Surrogate endpoints in clinical trials of chronic kidney disease progression: moving from single to multiple risk marker response scores.
OBJECTIVE
There is increased interest in developing surrogate endpoints for clinical trials of chronic kidney disease progression, as the established clinically meaningful endpoint end-stage renal disease requires large and lengthy trials to assess drug efficacy. We describe recent developments in the search for novel surrogate endpoints.


RESULTS
Declines in estimated glomerular filtration rate (eGFR) of 30% or 40% and albuminuria have been proposed as surrogates for end-stage renal disease. However, changes in eGFR or albuminuria may not be valid under all circumstances as drugs always have effects on multiple renal risk markers. Changes in each of these other 'off-target' risk markers can alter renal risk (either beneficially or adversely), and can thereby confound the relationship between surrogates that are based on single risk markers and renal outcome. Risk algorithms that integrate the short-term drug effects on multiple risk markers to predict drug effects on hard renal outcomes may therefore be more accurate. The validity of these risk algorithms is currently investigated.


CONCLUSIONS
Given that drugs affect multiple renal risk markers, risk scores that integrate these effects are a promising alternative to using eGFR decline or albuminuria. Proper validation is required before these risk scores can be implemented.
aDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands bMedicines Evaluation Board, Utrecht, The Netherlands.
Bauke
B
Schievink
Peter G M
PG
Mol
Hiddo J
HJ
Lambers Heerspink
D000419:Albuminuria / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D018450:Disease Progression; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000628:therapy*
D015415:Biomarkers