Collagen IV is the principal component of the glomerular basement membrane and it is released into the urine during its turnover. Increased urinary levels of collagen IV are found in several conditions where glomerular injury is found(2), Urinary collagen IV is a specific sensitive indicator of changes to the structure of glomerular matrix.

The Biotrin Nephrology SMARTASSAYS enable the simultaneous monitoring of the glomerulus (urinary collagen IV) and the proximal and distal tubules (αGST and πGST respectively) allowing new opportunities to study renal transplant pathology and physiology.

Renal Transplantation Research

Ischaemia-Reperfusion Injury

Renal ischaemia causes damage to the proximal renal tubule and this is associated with the release of ƒÑGST into the organ perfusate (3) or urine. αGST in the organ perfusate was the single best indicator of post transplant graft non-viability. An αGST level of below 2800mg / 100g kidney in the perfusate predicted a 98% likelihood of a functioning graft.

Transplant Monitoring

Transplantation involves the administration of potentially toxic drugs plus there is the risk of rejection episodes. By the assay of urinary GSTs the effects of therapeutic procedures on the kidney can be followed more precisely. For example, rejection episodes predominantly affect the distal tubules and so are associated with the release of urinary πGST(1). Conversely, toxic events predominantly affect the proximal tubules and so cause the release of αGST(1). Acute tubular necrosis leads to an increase in both αGST and πGST(1). This differential release of GSTs can help to identify the site and cause of renal dysfunction in transplant research and can be used to follow the effects of different therapeutic and experimental procedures.

Monitoring chronic transplant nephropathy or chronic rejection is a problem due to the absence of appropriate biomarkers and here urinary collagen IV could be especially valuable. Renal deposition of collagen IV is increased in chronic transplant nephropathy(5) and increased urinary levels of collagen IV are found in subjects with acute rejection(6) and chronic transplant nephropathy(7).

References:

1. Sundberg A.G.M. et al. (1994). Urinary pi class glutathione S-transferase as an indicator of tubular damage in the human kidney. Nephron 67: 308-316
2. Makino, H. et al. (1995). Urinary detection of type IV collagen and its increase in glomerulonephritis. Research Communications in Molecular Pathology and Pharmacology. 88(2) 215-223.
3. Daeman, J.-W. H.C. et al. (1997). Glutathione S-transferase as predictor of functional outcome in transplantation of machine preserved non-heart-beating donor kidneys. Transplantation 63 (1):89-93.
4. Yagame, M. et al. (1997). Significance of urinary type IV collagen in patients with diabetic nephropathy using a highly sensitive one-step sandwich enzyme immunoassay. Journal of Clinical and Laboratory Analysis 11: 110-116.
5. Kawase, T. et al. (2001). Collagen IV is upregulated in chronic transplant nephropathy. Transplantation Proceednings 33 1207-1208.
6. Haddad, C et al. (1996). Elevated urine collagen iv levels (UC.IV) correlate with the severity of acute renal transplant (Tx) rejection (AR). Poster No 196 Presented at the ATSP meeting, Dallas 1996.
7. Tonsho, M. et al. (2000). Measurement of urinary collagen type IV after renal transplantation. Transplantation Proceedings, 32 1780.