Approaches to testing new treatments in autosomal dominant polycystic kidney disease: insights from the CRISP and HALT-PKD studies.
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease characterized by a prolonged subclinical course of gradual renal cyst expansion, resulting in massively enlarged kidneys and renal failure by the fifth to sixth decade. Renal cyst expansion results in intrarenal ischemia and activation of the renin-angiotensin-aldosterone system (RAAS) and relates to the development and maintenance of hypertension in ADPKD. Hypertension relates to disease progression in ADPKD with regard to renal volume, proteinuria, cardiovascular complications, and progression to end-stage renal disease. Novel magnetic resonance imaging methods developed in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) provide accurate estimates of change in renal volume over a short period of time in ADPKD patients with intact renal function. In CRISP an increase in renal volume of 63.4 ml/yr was found. PKD1 status, male gender, hypertension, reduced renal blood flow, and proteinuria are associated with increased renal volume and change in renal volume over time. HALT-Polycystic Kidney Disease (HALT-PKD) is designed to test whether blockade of RAAS and/or rigorous blood pressure control play a role in slowing renal progression during early (using magnetic resonance imaging methods developed in CRISP) and during late (using measures, including composite of time to doubling of serum creatinine, onset of end-stage renal disease, or death) phases in ADPKD. Findings from CRISP and the rationale for interventions in ADPKD are described, and the design of the HALT-PKD clinical trial is outlined.
Chapman
Arlene B
AB
Emory University School of Medicine, 1364 Clifton Road, Room GG23, Atlanta, GA 30322, USA. Arlene.chapman@emoryhealthcare.org
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D018450:Disease Progression; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents