Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease

Background. Angiotensin-converting enzyme (ACE) inhibitors reduce urine pro tein excretion and slow the progression of renal disease. The beneficial ef fect in slowing the progression of renal disease is greater in patients wit h higher urine protein excretion at the onset of treatment. We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is du e to their greater antiproteinuric effect in these patients. Methods. Data were analyzed from 1860 patients enrolled in I I randomized c ontrolled trials comparing the effect of antihypertensive regimens, includi ng ACE inhibitors to regimens not including ACE inhibitors on the progressi on of non-diabetic renal disease. Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at bas eline and changes in urine protein excretion during follow-up. The Cox prop ortional hazards analysis was used to assess the relationship between chang es in urine protein excretion during follow-up and the effect of ACE inhibi tors on the time to doubling of baseline serum creatinine values or onset o f end-stage renal disease. Results. Mean (median) baseline urine protein excretion was 1.8 (0.94) g/da y. Patients with higher baseline urine protein excretion values had a great er reduction in proteinuria during the follow-up in association with treatm ent with ACE inhibitors and in association with lowering systolic and diast olic blood pressures (interaction P < 0.001 for all). A higher level of uri ne protein excretion during follow-up (baseline minus change) was associate d with a greater risk of progression [relative risk 5.56 (3.87 to 7.98) for each 1.0 g/day higher protein excretion]. After controlling for the curren t level of urine protein excretion, the beneficial effect of ACE inhibitors remained significant [relative risk for ACE inhibitors vs. control was 0.6 6 (0.52 to 0.83)], but there was no significant interaction between the ben eficial effect of ACE inhibitors and the baseline level of urine protein ex cretion. Conclusions. The antiproteinuric effects of ACE inhibitors and lowering blo od pressure are greater in patients with a higher baseline urine protein ex cretion. The greater beneficial effect of ACE inhibitors on renal disease p rogression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients. The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease. ACE inhibitors provide greater beneficial e ffect at all levels of current urine protein excretion.