Summary
- Alpha GST (αGST), GSTYb1 and RPA-1 are localised to distinct parts of the nephron.
- By the assay of a panel of biomarkers, injury to different parts of the nephron can be studied independently and simultaneously.
- Urinary levels of biomarkers correlate with the extent of renal injury.
- Urinary biomarkers change in advance of changes in serum creatinine.
Selected articles
Renal distribution of biomarkers
1) Glutathione transferases of classes alpha, mu and pi show selective expression in different regions of rat kidney.
Rozell, B., Hansson, H.A., Guthenberg, C, Tahir, M.K. and Mannervik, B. (1993). Xenobiotica. 23(8) 835-49.
Describes the basic distribution of GSTs in rat kidneys:
- αGST in the proximal tubule.
- GSTYb1 in the distal tubule.
2) Urinary antigens as markers of papillary toxicity. I. Identification and characterization of rat kidney papillary antigens with monoclonal antibodies.
Falkenberg, F.W., Hildebrand, H., Lutte, L., Schwengberg, S., Henke, B., Greshake, D., Schmidt, B., Friederich, A., Rinke, M., Schlüter, G. and Bomhard, E. (1996). Arch. Toxicol. 71(1-2) 80-92.
Describes the basic distribution of renal papillary antigens in rat kidney:
- RPA-1 (Pap X Clone 5C10) is localised to the collecting ducts.
- RPA-2 (Pap XIV Clone 1C11) is localised to the loops of Henle.
GSTs in nephrotoxicity studies
1) Comparative performance of novel markers of nephrotoxicity in the rat.
Harpur, E., Schuster, K., Betton, G., Bounous, D., Ennulat, D., Reifke, B., Mylecraine, L., Pettit, S., Hoffman, D., Gautier, J.C. and Beushausen, S. (2008). Poster presented at the 47th Toxexpo congress, Seattle, USA. March, 16-20, 2008.
- αGST was the best biomarker for detecting proximal tubular injury.
- RPA-1 was the best biomarker for detecting collecting duct injury.
2) Novel biomarkers for the detection of regional kidney damage in the rat.
Davies, D., Bradshaw, J., Coope, M., Westwood, R., Knight, R., Murfin, K. (2000). EMBODY meeting, Cambridge, UK, 3rd-7th April, 2000.
- Gentamycin (a proximal tubular toxin caused increases in urinary αGST. GSTYb1 remained low.
- Cyclosporin (a distal tubular toxin) caused the release of GSTYb1; αGST remained low.
3) Role of renal cysteine conjugate ß-lyase pathway in inhaled compound A nephrotoxicity in rats.
Kharasch, E.D., Hoffman, G.M., Thorning, D., Hankins, D.C. and Kilty, C.G. (1998). Anesthesiology 88(6) 1624-1633.
- Urinary αGST is very low in the absence of renal injury.
- The release of urinary αGST correlates with the extent of renal injury.
- Only 2% tubular necrosis is associated with a 5-fold increase in urinary αGST.
4) Radioimmunoassay measurement of urinary ligandin excretion in nephrotoxin treated rats.
Bass, N.M. et al. (1979). Clinical Science, 56 419-426.
- The release of αGST is related to the degree of proximal tubular necrosis.
- The release of αGST is related to the time course of the injury.
Renal Papillary Antigens in nephrotoxicity studies
1) Comparative performance of novel markers of nephrotoxicity in the rat.
Harpur, E., Schuster, K., Betton, G., Bounous, D., Ennulat, D., Reifke, B., Mylecraine, L., Pettit, S., Hoffman, D., Gautier, J.C. and Beushausen, S. (2008).
Poster presented at the 47th ToxExpo congress, Seattle, USA. March, 16-20, 2008.
- αGST was the best biomarker for detecting proximal tubular injury.
- RPA-1 was the best biomarker for detecting collecting duct injury.
2) Identification of renal papillary necrosis using an EIA for urinary Renal Papillary Antigen-1 (RPA-1); A new biomarker of collecting duct pathology.
Kilty, C.G., Shaw, M., Falkenberg, F. W., Elliott, G., Betton, G. and Roche, A. (2006). Poster presented at the Society of Toxicology 45th Annual Meeting, San Diego, USA. March 5-9, 2006.
- Administration of renal papillary toxins lead to the release of RPA-1 into the urine.
- The more severe the pathology, the greater the release of RPA-1.
3) Urinary antigens as markers of papillary toxicity. II: Application of monoclonal antibodies for the determination of papillary antigens in rat urine.
Hildebrand, H., Rinke, M., Schlüter, G., Bomhard, E. and Falkenberg FW.(1999).
Arch. Toxicol. 73(4-5) 233-45.
- Administration of renal papillary toxins lead to the release of RPA-1 into the urine.
