title: Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: A Biomarker of Disease Progression and Therapeutic Efficacy.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life-threatening monogenic disorder in humans, characterized by progressive development and expansion of fluid-filled cysts in the kidneys and other organs. Ongoing cyst growth leads to progressive kidney enlargement, whereas kidney function remains stable for decades as a result of hyperfiltration and compensation by unaffected nephrons. Kidney function irreversibly declines only in the late stages of the disease, when most of the parenchyma is lost to cystic and fibrotic tissue and the remaining compensatory capacity is overwhelmed. Hence, conventional kidney function measures, such as glomerular filtration rate, do not adequately assess disease progression in ADPKD, especially in its early stages. Given the recent development of potential targeted therapies in ADPKD, it has become critically important to identify relevant biomarkers that can be used to determine the degree of disease progression and evaluate the effects of therapeutic interventions on the course of the disease. We review the current evidence to provide an informed perspective on whether total kidney volume (TKV) is a suitable biomarker for disease progression and whether TKV can be used as an efficacy end point in clinical trials. We conclude that because cystogenesis is the central factor leading to kidney enlargement, TKV appears to be an appropriate biomarker and is gaining wider acceptance. Several studies have identified TKV as a relevant imaging biomarker for monitoring and predicting disease progression and support its use as a prognostic end point in clinical trials.
authors.affiliation: McGill University Health Centre, Montreal, Quebec, Canada. Electronic address: ahsan.alam@mcgill.ca.
authors.forename: Ahsan
authors.initials: A
authors.lastname: Alam
authors.affiliation: Yale School of Medicine, New Haven, CT.
authors.forename: Neera K
authors.initials: NK
authors.lastname: Dahl
authors.affiliation: Medical University of South Carolina, Charleston, SC.
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Lipschutz
authors.affiliation: Otsuka America Pharmaceutical, Inc, Princeton, NJ.
authors.forename: Sandro
authors.initials: S
authors.lastname: Rossetti
authors.affiliation: Otsuka Canada Pharmaceutical, Inc, Montreal, Quebec.
authors.forename: Patricia
authors.initials: P
authors.lastname: Smith
authors.affiliation: Halton Healthcare Services, Oakville, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sapir
authors.affiliation: St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Weinstein
authors.affiliation: St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: McFarlane
authors.affiliation: Hôpital du Sacré-Cœur de Montréal, Department of Medicine, Molecular and Integrative Physiology, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bichet
mesh_terms: D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D009929:Organ Size / Q000502:physiology; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers
keywords: ADPKD biomarker; Total kidney volume (TKV); autosomal dominant polycystic kidney disease (ADPKD); cystogenesis; decline in renal function; decreased kidney function; decreased renal function; disease progression; outcome measure; renal cyst