Worsening azotemia in older susceptible CKD patients on AB, often but not always associated with known precipitating risk factors, remains under-recognized. Sustained improved eGFR often follows the discontinuation of AB. The practising physician should be well aware of these syndromes. Our observations call for further study.

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.

Architect/Data Base Analyst/Programmer, NT Systems, Eau Claire, Wisconsin, USA Despite proven renoprotection from RAAS blockade and its increased application since the early 1990s, we have experienced an increasing CKD/ESRD epidemic, especially among U.S. diabetics. Consequently, some concerns regarding iatrogenic azotemia from RAAS blockade have surfaced. We hypothesized that susceptible CKD patients with normal renal arteries on conventional angiography, including MRA, but who have microvascular arteriolar narrowing in the renal circulation-mimicking large vessel renal artery stenosis, even without precipitating risk factors-could experience worsening azotemia after periods of time exceeding three months on stable doses of RAAS blockade. Between September 2002 and February 2005, as part of a larger prospective study of renal failure in CKD patients on RAAS blockade, we studied five patients with >25% higher serum creatinine and normal MRA without precipitating factors. RAAS blockade was discontinued. eGFR by MDRD was monitored. Five Caucasians (M:F = 1:4; age 68 years) were enrolled and followed-up at 29.6 months. The duration of RAAS blockade at enrollment was 34.6 months. The baseline eGFR had decreased from 28.4 ± 7.1 to 17.0 ± 7.4 ml/min/1.73 m 2 BSA (p < 0.001) at enrollment. One required temporary hemodialysis; no deaths occurred. eGFR increased from 17.0 ± 7.4 to 24.6 ± 9.5 ml/min/ 1.73 m 2 BSA (p=0.009), 29.6 (20-43) months after stopping the RAAS blockade. We conclude that worsening azotemia occurs in susceptible CKD patients on stable doses of RAAS blockade after long periods of time, despite normal renal arteries without precipitating risk factors. We submit that microvascular renal arteriolar narrowing is the pathophysiologic mechanism. These observations call for further study.

Despite decades of research, a full understanding of chronic kidney disease (CKD)-end stage renal disease (ESRD) progression remains elusive. The common consensus is a predictable, linear, progressive and time-dependent decline of CKD to ESRD. Acute kidney injury (AKI) on CKD is usually assumed to be transient, with recovery as the expected outcome. AKI-ESRD association in current nephrology literature is blamed on the so-called “residual confounding.” We had previously described a relationship between AKI events and rapid onset yet irreversible ESRD happening in a continuum in a high-risk CKD cohort. However, the contribution of the syndrome of rapid onset-ESRD (SORO-ESRD) to incident United States ESRD population remained conjectural. In this retrospective analysis, we analyzed serum creatinine trajectories of the last 100 consecutive ESRD patients in 4 Mayo Clinic chronic hemodialysis units to determine the incidence of SORO-ESRD. Excluding 9 patients, 31 (34%) patients, including two renal transplant recipients, had SORO-ESRD: 18 males and 13 females age 72 (range 50-92) years. Precipitating AKI followed pneumonia (8), acutely decompensated heart failure (7), pyelonephritis (4), post-operative (5), sepsis (3), contrast-induced nephropathy (2), and others (2). Time to dialysis was shortest following surgical procedures. Concurrent renin angiotensin aldosterone system blockade was higher with SORO-ESRD - 23% versus 5%, P = 0.0113. In conclusion, SORO-ESRD is not uncommon among the incident general US ESRD population. The implications for ESRD care planning, AV-fistula-first programs, general CKD care and any associations with renal ageing/senescence warrant further study.

Concerns have been raised regarding a possible link between the increasing utilization of RAAS blocking strategies in the United States and the increasing ESRD epidemic. Most reports of accelerated renal failure in CKD patients with renal artery stenosis on RAAS blockade are retrospective. We hypothesized that this syndrome is therefore poorly understood, may be under-recognized, and demanded prospective analysis. As part of a larger cohort of 100 CKD patients on RAAS blockade presenting with worsening renal failure (>25% increased serum creatinine from baseline) while concurrently on an ACE inhibitor and/or an angiotensin receptor blocker, 26 patients (26%) enrolled between September 2002 and February 2005 had hemodynamically significant renal artery stenosis. RAAS blockade was discontinued, standard nephrology care applied, and eGFR by MDRD monitored. They consisted of 26 Caucasian patients, M:F = 10:16, age 75.3 +/- 6.4 (63-87) years. Mean follow-up was 26.4 +/- 16.4 (1-49) months. Duration of RAAS blockade prior to enrollment was 20.2 +/- 16.4 (0.5-48) months. Contrary to previous reports, precipitating factors were often absent (15/26), unilateral RAS lesions in patients with dual kidneys was common (19/26), and progression to ESRD was frequent (5/26). Four-fifths of the ESRD patients were dead after 5.5 +/- 4.1 (1-11) months. A fifth patient with improved eGFR died after 14 months from metastatic gastric cancer. Excluding five patients who progressed to ESRD and two patients lost early to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 (11-47) to 36.7 +/- 16 (14-68) mL/min/1.73 m(2) BSA (p = 0.014) after 34.8 +/- 10.1 (14-49) months of follow-up. This improvement in eGFR was evident after weeks to months of stopping RAAS blockade in these patients with and without renal PTA and stenting. Nevertheless, renal PTA/stenting further improved eGFR in selected patients. We conclude that renal failure/ESRD associated with concurrent RAAS blockade in older CKD patients with renal stenosis remains poorly understood and mostly unrecognized. Unilateral lesions in patients with dual kidneys, absent precipitating factors, and progression to ESRD with high mortality, despite discontinuation of RAAS blockade, are more common than previously thought. Lower baseline eGFR (<35) predicted ESRD. Our findings call for a larger prospective study, especially given growing concerns of iatrogenic renal failure from RAAS blockade in the aging U.S. population. An aging U.S. population further raises the probability of the presence of increasing and unrecognized renal artery stenosis in our CKD patient population.