT2 receptor may have positive as wellas negative effects on the vasculature and end organs
  • Figure 16: Mechanism of action of ACE inhibitors

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