Rapid Kidney Function Decline and Mortality Risk in Older Adults

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

doi:10.1001/archinte.168.20.2212

Cited by 314 publications

(344 citation statements)

References 29 publications

(33 reference statements)

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“…Similar to previous work, in which adjustments were made for either the first or last eGFR in the antecedent period, we found a U-shaped relationship between eGFR slope and subsequent ACM risk. 11,[13][14][15][16] Direct, quantitative comparison between the results of these investigations and our own investigations are hampered by different indices of renal function change, different antecedent periods, and the use of rates, in some studies, rather than HRs to quantify mortality risk. However, Turin et al 12 found adjusted HRs for ACM of 1.14 and 1.68 for 4-ml/min per 1.73 m 2 per year declining and increasing slopes, respectively, compared with subjects with a stable eGFR value in a Canadian population-based study.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a previous study reported an association between higher ACM risk and positive eGFR slope using cystatin C as a filtration marker, although cystatin C levels are less affected by muscle mass than creatinine, suggesting that a rising eGFR may reflect a rising true GFR. 16 A rising prior true GFR may be caused by recovery from acute kidney disease associated with an acute illness, and it was the latter that was responsible for the observed increase in ACM risk rather than the rising true GFR per se. Finally, a rising true GFR could be seen with hyperfiltration in remnant nephrons, which could be associated with subsequent kidney disease progression, but it is not generally hypothesized to be associated with mortality.…”

Section: Discussionmentioning

confidence: 99%

“…Whether these observations are generalizable is uncertain, because they were on the basis of data from single centers 13,14 and/or cohorts with mean baseline eGFR values of $50 ml/min per 1.73 m 2 . [11][12][13][14][15][16] Improvement in eGFR in a CKD population might show different associations with mortality than that in a general population cohort. In addition, the U-shaped association might be driven by confounding factors, such as weight loss or heart failure.…”

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confidence: 99%

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Past Decline Versus Current eGFR and Subsequent Mortality Risk

Naimark

Grams

Matsushita

et al. 2015

JASN

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A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope ,25 ml/min per 1.73 m 2 per year, whereas 7% and 4% had a slope .5 ml/min per 1.73 m 2 per year, respectively. Compared with a slope of 0 ml/min per 1.73 m 2 per year, a slope of 26 ml/min per 1.73 m 2 per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m 2 per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus ,3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Past Decline Versus Current eGFR and Subsequent Mortality Risk

Naimark

Grams

Matsushita

et al. 2015

JASN

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“…The candidate variables included demographic variables (age, sex, and race), comorbid diseases (history of coronary heart disease [CHD], heart failure [HF], stroke, hypertension, or diabetes mellitus), tobacco use (never, former, or current), physical examination measures (systolic BP and body mass index in kilograms per meter 2 ), and laboratory values (eGFR [6], UACR, total cholesterol, and serum albumin). Although not available in the Health ABC Study, we also assessed change in eGFR over 4 years in the CHS, because a trajectory of change in kidney function is often used clinically to assess rate of progression of kidney disease and might also predict death (10). Medication use (antihypertensive and lipidlowering medications) was determined by participant pill bottles and recorded by study personnel.…”

Section: Candidate Predictor Variablesmentioning

confidence: 99%

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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“…Rapid loss of kidney function has been shown to predict cardiovascular events independent of baseline GFR [43].…”

Section: Cox Regression Models For Associations Of U-cysc Egfr Cysc mentioning

confidence: 99%

Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort

Helmersson‐Karlqvist¹,

Ärnlöv²,

Carlsson³

et al. 2014

Atherosclerosis

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Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort. Methods:The association between u-CysC and cardiovascular mortality was investigated in a Swedish community-based cohort of 604 men aged 78 years. During follow-up (mean 6.7 years), 203 participants died, of which 90 due to cardiovascular causes.Results: High u-CysC (>0.029 mg/mmol Cr) was associated with a more than 2-fold risk of cardiovascular death (multivariable hazard ratio for quintile 5 vs. 1: 2.5, 95% CI 1.2-5.2, p<0.05) in Cox regression models independent of cardiovascular risk factors, glomerular filtration rate (eGFR) and urinary Albumin. Participants with low eGFR (≤60 mL/min), albuminuria (≥ 3 mg/mmol Cr) and high u-CysC (>0.029 mg/mmol Cr) combined had a significantly higher cardiovascular mortality risk compared to participants with one or two of these biomarkers normal (hazard ratio 15, 95% CI: 6.7-36, P<0.001, compared to all three biomarkers normal). Conclusions

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Rapid Kidney Function Decline and Mortality Risk in Older Adults

Cited by 314 publications

References 29 publications

Past Decline Versus Current eGFR and Subsequent Mortality Risk

Past Decline Versus Current eGFR and Subsequent Mortality Risk

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

Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort

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