Albuminuria and Estimated Glomerular Filtration Rate Independently Associate with Acute Kidney Injury

Grams, Morgan E.; Astor, Brad C.; Bash, Lori D.; Matsushita, Kunihiro; Wang, Yaping; Coresh, Josef

doi:10.1681/asn.2010010128

Cited by 151 publications

(137 citation statements)

References 50 publications

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“…Almost all participants with undetectable urine albumin (n=2373; 99.5%) were categorized as ACR <10 mg, followed by ACR 10 to 29 mg (n=12), and ACR >30 mg/g (n=1). eGFR and ACR were classified into 3 categories of eGFR ≥90, 60 to 89, and 30 to 59 mL/min/1.73 m 2 and ACR <10, 10 to 29, and ≥30 mg/g, according to the clinical guidelines and literature 3, 21, 22…”

Section: Methodsmentioning

confidence: 99%

Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC (Atherosclerosis Risk in Communities) Study

Ishigami

Grams

Naik

et al. 2018

JAHA

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BackgroundReduced estimated glomerular filtration rate (eGFR) and elevated urinary albumin‐to‐creatinine ratio (ACR) individually increase risk of cardiovascular disease (CVD). We hypothesized that these associations are stronger among people with abnormal (both low and high) hemoglobin levels.Methods and ResultsUsing 5801 participants with available hemoglobin measures of the ARIC (Atherosclerosis Risk in Community) study in 1996–1998, we explored the cross‐sectional association of eGFR and ACR with hemoglobin levels and their longitudinal associations with CVD (heart failure, coronary heart disease, and stroke) risk through 2013. At baseline, 8.8% had anemia (<13 g/dL in men and <12 g/dL in women) and 7.2% had high hemoglobin (≥16 g/dL in men and ≥15 g/dL in women). The adjusted prevalence ratio of anemia was 2.12 (95% confidence interval, 1.59–2.82) for eGFR 30 to 59 compared with ≥90 mL/min per 1.73 m2 and 1.45 (1.07–1.95) for ACR ≥30 compared with <10 mg/g. ACR ≥30 mg/g was also associated with high hemoglobin (prevalence ratio, 1.57 [1.12–2.19] compared with <10 mg/g). During follow‐up, there were 1069 incident CVDs among 5098 CVD‐free participants at baseline. In multivariable Cox models, lower eGFR, higher ACR, and anemia were each independently associated with CVD risk, with the association of low eGFR being slightly stronger in anemia (P‐for‐interaction, 0.072). There was no hemoglobin‐ACR interaction; however, when CVD subtypes were analyzed separately, risk of coronary heart disease and stroke associated with high ACR was slightly stronger in high hemoglobin (P‐for‐interaction, 0.074).ConclusionsKidney function, albuminuria, and anemia were correlated and independently associated with CVD risk. Correlation and potential interaction for atherosclerotic CVD between albuminuria and high hemoglobin deserve further investigation.

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Section: Methodsmentioning

confidence: 99%

Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC (Atherosclerosis Risk in Communities) Study

Ishigami

Grams

Naik

et al. 2018

JAHA

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“…Patients hospitalized for AKI are at higher risk of developing ESRD and death (2,3). In addition, 46% of individuals who develop AKI will not fully recover and will be left with CKD, and 58% of patients will be hospitalized again within 1 year (1,2).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have also suggested that estimated GFR based on cystatin C or combined creatinine-cystatin C (eGFR CrCyC ) provides a more accurate measure of kidney function and may be more strongly associated with cardiovascular outcomes and all-cause mortality (10)(11)(12)(13)(14)(15). Two recent studies of middle-aged individuals have also suggested that UACR may be associated with AKI; however, there are few studies that have focused exclusively on elderly individuals or evaluated all three biomarkers (FGF-23, UACR, and eGFR CrCyC ) (2,3,16). We therefore evaluated FGF-23, UACR, and eGFR CrCyC , three different manifestations of kidney health, as risk factors for AKI hospitalizations in the CHS, a community-dwelling population of older adults.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor-23 and the Long-Term Risk of Hospital-Associated AKI among Community-Dwelling Older Individuals

Brown¹,

Katz²,

Ix³

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives AKI occurs frequently in older persons. Elevated circulating fibroblast growth factor-23 (FGF-23), a known marker of impaired mineral metabolism, may also reflect tubular dysfunction and risk of AKI. This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-tocreatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFR CrCyC ), as risk factors for AKI in elderly individuals.Design, setting, participants, & measurements Plasma FGF-23, UACR, and eGFR CrCyC were measured in 3241 community-dwelling elderly individuals in the Cardiovascular Health Study. Hospitalization for AKI was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Associations of each biomarker with AKI were evaluated using Cox proportional hazards models adjusted for demographics, cardiovascular risk factors, and biomarkers of kidney function.Results The mean participant age was 78 years; 60% of participants were women and 16% were African Compared with the highest quartile, the lowest quartile of eGFR CrCyC (,57 ml/min per 1.73 m 2 ) was associated with AKI with an HR of 2.15 (95% CI, 1.21 to 3.82).Conclusions FGF-23 adjusted for albuminuria, cardiovascular disease risk factors, and baseline eGFR is independently associated with a higher risk of AKI hospitalizations in community-dwelling elderly individuals. Further studies to understand the nature of this association are warranted.

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“…These variables, however, still do not completely capture burden of illness, because physiologic and laboratory variables were not included. Data on proteinuria, a potent risk factor for both AKI (12) and CKD progression (13), were lacking. Moreover, severity of illness is underestimated using diagnostic codes (14), and cardiovascular disease prediction is improved by using variables such as hemoglobin A1C rather than diabetes status alone (15).…”

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confidence: 99%

“…CKD is the most important prognostic factor for an AKI episode (12,20). Unless there is a prolonged ischemic event (e.g., cardiac arrest) with obvious acute tubular necrosis, teasing out the contribution of the episode of AKI toward further renal injury is nearly impossible.…”

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confidence: 99%

Is it AKI or Nonrecovery of Renal Function That Is Important for Long-Term Outcomes?

Coca

2013

Clinical Journal of the American Society of Nephrology

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Epidemiologic research examines relationships between exposures and outcomes, with the ultimate goal of improving patient outcomes. To affect a change and improve outcomes, the relationships described must not only be causal, but modifiable (1). Numerous studies have described independent associations between AKI and subsequent CKD and mortality (2). The majority of these studies focused on one dimension of AKI, "severity," via the magnitude of peak rise in serum creatinine (2-4). Recently, some investigations have examined long-term outcomes associated with other dimensions of AKI including duration (5) and kidney function after peak (i.e., recovery) (6-8).Pannu and colleagues performed a retrospective analysis of 190,962 Albertans to assess the modifying effect of renal recovery on the relationship between AKI and long-term outcomes (9). They found that participants who did not recover to within 25% of baseline GFR within 90 days of AKI were at higher risk for doubling of creatinine and ESRD, and for all-cause mortality. It is a well done study with several strengths. First, this is a large population-based study with appropriate inclusion/exclusion criteria, which limited selection bias. Participants were required to have serum creatinine measurement within 180 days before, $1 measurement during, and at least one measurement after hospitalization; only those who survived at least 90 days post-AKI were included in the analyses. Second, the AKI definition used for the primary exposure was appropriate (Kidney Disease Improving Global Outcomes stage 2). Third, the recovery definition was valid and sound (post-AKI creatinine value within 25% of baseline within 90 days, and sensitivity analyses performed using 10% increments to find the threshold for the association between recovery and outcomes). Finally, the dataset provided sufficient outcomes for robust analyses and multivariable adjustment, and there was adequate length of follow-up (median 3 years).Unlike other studies that have examined the association between reversible AKI and long-term outcomes (6,7), Pannu and colleagues treated reversible AKI (instead of the non-AKI group) as the referent group for their analyses. In the follow-up period, 27% of those who did not experience AKI recovery developed doubling of serum creatinine/ESRD compared with 7.5% in those that recovered (adjusted hazard ratio of approximately 4). These data certainly quantify the public health effect of irreversible AKI in a broad, nonselected population. Because nonrecovery from AKI results in a substantial healthcare burden, these data can help clinicians make plans for follow-up with patients, their primary care providers, and nephrologists after discharge (10).The authors did not make any claims about causality in their paper. Looking forward, however, it is important to determine whether we can affect and improve these outcomes. Reiterating the above, the relationship between the exposure and outcome must be causal in order to modify risk. Are the relationships between AKI and lo...

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Albuminuria and Estimated Glomerular Filtration Rate Independently Associate with Acute Kidney Injury

Cited by 151 publications

References 50 publications

Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC (Atherosclerosis Risk in Communities) Study

Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC (Atherosclerosis Risk in Communities) Study

Fibroblast Growth Factor-23 and the Long-Term Risk of Hospital-Associated AKI among Community-Dwelling Older Individuals

Is it AKI or Nonrecovery of Renal Function That Is Important for Long-Term Outcomes?

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