Kidney Safety

UPLC-MS/MS Biomarker


Using our biomarkers, Nextcea provides preemptive insight to drug candidates that may indicate potential kidney toxicity.

Oligonucleotide drugs and antibiotics has been known to cause kidney toxicity, a condition of which over two million patients battle every year. In efforts to guide clinical development, Nextcea is dedicated to the application of drug safety biomarkers that are quantitative, highly specific, and sensitive in order to provide insight into onset, severity, and recovery of toxicities.

Following treatment by drug candidates, urine samples from patients are received at Nextcea.

Nextcea measures Kidney Safety Protein Biomarkers in urine by UPLC-MS/MS to assess & pinpoint toxicity in kidney by drug candidates.

Kidney Safety

Nextcea measures kidney safety protein biomarkers in urine to assess & pinpoint toxicity in kidney by drug candidates

Sensitive urinary biomarkers are needed to detect kidney injury at the earliest stages. To monitor the onset and time-course of toxicity for pharmaceutical GLP clinical trial studies, Nextcea has developed and validated a proprietary UPLC-MS/MS assay to quantitate our biomarkers simultaneously in a single analysis.

The following proteins are among some of the biomarkers used to assess the risk of overall kidney toxicity. Additionally, with an abundancy of each protein to a specific nephron region, Nextcea is further able to use the correlation to represent and determine the nephron site of which potential kidney toxicity stems from.

Nextcea kidney safety biomarkers and their corresponding nephron region

The following assays were performed following treatment by drug candidates in order to determine the risk of kidney toxicity in nephrons such as in Loop of Henle, Glomerulus, or Proximal/Distal Tubules.

Kidney toxicity biomarker levels following treatment of drug candidate Gentamicin in rats

Tengstrand E, Zhang H, Liu N, Dunn K, Hsieh F. A multiplexed UPLC-MS/MS assay for the simultaneous measurement of urinary safety biomarkers of drug-induced kidney injury and phospholipidosis. Toxicol Appl Pharmacol. 2019 Mar 1;366:54-63. doi: 10.1016/j.taap.2019.01.012. Epub 2019 Jan 15. PMID: 30653977.

As biomarker levels rise, the indication of kidney toxicity becomes stronger. Conversely, a decrease in biomarker levels indicates a greater likelihood the drug candidate has subverted kidney toxicity. i.e. In Figure 2, following treatment of drug candidate Gentamicin, the rise in the Kim1 biomarker suggests Proximal tubules in nephron will likely to be damaged.

The PFC index is a group geometric mean of the fold changes from baseline of the six urine creatinine (uCr)-normalized urine biomarkers in subjects. (i.e. Six of the biomarkers listed above). A principal component analysis is then performed with the data to simplify and reduce the set of six individual biomarker measurements identified above into a single composite measurement. Nextcea determines the PFC Index for drug candidates, a calculation representing the threshold of pharmaceutical drug toxicity in kidneys.

Nextcea is capable of measuring kidney toxicity protein biomarkers to provide the FDA recommended PFC index, a calculation of the geometric mean or principal component analysis that determines the threshold of pharmaceutical drug toxicity in humans for drug candidates.