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Glomerular filtration rate (GFR) is a key index of renal function. The classic method for assessing GFR is the clearance of inulin. Several current methods using isotopic (125I-iothalamate, 51Cr-EDTA, or 99Tc-DTPA) or nonisotopic (iohexol or iothalamate) markers are available. Clinically, GFR is estimated (eGFR) from serum creatinine or cystatin C levels. Estimated GFR based on creatinine and/or cystatin are less accurate than measured GFR. The creatinine-based equations calculate higher eGFR values (suggesting better kidney function) for black individuals. This upward adjustment for all black individuals is embedded in eGFR calculations on the belief of higher serum creatinine concentrations among black individuals than among white individuals. Thus "race-corrected" eGFR has become a widely accepted and scientifically valid procedure. However, race is not a genetic or biological category. Rather, race is a social construction defined by region-specific cultural and historical ideas. Furthermore, there is no accepted scientific method for classifying people as black or white individuals. Studies typically rely on self-identification of race. However, any person in the United States with any known black ancestry is considered to be a black individual. This is known as the "one-drop rule," meaning that a single drop of "black blood" makes anyone a black individual. It does not matter if an individual has 50%, 25%, 5%, or 0.5% African ancestry. The limited accuracy and reliability of this approach would not be allowed for any other scientific variable. Admixture and migration have produced such broad variations that race categories should not be used as experimental variables. [ABSTRACT FROM AUTHOR]

Background: This study examines the association between cystatin C (cysC) levels and risks of progression of frailty status or death in older men.Methods: Prospective study of 2,613 men without overt frailty aged 67 years and older enrolled in the MrOS ancillary sleep study. Baseline measurements included serum cysC, serum creatinine, and frailty status. Repeat frailty status, performed an average of 3.4 years later, was assessed as an ordinal outcome of robust, intermediate stage (prefrail), frail or dead.Results: Mean age was 75.7 years. Men with higher cysC were older and had a higher comorbidity burden. After adjusting for age, clinical site, and race, higher cysC was associated with nearly twofold greater odds of being classified as intermediate stage versus robust (OR quartile 4 vs 1; 1.82, 95% confidence interval [CI] 1.35-2.45), a threefold greater odds of frailty versus robust (OR quartile 4 vs 1; 3.13, 95% CI 2.03-4.82), and a more than fivefold greater odds of death versus robust (OR quartile 4 vs 1; 5.48, 95% CI 2.98-10.08). Results were similar for cysC-based estimated glomerular filtration rate (eGFR). This relationship was attenuated but persisted after adjusting for additional potential confounders including baseline frailty status, body mass index, smoking status, comorbidity burden, self-reported disability, and serum albumin. In contrast, neither serum creatinine nor creatinine-based eGFR was associated in a graded manner with higher risks of development of frailty or death.Conclusions: In this cohort of older men without overt frailty, higher cysC and cysC-based eGFR, but not creatinine or creatinine-based estimates of GFR, were associated with increased risks of frailty or death. These findings suggest that higher cysC level may be a promising biomarker for unsuccessful aging as manifested by increased risks of frailty and death. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is the leading cause of end stage renal disease. Cystatin C, a marker of early renal impairment has been shown to be associated with diabetes. However, it is not clear if cystatin C is associated with prediabetes, an early stage in the hyperglycemic continuum where prevention efforts have been shown to be effective in delaying or preventing the onset of diabetes. We examined 2,033 participants from the National Health and Nutrition Examination Survey 1999-2002, aged ≥20 years (female 47.2 %) who were free of diabetes mellitus, chronic kidney disease and with body mass index <30 kg/m. Prediabetes (n = 541) was defined as a 2-h glucose concentration of 140-199 mg/dL, or a fasting glucose concentration of 110-125 mg/dL, or an A1C value of 5.7-6.4 %. Cystatin C levels were categorized into gender-specific quartiles for analysis. Elevated levels of serum cystatin C were associated with prediabetes after adjusting for potential confounders including serum total cholesterol, systolic blood pressure, body mass index and C-reactive protein. Compared to those with cystatin C in the lowest quartile, the multivariable odds ratio (95 % confidence interval) of prediabetes among those in the highest quartile was 2.08 (1.09-3.97), p for trend = 0.02. Although, this association was stronger among women and non-Hispanic whites, there was no significant interaction by sex ( p = 0.1) or by race-ethnicity ( p = 0.6). Our findings suggest that elevated levels of serum cystatin C are associated with prediabetes in a nationally representative sample of non-obese US adults. [ABSTRACT FROM AUTHOR]

The Chronic Kidney Disease in Children study is a cohort of about 600 children with chronic kidney disease (CKD) in the United States and Canada. The independent variable for our observations was a measurement of glomerular filtration rate (GFR) by iohexol disappearance (iGFR) at the first two visits 1 year apart and during alternate years thereafter. In a previous report, we had developed GFR estimating equations utilizing serum creatinine, blood urea nitrogen, height, gender, and cystatin C measured by an immunoturbidimetric method; however, the correlation coefficient of cystatin C and GFR (−0.69) was less robust than expected. Therefore, 495 samples were re-assayed using immunonephelometry. The reciprocal of immunonephelometric cystatin C was as well correlated with iGFR as was height/serum creatinine (both 0.88). We developed a new GFR estimating equation using a random 2/3 of 965 person-visits and applied it to the remaining 1/3 as a validation data set. In the validation data set, the correlation of the estimated GFR with iGFR was 0.92 with high precision and no bias; 91 and 45% of eGFR values were within 30 and 10% of iGFR, respectively. This equation works well in children with CKD in a range of GFR from 15 to 75 ml/min per 1.73 m2. Further studies are needed to establish the applicability to children of normal stature and muscle mass, and higher GFR. [ABSTRACT FROM AUTHOR]

Abstract: Previous animal studies have suggested that mild reductions in renal function, even before the development of clinically recognized chronic kidney disease (CKD), are associated with hypertension. However, few studies have examined this hypothesis in humans. We therefore examined the association between serum cystatin C levels and hypertension among subjects without clinically recognized CKD in a large multiethnic sample of US adults. We examined the National Health and Nutrition Examination Survey 1999–2002 participants >20 years of age (n = 2583, 54.5% women) without clinically recognized CKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or microalbuminuria). Serum cystatin C levels were categorized into quartiles (<0.76 mg/L, 0.76–0.86 mg/L, 0.87–0.97 mg/L, and >0.97 mg/L). Hypertension was defined as blood pressure (BP)-reducing medication use or having systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg. Higher serum cystatin C levels were found to be associated with hypertension in women, but not men. After adjusting for age, race-ethnicity, education, smoking, alcohol intake, body mass index, diabetes, total cholesterol and C-reactive protein, the odds ratio (95% confidence interval) of hypertension comparing quartile 4 of cystatin C to quartile 1 (referent) was 2.04 (1.13–3.69); P trend = .02 in women and 0.86 (0.53–1.41); P trend = .51 in men. In a representative sample of US adults, mild reductions in kidney function as measured by higher serum cystatin C levels among subjects without clinically recognized CKD are associated with hypertension in women, but not men. [Copyright &y& Elsevier]

Background. It has been suggested that cystatin C may be a superior measure of estimated glomerular filtration rate (eGFR) than creatinine-based methods. We aimed to assess the utility of cystatin C for clinical triage in community-based settings.Methods. We identified cystatin C thresholds that maximize sensitivity and specificity (MaxSn + Sp) for predicting death and subsequently applied classification tree methodology considering serum creatinine, creatinine-based eGFR, urinary albumin–creatinine ratio and conventional modifiable risk factors to define subgroups, interactions and hierarchical ranks in fasting US adults (National Health and Nutrition Examination Survey 1988–94, followed through 2006).Results. A threshold cystatin C value of 0.94 mg/L exhibited the best maximum combined value of sensitivity and specificity for predicting death (MaxSn + Sp, Sn 0.64/Sp 0.78). When all variables were considered jointly in a classification tree, cystatin C and albumin–creatinine ratio were the primary mortality discriminators in subgroups that added up to 41 and 14% of the study population, respectively; serum creatinine and creatinine-based eGFR were non-discriminatory.Conclusion. Cystatin C may be useful for risk-based clinical triage in public health settings. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated an association between moderate kidney dysfunction and sudden cardiac death in people with cardiovascular disease.Methods and Results: The study was a longitudinal analysis among 4465 participants from the Cardiovascular Health Study without prevalent cardiovascular disease at baseline. Cystatin C and creatinine were measured from baseline sera. Sudden cardiac death (SCD) was defined as a sudden pulseless condition from a cardiac origin in a previously stable individual that occurred out of the hospital or in the emergency room. The association between cystatin C tertiles and SCD was determined with multivariate Cox proportional hazards. A similar analysis compared SCD incidence across creatinine-based estimated glomerular filtration rate (eGFR) tertiles. Over a median follow-up of 11.2 years, 91 adjudicated SCD events occurred. The annual incidence of SCD events increased across cystatin C tertiles: 10 events per 10 000 person years in tertile 1, 25 events per 10 000 person years in tertile 2, and 32 events per 10 000 person-years in the highest cystatin C tertile. These associations persisted after multivariate adjustment: hazards ratio=2.72; 95% confidence interval, 1.44 to 5.16 in tertile 2 and hazards ratio=2.67; 95% confidence interval, 1.33 to 5.35 in tertile 3. After multivariate adjustment, the rate of SCD also increased in a linear distribution across creatinine-based eGFR tertiles: 15 events per 10 000 person-years in tertile 1, 22 events per 10 000 person-years in tertile 2, and 27 events per 10 000 person-years in tertile 3. No significant associations, however, remained between creatinine-based eGFR and SCD after multivariable adjustment.Conclusions: Impaired kidney function, as measured by cystatin C, has an independent association with SCD risk among elderly persons without clinical cardiovascular disease. [ABSTRACT FROM AUTHOR]

The article reports on the study that examines the slop of annual decline in estimated glomerular filtration rate (eGFR) using both serum creatinine and cystatin rates in the American older people. The study, conducted by Internal Medicine Dena E. Rifkin and colleagues, reveals that the association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, and prevalent coronary heart disease. It also suggests that rapid decline in eGFR is associated with an increased risk of cardiovascular and all-acute cause mortality in older adults.

Abstract: Background: Although high body mass index (BMI) is a risk factor for hypertension, diabetes, and cardiovascular disease, limited data exist on the association of overweight and obesity with early stages of kidney disease. Methods: Cross-sectional data for 5083 participants of the nationally representative Third National Health and Nutrition Examination Survey with an estimated glomerular filtration rate≥60 mL/min/1.73 m2 without micro- or macroalbuminuria were analyzed to determine the association between BMI and elevated serum cystatin C. Normal weight, overweight, class I obesity, and class II to III obesity were defined as a BMI of 18.5 to 24.9 kg/m2, 25.0 to 29.9 kg/m2, 30.0 to 34.9 kg/m2, and≥35.0 kg/m2, respectively. Elevated serum cystatin C was defined as≥1.09 mg/L (≥99th percentile for participants 20-39 years of age without diabetes, hypertension, micro- or macroalbuminuria, or stage 3-5 chronic kidney disease). Results: The age-standardized prevalence of elevated serum cystatin C was 9.6%, 12.9%, 17.4%, and 21.5% among adults of normal weight, overweight, class I obesity, and class II to III obesity, respectively (P trend < .001). After multivariate adjustment for demographics, behaviors, systolic blood pressure, and serum biomarkers, and compared with participants of normal weight, the odds ratio (95% confidence interval) of elevated serum cystatin C was 1.46 (1.02-2.10) for overweight, 2.36 (1.56-3.57) for class I obesity, and 2.82 (1.56-5.11) for class II to III obesity. Conclusion: A graded association exists between higher BMI and elevated serum cystatin C. Further research is warranted to assess whether reducing BMI favorably affects elevated serum cystatin C and the development of chronic kidney disease. [Copyright &y& Elsevier]

The article discusses the effect of Cystatin C on successful aging. A study was conducted to determine the relation between kidney function and aging success for a six-year follow-upcardiovascular health study in the United States. The level of Cystatin C of the Two thousand one hundred forty participants have been observed. The result of the study showed that even if the patient possess a relatively normal kidney function, the presence of cystatin C in a higher level, the greater unsuccessful aging it entails.

The article presents a study that determines the effectiveness of Cystatin C level as an indication of kidney function among human immunodeficiency virus (HIV) patients. The study involves the evaluation of the kidney functions in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) cohort which was composed of 1008 HIV infected individuals and 290 representative from the Coronary Artery Risk Development in Young Adults (CARDIA) study in the United States. It was found out that Cystatin C level was elevated among HIV infected patients and that its measurement is useful in identifying the risk for kidney and cardiovascular disease.

Patients, like those with ESRD, who have lost the ability to filter excess proteins from their bodies are at risk to develop beta-2-microglobin amyloidosis, also known as dialysis-related amyloidosis (DRA). When the kidneys do not work efficiently, a protein called beta-2-microglobulin can build up in the blood. Eventually, these molecules can form large deposits and potentially damage surrounding tissues. Currently, dialyzer membranes do not effectively remove these large molecules and, as the blood levels become elevated, deposits begin forming in bone, joints, and tendons resulting in pain and/or stiffness. Unfortunately, there is no known cure for DRA, although attempts are being made to develop dialyzer membranes that can more efficiently remove beta-2-microglobulin from the blood. Implications for practice include early diagnosis, patient teaching, optimal pain management and fall risk management.