Kids Kidney Research

Acute kidney failure has a high early mortality rate of between 30-50%. It can be cuased by a variety of ‘insults’ to the kidney, and can follow major surgery (e.g. after a heart operation) or exposure to environmental poisons. Even in those who recover from the initial insult, some individuals go on go get long-term kidney failure and this can be exacerbated by having ‘hypertension’ or high blood pressure. Therefore there is an urgent quest to design new therapies for this disease.

Recent studies have shown that breakdown of kidney blood vessels is associated with the development of acute renal disease. One way to maintain blood vessel number is to administer growth factors which play a role in vascular development. In this study, we aimed to determine whether two such ‘growth factors’, called ANGIOPOIETIN and VASCULAR ENDOTHELIAL GROWTH FACTOR, might have a therapeutic role in acute renal disease. The reasoning being that this could lead to the development of novel therapies for acute renal failure in the future.      

We first used a well-established model of acute kidney failure in mice to examine this idea. Here, we found that administration of ANGIOPOIETIN did indeed lead to an improvement in blood vessels in the damaged kidney. On the other hand, we made the surprising additional finding that the same ‘therapy’ actually increased inflammation in the damaged kidney, so that the overall effect was of ‘no improvement’.

We also used a model of kidney damaged induced by high blood pressure to establish whether VASCULAR ENDOTHELIAL GROWTH FACTOR might project the kidney. We found that this ‘therapy’ lowered blood pressure and to an extent prevented kidney tubule damage. On the other hand, the treatment worsened other parameters of injury.

What are the implications of this research? First, we have established ‘proof of principal’ that one can administer a growth factors in the context of acute kidney injury. Second, although our results show that some effects of such ‘therapies’ may be useful, there are ‘side-effects’ which indicate that further work is needed to optimise such treatments.

Main original research publications arising

• Long DA, Mu W, Price KL, Roncal C, Schreiner GF, Woolf AS, Johnson RJ.    Vascular endothelial growth factor administration does not improve microvascular disease in the salt-dependent phase of post-angiotensin II hypertension.     Am J Physiol Renal Physiol 291:F1298-F1254, 2006.
• Long DA, Gannon CM, Rudge JS, Ioffe E, Gnudi L, Yancopoulos GD, Woolf AS.    Angiopoietin-1 enhances inflammation and fibrosis in the chronic phase of murine folic-acid induced nephropathy
  Submitted for publication