Abstract
Background: Early rapid declines of kidney function may occur in patients with atherosclerotic renal artery stenosis with institution of medical therapy. The causes and consequences are not well understood. Methods and Results: Patients enrolled in the medical therapy–only arm of the CORAL (Cardiovascular Outcomes With Renal Artery Lesions) study were assessed for a rapid decline (RD) in estimated glomerular filtration rate (eGFR), defined as a ≥30% decrease from baseline to either 3 months, 6 months, or both. In the medical therapy–only cohort, eGFR was available in 359 subjects at all time points, the subjects were followed for a median of 4.72 years, and 66 of 359 (18%) subjects experienced an early RD. Baseline log cystatin C (odds ratio, 1.78 [1.11–2.85]; P=0.02), age (odds ratio, 1.04 [1.00–1.07]; P<0.05), and Chronic Kidney Disease Epidemiology Collaboration creatinine eGFR (odds ratio, 1.86 [1.15–3.0]; P=0.01) were associated with an early RD. Despite continued medical therapy only, the RD group had an improvement in eGFR at 1 year (6.9%; P=0.04). The RD and nondecline groups were not significantly different for clinical events and all-cause mortality (P=0.78 and P=0.76, respectively). Similarly, renal replacement therapy occurred in 1 of 66 (1.5%) of the RD patients and in 6 of 294 (2%) of the nondecline patients. The regression to the mean of improvement in eGFR at 1 year in the RD group was estimated at 5.8±7.1%. Conclusions: Early rapid declines in kidney function may occur in patients with renal artery stenosis when medical therapy is initiated, and their clinical outcomes are comparable to those without such a decline, when medical therapy only is continued.
| Original language | English (US) |
|---|---|
| Article number | e012366 |
| Journal | Journal of the American Heart Association |
| Volume | 8 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jun 4 2019 |
Keywords
- cardiovascular disease
- renal
- renal artery stenosis
- renal disease
- renovascular
- renovascular hypertension
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
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In: Journal of the American Heart Association, Vol. 8, No. 11, e012366, 04.06.2019.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Early Rapid Decline in Kidney Function in Medically Managed Patients With Atherosclerotic Renal Artery Stenosis
AU - Cooper, Emily L.
AU - Xie, Yanmei
AU - Nguyen, Hanh
AU - Brewster, Pamela S.
AU - Sholl, Haden
AU - Sharrett, Megan
AU - Ren, Kaili
AU - Chen, Tian
AU - Tuttle, Katherine R.
AU - Haller, Steven T.
AU - Jamerson, Kenneth
AU - Murphy, Timothy P.
AU - D'Agostino, Ralph B.
AU - Massaro, Joseph M.
AU - Henrich, William
AU - Cooper, Christopher J.
AU - Cutlip, Donald E.
AU - Dworkin, Lance D.
AU - Shapiro, Joseph I.
N1 - Funding Information: Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Numbers U01HL072734, U01HL072735, U01HL072736, and U01HL072737. Dr Cooper and Ms Brewster have received support from the National Heart, Lung, and Blood Institute, National Institutes of Health (5U01HL071556). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Drugs for this study were provided by AstraZeneca, device support was provided by Cordis Corporation, and supplemental financial support was granted by both Cordis Corporation and Pfizer Inc. Funding Information: Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Numbers U01HL072734, U01HL072735, U01HL072736, and U01HL072737. Dr Cooper and Ms Brewster have received support from the National Heart, Lung, and Blood Institute, National Institutes of Health (5U01HL071556). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Drugs for this study were provided by AstraZeneca, device support was provided by Cordis Corporation, and supplemental financial support was granted by both Cordis Corporation and Pfizer Inc. CORAL (NCT00081731) is a prospective, international, multicenter clinical trial that randomly assigned 931 participants with atherosclerotic RAS who received optimal medical therapy to stenting versus no stenting. Randomization occurred from May 2005 through January 2010. Optimal medical therapy for CORAL, including the use of antihypertensives, antiplatelet therapy, angiotensin receptor blockers, angiotensin converting enzyme inhibitors, and statins, has been previously published, as has the importance of optimal medical therapy in treating atherosclerotic RAS. The full CORAL data set is on the National Heart, Lung, and Blood Institute website (https://biolincc.nhlbi.nih.gov/studies/coral/), where investigators can request access to the data. All enrolling centers obtained institutional review committee approval and followed institutional and study guidelines. All participating subjects provided written informed consent. The results of the study have been previously described. Patients with RAS of at least 60% were eligible if they had hypertension while receiving ≥2 antihypertensive agents or had an eGFR <60 mL/min per 1.73 m2. Angiograms were analyzed for verification of stenosis by the Angiography Core Lab for the study at the University of Virginia. CORAL (NCT00081731) is a prospective, international, multicenter clinical trial that randomly assigned 931 participants with atherosclerotic RAS who received optimal medical therapy to stenting versus no stenting. Randomization occurred from May 2005 through January 2010. Optimal medical therapy for CORAL, including the use of antihypertensives, antiplatelet therapy, angiotensin receptor blockers, angiotensin converting enzyme inhibitors, and statins, has been previously published, as has the importance of optimal medical therapy in treating atherosclerotic RAS. The full CORAL data set is on the National Heart, Lung, and Blood Institute website (https://biolincc.nhlbi.nih.gov/studies/coral/), where investigators can request access to the data. All enrolling centers obtained institutional review committee approval and followed institutional and study guidelines. All participating subjects provided written informed consent. The results of the study have been previously described. Patients with RAS of at least 60% were eligible if they had hypertension while receiving ≥2 antihypertensive agents or had an eGFR <60 mL/min per 1.73 m2. Angiograms were analyzed for verification of stenosis by the Angiography Core Lab for the study at the University of Virginia. The current study sought to examine changes in kidney function within the medical therapy–only group. The primary aims were to (1) examine factors that predict RD of kidney function within the first 6 months of medical therapy and (2) determine the clinical outcomes of patients with early RD of kidney function. eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations at baseline, 3 and 6 months, and every 6 months for the duration of follow-up. RD was a dichotomous outcome and was defined as a ≥30% decrease in eGFR from baseline to either 3 months, 6 months, or both intervals. Nondecline (ND) was defined as those patients who did not demonstrate an RD. Continuous data were tested for goodness of fit to the normal distribution using the Shapiro–Wilk test. If not normally distributed, the log-transformation of the variable was assessed for normality. Continuous data are presented as mean± SD of the untransformed or log-transformed version or, if neither were normally distributed, as median with interquartile range. Categorical data are presented as frequency and percent. Comparisons of continuous data were evaluated using 2-sample t tests or Wilcoxon rank sum test. For categorical variables, the chi-square test or, if the frequency of counts for some factors was low (≤5), Fisher exact test was used to compare groups. Statistical significance was defined as a P<0.05. All analyses were performed using R software (version 3.0.0) and SAS (version 9.3). Analysis was performed comparing the RD and ND groups on each baseline characteristic, one at a time, using ANOVA adjusting for age and sex. A stepwise logistic regression with group (RD versus ND) as the outcome was then used to further identify characteristics significantly related to group membership. The model was examined for discriminate ability using area under the curve from receiver operating characteristic analysis and the Hosmer-Lemeshow goodness-of-fit test to assess model fit. Stepwise multivariate linear regression analysis was used to examine the independent predictors of percentage change in eGFR at 1-year follow-up and to assess the safety and clinical benefit of continued medical therapy. The covariates in the model included reference baseline GFR, rapid decline, sex, age, urine albumin to creatinine ratio (UACR), and cystatin C, and were selected by the stepwise method with the Akaike information criterion. The effect of RD on kidney function over time was estimated by applying the generalized linear mixed model with time (continuous variable) as a random coefficient. In models with an overall significant effect over time, post hoc tests were performed to determine which time-related pairs were significant. Bonferroni adjustment was used to avoid the potential for inflated type I errors. All multivariable models were tested for interaction between predictors and were found to be nonsignificant. We chose to test for regression to the mean (RTM), as it can lead to overestimation of the treatment effect if not properly adjusted. The nonparametric empirical likelihood method and kernel density estimation were applied to assess the RTM effect on follow-up repeated measurements of eGFR for both the RD and ND groups. Percentage change in eGFR within 6 months became the baseline reference value against which repeated measurements of eGFR were compared. ANCOVA was used for comparison between the groups considering the substantial decline in eGFR in the RD group. The primary outcome was the composite end point defined as the first occurrence of any secondary end points: cardiovascular or renal death, myocardial infarction, stroke, congestive heart failure, or progressive renal insufficiency (≥30% decline in GFR sustained over a period of 6 months) and permanent renal replacement). All-cause mortality was also evaluated as an outcome. Events occurring within 6 months, before the establishment of the RD or ND reference baseline, were censored. These patients were included in the analysis of RD and for follow-up events. The time-to-event analysis used the first event after the 6-month reference baseline. The predicted probability of the binary occurrence of the composite end point was calculated using logistic regression with adjustment for age, sex, baseline log urine albumin-to-creatinine ratio (LUACR), and baseline log cystatin C. Receiver operating characteristic was used to summarize the model performance. Time to event for the composite and mortality end points was examined using log-rank estimates to compare the RD and ND groups. Hazard ratios were calculated using the Cox proportional-hazards model adjusted for age, sex, and baseline LUACR and cystatin C. Model diagnostics were performed using the Cox-Snell residual plot test to check for goodness of fit. The proportional hazards assumption tests from the R function cox.zph in the survival package for all the survival models had P>0.05, indicating that the null hypothesis of proportional hazards was not rejected. The extended Cox model was used to test for interaction among model predictors and time. The time-dependent covariates were generated by building interactions of the predictors and a function of survival time and were included in the models. The P values for all time-covariate interactions in the survival models were >0.05, confirming the null hypothesis assumption of proportional hazards and indicating that the fitted Cox regression hazard models are adequate. Brewster receives or receives support from NIH, AstraZeneca, Cordis and Phizer. Tuttle receives or received support from the National Institutes of Health (NIH), AstraZeneca, Cordis, and Phizer. Jamerson receives or receives support from NIH, AstraZeneca, Cordis, and Phizer. Murphy receives or received support from NIH, AstraZeneca, Cordis, and Phizer. D'Agostino receives or received support from NIH, AstraZeneca, Cordis, and Phizer. Massaro receives or received support from NIH, AstraZeneca, Cordis, and Phizer. Henrich receives or received support from NIH, AstraZeneca, Cordis, and Phizer. Cooper receives or received support from NIH, AstraZeneca, Cordis, and Phizer. Cutlip receives or received support from NIH, AstraZeneca, Cordis, and Phizer. Dworkin receives or received support from NIH, AstraZeneca, Cordis, and Phizer. Shapiro receives or received support from NIH, AstraZeneca, Cordis, and Phizer. The remaining authors have no disclosures to report. Publisher Copyright: © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2019/6/4
Y1 - 2019/6/4
N2 - Background: Early rapid declines of kidney function may occur in patients with atherosclerotic renal artery stenosis with institution of medical therapy. The causes and consequences are not well understood. Methods and Results: Patients enrolled in the medical therapy–only arm of the CORAL (Cardiovascular Outcomes With Renal Artery Lesions) study were assessed for a rapid decline (RD) in estimated glomerular filtration rate (eGFR), defined as a ≥30% decrease from baseline to either 3 months, 6 months, or both. In the medical therapy–only cohort, eGFR was available in 359 subjects at all time points, the subjects were followed for a median of 4.72 years, and 66 of 359 (18%) subjects experienced an early RD. Baseline log cystatin C (odds ratio, 1.78 [1.11–2.85]; P=0.02), age (odds ratio, 1.04 [1.00–1.07]; P<0.05), and Chronic Kidney Disease Epidemiology Collaboration creatinine eGFR (odds ratio, 1.86 [1.15–3.0]; P=0.01) were associated with an early RD. Despite continued medical therapy only, the RD group had an improvement in eGFR at 1 year (6.9%; P=0.04). The RD and nondecline groups were not significantly different for clinical events and all-cause mortality (P=0.78 and P=0.76, respectively). Similarly, renal replacement therapy occurred in 1 of 66 (1.5%) of the RD patients and in 6 of 294 (2%) of the nondecline patients. The regression to the mean of improvement in eGFR at 1 year in the RD group was estimated at 5.8±7.1%. Conclusions: Early rapid declines in kidney function may occur in patients with renal artery stenosis when medical therapy is initiated, and their clinical outcomes are comparable to those without such a decline, when medical therapy only is continued.
AB - Background: Early rapid declines of kidney function may occur in patients with atherosclerotic renal artery stenosis with institution of medical therapy. The causes and consequences are not well understood. Methods and Results: Patients enrolled in the medical therapy–only arm of the CORAL (Cardiovascular Outcomes With Renal Artery Lesions) study were assessed for a rapid decline (RD) in estimated glomerular filtration rate (eGFR), defined as a ≥30% decrease from baseline to either 3 months, 6 months, or both. In the medical therapy–only cohort, eGFR was available in 359 subjects at all time points, the subjects were followed for a median of 4.72 years, and 66 of 359 (18%) subjects experienced an early RD. Baseline log cystatin C (odds ratio, 1.78 [1.11–2.85]; P=0.02), age (odds ratio, 1.04 [1.00–1.07]; P<0.05), and Chronic Kidney Disease Epidemiology Collaboration creatinine eGFR (odds ratio, 1.86 [1.15–3.0]; P=0.01) were associated with an early RD. Despite continued medical therapy only, the RD group had an improvement in eGFR at 1 year (6.9%; P=0.04). The RD and nondecline groups were not significantly different for clinical events and all-cause mortality (P=0.78 and P=0.76, respectively). Similarly, renal replacement therapy occurred in 1 of 66 (1.5%) of the RD patients and in 6 of 294 (2%) of the nondecline patients. The regression to the mean of improvement in eGFR at 1 year in the RD group was estimated at 5.8±7.1%. Conclusions: Early rapid declines in kidney function may occur in patients with renal artery stenosis when medical therapy is initiated, and their clinical outcomes are comparable to those without such a decline, when medical therapy only is continued.
KW - cardiovascular disease
KW - renal
KW - renal artery stenosis
KW - renal disease
KW - renovascular
KW - renovascular hypertension
UR - http://www.scopus.com/inward/record.url?scp=85069643053&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069643053&partnerID=8YFLogxK
U2 - 10.1161/JAHA.119.012366
DO - 10.1161/JAHA.119.012366
M3 - Article
C2 - 31433717
AN - SCOPUS:85069643053
SN - 2047-9980
VL - 8
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 11
M1 - e012366
ER -