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

Abstract

Reduction of proteinuria is a prerequisite for successful long-term renoprotection. 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 pharmacological regimens. The individual antiproteinuric response to angiotensin-converting enzyme (ACE) inhibition positively correlated to the response to angiotensin type I (AT1) receptor blockade in diabetic (r = 0.67, P < 0.01, N = 16) as well as nondiabetic patients (r = 0.75, P < 0.01, N = 12). This corresponded to the correlations for antihypertensive efficacy between ACE inhibition and AT1 receptor blockade in diabetic (r = 0.73, P < 0.001) as well as nondiabetic patients (r = 0.55, P < 0.05). Remarkably, the antiproteinuric response to ACE inhibition also correlated positively to the antiproteinuric response to indomethacin (r = 0.63, P < 0.05, N = 9). Thus, patients responding favorably to one class of antiproteinuric drugs also respond favorably to other classes of available drugs, supporting a main role for individual patient factors in responsiveness or resistance to antiproteinuric intervention. In the search for strategies to improve response in these high risk patients, combination-treatment (combining different drugs, and combining drugs with dietary measures like sodium and protein restriction), and the use of higher doses may provide more fruitful strategies to optimize renoprotection than shifting to other classes of the available drugs.