Association between Albuminuria, Kidney Function, and Inflammatory Biomarker Profile in CKD in CRIC

Gupta, Jayanta; Mitra, Nandita; Kanetsky, Peter A.; Devaney, Joe; Wing, Maria R.; Reilly, Muredach P.; Shah, Vallabh O.; Balakrishnan, Vaidyanathapura S.; Guzmán, Nicolás; Girndt, Matthias; Periera, Brian G.; Feldman, Harold I.; Kusek, John W.; Joffe, Marshall M.; Raj, Dominic S.

doi:10.2215/cjn.03500412

Cited by 427 publications

(339 citation statements)

References 55 publications

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“…Immune cells dominate the atherosclerotic lesion and exhibit evidence of activation. Findings from the Chronic Renal Insufficiency Cohort study showed that plasma levels of pro‐inflammatory cytokines and positive acute‐phase proteins were higher in subjects with lower levels of kidney function 12. We showed that specific inflammatory biomarkers are associated with cardiac geometry and risk of atrial fibrillation in patients with CKD 13, 14.…”

mentioning

confidence: 67%

Janus Face of Coronary Artery Disease and Chronic Kidney Disease

Barrows

Raj

2016

JAHA

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confidence: 67%

Janus Face of Coronary Artery Disease and Chronic Kidney Disease

Barrows

Raj

2016

JAHA

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“…Thus, function of interstitial fibroblasts producing erythropoietin may be impaired in this process. In addition, albuminuria is associated with low‐grade inflammation,31 a condition tightly linked to anemia 9…”

Section: Discussionmentioning

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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“…The utility of GFR as a biomarker and its sensitivity to inflammatory physiology has not been considered before in healthy adults. More typically, the clinical research has focused on patient populations already in need of hemodialysis or with chronic renal disease (Gupta et al 2012;Pertosa et al 2000). The ability to assess kidney function via creatinine and other biochemical indices from blood and urine specimens provides a unique tool for evaluating population health and for those interested in discerning the causes of disparities in health.…”

Section: Discussionmentioning

confidence: 99%

“…However, one can anticipate some national differences, given known differences in pro-inflammatory physiology and cardiovascular disease across these two populations (Coe et al 2011), which are likely to impact kidney function. Specifically, our analyses focused on IL-6, a pro-inflammatory cytokine readily measured in blood and known to affect renal function, and CRP, a commonly employed test in the clinical setting, because both indices have been associated with a reduced GFR and kidney disease (Sinha et al 2014;Tbahriti et al 2013;Gupta et al 2012).…”

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confidence: 99%

Aging and low-grade inflammation reduce renal function in middle-aged and older adults in Japan and the USA

Costello-White

Ryff

Coe

2015

AGE

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The objective of this study was to investigate the effects of low-grade inflammation on age-related changes in glomerular filtration rate (GFR) in middleaged and older white Americans, African-Americans, and Japanese adults. Serum creatinine, C-reactive protein (CRP), and interleukin-6 (IL-6) levels were determined for 1570 adult participants in two surveys of aging in the USA and Japan (N = 1188 and 382, respectively). Kidney function declined with age in both countries and was associated with IL-6 and CRP. IL-6 and CRP also influenced the extent of the arithmetic bias when calculating the GFR using the chronic kidney disease epidemiology (CKD-EPI) formula with just serum creatinine. Younger African-Americans initially had the highest GFR but showed a steep age-related decrement that was associated with elevated inflammation. Japanese adults had the lowest average GFR but evinced a large effect of increased inflammatory activity when over 70 years of age. Importantly, our results also indicate that low-grade inflammation is important to consider when evaluating kidney function solely from serum creatinine.

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Association between Albuminuria, Kidney Function, and Inflammatory Biomarker Profile in CKD in CRIC

Abstract: SummaryBackground and objectives Increased risk of mortality in patients with CKD has been attributed to inflammation. However, the association between kidney function, albuminuria, and biomarkers of inflammation has not been examined in a large cohort of CKD patients.

Cited by 427 publications

References 55 publications

Janus Face of Coronary Artery Disease and Chronic Kidney Disease

Janus Face of Coronary Artery Disease and Chronic Kidney Disease

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

Aging and low-grade inflammation reduce renal function in middle-aged and older adults in Japan and the USA

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