Summary
- By measuring urinary collagen IV, αGST and πGST, injury can be localised to the glomerulus, proximal and/or distal tubules.
- Increases in urinary πGST and collagen IV indicate early injury to the distal tubules and glomerulus in diabetic nephropathy.
- Elevated urinary collagen IV indicates progressive disease.
- Elevation of urinary αGST suggests that a parallel or additional pathology is occurring.
Selected Articles
Glutathione S-transferases
1) The potential use of urinary biomarkers for detecting and localising injury to the nephron in diabetes.
Cawood, T., Bashir, M., Brady, J., Murray, B. and O'Shea, D. (2009). Poster presented at the World Congress of Nephrology, Milan May 22-26 2009
- Urinary biomarkers were studied in 256 diabetic subjects.
- Urinary πGST (distal tubular injury) and collagen IV (glomerular injury) increased together with the severity of albuminuria.
- Distal tubular and glomerular injury appear to be early events in diabetic nephropathy.
2) Differentiation between renal injury and compensatory responses by the use of specific biomarkers.
Maxwell, P-R., et al. 2004. Poster presented at the 43rd Annual meeting of the American Society of Toxicology, Baltimore, March 21-25, 2004
- Diabetic nephropathy is associated with increased urinary πGST indicating early distal tubular injury.
- Urinary αGST was normal indicating that proximal tubular injury was unlikely.
3) The ZDSD/Pco Rat, a Type II Diabetic Model for Diabetic Nephropathy without Leptin or Leptin Receptor Mutations
- Renal biomarker assessment in a new rat model of type II diabetes. The publication shows that in these rats the distal marker GST Yb1 and collecting duct marker RPA-1 show elevations but none were seen in the proximal tubule marker alpha GST. These findings support the human studies that Argutus are undertaking.
Urinary Collagen IV
1) Urinary type IV collagen excretion reflects renal morphological alterations and type IV collagen expression in patients with type 2 diabetes mellitus.
Okonogi, H., Nishimura, M., Utsunomiya, Y., Hamaguchi, K., Tsuchida, H., Miura, Y., Suzuki, S., Kawamura, T., Hosoya, T. and Yamada, K. (2001). Clin. Nephrol. 55(5) 357-64.
- Urinary collagen IV was compared with biopsies in 20 diabetics.
- Urinary collagen IV levels correlate with the collagen IV deposition in the glomerulus.
- Urinary collagen IV levels correlate with the extent of tubulointerstitial injury.
2) Follow-up study on urinary type IV collagen in patients with early stage diabetic nephropathy.
Iijima T, Suzuki S, Sekizuka K, Hishiki T, Yagame M, Jinde K, Saotome N, Suzuki D, Sakai H, Tomino Y. (1998).
J. Clin. Lab. Anal. 12(6) 378-82.
- 94 outpatient diabetics studied.
- 44% of diabetes with normal albuminuria had elevated urinary collagen IV.
- Subjects with an increased urinary collagen IV had an increased risk of progression to albuminuria.
3) Significance of urinary type IV collagen in patients with diabetic nephropathy using a highly sensitive one-step sandwich enzyme immunoassay.
Yagame, M., Suzuki, D., Jinde, K., Saotome, N., Sato, H., Noguchi, M., Sakai, H., Kuramoto, T., Sekizuka, K., Iijima, T., Suzuki, S. and Tomino, Y. (1997). J. Clin. Lab. Anal. 11(2) 110-6.
- 298 diabetics and 80 controls studied.
- Urinary collagen IV correlates with increasing degrees of diabetic nephrology.
- Urinary collagen IV has a similar diagnostic power to urinary albumin to diagnose diabetic nephropathy.
