Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
Nephrol Dial Transplant. 2012 Mar;27(3):983-90. doi: 10.1093/ndt/gfr408. Epub 2011 Aug 22.
Renin-angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both under- and overtitration of sodium targeting can easily occur. We evaluated whether N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of volume expansion, predicts the benefits of sodium targeting in CKD patients.
In a cross-over randomized controlled trial, 33 non-diabetic CKD patients (proteinuria 3.8 ± 0.4 g/24 h, blood pressure 143/86 ± 3/2 mmHg, creatinine clearance 89 ± 5 mL/min) were treated during 6-week periods with placebo, angiotensin receptor blockade (ARB; losartan 100 mg/day) and ARB plus diuretics (losartan 100 mg/day plus hydrochlorothiazide 25 mg/day), combined with LS (93 ± 52 mmol Na(+)/24 h) and regular sodium diet (RS; 193 ± 62 mmol Na(+)/24 h, P < 0.001 versus LS), in random order. As controls, 27 healthy volunteers were studied.
NT-proBNP was elevated in patients during placebo + RS [90 (60-137) versus 35 (27-45) pg/mL in healthy controls, P = 0.001]. NT-proBNP was lowered by LS, ARB and diuretics and was normalized by ARB + diuretic + LS [39 (26-59) pg/mL, P = 0.65 versus controls]. NT-proBNP levels above the upper limit of normal (>125 pg/mL) predicted a larger reduction of blood pressure and proteinuria by LS and diuretics but not by ARB, during all steps of the titration regimen.
Elevated NT-proBNP levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of sodium targeting, but not RAAS blockade, in proteinuric CKD patients. Importantly, this applies to the untreated condition, as well as to the subsequent treatment steps, consisting of RAAS blockade and even RAAS blockade combined with diuretics. NT-proBNP can be a useful tool to identify CKD patients in whom sodium targeting can improve blood pressure and proteinuria.
肾素-血管紧张素-醛固酮系统（RAAS）阻断仅部分降低慢性肾脏病（CKD）患者的血压、蛋白尿以及肾脏和心血管风险，但通常需要钠靶向治疗[即低钠饮食（LS）和/或利尿剂]以实现最佳疗效。然而，钠靶向治疗的剂量不足或过量都很容易发生。我们评估了脑钠肽前体（NT-proBNP），一种容量扩张的生物标志物，是否可以预测钠靶向治疗对 CKD 患者的获益。
在一项交叉随机对照试验中，33 名非糖尿病 CKD 患者（蛋白尿 3.8 ± 0.4 g/24 h，血压 143/86 ± 3/2 mmHg，肌酐清除率 89 ± 5 mL/min）接受了为期 6 周的安慰剂、血管紧张素受体阻断剂（ARB；氯沙坦 100 mg/天）和 ARB 加利尿剂（氯沙坦 100 mg/天加氢氯噻嗪 25 mg/天）治疗，同时进行 LS（93 ± 52 mmol Na+/24 h）和 RS（193 ± 62 mmol Na+/24 h，P < 0.001 与 LS 相比），随机顺序进行。作为对照，对 27 名健康志愿者进行了研究。
在接受安慰剂+RS 治疗时，患者的 NT-proBNP 升高[90（60-137）比健康对照组的 35（27-45）pg/mL，P = 0.001]。LS、ARB 和利尿剂可降低 NT-proBNP，ARB+利尿剂+LS 可使 NT-proBNP 正常化[39（26-59）pg/mL，P = 0.65 与对照组相比]。NT-proBNP 水平高于正常值上限（>125 pg/mL）可预测 LS 和利尿剂治疗时血压和蛋白尿的降低幅度更大，但 ARB 治疗时则不然，在所有滴定方案的步骤中都是如此。
升高的 NT-proBNP 水平预测在蛋白尿性 CKD 患者中，钠靶向治疗而非 RAAS 阻断可带来更大的降压和降蛋白尿效果。重要的是，这适用于未治疗的情况，以及随后的治疗步骤，包括 RAAS 阻断，甚至 RAAS 阻断联合利尿剂。NT-proBNP 可以作为一种有用的工具，用于识别可通过钠靶向治疗改善血压和蛋白尿的 CKD 患者。
