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.
Wednesday
Saturday
Interruption of antiretroviral therapy is associated with increased plasma cystatin C.
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.
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.
Wednesday
Variation of serum creatinine, cystatin C, and creatinine clearance tests in persons with normal renal function
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
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
Thursday
Cystatin C and Creatinine in an HIV Cohort: The Nutrition for Healthy Living Study
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
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
Tuesday
Homocysteine, Cystatin C and N-Terminal-Pro Brain Natriuretic Peptide Vascular Risk Markers in Elderly Patients with Mental Illness
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.
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.
Wednesday
Serum cystatin C level for better assessment of glomerular filtration rate in cystic fibrosis patients treated by amikacin.
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.
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.
Tuesday
Clinical significance of cardiac troponins I and T in acute heart failure
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
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
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