Effects of Niaoduqing Particles(尿毒清颗粒)on Delaying Progression of Renal Dysfunction:A Post-trial,Open-Label,Follow-up Study
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摘要
Objective: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles(尿毒清颗粒) for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. Methods: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks(146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine(Scr) and estimated glomerular filtration rate(e GFR) after completion of the open-label treatment period. Results: After the double-blind period, the median(interquartile range) changes in Scr were 1.1(–13.0–24.1) and 11.7(–2.6–42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively(P=0.008), and the median changes in e GFRs were –0.2(–4.3–2.7) and –2.21(–5.7–0.8) mL·min~(-1)·1.73 m~(-2), respectively(P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0(–10.0–41.9) and 17.5(–6.0–50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively(P=0.214), and the median changes in eGFRs were –2.3(–6.4–1.9) and –3.7(–7.5–1.1) mL·min~(-1)·1.73 m~(-2), respectively(P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 m L·min~(-1)·1.73 m(-2) per year. Conclusions: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function.
Objective: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles(尿毒清颗粒) for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. Methods: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks(146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine(Scr) and estimated glomerular filtration rate(e GFR) after completion of the open-label treatment period. Results: After the double-blind period, the median(interquartile range) changes in Scr were 1.1(–13.0–24.1) and 11.7(–2.6–42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively(P=0.008), and the median changes in e GFRs were –0.2(–4.3–2.7) and –2.21(–5.7–0.8) mL·min~(-1)·1.73 m~(-2), respectively(P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0(–10.0–41.9) and 17.5(–6.0–50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively(P=0.214), and the median changes in eGFRs were –2.3(–6.4–1.9) and –3.7(–7.5–1.1) mL·min~(-1)·1.73 m~(-2), respectively(P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 m L·min~(-1)·1.73 m(-2) per year. Conclusions: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function.
Objective: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles(尿毒清颗粒) for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. Methods: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks(146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine(Scr) and estimated glomerular filtration rate(e GFR) after completion of the open-label treatment period. Results: After the double-blind period, the median(interquartile range) changes in Scr were 1.1(–13.0–24.1) and 11.7(–2.6–42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively(P=0.008), and the median changes in e GFRs were –0.2(–4.3–2.7) and –2.21(–5.7–0.8) mL·min~(-1)·1.73 m~(-2), respectively(P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0(–10.0–41.9) and 17.5(–6.0–50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively(P=0.214), and the median changes in eGFRs were –2.3(–6.4–1.9) and –3.7(–7.5–1.1) mL·min~(-1)·1.73 m~(-2), respectively(P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 m L·min~(-1)·1.73 m(-2) per year. Conclusions: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function.
引文
1.Webster AC,Nagler EV,Morton RL,Masson P.Chronic Kidney Disease.Lancet 2017;389:1238-1252.
2.Han Y,Ma FY,Tesch GH,Manthey CL,Nikolic-Paterson DJ.c-fms blockade reverses glomerular macrophage infiltration and halts development of crescentic anti-GBMglomerulonephritis in the rat.Lab Invest 2011;91:978-991.
3.Sun D,Chen Z,Eirin A,Zhu XY,Lerman A,Textor SC,et al.Hypercholesterolemia impairs nonstenotic kidney outcomes after reversal of experimental renovascular hypertension.Am J Hypertens 2016;29:853-859.
4.Kidney Disease:Improving Global Outcomes(KDIGO)CKDWork Group.KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.Kidney Inter 2013;3 Suppl:1-150.
5.Boffa JJ,Lu Y,Placier S,Stefanski A,Dussaule JC,Chatziantoniou C.Regression of renal vascular and glomerular fibrosis:role of angiotensinⅡreceptor antagonism and matrix metalloproteinases.J Am Soc Nephrol 2003;14:1132-1144.
6.Tuttle KR,Bakris GL,Toto RD,McGill JB,Hu K,Anderson PW.The effect of ruboxistaurin on nephropathy in type 2diabetes.Diabetes Care 2005;28:2686-2690.
7.Watson AM,Li J,Schumacher C,de Gasparo M,Feng B,Thomas MC,et al.The endothelin receptor antagonist avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice.Diabetologia2010;53:192-203.
8.Perez-Gomez MV,Sanchez-Nino MD,Sanz AB,Zheng B,Martin-Cleary C,Ruiz-Ortega M,et al.Targeting inflammation in diabetic kidney disease:early clinical trials.Expert Opin Investig Drugs 2016;25:1045-1058.
9.de Zeeuw D,Coll B,Andress D,Brennan JJ,Tang H,Houser M,et al.The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy.J Am Soc Nephrol 2014;25:1083-1093.
10.Jaber BL,Madias NE.Progression of chronic kidney disease:can it be prevented or arrested?Am J Med2005;118:1323-1330.
11.Li QP,Wei RB,Yang X,Zheng XY,Su TY,Huang MJ,et al.Protective effects and mechanisms of Shenhua Tablet on toll-like receptors in rat model of renal ischemia-reperfusion injury.Chin J Integr Med 2017.
12.Guo C,Rao XR.Understanding and therapeutic strategies of Chinese medicine on gut-derived uremic toxins in chronic kidney disease.Chin J Integr Med 2018;24:403-405.
13.Lu ZY,Liu SW,Xie YS,Cui SY,Liu XS,Geng WJ,et al.Inhibition of the tubular epithelial-to-mesenchymal transition in vivo and in vitro by the Uremic Clearance Granule.Chin J Integr Med 2013;19:918-926.
14.Huang YR,Wei QX,Wan YG,Sun W,Mao ZM,Chen HL,et al.Ureic Clearance Granule,alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats,compared with enalapril.J Ethnopharmacol 2014;155:1541-1552.
15.Zheng Y,Cai GY,He LQ,Lin HL,Cheng XH,Wang NS,et al.Efficacy and safety of Niaoduqing Particles for delaying moderate-to-severe renal dysfunction:a randomized,double-blind,placebo-controlled,multicenter clinical study.Chin Med J 2017;130:2402-2409.
16.Ma YC,Zuo L,Chen JH,Luo Q,Yu XQ,Li Y,et al.Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease.J Am Soc Nephrol2006;17:2937-2944.
17.The GISEN Group(Gruppo Italiano di Studi Epidemiologici in Nefrologia).Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric,non-diabetic nephropathy.Lancet 1997;349:1857-1863.
18.Perico N,Codreanu I,Schieppati A,Remuzzi G.Pathophysiology of disease progression in proteinuric nephropathies.Kidney Int 2005;(Suppl):S79-S82.
19.Le W,Liang S,Hu Y,Deng K,Bao H,Zeng C,et al.Longterm renal survival and related risk factors in patients with Ig Anephropathy:results from a cohort of 1155 cases in a Chinese adult population.Nephrol Dial Transplant 2012;27:1479-1485.
20.Ding RH,Liao YH.Recent research on therapeutic mechanisms of Niaoduqing for chronic renal failure.Med Recapitulate 2010;16:1530-1532.
21.Zhu XL,Wang YJ,Yang Y,Yang RC,Zhu B,Zhang Y,et al.Suppression of lipopolysaccharide-induced upregulation of toll-like receptor 4 by emodin in mouse proximal tubular epithelial cells.Mol Med Rep 2012;6:493-500.
22.Wang L,Chi YF,Yuan ZT,Zhou WC,Yin PH,Zhang XM,et al.AstragalosideⅣinhibits renal tubulointerstitial fibrosis by blocking TGF-beta/Smad signaling pathway in vivo and in vitro.Exp Biol Med(Maywood)2014;239:1310-1324.
23.Zhang WJ,Frei B.AstragalosideⅣinhibits NF-kappa Bactivation and inflammatory gene expression in LPS-treated mice.Mediators Inflamm 2015;2015:274314.
24.Jia Y,Huang F,Zhang S,Leung SW.Is Danshen(Salvia miltiorrhiza)Dripping Pill more effective than isosorbide dinitrate in treating angina pectoris?A systematic review of randomized controlled trials.Int J Cardiol 2012;157:330-340.
25.Pan H,Li D,Fang F,Chen D,Qi L,Zhang R,et al.Salvianolic acid A demonstrates cardioprotective effects in rat hearts and cardiomyocytes after ischemia/reperfusion injury.J Cardiovasc Pharmacol 2011;58:535-542.
26.Yang R,Chang L,Guo BY,Wang YW,Wang YL,Jin X,et al.Compound Danshen Dripping Pill pretreatment to prevent contrast-induced nephropathy in patients with acute coronary syndrome undergoing percutaneous coronary intervention.Evid Based Complement Alternat Med 2014;2014:256268.
2.Han Y,Ma FY,Tesch GH,Manthey CL,Nikolic-Paterson DJ.c-fms blockade reverses glomerular macrophage infiltration and halts development of crescentic anti-GBMglomerulonephritis in the rat.Lab Invest 2011;91:978-991.
3.Sun D,Chen Z,Eirin A,Zhu XY,Lerman A,Textor SC,et al.Hypercholesterolemia impairs nonstenotic kidney outcomes after reversal of experimental renovascular hypertension.Am J Hypertens 2016;29:853-859.
4.Kidney Disease:Improving Global Outcomes(KDIGO)CKDWork Group.KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.Kidney Inter 2013;3 Suppl:1-150.
5.Boffa JJ,Lu Y,Placier S,Stefanski A,Dussaule JC,Chatziantoniou C.Regression of renal vascular and glomerular fibrosis:role of angiotensinⅡreceptor antagonism and matrix metalloproteinases.J Am Soc Nephrol 2003;14:1132-1144.
6.Tuttle KR,Bakris GL,Toto RD,McGill JB,Hu K,Anderson PW.The effect of ruboxistaurin on nephropathy in type 2diabetes.Diabetes Care 2005;28:2686-2690.
7.Watson AM,Li J,Schumacher C,de Gasparo M,Feng B,Thomas MC,et al.The endothelin receptor antagonist avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice.Diabetologia2010;53:192-203.
8.Perez-Gomez MV,Sanchez-Nino MD,Sanz AB,Zheng B,Martin-Cleary C,Ruiz-Ortega M,et al.Targeting inflammation in diabetic kidney disease:early clinical trials.Expert Opin Investig Drugs 2016;25:1045-1058.
9.de Zeeuw D,Coll B,Andress D,Brennan JJ,Tang H,Houser M,et al.The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy.J Am Soc Nephrol 2014;25:1083-1093.
10.Jaber BL,Madias NE.Progression of chronic kidney disease:can it be prevented or arrested?Am J Med2005;118:1323-1330.
11.Li QP,Wei RB,Yang X,Zheng XY,Su TY,Huang MJ,et al.Protective effects and mechanisms of Shenhua Tablet on toll-like receptors in rat model of renal ischemia-reperfusion injury.Chin J Integr Med 2017.
12.Guo C,Rao XR.Understanding and therapeutic strategies of Chinese medicine on gut-derived uremic toxins in chronic kidney disease.Chin J Integr Med 2018;24:403-405.
13.Lu ZY,Liu SW,Xie YS,Cui SY,Liu XS,Geng WJ,et al.Inhibition of the tubular epithelial-to-mesenchymal transition in vivo and in vitro by the Uremic Clearance Granule.Chin J Integr Med 2013;19:918-926.
14.Huang YR,Wei QX,Wan YG,Sun W,Mao ZM,Chen HL,et al.Ureic Clearance Granule,alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats,compared with enalapril.J Ethnopharmacol 2014;155:1541-1552.
15.Zheng Y,Cai GY,He LQ,Lin HL,Cheng XH,Wang NS,et al.Efficacy and safety of Niaoduqing Particles for delaying moderate-to-severe renal dysfunction:a randomized,double-blind,placebo-controlled,multicenter clinical study.Chin Med J 2017;130:2402-2409.
16.Ma YC,Zuo L,Chen JH,Luo Q,Yu XQ,Li Y,et al.Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease.J Am Soc Nephrol2006;17:2937-2944.
17.The GISEN Group(Gruppo Italiano di Studi Epidemiologici in Nefrologia).Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric,non-diabetic nephropathy.Lancet 1997;349:1857-1863.
18.Perico N,Codreanu I,Schieppati A,Remuzzi G.Pathophysiology of disease progression in proteinuric nephropathies.Kidney Int 2005;(Suppl):S79-S82.
19.Le W,Liang S,Hu Y,Deng K,Bao H,Zeng C,et al.Longterm renal survival and related risk factors in patients with Ig Anephropathy:results from a cohort of 1155 cases in a Chinese adult population.Nephrol Dial Transplant 2012;27:1479-1485.
20.Ding RH,Liao YH.Recent research on therapeutic mechanisms of Niaoduqing for chronic renal failure.Med Recapitulate 2010;16:1530-1532.
21.Zhu XL,Wang YJ,Yang Y,Yang RC,Zhu B,Zhang Y,et al.Suppression of lipopolysaccharide-induced upregulation of toll-like receptor 4 by emodin in mouse proximal tubular epithelial cells.Mol Med Rep 2012;6:493-500.
22.Wang L,Chi YF,Yuan ZT,Zhou WC,Yin PH,Zhang XM,et al.AstragalosideⅣinhibits renal tubulointerstitial fibrosis by blocking TGF-beta/Smad signaling pathway in vivo and in vitro.Exp Biol Med(Maywood)2014;239:1310-1324.
23.Zhang WJ,Frei B.AstragalosideⅣinhibits NF-kappa Bactivation and inflammatory gene expression in LPS-treated mice.Mediators Inflamm 2015;2015:274314.
24.Jia Y,Huang F,Zhang S,Leung SW.Is Danshen(Salvia miltiorrhiza)Dripping Pill more effective than isosorbide dinitrate in treating angina pectoris?A systematic review of randomized controlled trials.Int J Cardiol 2012;157:330-340.
25.Pan H,Li D,Fang F,Chen D,Qi L,Zhang R,et al.Salvianolic acid A demonstrates cardioprotective effects in rat hearts and cardiomyocytes after ischemia/reperfusion injury.J Cardiovasc Pharmacol 2011;58:535-542.
26.Yang R,Chang L,Guo BY,Wang YW,Wang YL,Jin X,et al.Compound Danshen Dripping Pill pretreatment to prevent contrast-induced nephropathy in patients with acute coronary syndrome undergoing percutaneous coronary intervention.Evid Based Complement Alternat Med 2014;2014:256268.