Contains Nonbinding Recommendations 
 
 
Qualification of BiomarkerTotal Kidney Volume in Studies for 
Treatment of Autosomal Dominant Polycystic Kidney Disease 
 
Guidance for Industry 
 
 
This guidance represents the current thinking of the Food and Drug Administrations (FDA) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the 
public.  You can use an alternative approach if it satisfies the requirements of the applicable 
statutes and regulations.  To discuss an alternative approach, contact the Center for Drug 
Evaluation and Research (CDER) Biomarker Qualification Program (email:  CDER-
BiomarkerQualificationProgram@fda.hhs.gov).   
 
 
 
Drug Development Tool (DDT) Type:  Biomarker   
Referenced Biomarker(s):  Total Kidney Volume (TKV) 
 
TKV is defined as the sum of the volume of the left and right kidneys.  
 
I.  SUMMARY OF GUIDANCE 
 
A.  Purpose of Guidance 
 
This guidance provides a qualified context of use (COU) for the biomarker TKV in studies for 
the treatment of autosomal dominant polycystic kidney disease (ADPKD).  This guidance also 
describes the experimental conditions and constraints for which this biomarker is qualified 
through the CDER Biomarker Qualification Program.  This biomarker can be used by drug 
developers for the qualified COU in submissions of investigational new drug applications 
(INDs), new drug applications (NDAs), and biologics license applications (BLAs) without the 
relevant CDER review group reconsidering and reconfirming the suitability of the biomarker.   
 
B.  Application of Guidance 
 
This guidance applies to the use of TKV in studies for the treatment of ADPKD.  It does not 
change any regulatory status, decisions, or labeling of any medical imaging device used in the 
medical care of patients. 
 
TKV use in drug development outside of the qualified COU will be considered by FDA on a 
case-by-case basis in regulatory submissions.  In such cases, additional information relevant to 
the expanded use may be requested by the CDER product review team.  
 
 
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  Contains Nonbinding Recommendations 
 
DDT Tracking Number:  [DDTBMQ-000021]     
 
II.  CONTEXT OF USE  
 
A.  Use Statement   
 
This guidance provides qualification recommendations for the use of TKV, measured at 
baseline, as a prognostic enrichment biomarker to select patients with ADPKD at high risk for a 
progressive decline in renal function (defined as a confirmed 30% decline in the patients 
estimated glomerular filtration rate (eGFR)) for inclusion in interventional clinical trials.  This 
biomarker may be used in combination with the patients age and baseline eGFR as an 
enrichment factor in these trials.   
 
B.  Conditions for Qualified Use  
 
  1.  Quantitative Imaging Biomarker 
 
TKV should be calculated from the left and right kidneys measured with a 
validated and standardized image acquisition and analysis protocol within the 
trial.  (Please see supporting documentation for details at Biomarker 
Qualification Program:  Qualified Biomarkers and Supporting Information.) 
 
  2.  TKV-Based Patient Selection in Clinical Trials 
 
a.  PATIENT POPULATION   
 
Patients with ADPKD should be at least 12 years of age 
 
b.  PATIENT SELECTION  
 
Baseline TKV can be used in combination with the patients age and 
baseline eGFR as an enrichment factor in ADPKD clinical trials to select 
ADPKD patients at high risk for a progressive decline in renal function.  
(Please see supporting documentation for details at Biomarker 
Qualification Program:  Qualified Biomarkers and Supporting 
Information.) 
 
c.  MEASUREMENT APPLICABILITY  
 
Various imaging modalities and post-processing methods are available to determine TKV.  
These modalities have different levels of precision.  For patients with ADPKD at high risk for a 
confirmed 30% decline in their eGFR, TKV was qualified based on a collection of data from 
multiple study sites, as well as on results from imaging modalities (i.e., magnetic resonance 
imaging (MRI), computed tomography (CT), or ultrasound (US)) and from analysis 
methodologies (i.e., stereology and ellipsoid calculations).  
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