CYSTATIN C RESEARCH

Cystatin C Level as a Predictor of Death and Cardiovascular Events After Liver Transplantation

2011-11-15T10:08:00.000-06:00

Abstract
Background
The diagnosis of renal failure is important in cirrhosis. Cystatin C (Cys) has been suggested not only to be a sensitive marker of renal function, but also a stronger predictor of the risk of death and cardiovascular events in heart failure. Our aims were to investigate plasma Cys concentrations for the detection of moderately impaired renal function and its association with mortality and cardiovascular events among cirrhotic patients after liver transplantation (OLT).

Methods
Clinical and biochemical data, including Cys levels, were analyzed in 99 cirrhotic candidates for OLT. We recorded cardiovascular events.

Results
Receiver-operator characteristics curves showed a similar efficiency to detect a creatinine clearance <60 mL/min per 1.73m2 (Cys = 0.753; creatinine [Cr] = 0.799; glomerular filtration rate [GFR, Cockcroft–Gault formula] = 0.842; urea = 0.823; P = .001). However, at cutoff concentrations of 1.3 mg/dL, Cr showed great specificity (96%) but poor sensitivity (13%), while the sensitivity of Cys was superior (83%) with moderate specificity (55%) at a cutoff of 1400 ng/mL. Over a median follow-up of 2.7 years, 14 patients developed a cardiovascular event, including, 11 who displayed Cys levels >1400 ng/mL before OLT, showing a significant difference (P < .05) compared to patients who showed no cardiovascular event. Kaplan–Meier analysis Cys discriminated significantly better than the Model for End-Stage Liver Disease score between survivors and nonsurvivors (P < .05).

Conclusion
Cys determinations could be a valuable tool for early diagnosis of renal dysfunction among cirrhotic patients. Furthermore, it may predict the risk of death and cardiovascular events after OLT.

Transplantation Proceedings
Volume 43, Issue 3, April 2011, Pages 732-734

Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation

2011-04-04T13:02:00.000-05:00

Abstract
Background. The plasma level of cystatin C is a better marker than plasma creatinine for successful aging. It has been assumed that the advantage of cystatin C is not only due to it being a better marker for glomerular filtration rate (GFR) than creatinine, but also because an inflammatory state of a patient induces a raised cystatin C level. However, the observations of an association between cystatin C level and inflammation stem from large cohort studies. The present work concerns the cystatin C levels and degree of inflammation in longitudinal studies of individual subjects without inflammation, who undergo elective surgery.

Methods. Cystatin C, creatinine, and the inflammatory markers CRP, serum amyloid A (SAA), haptoglobin and orosomucoid were measured in plasma samples from 35 patients the day before elective surgery and subsequently during seven consecutive days.

Results. Twenty patients had CRP-levels below 1 mg/L before surgery and low levels of the additional inflammatory markers. Surgery caused marked inflammation with high peak values of CRP and SAA on the second day after the operation. The cystatin C level did not change significantly during the observation period and did not correlate significantly with the level of any of the four inflammatory markers. The creatinine level was significantly reduced on the first postoperative day but reached the preoperative level towards the end of the observation period.

Conclusion. The inflammatory status of a patient does not influence the role of cystatin C as a marker of successful aging, nor of GFR.

Anders Grubb1, Jonas Björk2, Ulf Nyman3, Joanna Pollak1,5, Johan Bengzon4, Gustav Östner1 & Veronica Lindström1
Department of Clinical Chemistry, Lund University Hospital, Lund, Sweden

Competence Centre for Clinical Research, Lund University Hospital, Lund, Sweden

Department of Radiology, University of Lund, Lasarettet Trelleborg, Trelleborg, Sweden

Department of Neurosurgery, Lund University Hospital, Lund, Sweden

Department of Laboratory Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland

Serum Cystatin C Is an Early Predictive Biomarker of Acute Kidney Injury after Pediatric Cardiopulmonary Bypass

2010-09-15T16:05:00.000-05:00

Background and objectives: Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). Serum creatinine (SCr), the current standard, is an inadequate marker for AKI since a delay occurs before SCr rises. Biomarkers that are sensitive and rapidly measurable could allow early intervention and improve patient outcomes. We investigated the value of serum cystatin C as an early biomarker for AKI after pediatric CPB.

Design, setting, participants, & measurements: We analyzed data from 374 prospectively enrolled children undergoing CPB. Serum samples were obtained before and at 2, 12, and 24 hours after CPB. Cystatin C was quantified by nephelometry. The primary outcome was AKI, defined as a 50% increase in SCr. Secondary outcomes included severity and duration of AKI, hospital length of stay, and mortality. A multivariable stepwise logistic regression analysis was used to assess predictors of AKI.

Results: One hundred nineteen patients (32%) developed AKI using SCr criteria. Serum cystatin C concentrations were significantly increased in AKI patients at 12 hours after CPB (P < 0.0001) and remained elevated at 24 hours (P < 0.0001). Maximal sensitivity and specificity for prediction of AKI occurred at a 12-hour cystatin C cut-off of 1.16 mg/L. The 12-hour cystatin C strongly correlated with severity and duration of AKI as well as length of hospital stay. In multivariable analysis, 12-hour cystatin C remained a powerful independent predictor of AKI.

Conclusion: Serum cystatin C is an early predictive biomarker for AKI and its clinical outcomes after pediatric CPB

Catherine D. Krawczeski*, Rene G. Vandevoorde, Thelma Kathman, Michael R. Bennett, Jessica G. Woo, Yu Wang, Rachel E. Griffiths*, and Prasad Devarajan
* The Heart Institute and the Divisions of Nephrology and Hypertension and Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio

Cystatin C and Sudden Cardiac Death Risk in the Elderly

2010-02-22T15:49:00.000-06:00

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 10000 person years in tertile 1, 25 events per 10000 person years in tertile 2, and 32 events per 10000 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 10000 person-years in tertile 1, 22 events per 10000 person-years in tertile 2, and 27 events per 10000 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.

Rajat Deo, MD; Nona Sotoodehnia, MD, MPH; Ronit Katz, DPhil; Mark J. Sarnak, MD, MS; Linda F. Fried, MD, MPH; Michel Chonchol, MD; Bryan Kestenbaum, MD; Bruce M. Psaty, MD, PhD; David S. Siscovick, MD, MPH and Michael G. Shlipak, MD, MPH
From the Division of Cardiology (R.D.), University of Pennsylvania, Philadelphia;

the Division of Cardiology (N.S.), University of Washington, Seattle; Collaborative Health Studies Coordinating Center (R.K.), University of Washington, Seattle; the Division of Nephrology (M.J.S.), Tufts Medical Center, Boston, Mass;

The Renal-Electrolyte Division (L.F.F.), University of Pittsburgh School of Medicine, and the Renal Section, VA Pittsburgh Healthcare System, Pittsburgh, Pa; the Division of Renal Diseases and Hypertension (M.C.), University of Colorado Health Sciences Center, Denver; the Division of Nephrology (B.K.), University of Washington, Veterans Affairs Puget Sound Health Care System, Seattle, Wash; the Cardiovascular Health Research Unit (B.M.P., D.S.S.), Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle; Center for Health Studies, Group Health, Seattle, Wash; and General Internal Medicine Section (M.G.S.), Veterans Affairs Medical Center, San Francisco, Calif, and Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco.

Kidney function estimated from serum creatinine and cystatin C and peripheral arterial disease

2009-12-18T14:49:00.001-06:00

Aims: Serum cystatin C, a novel marker of kidney function, is reported to be superior to serum creatinine as a risk factor for atherosclerotic disease, but associations may vary across vascular beds.

Methods and results: A cross-sectional study of chronic kidney disease (CKD) and peripheral arterial disease (PAD) in 3089 adult participants aged 40+ from the 1999–2002 National Health and Nutrition Examination Survey (NHANES). Kidney function, assessed by estimated glomerular filtration rate (eGFR), was determined from serum creatinine and cystatin C using established equations. Peripheral arterial disease defined by an ankle brachial index <0.90.

Glomerular filtration rate estimated using cystatin C was more strongly associated with PAD compared with eGFR using serum creatinine before and after multivariable adjustment. Further, after adjustment for cystatin C, kidney function based on serum creatinine was no longer significantly associated with PAD.

However, cystatin C remained significantly associated with PAD even after adjustment for GFR estimated by serum creatinine. Compared with optimal kidney function (eGFRserum creatinine 60, eGFRcystatin C >90), the odds ratio for PAD was 3.11 (95% confidence interval 1.26–7.64) for preclinical CKD (eGFRserum creatinine 60, eGFRcystatin C <76.7) and 5.07 (3.01–8.52) for ‘confirmed’ CKD (eGFRserum creatinine <60, eGFRcystatin C <60).

Conclusion: Chronic kidney disease was strongly and independently associated with PAD. Cystatin C was a more potent marker of lower extremity PAD when compared with the serum creatinine equation currently used in clinical practice. Our results suggest that cystatin C may have clinical utility when combined with serum creatinine in evaluation of individuals who may have PAD.

Elizabeth Selvin1,2,*, Anna Köttgen1 and Josef Coresh1,2
1 Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument Street, Suite 2-600, Baltimore, MD 21287, USA
2 Division of General Internal Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

Kidney Function Decline Increases Risk Of Heart Failure And Premature Death

2009-11-18T15:51:00.003-06:00

ScienceDaily (Nov. 9, 2009) — cystatin C Research: Declining kidney function is linked to a higher risk of heart failure, heart attack, peripheral arterial disease, and early death in individuals with or without kidney disease, according to a pair of studies appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN).

The findings indicate that poor kidney function may raise an individual's risk for cardiovascular complications. To evaluate heart health, clinicians should factor in not only their patients' current level of kidney function, but also changes in kidney function over time.

Chronic kidney disease (CKD) patients have an increased risk of developing and dying from cardiovascular disease, but the links between kidney function and heart health are not well understood. Michael Shlipak, MD (San Francisco VA Medical Center and University of California, San Francisco), Mark Sarnak, MD (Tufts-New England Medical Center), and their colleagues studied clinical information from individuals who were enrolled in the Cardiovascular Health Study, a community-based study of elderly people.

Using a new blood test of kidney function, called cystatin C , the researchers looked for links between changes in kidney function during a period of seven years with the incidence of heart failure, heart attack, stroke, and peripheral arterial disease (obstruction of large arteries in the arms and legs) during the subsequent eight years. Among 4,378 eligible participants in the study, those with rapid kidney decline (1,083 patients) demonstrated a 32% increased risk of experiencing heart failure, a 48% increased risk of having a heart attack, and a 67% increased risk of developing peripheral arterial disease. (They did not have an increased risk of suffering a stroke.)

Importantly, researchers identified an association between rapid kidney function decline and heart complications in patients with and without CKD. Treatments that slow the decline of kidney function and stabilize it in the normal range, before kidney disease develops, could have substantial health benefits.

In the second study, Kunihiro Matsushita, MD, PhD, Josef Coresh, MD, PhD (Johns Hopkins University), and their colleagues examined the effects of changes in kidney function in 13,029 participants of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based sample of individuals aged 45 to 64 years. The researchers followed patients from 1987 to 2006, and monitored participants' kidney function at the start of the study, three years into the study, and nine years into the study. Investigators found that a large drop in kidney function over time -- regardless of the initial level of function -- increased one's risk of developing heart disease and of dying early. Patients whose kidney function dropped by more than 5.6% per year demonstrated a 30% increased risk of developing heart disease and a 22% increased risk of dying prematurely compared to patients with stable kidney function.

Physicians regularly monitor kidney function in elderly patients and patients with diabetes and hypertension to optimize the dose of prescription drugs excreted by the kidneys. This study indicates that physicians who detect a decline in patients' kidney function over time should view this as a sign of increased risk of heart disease and premature death.

"Our results suggest there may be clinical value in sequential kidney function data, often measured in routine care, even among individuals with mildly reduced kidney function," the authors wrote.

Dr. Shlipak's and Dr. Sarnak's co-authors include Ronit Katz, DPhil, Bryan Kestenbaum, MD, David Siscovick, MD (University of Washington); Linda Fried, MD (VA Pittsburgh Healthcare System); Anne Newman, MD (University of Pittsburgh); and Dena Rifkin, MD (Tufts-New England Medical Center). Dr. Matsushita's and Dr. Coresh's co-authors include Elizabeth Selvin, PhD, Lori Bash, PhD, Brad Astor, PhD (Johns Hopkins University), and Nora Franceschini, MD (University of North Carolina).

cystatin C and CRP:Change of glomerular filtration rate in healthy adults with aging

2009-08-20T10:36:00.000-05:00

AIM: In order to determine the relationship between glomerular filtration rate (GFR) and age, the associated factors, and the accurate method of GFR in healthy adults, we conducted a cross-sectional study in community-dwelling adults in Beijing.

METHODS: Renal function of 201 clinically healthy subjects was determined using technetium-99 m-labelled diethylene triamine pentacetic acid ((99m)Tc-DTPA). Estimated GFR was calculated with the Cockcroft-Gault (CG) equation, abbreviated Modification of Diet in Renal Disease (MDRD) equation, and plasma clearance of creatinine (Ccr). Serum cystatin C, biomarkers of inflammatory and endothelial cells were analyzed as well. Protein intake, carotid artery intima-media thickness and plaque formation were assayed as well.

RESULTS: Glomerular filtration rate was negatively associated with age and the correlation coefficient for (99m)Tc-GFR, CG-GFR, MDRD-GFR, Ccr were -0.643, -0.736, -0.55 and -0.619, respectively (P < 0.001), while the correlation coefficient between cystatin C and age was 0.681 (P < 0.001). Estimated GFR were associated with measured GFR, and the correlation coefficient for Ccr, CG-GFR and MDRD-GFR were 0.813, 0.582 and 0.418, respectively (P < 0.001). The area under the receiver-operator curve of Ccr was larger, CG was smaller while MDRD was the smallest, and the difference was significant (P < 0.001). So a predicted equation was presented by cystatin C and C-reactive protein for the elderly.

CONCLUSION: In the clinically healthy adults, GFR declined with age. MDRD and CG equation are not suitable to estimate GFR in healthy adults. The predicted equation established by cystatin C and C-reactive protein may be more accurate.

Sun X, Chen Y, Chen X, Wang J, Xi C, Lin S, Liu X.
Institute of Nephrology of PLA, General Hospital of PLA, Beijing, China

Cystatin C in cerebrospinal fluid as a biomarker of ALS.

2009-05-20T16:07:00.000-05:00

Department of Neurology, Graduate School of Medicine, Hokkaido University, Sapporo City, Hokkaido, Japan. tujitti@jb3.so-net.ne.jp

Amyotrophic lateral sclerosis (ALS) is diagnosed on the basis of progressive symptoms in both the upper and lower motor neurons. Because there are no specific biomarkers for ALS, it is difficult to diagnose this disease in its early stages. Cerebrospinal fluid (CSF) samples were obtained from 14 patients in the early stages of ALS, from 13 with polyneuropathy, and from 16 with other neurological disorders. The concentration of cystatin C in the CSF was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. The concentration of cystatin C in the CSF was significantly lower in ALS patients than in the control subjects who were patients with polyneuropathy or other neurological diseases (patients with ALS, polyneuropathy, and other diseases exhibited 5.5 +/- 0.3, 6.7 +/- 0.4, and 6.9 +/- 0.3 mg/L cystatin C, respectively; ALS patients vs. control subjects: p = 0.014 and ALS patients vs. polyneuropathy patients: p = 0.024). Cystatin C may be a useful biomarker of ALS and can be used to distinguish between ALS and polyneuropathy.

Interruption of antiretroviral therapy is associated with increased plasma cystatin C.

2009-01-03T12:29:00.002-06:00

CLINICAL SCIENCE

AIDS. 23(1):71-82, January 2, 2009.
Mocroft, Amanda a; Wyatt, Christina b; Szczech, Lynda c; Neuhaus, Jacquie d; El-Sadr, Wafaa e; Tracy, Russell f; Kuller, Lewis g; Shlipak, Michael h; Angus, Brian i,j; Klinker, Harting k; Ross, Michael b;

Abstract:
Background: Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4+ cell count (drug conservation) had altered cystatin C levels compared with those randomized to continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C.

Methods: Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the drug conservation and viral suppression groups, respectively. Logistic regression was used to model the odds of at least 0.15 mg/dl increase in cystatin C (1 SD) in the first month after randomization, adjusting for demographic and clinical characteristics.

Results: At randomization, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug conservation and viral suppression arms, respectively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl increase in cystatin C in the drug conservation and viral suppression arms, respectively (P = 0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, participants in the viral suppression arm had significantly reduced odds of at least 0.15 mg/dl increase in cystatin C in the first month (odds ratio 0.42; 95% confidence interval 0.23-0.74, P = 0.0023).

Conclusion: These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function.

Variation of serum creatinine, cystatin C, and creatinine clearance tests in persons with normal renal function

2008-07-30T16:28:00.001-05:00

Background
To determine the potential sensitivity of several renal function tests for detecting early changes in renal function, we compared the within-individual (W-I) variation over 5 months of serum creatinine, serum cystatin C, and creatinine clearance.

Methods
On 31 healthy subjects, blood and timed urine specimens were collected once each month to get 6 collections. Creatinine (enzymatic) in serum and urine and cystatin C (immunonephelometric) in serum were measured and glomerular filtration rate (GFR) by creatinine clearance and the Modification of Diet in Renal Disease (MDRD) equation were calculated. To compare W-I variations between different creatinine methods, we also measured creatinine by both enzymatic and kinetic alkaline picrate methods on 15 sets of frozen samples.

Results
For the 31 volunteers, the mean W-I variations for serum creatinine (5.8%) and cystatin C(5.4%) were both much lower than the W-I variation of creatinine clearance (18.7%). As expected, the MDRD GFR had a similar W-I variation (6.7%) to that of serum creatinine and its values were markedly different than GFR by creatinine clearance. On the 15 sets of frozen samples, the W-I variation of creatinine measured by the enzymatic method (CV 5.2%) was slightly less than by the picrate method (CV 6.2%).

Conclusions
The low W-I variation of both serum cystatin C and serum creatinine suggests that serial measurements of either would detect a changes in renal function earlier than would GFR by creatinine clearance or MDRD equation, which allows reporting only for GFRs < 60 ml/min/1.7 m2. While we measured only creatinine clearance, the large variability, difficulty, and cost of all clearance measurements make them impractical for routine monitoring of patients.

ARTICLE

Cystatin C and Creatinine in an HIV Cohort: The Nutrition for Healthy Living Study

2008-07-24T16:39:00.002-05:00

Background
Human immunodeficiency virus (HIV)-infected persons have an increased risk of chronic kidney disease (CKD). Serum creatinine level may underestimate the prevalence of CKD in subjects with decreased lean body mass or liver disease. Level of serum cystatin C, an alternative kidney function marker, is independent of lean body mass.

Study Design
Cross-sectional.

Setting & Participants
250 HIV-infected subjects on highly active antiretroviral therapy in the Nutrition for Healthy Living (NFHL) cohort; 2,628 National Health and Nutrition Examination Survey (NHANES) 2001-2002 subjects.

Predictors & Outcomes
Comparison of serum creatinine levels in NFHL to those in NHANES subjects; comparison of CKD in NFHL subjects ascertained using serum creatinine versus cystatin C levels.

Measurements
Standardized serum creatinine, serum cystatin C, glomerular filtration rate (GFR) estimated from serum creatinine and cystatin C levels.

Results
Creatinine levels were lower in NFHL than NHANES subjects despite greater rates of hepatitis, diabetes, and drug use (mean difference, −0.18 mg/dL; P < 0.001 adjusted for age, sex, and race). Of NFHL subjects, only 2.4% had a creatinine-based estimated GFR less than 60 mL/min/1.73 m2, but 15.2% had a cystatin-based estimated GFR less than 60 mL/min/1.73 m2.

Limitations
GFR was estimated rather than measured. Other factors in addition to GFR may affect creatinine and cystatin C levels. Measurements of proteinuria were not available.

Conclusions
Serum creatinine levels may overestimate GFRs in HIV-infected subjects. Kidney disease prevalence may be greater than previously appreciated.

ARTICLE

Homocysteine, Cystatin C and N-Terminal-Pro Brain Natriuretic Peptide Vascular Risk Markers in Elderly Patients with Mental Illness

2008-07-22T15:57:00.002-05:00

Background:

There is increasing evidence that vascular disease contributes to cognitive impairment and dementia. Clarification of the role of vascular risk factors in dementia is important because most are modifiable, in contrast to other risk factors such as age and genetics.

Methods:
In 451 patients with mental illness we have investigated three biochemical markers related to vascular disease, total plasma homocysteine (tHcy), cystatin C, and N-terminal-pro brain natriuretic peptide (NT-proBNP), and their association with vascular disease, diagnoses, and brain imaging findings (CT). Results: Plasma tHcy, serum cystatin C, and serum N-terminal-pro brain natriuretic peptide (NT-proBNP)showed significantly increased frequencies of elevated levels in patients with vascular disease, in patients with a pathological CT finding indicating cerebrovascular disease, and in patients above 75 years of age.

Conclusion:
It is possible that the control of conventional vascular risk factors and therapy could be guided by the level of plasma tHcy, serum cystatin C, and serum NT-proBNP. Patients with an elevation of any of these three parameters could be selected for a lower target level of risk factors such as blood pressure, hyperlipidemia etc. than conventional target levels.

Serum cystatin C level for better assessment of glomerular filtration rate in cystic fibrosis patients treated by amikacin.

2008-07-16T14:11:00.002-05:00

BACKGROUND AND OBJECTIVE:
Monitoring of renal function in cystic fibrosis (CF) patients is essential. The dosage regimen of amikacin is regularly modified according to the patient's glomerular filtration rate (GFR). The aim of the study was to evaluate the use of
cystatin C (CyC) for monitoring amikacin therapy along with other markers of renal tubular and glomerular function, and damage [N-acetyl-beta-d glucosaminidase (NAG), creatinine level and creatinine clearance].

METHODS:
We compared the GFR, estimated from the serum concentrations of creatinine (Cockcroft-Gault formula) and cystatin C (CyC) (Grubb's formula). Seventy-one patients (mean age 12 years; range 4-28 years) with CF were treated by intermittent intravenous infusion of amikacin. Tubular nephrotoxicity was investigated by measurement of urine NAG/urine creatinine ratio (U-NAG/U-creatinine). Concentrations of all markers were measured before starting amikacin therapy and at days 3, 5, 7, 10 and 12. Fluorescence polarization analysis, turbidimetry, enzymatic phototometric creatinine deaminase method and fluorimetry were used for determination of serum amikacin, serum CyC, creatinine and urine NAG activity. Receiver operating characteristic (ROC) analysis was performed to assess the influence of GFR estimated from serum creatinine and serum CyC for the prediction of amikacin clearance during aminoglycoside therapy.

RESULTS:
Significant differences in the rate of U-NAG/U-creatinine were noted before and after treatment with amikacin (P < 0.001). Serum creatinine levels and creatinine clearance at the end of amikacin therapy (12th day) did not show any significant differences in comparison with the levels measured before the start of therapy (0th day). At days 5, 7, 10 and 12, serum CyC levels showed a significant elevation (P < 0.001), and cystatin C (CyC) clearance showed a significant decrease (P < 0.001) in comparison with the levels measured at day 0. The ratio of amikacin clearance/creatinine clearance decreased with therapy whereas the amikacin clearance/CyC and amikacin clearance/CyC clearance increased.

CONCLUSION: We showed that the rate of U-NAG/U-creatinine is a suitable marker for monitoring tubular nephrotoxicity in CF patients. Serum creatinine and estimated creatinine clearance are modest predictors of GFR in CF patients. cystatin C (CyC) appears to be a better marker of GFR than serum creatinine concentration or creatinine clearance in our study. Serum CyC levels and CyC clearance showed greater ability to predict amikacin clearance during therapy than creatinine clearance.

Clinical significance of cardiac troponins I and T in acute heart failure

2008-07-15T16:01:00.003-05:00

Background
Elevated cardiac troponin (cTn) levels are relatively common in acute heart failure (AHF).

Aims
To evaluate the prevalence and prognostic significance of elevated cTnI and cTnT in AHF.

Methods
FINN-AKVA is a prospective, multicenter study in AHF. In this analysis, 364 non-ACS patients with measurements of cTnI and cTnT taken on admission and 48 h thereafter were analyzed.

Results
Of the 364 AHF patients, 51.1% had cTnI and 29.7% cTnT levels above the cut-off value. Six-month all-cause mortality was 18.7%. Both cTnI (OR 2.0, 95% CI 1.2–3.5, p = 0.01) and cTnT (OR 2.6, 95% CI 1.5–4.4, p = 0.0006) were associated with adverse outcome. The mortality risk was proportional to the magnitude of cTn release. On multivariable analysis, Cystatin C (OR 6.3, 95% CI 3.2–13, p < 0.0001), logNT-proBNP (OR 1.4, 95% CI 1.0–1.8, p = 0.03) and systolic blood pressure on admission (/10 mm Hg increase, OR 0.9, 95% CI 0.8–0.9, p = 0.0004) were independent risk markers, whereas the troponins were not significantly associated with increased mortality.

Conclusions
cTn elevations are frequent in AHF patients without ACS. cTnI is more often elevated than cTnT. Both cTnI and cTnT elevations are associated with increased mortality proportional to the degree elevation but they do not act as independent risk markers.

ARTICLE

Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD.

2008-07-01T14:29:00.004-05:00

Serum cystatin C was proposed as a potential replacement for serum creatinine in glomerular filtration rate (GFR) estimation. We report the development and evaluation of GFR-estimating equations using serum cystatin C alone and serum cystatin C, serum creatinine, or both with demographic variables.

STUDY DESIGN: Test of diagnostic accuracy.

SETTING & PARTICIPANTS: Participants screened for 3 chronic kidney disease (CKD) studies in the United States (n = 2,980) and a clinical population in Paris, France (n = 438).

REFERENCE TEST: Measured GFR (mGFR).

INDEX TEST: Estimated GFR using the 4 new equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both with age, sex, and race. New equations were developed by using linear regression with log GFR as the outcome in two thirds of data from US studies. Internal validation was performed in the remaining one third of data from US CKD studies; external validation was performed in the Paris study.

MEASUREMENTS: GFR was measured by using urinary clearance of iodine-125-iothalamate in the US studies and chromium-51-EDTA in the Paris study. Serum cystatin C was measured by using Dade-Behring assay, standardized serum creatinine values were used.

RESULTS: Mean mGFR, serum creatinine, and serum cystatin C values were 48 mL/min/1.73 m(2) (5th to 95th percentile, 15 to 95), 2.1 mg/dL, and 1.8 mg/L, respectively. For the new equations, coefficients for age, sex, and race were significant in the equation with serum cystatin C, but 2- to 4-fold smaller than in the equation with serum creatinine. Measures of performance in new equations were consistent across the development and internal and external validation data sets. Percentages of estimated GFR within 30% of mGFR for equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both levels with age, sex, and race were 81%, 83%, 85%, and 89%, respectively. The equation using serum cystatin C level alone yields estimates with small biases in age, sex, and race subgroups, which are improved in equations including these variables.

LIMITATIONS: Study population composed mainly of patients with CKD.

CONCLUSIONS: Serum cystatin C level alone provides GFR estimates that are nearly as accurate as serum creatinine level adjusted for age, sex, and race, thus providing an alternative GFR estimate that is not linked to muscle mass. An equation including serum cystatin C level in combination with serum creatinine level, age, sex, and race provides the most accurate estimates.

NGAL (neutrophil gelatinase-associated lipocalin) and cystatin C: Are they good predictors of contrast nephropathy after percutaneous coronary interve

2008-06-16T15:13:00.003-05:00

The aim of the study was to assess whether neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin C could predict contrast-induced nephropathy in non-diabetic patients (n = 60, mean age 60 ± 11 years) with normal serum creatinine undergoing elective PCI. We found a significant rise in serum NGAL after 2, 4 and 8 h, and in urinary NGAL after 4, 8 and 24 h after PCI. Cystatin C rose significantly 8 and 24 h after the procedure. Prevalence of CIN was 10%. We found 90% sensitivity and 74% specificity of serum and 76% sensitivity and 80% specificity of urinary NGAL increase. NGAL may represent a sensitive early biomarkers of renal impairment after PCI.

H. Bachorzewska-Gajewskaa, 1, J. Malyszkoa, b, , 1, E. Sitniewskaa, J.S. Malyszkoa, B. Poniatowskia, K. Pawlaka and S. Dobrzycki

ARTICLE

Serum Cystatin C and Increased Coronary Heart Disease Prevalence in US Adults Without Chronic Kidney Disease

2008-05-23T15:51:00.006-05:00

Previous studies indicated that serum cystatin C, a marker of renal function, was associated with cardiovascular disease (CVD). However, few data about this association are available for persons without chronic kidney disease or albuminuria. Data from 4,991 subjects in the 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. Subjects were categorized into quartiles of serum cystatin C and compared for prevalence of CVD. CVD was defined as a history of myocardial infarction, angina, or stroke. After age standardization, prevalences of CVD from the lowest to highest quartile of serum cystatin C were 6.0%, 8.8%, 11.8%, and 16.7% (p-trend = 0.006). Also, age-standardized prevalences of myocardial infarction across quartiles of serum cystatin C were 1.9%, 4.4%, 6.6%, and 8.6%; age-standardized prevalences of angina were 2.4%, 4.4%, 4.2%, and 7.1%; and age-standardized prevalences of stroke were 2.5%, 1.6%, 3.5%, and 4.4% (each p-trend <0.05). Each 1-SD higher serum cystatin C level was associated with a multivariate prevalence ratio of CVD of 1.55 (95% confidence interval [CI] 1.13 to 2.13), and multivariate-adjusted prevalence ratios were 1.44 (95% CI 1.01 to 2.07), 1.64 (95% CI 1.02 to 2.64), and 1.65 (95% CI 1.06 to 2.56) for myocardial infarction, angina, and stroke, respectively. In conclusion, a graded association exists between higher serum cystatin C and increased CVD prevalence in patients without established chronic kidney disease.

Paul Muntner PhDa, , , Devin Mann MD, MSb, Jonathan Winston MDb, Sameer Bansilal MDc and Michael E. Farkouh MD, MScc

Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, New York USA.

Department of Medicine, Mount Sinai School of Medicine, New York, New York USA.

The Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Mount Sinai School of Medicine, New York, New York

Small kidney changes linked to high blood pressure

2008-04-03T12:26:00.005-05:00

NEW YORK (Reuters Health) - Changes in kidney function appear to influence the occurrence of high blood pressure in individuals without overt kidney or cardiovascular disease , according to a report in the Annals of Internal Medicine.

The results suggest that early-stage kidney damage plays an important role in the development of high blood pressure, also referred to as hypertension, Dr. Bryan Kestenbaum, from the University of Washington in Seattle, and associates state.

The researchers evaluated the kidney function of 2,767 subjects who participated in the Multi-Ethnic Study of Atherosclerosis, a community-based study focusing on symptom-free cardiovascular disease. None of the subjects had hypertension, cardiovascular disease or symptoms of kidney disease when the study began.

The main outcome measure was the development of hypertension, defined as a blood pressure of at least 140/90 mm Hg, or the use of antihypertensive medications. Kestenbaum's group also monitored levels of cystatin C, a blood protein filtered out of the blood by the kidneys that is commonly used as a measure of kidney function. High cystatin C levels after some heart attacks predict a poor patient outcome.

Nearly 20 percent of the subjects developed hypertension after an average of 3.1 years, the report indicates.

When the investigators analyzed the data, taking into account other factors that may have contributed to an increase in blood pressure, they found that for each 15-nmol/L rise in cystatin C levels, there was a 15-percent increase in the risk of developing hypertension.

By contrast, the subjects with the highest ratios of albumin - creatinine , which is also associated with irregular kidney function and a risk of cardiovascular disease, was not associated with an increased risk of hypertension when compared with those with the lowest levels.

While the findings suggest that variation in kidney function influences the risk of hypertension, the reason for such variation is unclear, the authors note.

Some explanations are that these individuals have been born with an abnormal number of nephrons, basic structure, or they were exposed early in life to heavy metals, such as lead, which both can cause kidney disease.

SOURCE: Annals of Internal Medicine. April 1, 2008.

Cystatin C and other cardiovascular markers in hypertension

2008-01-29T14:25:00.001-06:00

BACKGROUND AND OBJECTIVE: The aim of the study was to assess the relationship of cystatine C to other cardiovascular risk factors in hypertension .

PATIENTS AND METHOD: Cross-sectional study in hypertensive outpatients with normal creatinine values (< 1.6 mg/dl for males and < 1.4 mg/dl for women). Cystatin C was analyzed by immunonephelometry.

RESULTS: 283 patients (47% male) were evaluated. Cystatin C values were 0.65 (0.27) mg/l (median, intercuartile range, percentile 70 = 0.76 mg/l), and were correlated to the estimated glomerular filtration rate (GFR) (ml/min/1.73 m2), C reactive protein , and urinary albumin excretion (UAE). In multiple regression analysis the GFR was the most significant factor and explained 38% of cystatine C variability. GFR, (odds ratio [OR] = 5.84; 95% confidence interval [CI], 2.27-15.03; p < 0.001), age (OR = 1.05; 95% CI, 1.02-1.08; p < 0.001), and CRP (OR = 2.03; 95% CI, 1.07-3.84; p = 0.03), but not UAE >= 30 mg/24 h, were independent factors related to the presence of high levels (> 0.76 mg/l) of cystatine C in a logistic regression analysis. 58% of patients with UAE >= 30 mg/24h had cystatin C values < 0,76 mg/l.

CONCLUSIONS: In hypertensive patients, the GFR is the most important factor related to cystatine C values. Increased levels of cystatine C do not correspond to UAE augmentation.

Med Clin (Barc). 2008 Jan 19;130(1):1-5.Unidad de Hipertensión Arterial y Riesgo Vascular. Servicio de Medicina Interna. Hospital de Sagunto. Agencia Valenciana de Salud. Valencia. España

CST3 CYSTATIN C

2007-12-20T10:43:00.001-06:00

GeneID: 1471

Cystatin 3 , usually called Cystatin C (also CST3 and Gamma trace) is a serum protein used mainly as a measure of glomerular filtration rate . It is a single 120-residue polypeptide belonging to the type 2 cystatin gene family. Studies have shown that Cystatin C allows a more precise testing of kidney function than creatinine.

The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors , while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes the most abundant extracellular inhibitor of cysteine proteases , which is found in high concentrations in biological fluids and is expressed in virtually all organs of the body. A mutation in this gene has been associated with amyloid angiopathy . Expression of this protein in vascular wall smooth muscle cells is severely reduced in both atherosclerotic and aneurysmal aortic lesions, establishing its role in vascular disease.