Role of patient factors in therapy resistance to antiproteinuric intervention in nondiabetic and diabetic nephropathy

Reduction of proteinuria is a prerequisite for successful long-term renopro tection. To investigate whether individual patient factors are determinants of antiproteinuric efficacy, we analyzed individual responses to different modes of antiproteinuric intervention in nondiabetic and diabetic patients , obtained in prior studies comparing the efficacy of various pharmacologic al regimens. The individual antiproteinuric response to angiotensin-convert ing enzyme (ACE) inhibition positively correlated to the response to angiot ensin type I (AT1) receptor blockade in diabetic (r = 0.67, P < 0.01, N = 1 6) as well as nondiabetic patients (r = 0.75, P < 0.01, N = 12). This corre sponded to the correlations for antihypertensive efficacy between ACE inhib ition and ATI receptor blockade in diabetic (r = 0.73, P < 0.001) as well a s nondiabetic patients (r = 0.55, P < 0.05). Remarkably, the antiproteinuri c response to ACE inhibition also correlated positively to the antiproteinu ric response to indomethacin (r = 0.63, P < 0.05, N = 9). Thus, patients re sponding favorably to one class of antiproteinuric drugs also respond favor ably to other classes of available drugs, supporting a main role for indivi dual patient factors in responsiveness or resistance to antiproteinuric int ervention. In the search for strategies to improve response in these high r isk patients, combination-treatment (combining different drugs, and combini ng drugs with dietary measures like sodium and protein restriction), and th e use of higher doses may provide more fruitful strategies to optimize reno protection than shifting to other classes of the available drugs.