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

doi:10.1038/nbt0510-436

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.

Abstract - Next-generation biomarkers for detecting kidney toxicity | Full Text - Next-generation biomarkers for detecting kidney toxicity | PDF (391 KB) - Next-generation biomarkers for detecting kidney toxicity

Focus on The Predictive Safety Testing Consortium

Evolution of biomarker qualification at the health authorities - pp441 - 443

Federico Goodsaid & Marisa Papaluca

doi:10.1038/nbt0510-441

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.

Abstract - Evolution of biomarker qualification at the health authorities | Full Text - Evolution of biomarker qualification at the health authorities | PDF (314 KB) - Evolution of biomarker qualification at the health authorities

Focus on The Predictive Safety Testing Consortium

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

doi:10.1038/nbt.1634

Abstract - Towards consensus practices to qualify safety biomarkers for use in early drug development | Full Text - Towards consensus practices to qualify safety biomarkers for use in early drug development | PDF (307 KB) - Towards consensus practices to qualify safety biomarkers for use in early drug development | Supplementary information

Focus on The Predictive Safety Testing Consortium

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

doi:10.1038/nbt.1625

Abstract - Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium | Full Text - Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium | PDF (293 KB) - Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium

Focus on The Predictive Safety Testing Consortium

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

doi:10.1038/nbt.1622

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.

Abstract - Urinary clusterin, cystatin C, [beta]2-microglobulin and total protein as markers to detect drug-induced kidney injury | Full Text - Urinary clusterin, cystatin C, β2-microglobulin and total protein as markers to detect drug-induced kidney injury | PDF (1,328 KB) - Urinary clusterin, cystatin C, β2-microglobulin and total protein as markers to detect drug-induced kidney injury | Supplementary information

Focus on The Predictive Safety Testing Consortium

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

doi:10.1038/nbt.1624

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.

Abstract - Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury | Full Text - Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury | PDF (1,393 KB) - Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury | Supplementary information

Focus on The Predictive Safety Testing Consortium

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

doi:10.1038/nbt.1623

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.

Abstract - Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies | Full Text - Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies | PDF (1,024 KB) - Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies | Supplementary information

Focus on The Predictive Safety Testing Consortium

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

doi:10.1038/nbt.1627

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.

Abstract - A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function | Full Text - A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function | PDF (1,137 KB) - A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function | Supplementary information