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Percutaneous Renal Artery Interventions / Albertal et al Greetings, and thank you for publishing with SAGE Publications. Your article has been copyedited, and we have a few queries for you. Please address these queries when you send yourproof corrections to the production editor. Thank you for your time and effort.
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Differently to Percutaneous RenalArtery Interventions? M. Albertal, MD, PhD, G. Nau, MD, L. T. Padilla, MD,F. A. Cura, MD, PhD, J. Thierer, MD, and J. A. Belardi, MD Background: Women have higher risk of contrast- a significant improvement in GFR and systolic blood induced nephropathy than men. The purpose of this pressure, while females did not. The presence of severe study was to determine the relative impact of gender CKD and male gender were the only predictors of long- on long-term renal function after percutaneous renal term GFR improvement. Conclusion: Male patients interventions (PRI). Methods and Results: We included and patients with poor baseline renal function showed all patients undergoing PRI. Men (n ¼ 72) and women an important benefit with PRI, suggesting that it is (n ¼ 28) had similar age, men had more diabetes, cor- not too late for renal revascularization if properly onary and peripheral artery disease, higher serum crea- tinine and similar glomerular filtration rate (GFR), andprevalence of chronic kidney disease (CKD) stage !3 renal artery stenosis; gender; angioplasty; when compared with females. At follow-up, men had Therefore, the aim of our study was to compare long-term renal function outcome in men and Renal artery stenosis is a recognized cause of chronic kidney disease (CKD)1-4 and conveys significant riskof cardiac morbidity and mortality.5,6 Percutaneousrenal artery intervention (PRI) carries the potential for renal function preservation and even improve-ment if properly indicated.1,7-10 Recent reports indi- We retrospectively reviewed a subset of 100 consec- cate that women are specifically prone to renal injury utive patients with de novo renal artery stenosis who after contrast exposure.11,12 Women’s clinical bene- underwent single or bilateral PRI from January 1999 fit expected by PRI can potentially be offset by the to October 2007. Data were prospectively collected development of contrast-induced injury. After PRI, in a dedicated database from the interventional car- a link between renal function preservation and gen- diology department at the Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina. Percuta-neous renal intervention was performed in patientswith significant angiographic stenosis (diameter ste-nosis of !70%). Percutaneous renal interventionwas performed either (1) as a result of an incidentalangiographic finding, (2) in patients with a positive From the Research Department (MA, JT), and Department ofInterventional Cardiology and Endovascular Therapeutics (GN, noninvasive imaging test, (3) due to uncontrolled LTP, FAC, JAB), Instituto Cardiovascular de Buenos Aires, hypertension, or (4) unexplained CKD. The preinter- Ciudad Auto´noma de Buenos Aires, Argentina.
ventional workup and follow-up visits included mea- Address correspondence to: M. Albertal, Research Department, surement of serum creatinine and systolic blood Instituto Cardiovascular de Buenos Aires, Blanco Encalada pressure (SBP) and diastolic blood pressure (DBP) 1543, Ciudad Auto´noma de Buenos Aires, Argentina; e-mail:marianoalbertal@gmail.com.
and number of antihypertensive drugs.
Baseline Characteristics of the Study Population According to Gender NOTE: CKD ¼ chronic kidney disease.
Glomerular filtration rate (GFR) was calculated using the modification of diet in renal disease equation(MDRD;mL/minper1.73m2):186Â (serumcreatinine Patient demographics are detailed in Table 1.
in mg/dL)À1.154 Â (age)À0.203 Â (0.742 for women).
Although age and proportion of hypertension was Percutaneous renal intervention was performed similar between groups, females (n ¼ 28) had a lower as previously described.8 In 22 patients, we per- proportion of comorbid conditions including dia- formed bilateral renal artery stenting. Dual antipla- betes mellitus, coronary, and peripheral artery dis- telet therapy was started at least the day before ease. Baseline serum creatinine was significantly intervention and routinely consisted of 75 mg of clo- lower in females, but GFR values and prevalence of pidogrel daily for 4 weeks and 100 mg of aspirin chronic renal failure (CKD stage !3) were similar indefinitely. Immediately before the intervention, in both groups. Females had less proportion of we administered a fixed bolus dose of 5000 IU of patients undergoing stenting, whereas bilateral PRI was performed in similar proportion in both groups.
The primary end point was the proportion of patients with !20% GFR improvement at follow-up. As secondary end points, we assessed the propor- tion of patients with !20% GFR decline prior to hos- pital discharge and at follow-up visit, average Median follow up was 1.7 years (25%-75% IQ 1.2- reduction in number of antihypertensive drugs, aver- 2.7 years). Systolic blood pressure decreased signifi- age reduction in SBP and/or DBP at follow-up.
cantly in both groups, mean SBP reduction was 5.2%in males and 3.4% in females, P ¼ .663; Figure 1).
Diastolic blood pressure and the number of antihy-pertensive drugs did not vary in either group.
Data were expressed as mean + standard deviationor median, and interquartile (IQ) range values wereused for continuous variables. Categorical data were expressed as percentages. Student t test and 2 test were used to make comparisons between the men and the women. The nonparametric Wilcoxon ranksum test was used to compare continuous variables A total of 89 of 100 patients had postprocedural when the data were not normally distributed. Multi- serum creatinine available. Acute in-hospital GFR variate logistic regression analysis was performed to decline (!20%) was observed in 15.7 % (14/89) of predict (a) !20% GFR improvement, and (b) the patients. Acute decline in GFR was more fre- !20% GFR decline, both at follow-up visits. A P < quent in patients who exhibit long-term decline in GFR [35.7% (5/14) vs 9.5% (7/74), P ¼ .021], Percutaneous Renal Artery Interventions / Albertal et al 139.7 139.5 140.3
129.7 129.3 130.7
Baseline
Baseline
Creatinine
Baseline
Baseline
* P > .005 vs Baseline
SBP, DBP, serum creatinine, and GFR changes at follow-up. Note that SBP and renal function parameters improved in the overall and male populations, while no improvement was observed in females. DBP indicates diastolic blood pressure; FUP ¼ follow-up; GFR ¼ glomerular filtration rate; SBP ¼ systolic blood pressure.
whereas there was no association between acute 16.2; 95% CI 4.3-105.8, P > .001) as independent decline and long-term improvement. In addition, neither gender type nor the degree of CKD corre- Multivariate analysis to predict GFR decline at lated with acute in-hospital GFR decline.
follow-up identified CKD stage !3 (OR 0.07; 95% Forty-eight percentage of patients improved their CI 0.017-0.25, P ¼ .0001), male gender (OR 0.14, GFR at follow-up, whereas 20% had a substantial 95% CI 0.03-0.59, P ¼ .007) as independent predic- decline in their GFR. Improvement in GFR was less tors of GFR decline at follow-up. Age, diabetes mel- common in females than men (Figure 2) and more litus, basal SBP and DBP values, and number common in patients with CKD stage !3 than in of antihypertensive drugs were not independent patients with milder CKD or normal GFR (Figure 3).
predictors of either improvement or decline at Patients with and without baseline statin use had sim- ilar GFR improvement rate (22% vs 17.9%, P ¼ .38).
In contrast, GFR decline at follow-up was more frequent in women than in men and less common in patients with CKD stage !3 than in earlier CKDstages (Figures 2 and 3).
In our study, almost half of our population had a To identify predictors of GFR improvement, we clinically meaningful improvement in GFR, espe- performed a multivariate logistic analysis and identi- cially in men and in patients with severe CKD.
fied the presence of CKD stage !3 (OR 29.6; 95% Females were associated with more frequent decline CI 8.3-105.8, P > .001) and male gender (OR Overall population
Improve (≥20% increase in GFR)
Worse (≥20% decline in GFR)
* P < .001 vs Females
GFR response at follow-up is shown in the overall population (above) and according to gender (below). Note that males showed a greater proportion of patients with !20% GFR improvement than females. GFR indicates glomerular filtration rate.
CKD stage 0-2
CKD stage 3-5
*P < .001 vs Stage 3-5
GFR response at follow-up is shown according to baseline renal function. Note that patients with baseline significant renal impairment achieved greater benefit. CKD indicates chronic kidney disease; GFR ¼ glomerular filtration rate.
Atherosclerotic renal artery stenosis is quite pre- American College of Cardiology meeting in 2008 valent worldwide,13-15 especially in patients with clearly indicated that stenting these lesions does not atherosclerosis in other vascular beds. Preliminary result in any improvement in blood pressure and/or results from the ASTRAL trial presented in the renal function when compared with optimal medical Percutaneous Renal Artery Interventions / Albertal et al therapy.16 Thus, current indication on ARAS stent- definitively conclude that blood loss did not impact ing is to say the least, controversial. In an attempt GFR values, as a result renal hypoxic insult. Fourth, to predict clinical benefit after PRI, several investiga- postprocedural GFR was not mandatory in our study.
tors have evaluated the adjunctive use of different It is possible that primary physicians ordered such laboratory test (ie, serum creatinine) in those Doppler-derived resistance index, use of brain patients, in whom they feel were at greater risk for natriuretic peptide levels, measuring renal frame developing contrast-induced nephropathy, generat- count, and renal blush).17-19 From all these para- ing a potential bias. The latter prevents an accurate meters, fractional flow reserve may be the more estimation of the procedural renal risk.
accurate predictor of lesion hemodynamic severity Despite these above-mentioned limitations, our and blood pressure response. However, it is not avail- results suggest that women had a lower benefit from able in every laboratory and it is possible to have PRI, while patients with severe CKD had greater essential hypertension and later developed a hemo- chances for renal function improvement or stabiliza- dynamically significant renal artery stenosis. This latter case may not necessarily derive benefit fromPRI. Several studies have suggested that patientswith bilateral renal artery stenosis or with concomi-tant renal impairment derive benefit from PRI.7 In line with previous studies, 70.5% (43/61) of ourpatients with CKD !3 improved their GFR with only 1. Watson PS, Hadjipetrou P, Cox SV, Piemonte TC, 6.6% (4/61) of these patients exhibiting a meaningful Eisenhauer AC. Effect of renal artery stenting on renalfunction and size in patients with atherosclerotic reno- vascular disease. Circulation. 2000;102(14):1671-1677.
Previous studies have shown that women experi- 2. Wollenweber J, Sheps SG, Davis GD. Clinical course of ence greater GFR decline after contrast expo- atherosclerotic renovascular disease. Am J Cardiol.
sure.11,12,20,21 Evidence from animal and human studies indicates that males have more glomeruli and 3. Schreiber MJ, Pohl MA, Novick AC. The natural history larger total glomerular volume than females,22 which of atherosclerotic and fibrous renal artery disease. Urol may provide males with greater protection against nephrotoxicity, ischemic-related injury, and also 4. Zierler RE, Bergelin RO, Isaacson JA, Strandness DE Jr.
hyperfiltration. In addition, postmenopausal women Natural history of atherosclerotic renal artery stenosis: a have low intrarenal medullary vasodilatory prosta- prospective study with duplex ultrasonography. J Vasc glandin production,23 a potential factor for increased Surg. 1994;19(2):250-257;discussion 257-258.
susceptibility to acute tubular necrosis.
5. Conlon PJ, Little MA, Pieper K, Mark DB. Severity of renal vascular disease predicts mortality in patients The present study represents a retrospective view undergoing coronary angiography. Kidney Int. 2001; a prospectively collected data at a single institution.
In our study, several limitations deserve to be men- 6. Isles C, Main J, O’Connell J, et al. Survival associated tioned. First, there are no data available regarding with renovascular disease in Glasgow and Newcastle: a procedural contrast volume or measures implemen- collaborative study. Scott Med J. 1990;35(3):70-73.
ted to prevent contrast-induced nephropathy (eg, 7. Bates MC, Campbell JE, Broce M, Lavigne PS, hydration or administration of prophylactic medica- Riley MA. Serum creatinine stabilization following renal tions such as N-acetylcysteine). Second, baseline artery stenting. Vasc Endovascular Surg. 2008;42(1): medications taken by the patients that may bear a potential for renal damage during the procedure 8. Dorros G, Jaff M, Mathiak L, et al. Renal function and survival after renal artery stent revascularization maybe influenced by embolic debris. J Invasive Cardiol.
(NSAIDs) or metformin have not been recorded. The latter may be relevant because prior use of NSAIDs 9. Harden PN, MacLeod MJ, Rodger RS, et al. Effect of or metformin may result in contrast-induced nephro- renal-artery stenting on progression of renovascular pathy. Third, women are usually associated with ane- renal failure. Lancet. 1997;349(9059):1133-1136.
mia and greater blood loss during a percutaneous 10. Zeller T, Frank U, Muller C, et al. Predictors of improved intervention.24-26 However, we did not have data renal function after percutaneous stent-supported angio- regarding the development of periprocedural hema- plasty of severe atherosclerotic ostial renal artery steno- toma during this period in our database to sis. Circulation. 2003;108(18):2244-2249.
11. Sidhu RB, Brown JR, Robb JF, et al. Interaction of gen- 20. Gill NK, Piccione EA, Vido DA, Clark BA, Shannon RP.
der and age on post cardiac catheterization contrast- Gender as a risk factor for contrast nephropathy: effects of hydration and N-acetylcysteine. Clin Cardiol.
12. Iakovou I, Dangas G, Mehran R, et al. Impact of gender 21. Mueller C, Buerkle G, Perruchoud AP, Buettner HJ.
on the incidence and outcome of contrast-induced Female sex and risk of contrast nephropathy after percu- nephropathy after percutaneous coronary intervention.
taneous coronary intervention. Can J Cardiol. 2004; J Invasive Cardiol. 2003;15(1):18-22.
13. Ram CV. Renovascular hypertension. Curr Opin 22. Neugarten J, Kasiske B, Silbiger SR, Nyengaard JR.
Nephrol Hypertens. 1997;6(6):575-579.
Effects of sex on renal structure. Nephron. 2002;90(2): 14. Derkx FH, Schalekamp MA. Renal artery stenosis and hypertension. Lancet. 1994;344(8917):237-239.
23. Tada Y, Ichihara A, Koura Y, et al. Ovariectomy 15. Dworkin LD, Jamerson KA. Is renal artery stenting the enhances renal cortical expression and function of correct treatment of renal artery stenosis? Case against cyclooxygenase-2. Kidney Int. 2004;66(5):1966-1976.
angioplasty and stenting of atherosclerotic renal artery ste- 24. Byrne J, Spence MS, Fretz E, et al. Body mass index, nosis. Circulation. 2007;115(2):271-276;discussion 276.
16. Kalra PA. Stenting makes no difference in renal artery percutaneous coronary intervention (from the British disease. Presented at Late-Breaking Clinical Trials Ses- Columbia Cardiac Registry). Am J Cardiol. 2009; sion: Society for Cardiovascular Angiography and Interventions-American College of Cardiology Innova- 25. Manoukian SV, Feit F, Mehran R, et al. Impact of major tions in Intervention (SCAI-ACCi2) 2008; Chicago, IL.
bleeding on 30-day mortality and clinical outcomes in 17. Subramanian R, White CJ, Rosenfield K, et al. Renal patients with acute coronary syndromes: an analysis fractional flow reserve: a hemodynamic evaluation of moderate renal artery stenoses. Catheter Cardiovasc 26. Akhter N, Milford-Beland S, Roe MT, Piana RN, Kao J, 18. Silva JA, Chan AW, White CJ, et al. Elevated brain Shroff A. Gender differences among patients with acute natriuretic peptide predicts blood pressure response coronary syndromes undergoing percutaneous coronary after stent revascularization in patients with renal artery intervention in the American College of Cardiology- stenosis. Circulation. 2005;111(3):328-333.
National Cardiovascular Data Registry (ACC-NCDR).
19. Mulumudi MS, White CJ. Renal frame count: a quanti- tative angiographic assessment of renal perfusion.
Catheter Cardiovasc Interv. 2005;65(2):183-186.
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