The Predictive Safety Testing Consortium



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Biomarkers on a roll p431


A consortium of industry, nonprofit institutions and regulators outlines a rolling biomarker qualification process, providing the first clear path for translation of such markers from discovery to preclinical and clinical practice.



Focus on The Predictive Safety Testing Consortium

Research at the interface of industry, academia and regulatory science pp432 - 433

William B Mattes, Elizabeth Gribble Walker, Eric Abadie, Frank D Sistare, Jacky Vonderscher, Janet Woodcock & Raymond L Woosley




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Glossary pp434 - 435



Opinion and Comment


Focus on The Predictive Safety Testing Consortium

Next-generation biomarkers for detecting kidney toxicity pp436 - 440

Joseph V Bonventre, Vishal S Vaidya, Robert Schmouder, Peter Feig & Frank Dieterle


There is a paucity of biomarkers that reliably detect nephrotoxicity. The Predictive Safety Testing Consortium (PSTC) faced several challenges in identifying novel safety biomarkers in the renal setting.

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Evolution of biomarker qualification at the health authorities pp441 - 443

Federico Goodsaid & Marisa Papaluca


By streamlining the qualification process for biomarkers, coordinated protocols recently implemented at the different regulatory agencies can facilitate progress and provide impetus to novel biomarker discovery and validation.


News and Views

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A roadmap for biomarker qualification pp444 - 445

David G Warnock & Carl C Peck


A collaborative effort between pharmaceutical companies, regulatory agencies and academia to qualify biomarkers for kidney toxicity provides a model for investigating and identifying reliable safety markers for preclinical applications.




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Towards consensus practices to qualify safety biomarkers for use in early drug development pp446 - 454

Frank D Sistare, Frank Dieterle, Sean Troth, Daniel J Holder, David Gerhold, Dina Andrews-Cleavenger, William Baer, Graham Betton, Denise Bounous, Kevin Carl, Nathaniel Collins, Peter Goering, Federico Goodsaid, Yi-Zhong Gu, Valerie Guilpin, Ernie Harpur, Alita Hassan, David Jacobson-Kram, Peter Kasper, David Laurie, Beatriz Silva Lima, Romaldas Maciulaitis, William Mattes, Gérard Maurer, Leslie Ann Obert, Josef Ozer, Marisa Papaluca-Amati, Jonathan A Phillips, Mark Pinches, Matthew J Schipper, Karol L Thompson, Spiros Vamvakas, Jean-Marc Vidal, Jacky Vonderscher, Elizabeth Walker, Craig Webb & Yan Yu


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Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium pp455 - 462

Frank Dieterle, Frank Sistare, Federico Goodsaid, Marisa Papaluca, Josef S Ozer, Craig P Webb, William Baer, Anthony Senagore, Matthew J Schipper, Jacky Vonderscher, Stefan Sultana, David L Gerhold, Jonathan A Phillips, Gérard Maurer, Kevin Carl, David Laurie, Ernie Harpur, Manisha Sonee, Daniela Ennulat, Dan Holder, Dina Andrews-Cleavenger, Yi-Zhong Gu, Karol L Thompson, Peter L Goering, Jean-Marc Vidal, Eric Abadie, Romaldas Maciulaitis, David Jacobson-Kram, Albert F Defelice, Elizabeth A Hausner, Melanie Blank, Aliza Thompson, Patricia Harlow, Douglas Throckmorton, Shen Xiao, Nancy Xu, William Taylor, Spiros Vamvakas, Bruno Flamion, Beatriz Silva Lima, Peter Kasper, Markku Pasanen, Krishna Prasad, Sean Troth, Denise Bounous, Denise Robinson-Gravatt, Graham Betton, Myrtle A Davis, Jackie Akunda, James Eric McDuffie, Laura Suter, Leslie Obert, Magalie Guffroy, Mark Pinches, Supriya Jayadev, Eric A Blomme, Sven A Beushausen, Valérie G Barlow, Nathaniel Collins, Jeff Waring, David Honor, Sandra Snook, Jinhe Lee, Phil Rossi, Elizabeth Walker & William Mattes



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Urinary clusterin, cystatin C, β2-microglobulin and total protein as markers to detect drug-induced kidney injury pp463 - 469

Frank Dieterle, Elias Perentes, André Cordier, Daniel R Roth, Pablo Verdes, Olivier Grenet, Serafino Pantano, Pierre Moulin, Daniel Wahl, Andreas Mahl, Peter End, Frank Staedtler, François Legay, Kevin Carl, David Laurie, Salah-Dine Chibout, Jacky Vonderscher & Gérard Maurer


Current biomarkers for detecting kidney damage, such as serum creatinine (SCr) and blood urea nitrogen (BUN), lack the sensitivity needed for use in drug development. Urinary clusterin outperforms SCr and BUN in detecting proximal tubular injury, and urinary total protein, cystatin C and β2-microglobulin each outperform either SCr or BUN in detecting glomerular injury.

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Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury pp470 - 477

Yan Yu, Hong Jin, Daniel Holder, Josef S Ozer, Stephanie Villarreal, Paul Shughrue, Shu Shi, David J Figueroa, Holly Clouse, Ming Su, Nagaraja Muniappa, Sean P Troth, Wendy Bailey, John Seng, Amy G Aslamkhan, Douglas Thudium, Frank D Sistare & David L Gerhold


Exposure of rats to kidney toxicants reduces levels of urinary trefoil factor 3 (TFF3) and increases levels of urinary albumin. Whereas urinary albumin outperforms either serum creatinine (SCr) or blood urea nitrogen (BUN) for detecting kidney tubule damage, urinary TFF3 abundance complements the capacity of combined SCr and BUN levels to detect renal injury.

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Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies pp478 - 485

Vishal S Vaidya, Josef S Ozer, Frank Dieterle, Fitz B Collings, Victoria Ramirez, Sean Troth, Nagaraja Muniappa, Douglas Thudium, David Gerhold, Daniel J Holder, Norma A Bobadilla, Estelle Marrer, Elias Perentes, André Cordier, Jacky Vonderscher, Gérard Maurer, Peter L Goering, Frank D Sistare & Joseph V Bonventre


Urinary kidney injury-1 (Kim-1) outperforms serum creatinine, blood urea nitrogen and urinary N-acetyl-β-D-glucosaminidase in detecting kidney damage induced in rats by a range of nephrotoxicants. Earlier detection of renal injury, enabled by monitoring levels of urinary Kim-1, should enable elimination of nephrotoxic candidates sooner in the drug development pipeline.

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A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function pp486 - 494

Josef S Ozer, Frank Dieterle, Sean Troth, Elias Perentes, André Cordier, Pablo Verdes, Frank Staedtler, Andreas Mahl, Olivier Grenet, Daniel R Roth, Daniel Wahl, François Legay, Daniel Holder, Zoltan Erdos, Katerina Vlasakova, Hong Jin, Yan Yu, Nagaraja Muniappa, Tom Forest, Holly K Clouse, Spencer Reynolds, Wendy J Bailey, Douglas T Thudium, Michael J Topper, Thomas R Skopek, Joseph F Sina, Warren E Glaab, Jacky Vonderscher, Gérard Maurer, Salah-Dine Chibout, Frank D Sistare & David L Gerhold


A panel of urinary biomarkers enables the progression of renal injury and subsequent repair and recovery to be monitored after exposure of rats to either carbapenem A or gentamicin. The authors complement this study by demonstrating that serum cystatin C is more sensitive and specific than serum creatinine and blood urea nitrogen in monitoring generalized renal function after exposure to nephrotoxicants.