Comment on: Have we reached the limits for the treatment of diabetic nephropathy?

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 naïve 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.