Clinical Nephrotoxicity

Summary
  • Alpha GST (αGST), Pi GST (πGST) 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 GSTs change in advance of changes in serum creatinine.

 

Selected articles

 

Renal distribution of biomarkers

1) Distribution of glutathione S-transferase isoenzymes in human kidney: basis for possible markers of renal injury.
Harrison, D.J., Kharbanda, R., Cunningham, D.S., McLellan, L.I. and Hayes JD. (1989). J. Clin. Pathol. 42(6) 624-8.

  • αGST is found in the proximal tubules
  • πGST is found in the distal tubules

 

GSTs in nephrotoxicity

 Amphoptericin B

1) Assessment of effective renal plasma flow, enzymuria, and cytokine release in healthy volunteers receiving a single dose of Amphotericin B desoxycholate.
Pai, M.P., Norenberg, J.P., Telepak, R.A., Sidney, D.S. and Yang, S. (2005). Antimicrob. Agents Chemother. 49(9) 3784-3788.

  • Amphotericin B toxicity was studied in 12 healthy individuals.
  • GSTs could demonstrate the increased sensitivity of males to Amphotericin.
  • Both proximal and distal tubular effects could be seen.

 

Sevoflurane / Compound A

1) Dose of compound A, not Sevoflurane®, determines changes in the biochemical markers of renal injury in healthy volunteers.
Goldberg, M.E. et al. (1999). Anesthesia and Analgesia 88 437-445.

  • 14 healthy volunteers exposed to Sevoflurane anesthesia.
  • αGST release correlated closely with exposure to Compound A.

 

Cyclosporin

1) Urinary glutathione transferase as an early marker of renal impairment in psoriasis patients treated with Cyclosporin A (CsA).
Kirby, K.B. et al. (1997). Paper presented at the XIVth International Congress of Nephrology, 25-29 May 1997, Sydney, Australia.

  • 22 patients followed for 6 months.
  • Urinary αGST rose six weeks in advance of changes in serum creatinine.

 

2) Decreased nephrotoxicity after the use of a microemulsion preparation of cyclosporin A compared to a conventional solution.

Ahlmén, J., Sundberg, A, Gustavsson, A and Strömbom, U. (1995). Transplantation Proceedings, 27(6) 3432-3437.

  • Cyclosporin toxicity studied in 27 patients.
  • αGST release could indicate the relative toxicities of different forms of cyclosporin.

 

Contrast media

1) Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury.
Drager, L.F., Andrade, L., Barros de Toledo, J.F., Laurindo, F.R., Machado César, L.A. and Seguro, A.C. (2004).
Nephrol. Dial. Transplant. 19(7) 1803-7.

  • 24 subjects studied.
  • Administration of N-Acetylcysteine lead to decreased αGST release.

 

2) A prospective study of urinary ligandin in patients at risk of renal tubular injury.
Sherman, R.A. et al. (1985). Uremia Investigation 8 111-115.

  • 6 subjects exposed to varying doses of contrast media.
  • Higher doses of contrast media lead to αGST release.
  • Kinetics of renal effects could be followed.

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