Late-onset renal failure from RAAS blockade

Abstract

on the kidney. In proteinuric rats, the combination of ACEi and a low sodium diet elicits pronounced renal interstitial damage, despite a significant reduction of proteinuria. 2 As similar effects were found in healthy rats, the renal damage was not owing to particularities of the model, but related to the ACEi regimen. This is in line with earlier data in experimental renal transplantation, with monotherapy ACEi. 3 These data are distressing, as the ACEi regimens induced renal fibrosis in spite of a reduction in proteinuria and blood pressure, that is, an improvement of the established clinical criteria for a good response to therapy. In human, it is usually not feasible to monitor renal structural damage during therapy. Accordingly, considering the dissociation between renal fibrosis and the intermediate parameters blood pressure and proteinuria, therapy-associated progressive renal damage during renin-angiotensin system blockade in human cannot easily be recognized, and would require large, hard end point studies to become manifest. Although the mechanism underlying the ACEiinduced renal fibrosis deserves further study, our data provide a possible explanation for the increased risk of end-stage renal disease found by Suissa et al. 1 The incidence of end-stage renal disease is increasing worldwide, despite extensive use of renin-angiotensin system blockers. It would be prudent not to take their long-term renoprotective effect for granted, scrutinize their effects on renal structural damage in experimental studies, and critically evaluate their outcome in human during long-term follow-up. 1. Suissa S, Hutchinson T, Brophy JM et al. ACE-inhibitor use and the long-term risk of renal failure in diabetes. Kidney Int 2006; 69: 913-919. 2. Hamming I, Navis G, Kocks M et al. ACE inhibition has adverse renal effects during dietary sodium restriction in proteinuric and healthy rats.

Late Onset Azotemia from RAAS Blockade in CKD Patients with Normal Renal Arteries and No Precipitating Risk Factors

“…Our preliminary results were published previously. [41,42] Prompt discontinuation of RAAS blockade led to significant and sustained improvement in four patients, whereas a 50% dose reduction in the fifth patient of candesartan, an ARB, produced similar improvements in eGFR. Mean serum creatinine decreased from 3.4 ± 1.1 (1.8-4.6) mg/dL to 2.1 ± 0.6 (1.4-3.0) mg/dL (p = 0.049, n = 5) 29.6 (20-43) months after RAAS blockade was discontinued in four patients and halved in the fifth.…”

Can ACE Inhibitors and Angiotensin Receptor Blockers Be Detrimental in CKD Patients?

“…In the last 5 years, we have published several reports from our single-center experience describing sometimes reversible AKI in CKD patients associated with concurrent RAAS blockade [55,56,71,72,73,74,75,76,95]. The clinical circumstances under which we described worsening renal failure associated with concurrent RAAS blockade include the absence of any identifiable so-called precipitating risk factor [72], in association with multiple varied risk factors such as infections, heart failure exacerbation, hypotension and dehydration [70,72], in association with renal artery stenosis [75,76], in hospitalized patients [95], and in association with contrast-induced nephropathy [73,96].…”

“…These RCTs have several design flaws, and questions abound regarding the general applicability of the trial findings from these RCTs to the general CKD population, more so the older (>65-year-old) CKD patients [55,56,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80]. The several limitations and concerns raised regarding the veracity of the claims of these RCTs as well as doubts regarding the general applicability of the recommendations of the large RAAS blockade RCTs to especially the older CKD patient population include the following:…”

“…Many of the published large RAAS blockade randomized controlled trials (RCTs), upon which current evidence-based practice for the increasing use of the ACEIs and ARBs for renoprotection derived from, have strong deficiencies that have been highlighted over the years [55,56,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80]. These RCTs have several design flaws, and questions abound regarding the general applicability of the trial findings from these RCTs to the general CKD population, more so the older (>65-year-old) CKD patients [55,56,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80].…”

Late onset renal failure from angiotensin blockade (LORFFAB) and the syndrome of rapid onset endstage renal disease (SORO-ESRD) revisited – Two case reports from Mayo Clinic Health System, Northwestern Wisconsin, USA; a review paper

“…Since our first report of the syndrome of LORFFAB in 2005, over the last ten or more years, we have variously described the features of this syndrome in various journal publications, book chapters and editorial pieces as well as in professional academic intellectual forums and presentations (1)(2)(3)(4)(5)(6). It was indeed our work at the Mayo Clinic Health System in Northwestern Wisconsin that spurred the work of El Nahas and his group from the Sheffield Kidney Institute, Sheffield in the United Kingdom who concluded in 2010 that discontinuation of ACEI/ARB had undoubtedly delayed the onset of RRT in the majority of those studied and that this observation might justify a rethink of our approach to the inhibition of the renin-angiotensin-aldosterone system (RAAS) in patients with advanced CKD who are nearing the start of RRT (11,12).…”