Rapid Decline of Kidney Function Increases Cardiovascular Risk in the Elderly

Shlipak, Michael G.; Katz, Ronit; Kestenbaum, Bryan; Siscovick, David S.; Fried, Linda F.; Newman, Anne B.; Rifkin, Dena E.; Sarnak, Mark J.

doi:10.1681/asn.2009050546

Cited by 237 publications

(246 citation statements)

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“…We elected to use cystatin C to estimate eGFR in our primary analysis, because prior work has shown that cystatin C estimates larger declines in kidney function compared with creatinine-based eGFR (33) and that these declines predict adverse events (26,27). eGFR was determined from cystatin C using the 2012 CKD Epidemiology Collaboration equation, which includes age and sex (34).…”

Section: Discussionmentioning

confidence: 99%

“…Most studies to date have primarily focused on the association between NT-proBNP and TnT and cardiovascular and/or all-cause death. However, kidney outcomes are also important in management of highrisk patients, because decreased kidney function and kidney function decline are well established risk factors for cardiovascular disease (CVD) and mortality (25)(26)(27). Subclinical cardiac abnormalities-as indicated by preclinical elevations in NT-proBNP and TnT-may potentially identify physiologic processes that contribute to loss of kidney function.…”

Section: Introductionmentioning

confidence: 99%

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NT-ProBNP and Troponin T and Risk of Rapid Kidney Function Decline and Incident CKD in Elderly Adults

Bansal

Katz

Dalrymple

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Elevations in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.Design, setting, participants, & measurements N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR$30%, and incident CKD was defined as the onset of serum cystatin C eGFR,60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.Results In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide (.237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (.10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50).Conclusions Elevated N-terminal pro-B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NT-ProBNP and Troponin T and Risk of Rapid Kidney Function Decline and Incident CKD in Elderly Adults

Bansal

Katz

Dalrymple

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…Rapid decline in kidney function has been found to be associated with cardiovascular events and death in the elderly (10,19), but it was not statistically significant in our multivariable regression models for mortality and thus, was not retained in the final model. Serum albumin was shown to be predictive of 5-year mortality in a previous analysis in the CHS that included participants with and without CKD (20); however, it did not improve prediction of death in our analysis, which was limited to those with CKD.…”

Section: Discussionmentioning

confidence: 91%

Development and Validation of a Model to Predict 5-Year Risk of Death without ESRD among Older Adults with CKD

Bansal

Katz

Boer

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives CKD is associated with mortality. Accurate prediction tools for mortality may guide clinical decision-making, particularly among elderly persons with CKD.Design, setting, participants, & measurements A prediction equation was developed for 5-year risk of mortality among participants with CKD in the Cardiovascular Health Study. Sixteen candidate predictor variables were explored, which included demographics, physical examination measures, comorbidity, medication use, and kidney function measures (eGFR calculated from serum creatinine and the CKD Epidemiology Collaboration equation and the urine albumin-to-creatinine ratio). Models were developed using Cox regression and evaluated using c statistics. A final parsimonious model was externally validated in an independent cohort of communityliving elders with CKD in the Health, Aging, and Body Composition Study.Results The development cohort included 828 participants who had a mean age of 80 (65.6) years and an eGFR of 47 (611) ml/min per 1.73 m 2 , and median albumin-to-creatinine ratio of 13 (interquartile range 6-51) mg/g. The validation cohort included 789 participants who had a mean age of 74 (62.8) years and an eGFR of 50 (69) ml/min per 1.73 m 2 , and median albumin-to-creatinine ratio of 13 (interquartile range 6-42) mg/g. The final model for 5-year mortality risk included age, sex, race, eGFR, urine albumin-to-creatinine ratio, smoking, diabetes mellitus, and history of heart failure and stroke (c statistic=0.72; 95% confidence interval, 0.68 to 0.74). When a pointbased system was assigned for each of nine variables in the equation, the estimated risk of death within 5 years ranged from 3.8% among participants with the lowest scores to 83.6% among participants with nine points. The model performed fair in external validation (c statistic=0.69; 95% confidence interval, 0.64 to 0.74).Conclusions A simple prediction tool using nine readily available clinical variables can assist in predicting 5-year mortality risk in elderly patients with CKD, which may be useful in counseling patients and guiding clinical decision making.

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“…3 Decline in kidney function may be a stronger prognostic indicator than static measures of reduced estimated GFR (eGFR). In particular, patients with rapid kidney function decline (RKFD) are at increased risk for CVD and mortality [4][5][6][7] ; even among those with mildly reduced kidney function at baseline. 5,7 Dynamic eGFR assessment is necessary to identify this silently progressing, high-risk group; however, serial assessment in the general population is not cost-effective.…”

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confidence: 99%

Dipstick Proteinuria as a Screening Strategy to Identify Rapid Renal Decline

Clark

Macnab²,

Sontrop³

et al. 2011

Journal of the American Society of Nephrology

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Rapid kidney function decline (RKFD) predicts cardiovascular morbidity and mortality, but serial assessment of estimated GFR (eGFR) is not cost-effective for the general population. Here, we evaluated the predictive value of albuminuria and three thresholds of dipstick proteinuria to identify RKFD in 2,574 participants in a community-based prospective cohort study with a median of 7 years follow-up. Median change in eGFR was Ϫ0.78 ml/min per 1.73 m 2 per year; with 8.5% experiencing RKFD, defined as a Ͼ5% annual eGFR decline from baseline. Of those with RKFD, 65% advanced to a new CKD stage compared with 19% of those without RKFD. Dipstick protein Ն1 g/L was a stronger predictor of RKFD than albuminuria. Overall, 2.5% screened positive for dipstick protein Ն1 g/L at baseline; one of every 2.6 patients would have RKFD if all were followed with serial eGFR measurement. Overall, the screening strategy correctly identified progression status for 90.8% of patients, mislabeled 1.5% as RKFD, and missed 7.7% with eventual RKFD. Among those with risk factors (cardiovascular disease, age Ͼ60, diabetes, or hypertension), the probability of identifying RKFD from serial eGFR measurements increased from 13 to 44% after incorporating dipstick protein (Ն1g/L threshold). In summary, inexpensive screening with urine dipstick should allow primary care physicians to follow fewer patients with serial eGFR assessment but still identify those with rapid decline of kidney function.

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Rapid Decline of Kidney Function Increases Cardiovascular Risk in the Elderly

Cited by 237 publications

References 23 publications

NT-ProBNP and Troponin T and Risk of Rapid Kidney Function Decline and Incident CKD in Elderly Adults

NT-ProBNP and Troponin T and Risk of Rapid Kidney Function Decline and Incident CKD in Elderly Adults

Development and Validation of a Model to Predict 5-Year Risk of Death without ESRD among Older Adults with CKD

Dipstick Proteinuria as a Screening Strategy to Identify Rapid Renal Decline

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