Steno Diabetes Center, Gentofte, Denmark.
J Hypertens. 2013 Aug;31(8):1646-52. doi: 10.1097/HJH.0b013e328362217c.
Urinary levels of renin-angiotensin-aldosterone system (RAAS) components may reflect renal RAAS activity and/or the renal efficacy of RAAS inhibition. Our aim was to determine whether urinary angiotensinogen and renin are circulating RAAS-independent markers during RAAS blockade.
Urinary and plasma levels of angiotensinogen, renin, and albumin were measured in 22 patients with type 2 diabetes, hypertension, and albuminuria, during 2-month treatment periods with placebo, aliskiren, irbesartan, or their combination in random order in a crossover study.
Aliskiren and irbesartan both increased plasma renin 3-4-fold, and above 10-fold when combined. Irbesartan decreased plasma angiotensinogen by approximately 25%, and no changes in plasma angiotensinogen were observed during the combination. Urine contained aliskiren at micromolar levels, blocking urinary renin by above 90%. Both blockers reduced urinary angiotensinogen, significant for irbesartan only. Combination blockade reduced urinary angiotensinogen even further. Reductions in urinary angiotensinogen paralleled albuminuria changes, and the urine/plasma concentration ratio of angiotensinogen was identical to that of albumin under all conditions. In contrast, urinary renin did not follow albumin, and remained unaltered after all treatments. Yet, the urine/plasma concentration ratio of renin was more than 100-fold higher than that of angiotensinogen and albumin, and approximately 4-fold reduced by single RAAS blockade, and more than 10-fold by dual RAAS blockade.
Aliskiren filters into urine and influences urinary renin measurements. The urine/plasma renin ratio, but not urinary renin alone, may reflect the renal efficacy of RAAS blockade. Urinary angiotensinogen is a marker of filtration barrier damage rather than intrarenal RAAS activity.
肾素-血管紧张素-醛固酮系统（RAAS）成分的尿水平可能反映肾 RAAS 活性和/或 RAAS 抑制的肾疗效。我们的目的是确定在 RAAS 阻断期间，尿血管紧张素原和肾素是否为循环 RAAS 独立的标志物。
在一项交叉研究中，22 例 2 型糖尿病、高血压和蛋白尿患者在 2 个月的安慰剂、阿利克仑、厄贝沙坦或其联合治疗期间，测量尿和血浆中血管紧张素原、肾素和白蛋白的水平。
阿利克仑和厄贝沙坦均可使血浆肾素增加 3-4 倍，联合使用时增加 10 倍以上。厄贝沙坦使血浆血管紧张素原降低约 25%，而联合治疗期间未观察到血浆血管紧张素原的变化。尿液中含有微摩尔水平的阿利克仑，使尿肾素阻断率超过 90%。两种阻滞剂均降低尿血管紧张素原，仅对厄贝沙坦有显著作用。联合阻断进一步降低尿血管紧张素原。尿血管紧张素原的降低与白蛋白尿的变化平行，在所有条件下，尿血管紧张素原与白蛋白的尿液/血浆浓度比相同。相比之下，尿肾素不随白蛋白变化，并且在所有治疗后均保持不变。然而，肾素的尿液/血浆浓度比是血管紧张素原和白蛋白的 100 多倍，并且在单一 RAAS 阻断后降低约 4 倍，在双重 RAAS 阻断后降低 10 多倍。
阿利克仑滤入尿液并影响尿肾素的测量。尿肾素比值，而不仅仅是单独的尿肾素，可能反映 RAAS 阻断的肾疗效。尿血管紧张素原是滤过屏障损伤的标志物，而不是肾内 RAAS 活性的标志物。
