De novo HBV infection in a Mayo Clinic hemodialysis population: economic impact of reduced HBV testing and a call for changes in current US CDC guidelines on HBV testing protocols.

Hemodialysis (HD) exposes end-stage renal disease patients to significantly higher risks for Hepatitis B Virus (HBV) infection, a major public health scourge. Therefore, current US CDC guidelines, last revised in 2001, call for monthly HbsAg tests. The charge to Medicare per HbsAg test is $100. In an economic analysis, we hypothesized that in the new environment of Medicare Fee Bundling, this is unwise and wasteful if de novo HBV infection rate among HD patients is <1%. We determined de novo HBV infection rate among a Mayo Clinic HD cohort, July 2000-July 2010. A retrospective analysis of all relevant medical records of the cohort was completed to identify de novo HBV infection. Nine hundred sixty-five HD patients were analyzed. One case of de novo HBV infection was identified in a 54-year old known IV drug user, a previous Hepatitis C carrier. This translates to a de novo HBV case incidence rate of 0.1%. De novo HBV infection among HD patients in the US, 2000-2010, is only 0.1%. In the early 1970s, rates were as high as 30%. We recommend 3-monthly HbsAg testing, but to continue current monthly testing for IV drug users and other high-risk groups. Huge cost savings would result, without any compromise of quality outcomes. With over 500,000 HD patients, this represents a mind-boggling $40 billion savings in Medicare charges over 10 years. The US CDC should revise these outdated guidelines, last revised in 2001, to fall in line with current clinical realities on the ground.

Non-dilated obstructive uropathy - an unrecognized cause of acute renal failure in hospitalized US patients: three case reports seen over 6 months in a northwestern Wisconsin nephrology practice.

The syndrome of non-dilated obstructive uropathy (NDOU) and acute renal failure (ARF) is well reported. However, the literature suggests that this syndrome is rare, accounting for less than 5% of cases of urinary obstruction. Our recent experience with three cases of NDOU seen within a space of months implies otherwise. Between March 2009 and October 2009, in a small Midwestern American town Nephrology practice, we successfully managed three cases of NDOU. They all presented with newly symptomatic ARF. Renal imaging revealed no dilatation in both kidneys in one, only unilateral dilatation in the second, and dilatation was absent in a single functioning kidney in the third. They comprised of two males and one female, mean age 61 years (peak creatinine: 320-880 µmol/L). Despite the absence of dilatation on renal imaging, strong suspicion for NDOU led to decompression procedures with prompt recovery of kidney function in all three patients - two required percutaneous nephrostomy tube placements and/or ureteric stents and one responded to simple Foley catheter drainage. One required temporary hemodialysis. We submit that NDOU may be more common than previously speculated. A high index of suspicion is warranted as significant renal salvage can often be achieved by timely decompression procedures.

Renal failure and concurrent RAAS blockade in older CKD patients with renal artery stenosis: an extended Mayo Clinic prospective 63-month experience.

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.

Late-onset renal failure from angiotensin blockade (LORFFAB) in 100 CKD patients.

INTRODUCTION: Notwithstanding proven renoprotection from RAAS blockade (AB) with ACE inhibitors and ARBs, and despite increasing utilization of AB in the US, we have continued to experience a CKD/ESRD epidemic. Given concerns for iatrogenic CKD/ESRD, we designed a prospective study to analyze the course of eGFR following withdrawal of AB in such patients. PATIENTS: Between September 2002 and February 2005, all consecutive CKD patients on AB presenting with >25% increase in baseline serum creatinine were enrolled. eGFR following withdrawal of AB was monitored. The main outcome measures were serum creatinine, MDRD eGFR, and UA/Cr. RESULTS: 100 Caucasians, M:F=52:48, mean age 71.5 years were enrolled. Mean follow up was 26 months. Sixteen patients progressed to ESRD, of whom seven died. In 74, eGFR improved from 23.9+/-9 (7-47) to 39.2+/-15.4 (17-89) ml/min/1.73 m(2) BSA, 26.5 (3-46) months after stopping AB (P=0.001). The majority of the cohort, 95 patients, had known risk factors: 26 with RAS, 12 hypovolemia, 11 sepsis, 10 NSAIDs/cox II inhibitor use/abuse, 7 CIN, 2 congestive heart failure, 2 obstructive uropathy, and 27 with other medical and surgical causes, including malignancies, postoperative states, and infections. In the 26 with RAS, 5 with higher baseline creatinine -2.1+/-0.6 versus 1.5+/-0.4 mg/dL, P=0.013, progressed to ESRD; 4/5 ESRD patients died after 6.3 months. The remaining five patients (one male and four females), mean age 68 (44-83) years, demonstrated sustained improved eGFR with discontinuation (four) or reduction (one) of RAAS blockade, despite normal renal arteries and the absence of known traditional risk factors. UA/Cr generally increased following withdrawal of AB. CONCLUSIONS: 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.

Does renin-angiotensin aldosterone system blockade exacerbate contrast-induced nephropathy in patients with chronic kidney disease? A prospective 50-month Mayo Clinic study.

Contrast induced nephropathy, a leading cause of new-onset renal failure in U.S. hospitals, may be accelerated by concurrent RAAS blockade in CKD patients. Current literature is inconclusive. Between September 2002 and February 2005, we prospectively enrolled all CKD patients on RAAS blockade who developed contrast-induced nephropathy. RAAS blockade was discontinued, standard nephrology care applied, and eGFR by MDRD was monitored. Seven patients (M:F, 3:4; age, 72.3 years) were enrolled. Mean duration of RAAS blockade at enrollment was 25.8 months. Baseline vs. enrollment eGFR was 45.5 +/- 17 vs. 16.6 +/- 6.8 mL/min/1.73 m(2), p = 0.009. Three of the seven patients (43%) required dialysis, one temporarily. Two older patients (mean age, 81.5 vs. 68.6 years, p = 0.017) progressed to ESRD. eGFR in five non-ESRD patients increased from 18.5 +/- 7.1 to 41.0 +/- 27.1 mL/min/1.73 m(2) after 29.4 months. Baseline eGFR was lower in the two patients who developed ESRD (29.5 vs. 51.2 mL/min/1.73 m(2)). Two patients exhibited very steep serum creatinine trajectories, indicative of rapid loss of eGFR. New onset proteinuria was observed. We have demonstrated very bad renal outcomes with three of seven (43%) patients requiring dialysis, with two (29%) progressing to ESRD. In two patients, loss of eGFR was clearly accelerated. These findings support the view that concurrent RAAS blockade, particularly in older CKD patients, exacerbates contrast-induced nephropathy. Also, lower baseline eGFR predicted worse renal outcomes. We support the recommendation to withhold RAAS blockade, 48 hours before contrast exposure, to improve renal outcomes.

Late onset azotemia from RAAS blockade in CKD patients with normal renal arteries and no precipitating risk factors.

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.

Late onset renal failure from angiotensin blockade (LORFFAB): a prospective thirty-month Mayo Health System clinic experience.

BACKGROUND: Worsening azotemia following initiation of angiotensin blockade (AB), in patients with CKD, RAS with/without precipitating factors is recognized. Small increases in serum creatinine following initiation of AB occur and must not warrant drug discontinuation. We anecdotally had observed improvement in CKD in patients with normal renal arteries and no precipitating factors, following termination of AB. The worldwide ESRD epidemic, coincident with increasing use of AB, prompted us to hypothesize a late-onset azotemia in such CKD patients. MATERIAL/METHODS: Over 30 months, 103 patients with worsening azotemia, while on AB were evaluated. Ninety-seven patients with abnormal MRA and/or with precipitating factors were excluded. In the remaining five, AB was discontinued, and GFR monitored. RESULTS: One male, four females, mean age 66.2 years. Three diabetic/hypertensives, one SLE/hypertensive, one diabetic/kidney transplant recipient. Mean stable AB, 25.2 months, (6-66 months). Mean follow up, 11.8 months. One month following discontinuation of AB, GFR increased by a mean 45%. Mean serum creatinine decreased from 2.9+/-0.9 to 1.8+/-0.4 mg/dL (p=0.04). Uremic symptoms in 3, hyperkalemia in one, secondary hyperparathyroidism in one, resolved. Two with anemia, now require less erythropoietin. CONCLUSIONS: We called this unrecognized potentially reversible late-onset worsening azotemia, occurring several months to years on stable AB, in CKD patients with normal renal arteries, without precipitating factors, late-onset renal failure from angiotensin blockade (LORFFAB). Pathophysiologically, the concept of microvascular RAS is invoked. The extent of LORFFAB, with millions of patients worldwide on AB, remains conjectural and warrants further investigation.