Prediction of chronic renal allograft dysfunction from evaluations of TGFBeta1 and the renin-angiotensin system

Growth factors, cytokines, and the renin-angiotensin system (RAS) are involved in chronic allograft dysfunction. However, it is unclear whether clinical evaluations of TGFBeta1 and the RAS in longterm stable transplant patients can predict the development of chronic allograft dysfunction.

Urinary TGFBeta1 excretion and the response of plasma renin activity (PRA) to angiotensin I converting-enzyme inhibition (ACE-I) were prospectively examined in transplant patients who had had stable graft function (n = 16) for at least 1 year after renal transplantation. Four-year follow-up studies were undertaken to evaluate the impact of these parameters on the development of chronic allograft dysfunction.

Urinary TGFBeta1 excretion and PRA response to ACE-I in renal transplant patients who developed chronic allograft nephropathy 4 years after the evaluations (n = 7) were significantly higher and greater, respectively, than these values in those who did not ( n = 9; P < 0.01). If the cutoff level for urinary TGFBeta1 excretion was 250 pg/min, the 4-year positive predictive value (PPV) with respect to the development of chronic allograft nephropathy was 83% and the negative predictive value (NPV) was 78% (sensitivity [sen.], 71%; specificity [sp.], 88%). If the cutoff level for PRA at 60 min after ACE-I was 4.0 ng/ml per h, the 4-year PPV was 71% and NPV was 75% (sen., 70%; sp., 75%). The stable transplant patients with high TGFBeta1 excretion and exaggerated PRA response showed significantly higher rates of chronic allograft dysfunction than those with low TGFBeta1 excretion and weak PRA response.

This study demonstrates that some transplant patients with longterm stable graft function show increases in the activities of the TGFBeta system and the RAS. Evaluations of urinary TGFBeta1 excretion and PRA response to ACE-I present a possibility for predicting the development of chronic allograft dysfunction, with significant 4-year predictive values.