延缓慢性肾病的进展：残余蛋白尿这一被忽视的问题。

Retarding progression of chronic renal disease: the neglected issue of residual proteinuria.

作者信息

Ruggenenti Piero, Perna Annalisa, Remuzzi Giuseppe

机构信息

Mario Negri Institute for Pharmacological Research and Unit of Nephrology, Ospedali Riuniti, Azienda Ospedaliera, Bergamo, Italy.

出版信息

Kidney Int. 2003 Jun;63(6):2254-61. doi: 10.1046/j.1523-1755.2003.00033.x.

DOI:10.1046/j.1523-1755.2003.00033.x

PMID:12753315

Abstract

BACKGROUND

Findings that early changes in proteinuria independently predict long-term glomular filtration rate (GFR) decline (Delta GFR) would highlight proteinuria as a major determinant of progression in chronic renal disease.

METHODS

We investigated whether percent changes (3 months vs. baseline) in proteinuria (adjusted for concomitant changes in GFR) and residual proteinuria at 3 months, predicted Delta GFR [over a median (IQ range) follow up of 31.3 (24.5 to 50.3) months] in 273 patients with proteinuric chronic nephropathies enrolled in the Ramipril Efficacy In Nephropathy (REIN) study.

RESULTS

Short-term changes and residual proteinuria (r = -0.23, P = 0.0001 for both) significantly correlated with Delta GFR and, at multivariate analyses, independently predicted Delta GFR (beta = -0.23, P = 0.0002; beta = -0.21, P = 0.0004, respectively). For comparable levels of residual proteinuria, patients with greater short-term reduction had slower Delta GFR (-0.28 +/- 0.04 mL/min/1.73 m2/ vs. -0.53 +/- 0.07 mL/min/1.73 m2/month, P = 0.04). On ramipril and conventional treatment, specular short-term changes in proteinuria (-18.2 +/- 3.5% vs. 24.2 +/- 6.7%, P < 0.0001, respectively) were associated with significantly different Delta GFRs. However, similar changes in proteinuria resulted in a difference in Delta GFR (ramipril, 0.39 +/- 0.07 mL/min/1.73 m2/month; conventional therapy, 0.74 +/- 0.11 mL/min/1.73 m2/month; P < 0.01) that was sevenfold higher (0.35 vs. 0.05 mL/min/1.73 m2/month) in patients with basal proteinuria > or =3 g/24 hours as compared to those with basal proteinuria 1 to 3 g/24 hours (ramipril, 0.25 +/- 0.06 mL/min/1.73 m2/month; conventional therapy, 0.30 +/- 0.07 mL/min/1.73 m2/month; P = NS).

CONCLUSION

Regardless of blood pressure control and treatment randomization, short-term changes in proteinuria and residual proteinuria reliably predict long-term disease progression. Reducing proteinuria is renoprotective, particularly in nephrotic patients. As for arterial hypertension, proteinuria should be a specific target for renoprotective treatment.

摘要

背景

蛋白尿早期变化能独立预测长期肾小球滤过率（GFR）下降（ΔGFR），这一发现将突出蛋白尿是慢性肾病进展的主要决定因素。

方法

我们在273例蛋白尿性慢性肾病患者中进行了研究，这些患者参加了雷米普利肾病疗效（REIN）研究，观察蛋白尿的百分比变化（3个月时与基线相比，已校正GFR的伴随变化）和3个月时的残余蛋白尿是否能预测ΔGFR[中位（四分位间距）随访时间为31.3（24.5至50.3）个月]。

结果

短期变化和残余蛋白尿（两者r均为-0.23，P均为0.0001）与ΔGFR显著相关，在多变量分析中，它们能独立预测ΔGFR（β分别为-0.23，P = 0.0002；β为-0.21，P = 0.0004）。对于残余蛋白尿水平相当的患者，短期降低幅度更大的患者其ΔGFR较慢（-0.28±0.04 mL/min/1.73 m²/月对-0.53±0.07 mL/min/1.73 m²/月，P = 0.04）。在接受雷米普利和传统治疗时，蛋白尿的明显短期变化（分别为-18.2±3.5%对24.2±6.7%，P < 0.0001）与显著不同的ΔGFR相关。然而，蛋白尿的类似变化导致ΔGFR存在差异（雷米普利组为0.39±0.07 mL/min/1.73 m²/月；传统治疗组为0.74±0.11 mL/min/1.73 m²/月；P < 0.01），基础蛋白尿≥3 g/24小时的患者与基础蛋白尿1至3 g/24小时的患者相比，这种差异高7倍（0.35对0.05 mL/min/1.73 m²/月）（雷米普利组为0.25±0.06 mL/min/1.73 m²/月；传统治疗组为0.30±0.07 mL/min/1.73 m²/月；P = 无显著差异）。