Stankovic Ana R, Fisher Naomi D L, Hollenberg Norman K
Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
J Am Soc Nephrol. 2006 Dec;17(12):3293-9. doi: 10.1681/ASN.2006080859. Epub 2006 Nov 8.
Prorenin is a powerful marker for risk of nephropathy and retinopathy in diabetes, but the responsible mechanism remains unclear. Studied were 35 patients with diabetes (18 with type 1 and 17 with type 2) and 69 age-matched healthy subjects with para-aminohippurate and inulin clearances and their response to captopril. All patients with diabetes had normal renal function and no microalbuminuria. Prorenin was calculated as the difference between total renin and active renin. Active renin level in patients with diabetes (11.6 +/- 0.9 microU/ml) was significantly lower than in normal subjects (14.5 +/- 1.3 microU/ml; P < 0.05); despite this, the renal vascular response to captopril was much larger (82.9 +/- 11.5 versus 13.6 +/- 5.8 ml/min per 1.73 m(2); P < 0.01). Prorenin in both patients with type 1 and type 2 diabetes (175.7 +/- 15.1 microU/ml) also was significantly higher than in normal subjects (128 +/- 5.8 microU/ml; P < 0.01). Active renin correlated with prorenin in normal subjects (r = 0.44, P = 0.0002), and this correlation was much more striking in patients with diabetes (r = 0.72, P = 0.0001). The active renin and prorenin correlation was identical in type 1 and type 2 diabetes. There was a clear correlation between plasma prorenin and the renovascular response to captopril in patients with diabetes (P < 0.01) but not in normal subjects (P > 0.13). The strong correlation between plasma prorenin concentration and the renovascular response to captopril in diabetes supports the hypothesis of a direct effect of prorenin, but the unanticipated high degree of correlation between plasma prorenin and active renin limits the conclusions that can be drawn.
肾素原是糖尿病肾病和视网膜病变风险的有力标志物，但其相关机制仍不清楚。对35例糖尿病患者（18例1型糖尿病和17例2型糖尿病）和69例年龄匹配的健康受试者进行了对氨基马尿酸和菊粉清除率及其对卡托普利反应的研究。所有糖尿病患者肾功能正常且无微量白蛋白尿。肾素原通过总肾素与活性肾素的差值计算得出。糖尿病患者的活性肾素水平（11.6±0.9微单位/毫升）显著低于正常受试者（14.5±1.3微单位/毫升；P<0.05）；尽管如此，糖尿病患者对卡托普利的肾血管反应要大得多（每1.73平方米为82.9±11.5对13.6±5.8毫升/分钟；P<0.01）。1型和2型糖尿病患者的肾素原水平（175.7±15.1微单位/毫升）也显著高于正常受试者（128±5.8微单位/毫升；P<0.01）。正常受试者中活性肾素与肾素原相关（r = 0.44，P = 0.0002），而在糖尿病患者中这种相关性更为显著（r = 0.72，P = 0.0001）。1型和2型糖尿病患者中活性肾素与肾素原的相关性相同。糖尿病患者血浆肾素原与对卡托普利的肾血管反应之间存在明显相关性（P<0.01），而正常受试者中不存在这种相关性（P>0.13）。糖尿病患者血浆肾素原浓度与对卡托普利的肾血管反应之间的强相关性支持了肾素原具有直接作用的假说，但血浆肾素原与活性肾素之间意外的高度相关性限制了所得出的结论。
