Efficacy and safety of Shenyankangfu tablets for primary glomerulonephritis: study protocol for a randomized controlled trial

Jia Kou, Jie Wu, Hong-tao Yang, Ya-ni He, Jing-ai Fang, Yue-yi Deng, Yuan-sheng Xie, Li-fang Nie, Hong-li Lin, Guang-yan Cai, Xiang-mei Chen, Jia Kou, Jie Wu, Hong-tao Yang, Ya-ni He, Jing-ai Fang, Yue-yi Deng, Yuan-sheng Xie, Li-fang Nie, Hong-li Lin, Guang-yan Cai, Xiang-mei Chen

Abstract

Background: Chronic kidney disease is a common disease. Most chronic kidney diseases evolve from primary glomerulonephritis. Proteinuria is an independent risk factor for the progression of chronic kidney disease. The general consensus is that therapy administered to decrease proteinuria should include steroids and/or immunosuppressants, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. However, the side effects of, and adverse reactions to, these agents reduce the benefits to patients. In addition, the cost of these drugs is relatively high. Therefore, identification of inexpensive and effective drugs to decrease proteinuria is urgently needed. Shenyankangfu tablets have been a widely applied Chinese patent medicine for many years to decrease proteinuria. However, there is a lack of research-derived data regarding the clinical use. Therefore, we designed the present randomized controlled clinical trial to compare the efficacy and safety of Shenyankangfu tablets versus losartan potassium for control of proteinuria in patients with primary glomerulonephritis.

Methods/design: This study will be a multicenter, prospective, double-blind, double-dummy, randomized controlled clinical trial. We will enroll 720 patients diagnosed with primary glomerulonephritis. The eligible patients will be randomly divided into the following groups at a 1:1:1:1:1 ratio: Shenyankangfu tablets group, losartan potassium 50 mg group, losartan potassium 100 mg group, Shenyankangfu tablets + losartan potassium 50 mg group, and Shenyankangfu tablets + losartan potassium 100 mg group. All groups will be followed up for 48 weeks; follow-up visits will be performed, at weeks 0, 4, 8, 12, 24, 36, and 48. The primary efficacy outcome will be the post-treatment change in the 24-hour proteinuria level, and the secondary efficacy outcomes will be the post-treatment changes in the serum creatinine level, estimated glomerular filtration rate, traditional Chinese medicine syndrome score, and serum albumin level.

Discussion: The results of this trial will provide solid data for use in evidence-based medicine with respect to the efficacy and safety of Shenyankangfu tablets for control of proteinuria in patients with primary glomerulonephritis compared to those of losartan potassium. Moreover, we infer that therapy comprising Shenyankangfu tablets + losartan potassium can decrease proteinuria to a larger extent than Shenyankangfu tablets or losartan potassium can alone.

Trial registration: This trial was registered on 12 February 2014 at ClinicalTrials.gov (ID number NCT02063100).

Figures

Figure 1
Figure 1
Trial flow diagram. SYKFT, Shenyankangfu Tablets.

References

    1. Nugent RA, Fathima SF, Feigl AB, Chyung D. The burden of chronic kidney disease on developing nations: a 21st century challenge in global health. Nephron Clin Pract. 2011;118:c269–c277. doi: 10.1159/000321382.
    1. Eknoyan G, Lameire N, Barsoum R, Eckardt KU, Levin A, Levin N, Locatelli F, MacLeod A, Vanholder R, Walker R, Wang H. The burden of kidney disease: improving global outcomes. Kidney Int. 2004;66:1310–1314. doi: 10.1111/j.1523-1755.2004.00894.x.
    1. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612. doi: 10.7326/0003-4819-150-9-200905050-00006.
    1. Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, Chen M, He Q, Liao Y, Yu X, Chen N, Zhang JE, Hu Z, Liu F, Hong D, Ma L, Liu H, Zhou X, Chen J, Pan L, Chen W, Li X, Wang H. Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet. 2012;379:815–822. doi: 10.1016/S0140-6736(12)60033-6.
    1. Codreanu I, Perico N, Sharma SK, Schieppati A, Remuzzi G. Prevention programmes of progressive renal disease in developing nations. Nephrology (Carlton) 2006;11:321–328. doi: 10.1111/j.1440-1797.2006.00587.x.
    1. Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt KU, Nahas ME, Jaber BL, Jadoul M, Levin A, Powe NR, Rossert J, Wheeler DC, Lameire N, Eknoyan G. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes. Kidney Int. 2007;72:247–259. doi: 10.1038/sj.ki.5002343.
    1. Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, King AJ, Klahr S, Massry SG, Seifter JL. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995;123:754–762. doi: 10.7326/0003-4819-123-10-199511150-00003.
    1. Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, Quinn RR, Wiebe N, Tonelli M. Relation between kidney function, proteinuria, and adverse outcomes. JAMA. 2010;303:423–429. doi: 10.1001/jama.2010.39.
    1. Irie F, Iso H, Sairenchi T, Fukasawa N, Yamagishi K, Ikehara S, Kanashiki M, Saito Y, Ota H, Nose T. The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population. Kidney Int. 2006;69:1264–1271. doi: 10.1038/sj.ki.5000284.
    1. Perkovic V, Verdon C, Ninomiya T, Barzi F, Cass A, Patel A, Jardine M, Gallagher M, Turnbull F, Chalmers J, Craig J, Huxley R. The relationship between proteinuria and coronary risk: a systematic review and meta-analysis. PLoS Med. 2008;5:e207. doi: 10.1371/journal.pmed.0050207.
    1. Conley J, Tonelli M, Quan H, Manns BJ, Palacios-Derflingher L, Bresee LC, Khan N, Hemmelgarn BR. Association between GFR, proteinuria, and adverse outcomes among White, Chinese, and South Asian individuals in Canada. Am J Kidney Dis. 2012;59:390–399. doi: 10.1053/j.ajkd.2011.09.022.
    1. de Goeij MC, Liem M, de Jager DJ, Voormolen N, Sijpkens YW, Rotmans JI, Boeschoten EW, Dekker FW, Grootendorst DC, Halbesma N. Proteinuria as a risk marker for the progression of chronic kidney disease in patients on predialysis care and the role of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatment. Nephron Clin Pract. 2012;121:c73–c82. doi: 10.1159/000342392.
    1. Lea J, Greene T, Hebert L, Lipkowitz M, Massry S, Middleton J, Rostand SG, Miller E, Smith W, Bakris GL. The relationship between magnitude of proteinuria reduction and risk of end-stage renal disease: results of the African American study of kidney disease and hypertension. Arch Intern Med. 2005;165:947–953. doi: 10.1001/archinte.165.8.947.
    1. de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004;65:2309–2320. doi: 10.1111/j.1523-1755.2004.00653.x.
    1. Nakao N, Seno H, Kasuga H, Toriyama T, Kawahara H, Fukagawa M. Effects of combination treatment with losartan and trandolapril on office and ambulatory blood pressures in non-diabetic renal disease: a COOPERATE-ABP substudy. Am J Nephrol. 2004;24:543–548. doi: 10.1159/000081953.
    1. Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, Marcantoni C, de Jong PE, de Zeeuw D, Shahinfar S, Ruggenenti P, Remuzzi G, Levey AS. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Kidney Int. 2001;60:1131–1140. doi: 10.1046/j.1523-1755.2001.0600031131.x.
    1. Ruggenenti P, Perna A, Gherardi G, Benini R, Remuzzi G. Chronic proteinuric nephropathies: outcomes and response to treatment in a prospective cohort of 352 patients with different patterns of renal injury. Am J Kidney Dis. 2000;35:1155–1165. doi: 10.1016/S0272-6386(00)70054-0.
    1. KDIGO Clinical practice guideline for glomerulonephritis. Kidney Int Suppl. 2012;2:139–259. doi: 10.1038/kisup.2012.9.
    1. Fernandez-Juarez G, Barrio V, de Vinuesa SG, Goicoechea M, Praga M, Luno J. Dual blockade of the renin-angiotensin system in the progression of renal disease: the need for more clinical trials. J Am Soc Nephrol. 2006;17:S250–S254. doi: 10.1681/ASN.2006080922.
    1. Coppo R, Peruzzi L, Amore A, Piccoli A, Cochat P, Stone R, Kirschstein M, Linne T. IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme inhibitors in children and young people with IgA nephropathy and moderate proteinuria. J Am Soc Nephrol. 2007;18:1880–1888. doi: 10.1681/ASN.2006040347.
    1. Praga M, Gutierrez E, Gonzalez E, Morales E, Hernandez E. Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol. 2003;14:1578–1583. doi: 10.1097/01.ASN.0000068460.37369.DC.
    1. Li PK, Leung CB, Chow KM, Cheng YL, Fung SK, Mak SK, Tang AW, Wong TY, Yung CY, Yung JC, Yu AW, Szeto CC. Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis. 2006;47:751–760. doi: 10.1053/j.ajkd.2006.01.017.
    1. Yang Y, Ohta K, Shimizu M, Nakai A, Kasahara Y, Yachie A, Koizumi S. Treatment with low-dose angiotensin-converting enzyme inhibitor (ACEI) plus angiotensin II receptor blocker (ARB) in pediatric patients with IgA nephropathy. Clin Nephrol. 2005;64:35–40. doi: 10.5414/CNP64035.
    1. The K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease.,
    1. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–869. doi: 10.1056/NEJMoa011161.
    1. Chan JC, Wat NM, So WY, Lam KS, Chua CT, Wong KS, Morad Z, Dickson TZ, Hille D, Zhang Z, Cooper ME, Shahinfar S, Brenner BM, Kurokawa K. Renin angiotensin aldosterone system blockade and renal disease in patients with type 2 diabetes. An Asian perspective from the RENAAL Study. Diabetes Care. 2004;27:874–879. doi: 10.2337/diacare.27.4.874.
    1. Iino Y, Hayashi M, Kawamura T, Shiigai T, Tomino Y, Yamada K, Kitajima T, Ideura T, Koyama A, Sugisaki T, Suzuki H, Umemura S, Kawaguchi Y, Uchida S, Kuwahara M, Yamazaki T. Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study. Clin Exp Nephrol. 2003;7:221–230. doi: 10.1007/s10157-003-0241-3.
    1. Park HC, Xu ZG, Choi S, Goo YS, Kang SW, Choi KH, Ha SK, Lee HY, Han DS. Effect of losartan and amlodipine on proteinuria and transforming growth factor-beta1 in patients with IgA nephropathy. Nephrol Dial Transplant. 2003;18:1115–1121. doi: 10.1093/ndt/gfg090.
    1. Andersen S, Rossing P, Juhl TR, Deinum J, Parving HH. Optimal dose of losartan for renoprotection in diabetic nephropathy. Nephrol Dial Transplant. 2002;17:1413–1418. doi: 10.1093/ndt/17.8.1413.
    1. Laverman GD, Henning RH, de Jong PE, Navis G, de Zeeuw D. Optimal antiproteinuric dose of losartan in nondiabetic patients with nephrotic range proteinuria. Am J Kidney Dis. 2001;38:1381–1384. doi: 10.1053/ajkd.2001.29262.
    1. Tylicki L, Renke M, Rutkowski P, Rutkowski B, Lysiak-Szydlowska W. Randomized, controlled study of the effects of losartan versus enalapril in small doses on proteinuria and tubular injury in primary glomerulonephritis. Med Sci Monit. 2005;11:PI31–PI37.
    1. WMA declaration of Helsinki - Ethical principles for medical research involving human subjects.,
    1. Dixon JR., Jr The International Conference on Harmonization Good Clinical Practice guideline. Qual Assur. 1998;6:65–74.
    1. Good Clinical Practice of China Food and Drug Administration.,
    1. Zheng X. Guidelines for Clinical Research of Chinese Medicine (New Drug) Beijing: Chinese Medicine Science Press; 2002.
    1. National Institutes of Health . Guidance on Reporting Adverse Events to Institutional Review Boards for NIH-supported Multicenter Clinical Trials. Bethesda, MD: National Institutes of Health; 1999.
    1. Cheng J, Zhang W, Zhang X, He Q, Tao X, Chen J. ACEI/ARB therapy for IgA nephropathy: a meta-analysis of randomised controlled trials. Int J Clin Pract. 2009;63:880–888. doi: 10.1111/j.1742-1241.2009.02038.x.
    1. Lu H, Tang S, Su B. Clinical observation on treating 50 cases of chronic nephritis by Shenyan Kangfu tablets plus valsartan. Clin J Chin Med. 2012;4:79–80. doi: 10.4236/cm.2013.43012.
    1. Shu Y, She N, Liang Z, Quan D, Han T, Cheng G, Gong R. Random control study on treating CKD with Shenyan Kangfu tablet and double-dose irbesarta. Clin J Chin Med. 2013;5:7–8.
    1. Rychlík I, Jančová E, Tesař V, Kolský A, Lácha J, Stejskal J, Stejskalová A, Dušek J, Herout V. The Czech registry of renal biopsies. Occurrence of renal diseases in the years 1994–2000. Nephrol Dial Transplant. 2004;19:3040–3049. doi: 10.1093/ndt/gfh521.
    1. Simon P, Ramee M-P, Boulahrouz R, Stanescu C, Charasse C, Ang KS, Leonetti F, Cam G, Laruelle E, Autuly V. Epidemiologic data of primary glomerular diseases in western France. Kidney Int. 2004;66:905–908. doi: 10.1111/j.1523-1755.2004.00834.x.
    1. Gharavi AG, Yan Y, Scolari F, Schena FP, Frasca GM, Ghiggeri GM, Cooper K, Amoroso A, Viola BF, Battini G. IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22–23. Nat Genet. 2000;26:354–357. doi: 10.1038/81677.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다