Cystatin C versus Creatinine in Determining Risk Based on Kidney Function

Shlipak, Michael G.; Matsushita, Kunihiro; Ärnlöv, Johan; Inker, Lesley A.; Katz, Ronit; Polkinghorne, Kevan R.; Rothenbacher, Dietrich; Sarnak, Mark J.; Astor, Brad C.; Coresh, Josef; Levey, Andrew S.; Gansevoort, Ron T.

doi:10.1056/nejmoa1214234

Cited by 762 publications

(687 citation statements)

References 48 publications

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“…These findings highlight the importance of considering non-GFR determinants of kidney function measurements, in particular muscle mass, for examining outcomes such as frailty. Of note, eGFR SCr may not be an accurate measurement of kidney function in elderly adults with low muscle mass, and alternative markers of glomerular filtration, such as cystatin C, may be particularly important in this setting (17). Similar to the 2012 CKD-EPI cystatin C equation, the CKD-EPI eGFR SCr equation was not developed in an elderly cohort, and therefore the age coefficient may not be accurate in elderly cohorts such as ours.…”

Section: Discussionmentioning

confidence: 87%

Kidney Function and Prevalent and Incident Frailty

Dalrymple¹,

Katz²,

Rifkin³

et al. 2013

Clinical Journal of the American Society of Nephrology

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118

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SummaryBackground and objectives Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants.Design, setting, participants, & measurements CHS enrolled community-dwelling adults age $65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR cys ). Secondary analyses examined eGFR using serum creatinine (eGFR SCr ). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity.Results The mean age was 75 years and the median eGFR cys was 73 ml/min per 1.73 m 2 . Among participants with an eGFR cys ,45 ml/min per 1.73 m 2 , 24% had prevalent frailty. In multivariable analysis and compared with eGFR cys $90 ml/min per 1.73 m 2 , eGFR cys categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR cys categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR SCr were not associated with higher risk of prevalent or incident frailty.Conclusions In community-dwelling elders, lower eGFR cys was associated with a higher risk of prevalent and incident frailty whereas lower eGFR SCr was not. These findings highlight the importance of considering non-GFR determinants of kidney function.

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Section: Discussionmentioning

confidence: 87%

Kidney Function and Prevalent and Incident Frailty

Dalrymple¹,

Katz²,

Rifkin³

et al. 2013

Clinical Journal of the American Society of Nephrology

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123

118

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“…112 , 113 Cystatin C is freely filtered by the glomeruli, reabsorbed by tubular epithelial cells, and broken down; therefore, increased concentrations of Cystatin C in serum is related to impaired glomerular filtration. 114 −116 It is also associated with increased left ventricular mass, a precursor to cardiac left ventricular hypertrophy (LVH) 117 , which is associated with increased risk of hypertension.…”

Section: Discussionmentioning

confidence: 99%

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

et al. 2018

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Background: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring. Results: The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs). Conclusions: We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in metabolite production of short chain fatty acids. These results suggest that early-life exposure to hyperandrogenemia in daughters of women with PCOS may lead to long-term alterations in gut microbiota and cardiometabolic function.

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“…Indeed, eGFRcys has been shown to have stronger associations with prognosis than eGFRcr, even in the general population. 29 …”

Section: Discussionmentioning

confidence: 99%

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study

Ballew

Chen

Daya

et al. 2017

American Journal of Kidney Diseases

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104

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Background Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Study Design Observational study. Setting & Participants 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011–2013). Predictor Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr) and serum cystatin C (eGFRcys) and urine albumin-creatinine ratio (ACR). Outcomes Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). Results In total, 341 participants (7%) were classified as frail, 1475 (30%) had eGFRcr <60 ml/min/1.73 m2, 2480 (50%) had eGFRcys <60 ml/min/1.73 m2, and 1006 (20%) had albuminuria ≥30 mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys <60 ml/min/1.73 m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and ACR. Frail individuals with eGFRcr 60–<75 ml/min/1.73 m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45–<60, 32% to 30–<45, and 3% to <30 ml/min/1.73 m2). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of non-frail), including classes requiring kidney clearance (e.g., digoxin) and associated with falls and subsequent complications (e.g., hypnotic/sedatives, anticoagulants). Limitations Cross-sectional study design. Conclusions Frail individuals had a high prevalence of reduce kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr. Given the substantial medication burden and uncertainty in CKD classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population.

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Cystatin C versus Creatinine in Determining Risk Based on Kidney Function

Cited by 762 publications

References 48 publications

Kidney Function and Prevalent and Incident Frailty

Kidney Function and Prevalent and Incident Frailty

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study

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