期刊论文详细信息
BMC Nephrology
Effect of add-on direct renin inhibitor aliskiren in patients with non-diabetes related chronic kidney disease
Wen-Sheng Liu3  Chih-Yu Yang2  Chih-Ching Lin2  Der-Cherng Tarng4  Wu-Chang Yang2  Yung-Tai Chen5  Szu-yuan Li1 
[1] Institute of Clinical of Medicine, National Yang-Ming University, Taipei, Taiwan;School of Medicine, National Yang-Ming University, Taipei, Taiwan;Division of Nephrology, Department of Medicine, Taipei City Hospital, Zhong-Xing Branch, Taipei, Taiwan;Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan;Department of Medicine, Taipei City Hospital Heping Fuyou Branch, Taipei, Taiwan
关键词: CKD;    Proteinuria;    Direct renin inhibitor;    Aliskiren;   
Others  :  1083122
DOI  :  10.1186/1471-2369-13-89
 received in 2012-02-02, accepted in 2012-07-12,  发布年份 2012
【 摘 要 】

Background

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney disease (CKD). Although dual RAAS inhibition results in worse renal outcomes than monotherapy in high risk type 2 diabetes patients, the effect of dual RAAS inhibition in patients with non-DM CKD is unclear. The aim of this study was to evaluate the potential renoprotective effect of add-on direct renin inhibitor in non-DM CKD patients.

Methods

We retrospectively enrolled 189 non-DM CKD patients who had been taking angiotensin II receptor blockers (ARBs) for more than six months. Patients were divided into an add-on aliskiren group and an ARB monotherapy group. The primary outcomes were a decline in glomerular filtration rate (GFR) and a reduction in urinary protein-to-creatinine ratio at six months.

Results

The baseline characteristics of the two groups were similar. Aliskiren 150 mg daily reduced the urinary protein-to-creatinine ratio by 26% (95% confidence interval, 15 to 37%; p < 0.001). The decline in GFR was smaller in the add-on aliskiren group (−2.1 vs. -4.0 ml/min, p = 0.038). Add-on aliskiren had a neutral effect on serum potassium in the non-DM CKD patients. In subgroup analysis, the proteinuria-reducing effect of aliskiren was more prominent in patients with a GFR less than 60 ml/min, and in patients with a urinary protein-to-creatinine ratio greater than 1.8. The effect of aliskiren in retarding the decline in GFR was more prominent in patients with hypertensive nephropathy than in those with glomerulonephritis.

Conclusion

Add-on direct renin inhibitor aliskiren (150 mg daily) safely reduced proteinuria and attenuated the decline in GFR in the non-DM CKD patients who were receiving ARBs.

【 授权许可】

   
2012 Chen et al.; licensee BioMed Central Ltd.

附件列表
Files Size Format View
Figure 3. 96KB Image download
Figure 2. 79KB Image download
Figure 1. 52KB Image download
Figure 3. 96KB Image download
Figure 2. 79KB Image download
Figure 1. 52KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】
  • [1]Schroten NF, Gaillard CA, van Veldhuisen DJ, Szymanski MK, Hillege HL, de Boer RA: New roles for renin and prorenin in heart failure and cardiorenal crosstalk. Heart Fail Rev 2012, 17(2):191-201.
  • [2]Remuzzi G, Perico N, Macia M, Ruggenenti P: The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl 2005, 99:S57-S65.
  • [3]Remuzzi G, Bertani T: Pathophysiology of progressive nephropathies. N Engl J Med 1998, 339(20):1448-1456.
  • [4]Taft JL, Nolan CJ, Yeung SP, Hewitson TD, Martin FI: Clinical and histological correlations of decline in renal function in diabetic patients with proteinuria. Diabetes 1994, 43(8):1046-1051.
  • [5]Ziyadeh FN, Goldfarb S: The renal tubulointerstitium in diabetes mellitus. Kidney Int 1991, 39(3):464-475.
  • [6]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(9069):1857-1863.
  • [7]Titan SM, M. Vieira J J, Dominguez WV, Barros RT, Zatz R: ACEI and ARB combination therapy in patients with macroalbuminuric diabetic nephropathy and low socioeconomic level: a double-blind randomized clinical trial. Clinical nephrology 2011, 76(4):273-83.
  • [8]Hull S, Dreyer G, Badrick E, Chesser A, Yaqoob MM: The relationship of ethnicity to the prevalence and management of hypertension and associated chronic kidney disease. BMC Nephrology 2011, 12:41. BioMed Central Full Text
  • [9]Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, Ponticelli C, Ritz E, Zucchelli P: Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 1996, 334(15):939-945.
  • [10]Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, Jiang JP, Liang M, Wang GB, Liu ZR, et al.: Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med 2006, 354(2):131-140.
  • [11]Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P: Effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. Ugeskr Laeger 2001, 163(40):5519-5524.
  • [12]Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C: Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008, 358(15):1547-1559.
  • [13]Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Ghadanfar M, Weissbach N, Xiang Z, et al.: Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association 2009, 24(5):1663-1671.
  • [14]Gross O, Girgert R, Rubel D, Temme J, Theissen S, Muller GA: Renal protective effects of aliskiren beyond its antihypertensive property in a mouse model of progressive fibrosis. Am J Hypertens 2011, 24(3):355-361.
  • [15]Bakris GL, Siomos M, Richardson D, Janssen I, Bolton WK, Hebert L, Agarwal R, Catanzaro D: ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. VAL-K Study Group. Kidney Int 2000, 58(5):2084-2092.
  • [16]Adler SG, Feld S, Striker L, Striker G, LaPage J, Esposito C, Aboulhosn J, Barba L, Cha DR, Nast CC: Glomerular type IV collagen in patients with diabetic nephropathy with and without additional glomerular disease. Kidney Int 2000, 57(5):2084-2092.
  • [17]Sun CY, Cherng WJ, Jian HZ, Hsu HH, Wu IW: Hsu HJ. Wu MS: Aliskiren reduced renal fibrosis in mice with chronic ischemic kidney injury-beyond the direct renin inhibition. Hypertens Res; 2011.
  • [18]Chen N, Hsu CC, Yamagata K, Langham R: Challenging chronic kidney disease: experience from chronic kidney disease prevention programs in Shanghai, Japan, Taiwan and Australia. Nephrology (Carlton) 2010, 15(Suppl 2):31-36.
  • [19]Wei SY, Chang YY, Mau LW, Lin MY, Chiu HC, Tsai JC, Huang CJ, Chen HC, Hwang SJ: Chronic kidney disease care program improves quality of pre-end-stage renal disease care and reduces medical costs. Nephrology (Carlton) 2010, 15(1):108-115.
  • [20]Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999, 130(6):461-470.
  • [21]Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M, Scolari F, Schena FP, Remuzzi G: Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 1999, 354(9176):359-364.
  • [22]Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001, 345(12):851-860.
  • [23]Porter AM: Ramipril in non-diabetic renal failure (REIN study) Ramipril Efficiency in Nephropathy Study. Lancet 1997, 350(9079):736. author reply 736–737
  • [24]Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK: Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008, 358(23):2433-2446.
  • [25]Persson F, Lewis JB, Lewis EJ, Rossing P, Hollenberg NK, Parving HH: Impact of baseline renal function on the efficacy and safety of aliskiren added to losartan in patients with type 2 diabetes and nephropathy. Diabetes Care 2010, 33(11):2304-2309.
  • [26]Tang SC, Leung JC, Lai KN: The kallikrein-kinin system. Contrib Nephrol 2011, 170:145-155.
  • [27]Wu WP, Chang CH, Chiu YT, Ku CL, Wen MC, Shu KH, Wu MJ: A reduction of unilateral ureteral obstruction-induced renal fibrosis by a therapy combining valsartan with aliskiren. Am J Physiol Renal Physiol 2010, 299(5):F929-F941.
  • [28]Choi DE, Jeong JY, Lim BJ, Chang YK, Na KR, Shin YT, Lee KW: Aliskiren ameliorates renal inflammation and fibrosis induced by unilateral ureteral obstruction in mice. JUrol 2011, 186(2):694-701.
  • [29]Weir MR, Bush C, Anderson DR, Zhang J, Keefe D, Satlin A: Antihypertensive efficacy, safety, and tolerability of the oral direct renin inhibitor aliskiren in patients with hypertension: a pooled analysis. J Am SocHypertens 2007, 1(4):264-277.
  • [30]López V, Martin M, Cobelo C, Aranda P, Cabello M, Sola E, Gutierrez C, Burgos D, Martínez D, Hernandez D: Renin-angiotensin system dual blockade using angiotensin receptor plus aliskiren decreases severe proteinuria in kidney transplant recipients. Transplant Proc 2010, 42(8):2883-2885.
  • [31]Tang SC, Lin M, Tam S, Au WS, Ma MK, Yap DY, Ho YW, Lai KN: Aliskiren combined with losartan in immunoglobulin A nephropathy: an open-labeled pilot study. Nephrol Dial Transplant 2012, 27(2):613-618.
  • [32]Nakamura T, Sato E, Amaha M, Kawagoe Y, Maeda S, Yamagishi SI: Addition of aliskiren to olmesartan ameliorates tubular injury in chronic kidney disease patients partly by reducing proteinuria. J Renin Angiotensin Aldosterone Syst 2011.
  文献评价指标  
  下载次数:32次 浏览次数:10次