Expert Opinion on Investigational Drugs
ISSN: 1354-3784 (Print) 1744-7658 (Online) Journal homepage: http://www.tandfonline.com/loi/ieid20
Comment on: Have we reached the limits for the treatment of diabetic nephropathy? Macaulay AC Onuigbo MD MSc FWACP FASN MBA To cite this article: Macaulay AC Onuigbo MD MSc FWACP FASN MBA (2014) Comment on: Have we reached the limits for the treatment of diabetic nephropathy?, Expert Opinion on Investigational Drugs, 23:6, 883-884 To link to this article: http://dx.doi.org/10.1517/13543784.2014.912376
Published online: 06 May 2014.
Submit your article to this journal
Article views: 133
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ieid20 Download by: [NUS National University of Singapore]
Date: 06 November 2015, At: 05:52
Letter to the Editor
Comment on: Have we reached the limits for the treatment of diabetic nephropathy? Macaulay AC Onuigbo Mayo Clinic Health System, Eau Claire, WI, USA
Downloaded by [NUS National University of Singapore] at 05:53 06 November 2015
Expert Opin. Investig. Drugs (2014) 23(6):883-884
We read with glued interest the excellent, wide-ranging and comprehensive review of the (limited) role of angiotensin inhibition (AI) in diabetic nephropathy [1]. Given the fact that despite over three decades of widespread and extensive global utilization of AI we have continued to experience a global pandemic of progression of chronic kidney disease (CKD) to end stage renal disease (ESRD) [2], we agree that it is about time to re-strategize on the current concepts of renoprotection [1-5]. Additionally, notwithstanding extensive research, it is still valid to postulate that in 2014, we do not yet have a full understanding of the mechanisms of CKD initiation, nor subsequent CKD propagation and progression to ESRD [1,2,4,5]. As was very lucidly articulated by Hajhosseiny et al., it is disparagingly naı¨ve to suppose that the blockage of just one pathogenetic disease mechanism will suffice [1]. Cognizant of the array and disparateness of the various putative pathogenetic mechanisms that initiate, trigger and propagate CKD to ESRD progression, it seems naively unscientific and unpretentiously simplistic for practicing nephrologists to surmise that single mechanism-blocking agents, such as ACE inhibitors and/or angiotensin receptor blockers, which can only antagonize the angiotensin cascade, would successfully, consistently and unfailingly deliver adequate, unqualified and qualitative renoprotection results in (diabetic and non-diabetic) CKD patients [2,5]. Without any fear of contradiction, despite what many authorities would have us believe, AI does not represent the proverbial ‘magic bullet’ for renoprotection for both diabetic and non-diabetic nephropathy [1-5]. Moreover, as we (and several other centers) have demonstrated, the paradoxical yet significant potential for iatrogenic nephrotoxicity from AI, more so in the older (> 65 years old) CKD patient, diabetic and non-diabetic, cannot be overemphasized [2-5]. While we support the continued use of AI in diabetic nephropathy management, we must continue to stress the mandatory need for continuous and indefinite monitoring of kidney function in these patients, to start initiation of AI at lower doses and up-titrate slowly, especially in the older CKD patient [2-5]. Besides, the treating physician must be ready at all times to consider withdrawal of AI in cases of accelerated renal failure of otherwise unproven etiology [2-5]. Finally, we support the call by Hajhosseiny et al. for more research to discover more ‘renal-friendly’ renoprotective agents [1,2,4,5]. Recently, we made the bold prediction that new ‘renal-friendly’ pharmacological agents that antagonize multiple pathogenetic mechanisms (multiple-pathway blockers), as compared to single-pathway blockers exemplified and typified by AI, would represent the future of renoprotection [2,5].
Declaration of interest The author states no conflict of interest and has received no payment in preparation of this manuscript.
10.1517/13543784.2014.912376 © 2014 Informa UK, Ltd. ISSN 1354-3784, e-ISSN 1744-7658 All rights reserved: reproduction in whole or in part not permitted
883
Letter to the Editor
Bibliography Hajhosseiny R, Khavandi K, Jivraj N, et al. Have we reached the limits for the treatment of diabetic nephropathy? Expert Opin Investig Drugs 2014;23(4):511-22
4.
2.
Onuigbo MAC. Renoprotection and the bardoxolone methyl story - is this the right way forward? A novel view of renoprotection in CKD trials: a new classification scheme for renoprotective agents. Nephron Extra 2013;3:36-49
5.
3.
Onuigbo MA. Reno-prevention versus renoprotection: a critical re-appraisal of the evidence-base from the large RAAS blockade trials after ONTARGET -- a call for more circumspection. QJM 2009;102:155-67
Downloaded by [NUS National University of Singapore] at 05:53 06 November 2015
1.
884
Onuigbo MA, Onuigbo N. Chronic kidney disease and RAAS blockade: a new view of renoprotection. Lambert Academic Publishing GmbH & Co. KG, London; 2011 Onuigbo MA. Epilogue - bold predictions and the future of renoprotection: the way forward with multiple pathway blockers -- making a case for novel non-angiotensin inhibiting renoprotective agents like corticotropin and pentoxifylline. In: Onuigbo MAC, editor. ACE inhibitors: medical uses, mechanisms of action, potential adverse effects and related topics. Volume 2. NOVA Publishers; New York, NY; 2013
Expert Opin. Investig. Drugs (2014) 23(6)
Affiliation Macaulay AC Onuigbo1,2,3 MD MSc FWACP FASN MBA 1 Associate Professor of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA 2 Nephrologist/Hypertension Specialist/ Transplant Physician, Mayo Clinic Health System, Department of Nephrology, 1221 Whipple Street, Eau Claire, WI 54702, USA 3 MBA Executive, Mayo Clinic Health System, Eau Claire, WI, USA Tel: +1 715 838 3891; Fax: +1 715 838 1946; E-mail: [email protected]
ISSN: 1354-3784 (Print) 1744-7658 (Online) Journal homepage: http://www.tandfonline.com/loi/ieid20
Comment on: Have we reached the limits for the treatment of diabetic nephropathy? Macaulay AC Onuigbo MD MSc FWACP FASN MBA To cite this article: Macaulay AC Onuigbo MD MSc FWACP FASN MBA (2014) Comment on: Have we reached the limits for the treatment of diabetic nephropathy?, Expert Opinion on Investigational Drugs, 23:6, 883-884 To link to this article: http://dx.doi.org/10.1517/13543784.2014.912376
Published online: 06 May 2014.
Submit your article to this journal
Article views: 133
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ieid20 Download by: [NUS National University of Singapore]
Date: 06 November 2015, At: 05:52
Letter to the Editor
Comment on: Have we reached the limits for the treatment of diabetic nephropathy? Macaulay AC Onuigbo Mayo Clinic Health System, Eau Claire, WI, USA
Downloaded by [NUS National University of Singapore] at 05:53 06 November 2015
Expert Opin. Investig. Drugs (2014) 23(6):883-884
We read with glued interest the excellent, wide-ranging and comprehensive review of the (limited) role of angiotensin inhibition (AI) in diabetic nephropathy [1]. Given the fact that despite over three decades of widespread and extensive global utilization of AI we have continued to experience a global pandemic of progression of chronic kidney disease (CKD) to end stage renal disease (ESRD) [2], we agree that it is about time to re-strategize on the current concepts of renoprotection [1-5]. Additionally, notwithstanding extensive research, it is still valid to postulate that in 2014, we do not yet have a full understanding of the mechanisms of CKD initiation, nor subsequent CKD propagation and progression to ESRD [1,2,4,5]. As was very lucidly articulated by Hajhosseiny et al., it is disparagingly naı¨ve to suppose that the blockage of just one pathogenetic disease mechanism will suffice [1]. Cognizant of the array and disparateness of the various putative pathogenetic mechanisms that initiate, trigger and propagate CKD to ESRD progression, it seems naively unscientific and unpretentiously simplistic for practicing nephrologists to surmise that single mechanism-blocking agents, such as ACE inhibitors and/or angiotensin receptor blockers, which can only antagonize the angiotensin cascade, would successfully, consistently and unfailingly deliver adequate, unqualified and qualitative renoprotection results in (diabetic and non-diabetic) CKD patients [2,5]. Without any fear of contradiction, despite what many authorities would have us believe, AI does not represent the proverbial ‘magic bullet’ for renoprotection for both diabetic and non-diabetic nephropathy [1-5]. Moreover, as we (and several other centers) have demonstrated, the paradoxical yet significant potential for iatrogenic nephrotoxicity from AI, more so in the older (> 65 years old) CKD patient, diabetic and non-diabetic, cannot be overemphasized [2-5]. While we support the continued use of AI in diabetic nephropathy management, we must continue to stress the mandatory need for continuous and indefinite monitoring of kidney function in these patients, to start initiation of AI at lower doses and up-titrate slowly, especially in the older CKD patient [2-5]. Besides, the treating physician must be ready at all times to consider withdrawal of AI in cases of accelerated renal failure of otherwise unproven etiology [2-5]. Finally, we support the call by Hajhosseiny et al. for more research to discover more ‘renal-friendly’ renoprotective agents [1,2,4,5]. Recently, we made the bold prediction that new ‘renal-friendly’ pharmacological agents that antagonize multiple pathogenetic mechanisms (multiple-pathway blockers), as compared to single-pathway blockers exemplified and typified by AI, would represent the future of renoprotection [2,5].
Declaration of interest The author states no conflict of interest and has received no payment in preparation of this manuscript.
10.1517/13543784.2014.912376 © 2014 Informa UK, Ltd. ISSN 1354-3784, e-ISSN 1744-7658 All rights reserved: reproduction in whole or in part not permitted
883
Letter to the Editor
Bibliography Hajhosseiny R, Khavandi K, Jivraj N, et al. Have we reached the limits for the treatment of diabetic nephropathy? Expert Opin Investig Drugs 2014;23(4):511-22
4.
2.
Onuigbo MAC. Renoprotection and the bardoxolone methyl story - is this the right way forward? A novel view of renoprotection in CKD trials: a new classification scheme for renoprotective agents. Nephron Extra 2013;3:36-49
5.
3.
Onuigbo MA. Reno-prevention versus renoprotection: a critical re-appraisal of the evidence-base from the large RAAS blockade trials after ONTARGET -- a call for more circumspection. QJM 2009;102:155-67
Downloaded by [NUS National University of Singapore] at 05:53 06 November 2015
1.
884
Onuigbo MA, Onuigbo N. Chronic kidney disease and RAAS blockade: a new view of renoprotection. Lambert Academic Publishing GmbH & Co. KG, London; 2011 Onuigbo MA. Epilogue - bold predictions and the future of renoprotection: the way forward with multiple pathway blockers -- making a case for novel non-angiotensin inhibiting renoprotective agents like corticotropin and pentoxifylline. In: Onuigbo MAC, editor. ACE inhibitors: medical uses, mechanisms of action, potential adverse effects and related topics. Volume 2. NOVA Publishers; New York, NY; 2013
Expert Opin. Investig. Drugs (2014) 23(6)
Affiliation Macaulay AC Onuigbo1,2,3 MD MSc FWACP FASN MBA 1 Associate Professor of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA 2 Nephrologist/Hypertension Specialist/ Transplant Physician, Mayo Clinic Health System, Department of Nephrology, 1221 Whipple Street, Eau Claire, WI 54702, USA 3 MBA Executive, Mayo Clinic Health System, Eau Claire, WI, USA Tel: +1 715 838 3891; Fax: +1 715 838 1946; E-mail: [email protected]
