Juxtaglomerular apparatus hyperplasia under dual angiotensin blockade. A footprint of adequate RAS inhibition or a concern for renal fibrosis?

BMC Nephrology

Jesús Egido¹  Catalina Martín-Cleary²  Antonio Barat⁴  Carmen Gomez-Guerrero³  Alberto Ortiz³  Beatriz Fernandez-Fernandez² 

[1] IIS-Fundación Jiménez Díaz, Avda, Reyes Católicos 2, 28040, Madrid, Spain;Nephrology, IIS-Fundacion Jimenez-Diaz, Autonoma University Madrid, Spain;Renal and Vascular Research Laboratory, IIS- Fundación Jimenez Díaz. Autonoma University Madrid, Madrid, Spain;Pathology division , Fundación Jimenez- Díaz, Madrid, Spain

关键词: Renin;    Paricalcitol;    Nephrotic syndrome;    Juxtaglomerular apparatus hyperplasia;    Angiotensin;   

Others  :  1083192
DOI  :  10.1186/1471-2369-13-21

 received in 2011-11-15, accepted in 2012-03-07,  发布年份 2012

【 摘 要 】

Background

Dual renin-angiotensin system blockade with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been advocated to minimize proteinuria. However, recent trials have questioned the renal safety of this approach. Our understanding on the molecular effects of dual blockade in humans is incomplete.

Case presentation

We present a patient with corticoid resistant nephrotic syndrome who developed marked juxtaglomerular apparatus hyperplasia and renin expression in the context of dual angiotensin system blockade.

Conclusions

Although renin may have profibrotic effects mediated by (pro)renin receptor activation, this report raises questions on the potential consequences of local renin activation on chronic kidney disease in patients with dual angiotensin blockade.

【 授权许可】

   
2012 Fernandez-Fernandez et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1 .

【 参考文献 】

• [1]Bakris GL: Dual RAAS blockade is desirable in kidney disease: con. Kidney Int 2010, 78:546-549.
• [2]Lattanzio MR, Weir MR: Have we fallen off target with concerns surrounding dual RAAS blockade? Kidney Int 2010, 78:539-545.
• [3]Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T: Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet. 2003;361:117–24. Retraction in. Lancet 2009, 374:1226.
• [4]Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, Wang X, Maggioni A, Budaj A, Chaithiraphan S, Dickstein K, Keltai M, Metsärinne K, Oto A, Parkhomenko A, Piegas LS, Svendsen TL, Teo KK, Yusuf S: ONTARGET investigators. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008, 372:547-553.
• [5]Esnault VL, Ekhlas A, Delcroix C, Moutel MG, Nguyen JM: Diuretic and enhanced sodium restriction results in improved antiproteinuric response to RAS blocking agents. J Am Soc Nephrol 2005, 16:474-481.
• [6]Vogt L, Waanders F, Boomsma F, de Zeeuw D, Navis G: Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan. J Am Soc Nephrol 2008, 19:999-1007.
• [7]de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, Parving HH, Pritchett Y, Remuzzi G, Ritz E, Andress D: Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet 2010, 376:1543-1551.
• [8]MacDonald JR, Susick RL Jr, Pegg DG, Dominick MA: Renal structure and function in rats after suprapharmacologic doses of quinapril, an angiotensin-converting enzyme inhibitor. J Cardiovasc Pharmacol 1992, 19:282-289.
• [9]Gulmann C, Osterby R, Bangstad HJ, Rudberg S: The juxtaglomerular apparatus in young type-1 diabetic patients with microalbuminuria, Effect of antihypertensive treatment. Virchows Arch 2001, 438:618-623.
• [10]Sharma A, Jain S, Gupta R, Guleria S, Agarwal S, Dinda A: Calcineurin inhibitor toxicity in renal allografts: morphologic clues from protocol biopsies. Indian J Pathol Microbiol 2010, 53:651-657.
• [11]Troxell ML, Scandling JD, Sibley RK: Renal juxtaglomerular apparatus hyperplasia. Nephrol Dial Transplant 2005, 20:2282-2283.
• [12]Gillum DM, Truong L: Effects of chronic volume expansion and enalapril on chronic cyclosporine nephropathy. Am J Physiol 1990, 258(4 Pt 2):F934-F939.
• [13]Daïkha-Dahmane F, Levy-Beff E, Jugie M, Lenclen R: Foetal kidney maldevelopment in maternal use of angiotensin II type I receptor antagonists. Pediatr Nephrol 2006, 21:729-732.
• [14]van der Heuvel M, Batenburg WW, Danser AH: Diabetic complications: a role for the prorenin-(pro)renin receptor-TGF-beta1 axis? Mol Cell Endocrinol 2009, 302:213-218.
• [15]Kelly DJ, Zhang Y, Moe G, Naik G, Gilbert RE: Aliskiren, a novel renin inhibitor, is renoprotective in a model of advanced diabetic nephropathy in rats. Diabetologia 2007, 50:2398-2404.
• [16]Li M, Batuman V: Vitamin D: a new hope for chronic kidney disease? Kidney Int 2009, 76:1219-1221.
• [17]Müller D, Müller DN: Battle against the renin-angiotensin system: help from an unexpected party. Nephrol Dial Transplant 2009, 24:1110-1112.
• [18]Zhang Z, Zhang Y, Ning G, Deb DK, Kong J, Li YC: Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: blockade of compensatory renin increase. Proc Natl Acad Sci U S A 2008, 105:15896-15901.
• [19]Freundlich M, Quiroz Y, Zhang Z, Zhang Y, Bravo Y, Weisinger JR, Li YC, Rodriguez-Iturbe B: Suppression of renin-angiotensin gene expression in the kidney by paricalcitol. Kidney Int 2008, 74:1394-1402.
• [20]Sanchez-Niño MD, Sanz AB, Carrasco S, Saleem MA, Mathieson PW, Valdivielso JM, Ruiz-Ortega M, Egido J, Ortiz A: Globotriaosylsphingosine actions on human glomerular podocytes: implications for Fabry nephropathy. Nephrol Dial Transplant 2011, 26:1797-1802.
• [21]Sanchez-Niño MD, Bozic M, Cordoba-Lanus E, Valcheva P, Gracia O, Ibarz M, Fernandez E, Navarro-Gonzalez JF, Ortiz A, Valdivielso JM: Beyond proteinuria: VDR activation reduces renal inflammation in experimental diabetic nephropathy. Am J Physiol Renal Physiol2011 Dec 14. [Epub ahead of print].