In critically ill patients sudden changes in glomerular filtration rate (GFR) are not instantly followed by parallel changes in serum creatinine. The aim of the present study was to analyze the utility of serum cystatin C as a marker of renal function in these patients.
Serum creatinine, serum cystatin C and 24-hour creatinine clearance (CCr) were determined in 50 critically ill patients (age 21–86 years; mean Acute Physiology and Chronic Health Evaluation II score 20 ± 9). They did not have chronic renal failure but were at risk for developing renal dysfunction. Serum cystatin C was measured using particle enhanced immunonephelometry. Twenty-four-hour body surface adjusted CCr was used as a control because it is the 'gold standard' for determining GFR.
Serum creatinine, serum cystatin C and CCr (mean ± standard deviation [range]) were 1.00 ± 0.85 mg/dl (0.40–5.61 mg/dl), 1.19 ± 0.79 mg/l (0.49–4.70 mg/l), and 92.74 ± 52.74 ml/min per 1.73 m2 (8.17–233.21 ml/min per 1.73 m2), respectively. Our data showed that serum cystatin C correlated better with GFR than did creatinine (1/cystatin C versus CCr: r = 0.832, P < 0.001; 1/creatinine versus CCr: r = 0.426, P = 0.002). Cystatin C was diagnostically superior to creatinine (area under the curve [AUC] for cystatin C 0.927, 95% confidence interval 86.1–99.4; AUC for creatinine 0.694, 95% confidence interval 54.1–84.6). Half of the patients had acute renal dysfunction. Only five (20%) of these 25 patients had elevated serum creatinine, whereas 76% had elevated serum cystatin C levels (P = 0.032).
Cystatin C is an accurate marker of subtle changes in GFR, and it may be superior to creatinine when assessing this parameter in clinical practice in critically ill patients.
This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m2 estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m2 estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.
Cystatin C; Diabetic Nephropathies; Albuminuria
Even mild renal impairment is associated with increased atherosclerosis and cardiovascular mortality. Cystatin C, a novel measure of renal function, is more sensitive than conventional creatinine-based measures for the detection of subtle renal impairment. Increased cystatin concentrations are also associated with cardiovascular risk, independent of conventional measures of renal function. We examined the hypothesis that cystatin C is elevated in systemic lupus erythematosus (SLE) and is associated with coronary atherosclerosis.
We measured serum cystatin C, creatinine, TNF-α, IL-6, coronary artery calcium score (CACS), Framingham risk score (FRS), Modified Diet in Renal Disease estimated glomerular filtration rate (MDRD-eGFR) and other clinical parameters in 118 patients with SLE and 83 control subjects. The independent association between concentrations of cystatin C and SLE was evaluated using multivariable linear regression models, and the relationship between renal measures and coronary calcium was assessed with multivariable proportional odds logistic regression models.
Cystatin C, but not other measures of renal function, was significantly higher in patients with SLE than controls (1.09[Interquartile range, IQR: 0.85–1.28]mg/L vs. 0.89 [IQR: 0.76–0.99]mg/L; P<0.001 after adjusting for age, race and sex and MDRD-eGFR). Cystatin C was significantly associated with SLICC (P=0.04), ESR (P<0.001), CRP (P=0.04), TNF-α (P=0.008) and IL-6 (P=0.01) after adjustment for age, race and sex. Cystatin C was not significantly correlated with coronary calcium score in SLE (rho=0.096, P= 0.31) and the association remained non-significant after adjustment for age, race, sex and Framingham risk score (P=0.99).
Cystatin C was higher in patients with SLE than control subjects even after adjustment for conventional measures of renal function. Cystatin C was significantly correlated with several markers of inflammation in SLE but was not associated with coronary atherosclerosis. Subtle renal dysfunction does not appear to be directly associated with accelerated atherosclerosis in SLE.
cystatin C; systemic lupus erythematosus; renal function; atherosclerosis; Inflammation
The low molecular weight protein cystatin C produced by all nucleated cells and eliminated by glomerular filtration is of special benefit as a marker of renal function. A study was therefore undertaken to investigate whether serum cystatin C could be used as a marker to identify patients with moderately impaired renal function. A cross-sectional descriptive hospital based study was carried out and serum cystatin C was measured in fifty subjects aged 12 to 74 years with a 24 hr creatinine clearance estimation done at the same time. The gold standard creatinine clearance was used to compare the predicted glomerular filtration rate measured using serum cystatin C. Predicted glomerular filtration rate gave a sensitivity of 82% and specificity of 68% with a diagnostic cut-off value of 1.25mg/L cystatin C for identification of patients with moderately impaired renal function with a single random blood sample.
Cystatin C; Creatinine; Glomerular Filtration Rate; Moderately Impaired Renal Function
Glomerular filtration rate (GFR) is widely estimated by serum creatinine based equations such as Cockcroft-Gault (CG) standardized for body surface, and an abbreviated formula derived from MDRD (modification of diet in renal disease) study. However, some studies suggested that creatinine based estimation of GFR formula can be replaced by cystatin C based formula.
The aim of this study was to determine whether cystatin C based equation could be used as an indicator for renal function in hemodialysis patients compared to MDRD equation; and whether cystatin C, a dialyzable molecule, was related to Kt/V, the marker for dialysis adequacy.
Patients and Methods
In this cross-sectional study, 98 patients on chronic hemodialysis were included. Plasma levels of urea and creatinine were measured before and after dialysis, and cystatin C was measured before dialysis. GFR was calculated and compared.
The mean age of patients was 55.50 ± 16.10 (24-86) years and 66 cases were male (67.3%). The GFR was estimated at 6.05 ± 2.36 and 5.83 ± 2.19 cc/min by MDRD and cystatin C based formulas, respectively, with a significant correlation (r = 0.51; P < 0.001). Serum cystatin C level was 9.74 ± 2.47 mg/L which showed significant reverse correlation with both MDRD (r = -0.46; P < 0.001) and cystatin C based formulas (r = -0.87; P < 0.001). Neither creatinine nor serum cystatin C showed correlation with Kt/V, as the marker of dialysis adequacy.
Serum cystatin C may be considered as an indicator of renal function in patients under maintenance hemodialysis.
Cystatin C; Glomerular Filtration Rate; Creatinine; Renal Dialysis
In clinical practice the glomerular filtration rate (GFR) is estimated from serum creatinine-based equations like the Cockcroft-Gault formula (C&G) and Modification of Diet in Renal Disease formula (MDRD). Recently, serum cystatin C-based equations, the newer creatinine formula (The Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)), and equation that use both serum creatinine and cystatin C (CKD-EPI creatinine & cystatin formula) were proposed as new GFR markers. Present study compares serum creatinine-based equations, combined (including both serum creatinine and cystatin C) equation, and serum simple cystatin C formula (100/serum cystatin C) against 51CrEDTA clearance in 113 adult overweight Caucasians with diabetes mellitus type 2 (DM2) and chronic kidney disease (CKD). The results of present study demonstrated that the simple cystatin C formula could be a useful tool for the evaluation of renal function in overweight patients with DM2 and impaired kidney function in daily clinical practice in hospital and especially in outpatients. Despite the advantages of the simple cystatin C formula, cystatin C-based equations cannot completely replace the “gold standard” for estimation of the GFR in a population of DM2 patients with CKD, but may contribute to a more accurate selection of patients requiring such invasive and costly procedures.
Cystatin C is an emerging parameter for the assessment of renal allograft function. The objective of the study was to compare the efficacy of serum cystatin C (SCys) with the established parameter serum creatinine (SCr) in the assessment of renal function in renal transplant recipients (RTR). The glomerular filtration rate (GFR) of 30 renal transplant patients and 29 control subjects was determined using 99mTc Diethylene-triamine-penta-acetate (DTPA) method. SCr was measured using an automated Jaffe’s assay and SCys was measured using latex particle enhanced turbidimetric immuno assay (PETIA). The modification of diet in renal disease (MDRD) formula was used to calculate GFR from SCr, while the Le Bricon formula was used to derive GFR based on SCys. Statistical analysis was performed using MedCalc software. SCr and SCys levels were significantly higher, while DTPA clearance was significantly lower in RTR (P < 0.0001) when compared with controls. The correlation coefficient (r value) between calculated GFR based on MDRD method and DTPA clearance was 0.343 (P = 0.06) while the calculated GFR based on Le Bricon formula was 0.694 (P < 0.001). The results have shown that SCys is a better parameter than SCr in assessing renal function in RTR. The inclusion of SCys as an additional parameter would certainly help in detection of even a marginal decline in renal function and also in adjusting the dosage of immunosuppressive drugs.
Cystatin C; Creatinine; DTPA; Glomerular filtration rate
Cystatin C is a marker of kidney function that may also be associated with inflammation. In this study, we compared the relative strengths of association of cystatin C and estimated glomerular filtration rate (eGFR) with inflammatory biomarkers.
We measured serum cystatin C and creatinine in 990 outpatients with coronary artery disease enrolled in the Heart and Soul Study. GFR was estimated (eGFR) by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. We compared the associations of serum cystatin C and eGFR with C-reactive protein (CRP) and fibrinogen, after adjustment for 24 h creatinine clearance.
Cystatin C concentrations had moderate correlations with CRP (r=0.15, P<0.001) and fibrinogen (r=0.26, P<0.0001); eGFR had similar correlations with CRP (r=−0.17, P=0.01) and fibrinogen (r=−0.25, P<0.001) among persons with eGFR≤60 ml/min, but had no association with either biomarker among those with eGFR>60 ml/min (r=0.04, P=0.32; r=−0.03, P=0.38). Quartiles of cystatin C were strongly and directly associated with CRP (P=0.02) and fibrinogen (P<0.007) after multivariate adjustment. However, these associations disappeared after adjustment for creatinine clearance (P=0.26 and 0.23, respectively).
Cystatin C concentrations have moderate associations with CRP and fibrinogen that are not independent of creatinine clearance. Although a gold standard of kidney function is lacking, this analysis suggests that cystatin C captures an association of mildly impaired kidney function with increased inflammation.
chronic kidney disease; coronary artery disease; C-reactive protein; creatinine clearance; cystatin-C; inflammation
Markers of renal function (glomerular filtration rate (GFR)) are frequently used in the Swedish health care. GFR is usually estimated based on plasma creatinine concentration, but plasma cystatin C concentration, creatinine clearance, iohexol clearance, and 51Cr-EDTA clearance are also used. These markers are all part of the daily patient care, but there is little specific information on the clinical use of these markers. The aim of this study was to compare the use of these various GFR markers in different parts of Sweden and potential changes over time.
Retrospective study using questionnaires to collect information for the years 2006–2009 divided per county on the specific use of GFR markers with type of test reports.
Plasma/serum creatinine concentration (96%) is by far the dominating GFR marker in Sweden, while cystatin C concentration (3.5%), creatinine clearance (0.1%), iohexol clearance (0.1%), and 51Cr-EDTA clearance (0.1%) are less frequently used. The use of GFR markers, including creatinine, continues to increase on a national level with the exception of creatinine clearance and 51Cr-EDTA clearance. There were considerable variations between different counties in the use of GFR markers and the type of test reports that the laboratories provided.
The inter-county variations of GFR markers used in Sweden are large and indicate that savings associated with optimized test utilization in this regard could be substantial. Regional habits and traditions are likely to influence the variations in GFR marker use.
Clinical chemistry tests; diagnostic tests; family practice; glomerular filtration rate; health care costs; physician's practice patterns
Compared with controls, HIV-infected persons have a greater prevalence of kidney disease as assessed by high levels of cystatin C and albuminuria, but not as assessed by creatinine level. However, the clinical importance of elevated cystatin C and albuminuria in the HIV-infected population has not been studied.
We conducted an observational cohort study to determine the association of kidney disease (measured by albuminuria, cystatin C, and serum creatinine) with mortality.
Setting & Participants
922 HIV-infected persons enrolled in the FRAM (Fat Redistribution and Metabolic Change in HIV infection) study.
Serum cystatin C and serum creatinine were used to estimate glomerular filtration rate (eGFR). Albuminuria was defined as a positive urine dipstick (≥1+) or a urine albumin-creatinine ratio > 30 mg/g.
At baseline, reduced kidney function (eGFRSCysC <60 mL/min/1.73m2) or albuminuria was present in 28% of participants. After five years of follow-up, mortality was 48% among those with both eGFRSCysC <60 mL/min/1.73m2 and albuminuria, 23% in those with eGFRSCysC <60 mL/min/1.73m2 alone, 20% in those with albuminuria alone, and 9% in those with neither condition. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, and inflammatory markers, eGFRSCysC <60 mL/min/1.73m2 and albuminuria were associated with nearly a twofold increase in mortality, whereas eGFRSCr <60 mL/min/1.73m2 did not appear to have any substantial association with mortality. Together, eGFRSCysC <60 mL/min/1.73m2 and albuminuria accounted for 17% of the population-level attributable risk for mortality.
Vital status was unknown in 261 participants from the original cohort.
Kidney disease marked by albuminuria or increased cystatin C levels appears to be an important risk factor for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on serum creatinine to estimate kidney function in clinical practice.
kidney disease; mortality; HIV infection
Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with kidney disease, and for treating patients with drugs that are eliminated from the circulation by the kidneys. Cystatin C has been shown to be superior to creatinine for estimating GFR in several studies. However, studies showing that thyroid function has an impact on cystatin C have not addressed the question of whether the changes in cystatin C levels are due to changes in GFR or in cystatin C synthesis.
We report an account of a hyperthyroid patient with a discrepancy between the GFR estimates from cystatin C and creatinine. The cystatin C concentration (1.36 mg/L) was higher and gave an estimated GFR which was lower (51 mL/min/1.73 m2), while the creatinine concentration was lower (36 μmol/L) and gave a corresponding creatinine-estimated GFR that was higher (145 mL/min/1.73 m2) than the iohexol-estimated GFR (121 mL/min/1.73 m2) during the hyperthyroid period. After thyroidectomy, the creatinine concentration was 36 μmol/L and creatinine-estimated GFR was calculated as 73 mL/min/1.73 m2, while the cystatin C concentration and cystatin C-calculated GFR was 0.78 mg/L and 114 mL/min/1.73 m2, respectively.
In contrast to creatinine, cystatin C levels rose in the hyperthyroid state as compared to the euthyroid state. The cystatin C-estimated GFR was reduced compared to the iohexol-estimated GFR. This patient case shows that the hyperthyroid-associated changes in cystatin C levels are not due to changes in GFR. Thyroid function should thus be considered when both cystatin C and creatinine are used as markers of kidney function.
The present study aimed to determine the role of cystatin C as a prognostic factor for acute kidney injury and survival in cirrhotic patients.
The study investigated 53 liver cirrhosis patients. The renal function was evaluated by serum creatinine, serum and urine cystatin C, and 24-hour creatinine clearance on admission. Acute kidney injury was defined as a serum creatinine level exceeding the normal range (>1.2 mg/dl) and an increase of at least 50% from the baseline value. Multivariate analysis, receiver operating characteristic curve, and survival analysis were used to investigate prognostic factors for acute kidney injury and survival.
Nine of the 53 cirrhotic patients (17.0%) developed acute kidney injury within 3 months. Both serum creatinine and cystatin C were predictive factors for acute kidney injury in univariate analysis, with a diagnostic accuracy of 0.735 (95% confidence interval (CI), 0.525-0.945; p=0.028) for serum cystatin C and 0.698 (95% CI, 0.495-0.901, p=0.063) for creatinine. In multivariate analysis, only serum cystatin C was an independent risk factor for acute kidney injury. The sensitivity and specificity of a serum cystatin C level of >1.23 mg/L to acute kidney injury were 66% and 86%, respectively. Serum cystatin C was positively correlated with the Model for End-Stage Liver Disease (MELD) and MELD-Na scores (r=0.346 and p=0.011, and r=0.427 and p=0.001, respectively). Comparison of the survival rates over the observation period revealed that a serum cystatin C level of >1.23 mg/L was a useful marker for short-term mortality (p<0.001).
The accuracy in predicting acute kidney injury and short-term mortality was higher for a serum cystatin C level of >1.23 mg/L than for the serum creatinine concentration in patients with cirrhosis.
Cystatin C; Liver cirrhosis; Acute kidney injury
There is no literature available on the performance of cystatin C in Chronic Kidney Disease (CKD) patients of Indian population based on age group. Hence, this study is aimed to compare the diagnostic performance of serum cystatin C and creatinine with measured glomerular filtration rate (GFR) and estimated GFR (eGFR) in subjects of Indian origin.
The study was carried out at Tiruchirappalli, South India during the period of September 2010 to march 2011. One hundred and six CKD patients (82 males, 24 females) were enrolled and categorized into three groups based on age. The eGFR was calculated using Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae. Serum cystatin C was measured with a particle-enhanced nephelometric immunoassay (PENIA) method. GFR was measured using 99mTC - diethylene triamine penta aceticacid (DTPA) renal scan method.
Serum cystatin C showed significant correlation with measured GFR in all the three groups (r=-0.9735, r=-0.8975 and r=-0.7994 respectively) than serum creatinine (r=-0.7380, r=-0.6852 and r=-0.5127 respectively).
Serum cystatin C showed a high correlation with measured GFR in young and older patients with CKD than creatinine. Thus, cystatin C is a good alternative marker to creatinine in CKD patients.
GFR; eGFR; CKD; Cystatin C; Creatinine; 99mTC-DTPA
Proteinuria is a common manifestation of renal disease which is a significant cause of morbidity in patients with sickle cell disease (SCD).
To evaluate and compare cystatin C, β2‐microglobulin, and creatinine as markers of renal disease in relation to the degree of proteinuria and other complications of SCD.
24 h urine collections were used for estimation of urine protein and creatinine clearance in 59 patients with SCD. Results were correlated with plasma cystatin C, β2‐microglobulin, creatinine, glomerular filtration rate (GFR; derived from plasma creatinine by Cockcroft‐Gault, MDRD formulae, and calculated cystatin C clearance), and clinical and haematological variables.
Comparing the different methods of GFR, the proportion of patients with hyperfiltration (GFR >140 ml/min) were 30.5% (MDRD), 44.1% (Cockcroft‐Gault), and 10.2 % (calculated cystatin C clearance). Cystatin C was the most consistent marker of hyperfiltration. The endogenous markers of GFR showed an increasing trend with increasing proteinuria, but haematological variables were not correlated with cystatin C, β2‐microglobulin, or plasma creatinine. Urine protein excretion was correlated with age (r = 0.33) and significant proteinuria was present in 13.6% of patients. Patients with proteinuria had lower haemoglobin concentration (p = 0.027) than those without proteinuria but HbF was not related to the degree of proteinuria or to markers of GFR.
Markers of GFR show variable ability to identify hyperfiltration in patients with SCD, but cystatin C is the best endogenous marker. Proteinuria is associated with age, haemoglobin, and abnormalities of GFR. Routine screening is recommended to allow for early detection and intervention.
cystatin C; β2‐microglobulin; glomerular filtration rate; sickle cell disease
Background. Anaemia worsens as kidney function declines. Both conditions are associated with increased mortality. Serum cystatin C is purportedly a more sensitive marker of kidney disease and a better predictor of mortality than serum creatinine. However, studies suggest that extrarenal factors also influence cystatin C levels.
Methods. We determined whether estimates of glomerular filtration rate [estimated glomerular filtration rate (eGFR)] based on serum cystatin C alone or in combination with serum creatinine were superior to those based on serum creatinine in recognizing impaired kidney function in the setting of anaemia in a sub-sample of the Third National Health and Nutrition Examination Survey of the USA consisting of 6734 participants, 20 years or older.
Results. The prevalence of moderate to severe kidney disease (eGFR 15–59 mL/min/1.73 m2) among anaemic persons was 15–16% when based on serum creatinine alone (eGFRSCR) or combined with cystatin C (eGFRSCR + CYSC); this estimate increased to nearly 25% when kidney function was estimated by cystatin C (eGFRCYSC). The adjusted odds ratios of kidney disease in anaemic versus non-anaemic persons were slightly higher with eGFRCYSC than eGFRSCR and eGFRSCR + CYSC in younger adults [odds ratio (OR) = 5.22, 95% confidence interval (CI): 2.23, 12.17], women (OR = 5.34, 95% CI: 2.36, 12.06) and those with elevated C-reactive protein (CRP) (OR = 7.36, 95% CI: 1.98–27.36).
Conclusions. Impaired kidney function was common in individuals with anaemia. Among anaemic individuals, the prevalence estimate for kidney disease was notably higher when kidney function was estimated by cystatin C alone compared with the estimations by serum creatinine alone or in combination with serum cystatin C. eGFRCYSC may be particularly helpful in identifying kidney disease in the setting of anaemia among younger persons, women and those with elevated CRP. Regardless of which renal biomarker is used, our study suggests that an evaluation for underlying kidney disease should be considered in the standard workup of anaemia.
anaemia; chronic kidney failure; creatinine; cystatin C; glomerular filtration rate
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 infl ammation, who undergo elective surgery.
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
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.
The inflammatory status of a patient does not influence the role of cystatin C as a marker of successful aging, nor of GFR.
Cardiovascular disease; kidney function; surgery
Research on the relationship between urinary albumin excretion and serum cystatin C in diabetes is restricted to cross-sectional studies. In this study, we investigated how well serial measurements of serum cystatin C level reflect changes in the urinary albumin excretion rate.
We enrolled and retrospectively collected data on 1,058 participants with type 2 diabetes who were older than 18 years and who had more than 3 years of follow-up with serial measurements of albuminuria and serum cystatin C at an outpatient clinic.
With the use of a linear mixed model, we found that the albuminuria level for each patient over time corresponded with the annual change in serum cystatin C-based estimated glomerular filtration rate (cysC-eGFR) but did not correspond with the creatinine-based eGFR calculated by the modification of diet in renal disease formula (MDRD-eGFR). The discrepancy in the direction of the trend was smaller with cysC-eGFR than with MDRD-eGFR.
Serum cystatin C level reflects the trend in albuminuria level more accurately than serum creatinine level in Korean type 2 diabetes mellitus patients.
Albuminuria; Cystatin C; Creatinine; Diabetes mellitus, type 2; Diabetic nephropathies
Accurate diagnosis of acute kidney injury (AKI) is problematic especially in critically-ill patients in whom renal function is in an unsteady state.
Our aim was to evaluate the role of serum (S.) cystatin C as an early biomarker of AKI in critically-ill children.
Subjects and Methods:
S. creatinine and S. cystatin C were measured in 32 critically-ill children who were at risk for developing AKI. AKI was defined by both: Risk,-injury,-failure,-loss, and-endstage renal disease (RIFLE) classification and glomerular filtration rate (GFR) <80 ml/min/1.73 m2. GFR was estimated by both Schwartz formula and S. cystatin C-based equation.
S. cystatin C was not statistically higher in AKI patients compared with non-AKI by RIFLE classification (median 1.48 mg/l vs. 1.16 mg/l, P = 0.1) while S. creatinine was significantly higher (median 0.8 mg/dl vs. 0.4 mg/dl, P = 0.001). On estimating GFR by the two equations we found, a lag between rise of S. cystatin C and creatinine denoted by lower GFR by Schwartz formula in four patients, on other hand, six patients had elevated S. cystatin C with low GFR despite normal creatinine and GFR, denoting poor concordance between the two equations and the two markers. The ability of S. creatinine in predicting AKI was superior to S. cystatin with area under the curve (AUC) 0.95 with sensitivity and specificity (100% and 84.6%, respectively) using the RIFLE classification. The same findings were found when using Schwartz formula.
S. cystatin C is a poor biomarker for diagnosing AKI in critically-ill children.
Cystatin C; risk-injury-failure-loss-end stage renal disease criteria; schwartz formula
Parameters allowing regular evaluation of renal function in a paediatric intensive care unit (PICU) are not optimal. The aim of the present study was to analyse the utility of serum cystatin C and beta2-microglobulin (B2M) in detecting decreased glomerular filtration rate in critically ill children.
This was a prospective, observational study set in an eight-bed PICU. Twenty-five children were included. The inverses of serum creatinine, cystatin C, and B2M were correlated with creatinine clearance (CrC) using a 24-hour urine sample and CrC estimation by Schwartz formula (Schwartz). The diagnostic value of serum creatinine, cystatin C, and B2M to identify a glomerular filtration rate under 80 ml/minute per 1.73 m2 was evaluated using receiver operating characteristic (ROC) curve analysis.
Mean age was 2.9 years (range, 0.1 to 13.9 years). CrC was less than 80 ml/minute per 1.73 m2 in 14 children, and Schwartz was less than 80 ml/minute per 1.73 m2 in 9 children. Correlations between inverse of B2M and CrC (r = 0.477) and between inverse of B2M and Schwartz (r = 0.697) were better than correlations between inverse of cystatin C and CrC (r = 0.390) or Schwartz (r = 0.586) and better than correlations between inverse of creatinine and CrC (r = 0.104) or Schwartz (r = 0.442). The ability of serum cystatin C and B2M to identify a CrC rate and a Schwartz CrC rate under 80 ml/minute per 1.73 m2 was better than that of creatinine (areas under the ROC curve: 0.851 and 0.792 for cystatin C, 0.802 and 0.799 for B2M, and 0.633 and 0.625 for creatinine).
Serum cystatin C and B2M were confirmed as easy and useful markers, better than serum creatinine, to detect acute kidney injury in critically ill children.
Background. Serum creatinine (S-Cr)-based prediction equations are commonly used for estimating glomerular filtration rate (GFR). However, S-Cr concentration is also affected by other factors such as tubular secretion, muscle mass, diet, gender and age. Serum cystatin C (S-Cys C)-based prediction equations have been proposed as an improved potential alternative as S-Cys C levels are not influenced by many of the factors that affect creatinine concentration other than GFR. This may be of great benefit to patients with low muscle mass such as those infected with human immunodeficiency virus who are at increased risk for the development of renal impairment. The aim of this study was to develop and evaluate a S-Cys C-based prediction equation for different stages of renal disease in black South Africans.
Methods. One hundred patients with varying degrees of renal function were enrolled in the study. The plasma clearance of 51Cr-EDTA, a gold standard method, was used to measure GFR (mGFR). In addition, serum was analysed for S-Cr and S-Cys C on each participant. This dataset was split into a development dataset (n = 50) and a test dataset (n = 50). The development dataset was used to formulate a S-Cys C- and S-Cr-based prediction equation using multiple linear regression analysis. These equations together with the four-variable MDRD and CKD-EPI equation were then tested on the test dataset.
Results. In the test dataset, accuracy within 15% of measured GFR was 68% for the S-Cys C equation and 48% for the S-Cr equation. Root mean square error for S-Cr eGFR was 10.7 mL/min/1.73 m2 for those patients with mGFR < 60 mL/min/1.73 m2 and 25.5 mL/min/1.73 m2 for those patients with mGFR > 60 mL/min/1.73 m2. Root mean square error for S-Cys C eGFR was 10.2 mL/min/1.73 m2 for those patients with mGFR < 60 mL/min/1.73 m2 and 11.9 mL/min/1.73 m2 for those patients with mGFR > 60 mL/min/1.73 m2.
Conclusions. In this study, S-Cys C-based prediction equations appear to be more precise than those of S-Cr for those patients with mGFR > 60 mL/min/1.73 m2 and may therefore be of benefit in the earlier detection of renal impairment.
creatinine; cystatin C; glomerular filtration rate; MDRD
Renal function is a strong predictor of adverse events in heart failure. Current renal function measures are imperfect and Cystatin C (CysC) is promoted as a better marker of glomerular filtration rate (GFR). This study compares the prognostic utility of CysC and derived GFR estimates with other measures of renal function in patients with chronic heart failure.
Methods and Results
We measured serum CysC levels in 823 heart failure patients undergoing coronary angiography with follow-up of major adverse cardiovascular events (MACE = death, myocardial infarction, stroke). Cystatin C levels strongly correlated with creatinine (r = 0.73), blood urea nitrogen (r = 0.70), and eGFRMDRD (r = −0.62) (all p < 0.001). However, the correlation was lower in eGFR ≥ 60ml/min/1.73m2. CysC-based measures significantly improved areas under the ROC curve for the prediction of MACE, especially in eGFR ≥ 60ml/min/1.73m2 (p < 0.01). Net reclassification improvement was 22.2% (p < 0.001) in this group. CysC remained an independent predictor of MACE (p < 0.001) after adjustment for traditional risk factors and BNP.
Cystatin C is an independent predictor of adverse events in chronic heart failure. It adds prognostic value to creatinine, particularly in patients with “preserved” renal function.
heart failure; kidney; prognosis
Introduction. RIFLE and AKIN provide a standardised classification of acute kidney injury (AKI), but their categorical rather than continuous nature restricts their use to a research tool. A more accurate real-time description of renal function in AKI is needed, and some published data suggest that equations based on serum creatinine that estimate glomerular filtration rate (eGFR) can provide this. In addition, incorporating serum cystatin C concentration into estimates of GFR may improve their accuracy, but no eGFR equations are validated in critically ill patients with AKI. Aim. This study tests whether creatinine or cystatin-C-based eGFR equations, used in patients with CKD, offer an accurate representation of 4-hour creatinine clearance (4CrCl) in critically ill patients with AKI. Methods. Fifty-one critically ill patients with AKI were recruited. Thirty-seven met inclusion criteria, and the performance of eGFR equations was compared to 4CrCl. Results. eGFR equations were better than creatinine alone at predicting 4CrCl. Adding cystatin C to estimates did not improve the bias or add accuracy. The MDRD 7 eGFR had the best combination of correlation, bias, percentage error and accuracy. None were near acceptable standards quoted in patients with chronic kidney disease (CKD). Conclusions. eGFR equations are not sufficiently accurate for use in critically ill patients with AKI. Incorporating serum cystatin C does not improve estimates. eGFR should not be used to describe renal function in patients with AKI. Standards of accuracy for validating eGFR need to be set.
Renal dysfunction is associated with increased morbidity and mortality in intensive care patients. In most cases the glomerular filtration rate (GFR) is estimated based on serum creatinine and the Modification of Diet in Renal Disease (MDRD) formula, but cystatin C-estimated GFR is being used increasingly. The aim of this study was to compare creatinine and MDRD and cystatin C-estimated GFR in intensive care patients.
Retrospective observational study was performed, on patients treated within the general intensive care unit (ICU) during 2004–2006, in a Swedish university hospital.
GFR markers are frequently ordered in the ICU; 92% of the patient test results had cystatin C-estimated GFR (eGFRcystatinC) ≤ 80 mL/min/1.73 m2, 75% had eGFR ≤ 50 mL/min/1.73 m2, and 30% had eGFR ≤ 20 mL/min/1.73 m2. In contrast, only 46% of the patients had reduced renal function assessed by plasma creatinine alone, and only 47% had eGFRMDRD ≤ 80 mL/min/1.73 m2. The mean difference between eGFRMDRD and eGFRcystatinC was 39 mL/min/1.73 m2 for eGFRcystatinC values ≤ 60 mL/min/1.73 m2.
GFR is commonly assessed in the ICU. Cystatin C-estimated GFR yields markedly lower GFR results than plasma creatinine and eGFRMDRD. Many pharmaceuticals are eliminated by the kidney, and their dosage is adjusted for kidney function. Thus, the differences in GFR estimates by the methods used indicate that the GFR method used in the intensive care unit may influence the treatment.
Cystatin C; glomerular filtration rate; human; intensive care; kidney; MDRD
Several studies suggested that serum cystatin C (CysC) is more useful than serum creatinine (Cr) for the assessment of renal function in patients with liver cirrhosis. This study evaluated the clinical significance of CysC in patients with cirrhotic ascites and normal Cr level.
We enrolled patients with cirrhotic ascites and a normal serum Cr level (<1.2 mg/dL). GFR was measured by 99mTc-DTPA renal scan. Serum Cr, CysC, and Cr clearance (CCr) were measured on the same day. Significant renal impairment and severe renal impairment were defined as GFR <60 mL/min and GFR <30 mL/min, respectively.
Eighty-nine patients with cirrhotic ascites were enrolled in the study (63 men and 26 women; age, 55±11 years). Forty-seven (52.8%) and 42 (47.2%) patients were in Child-Pugh grade B and C, respectively. Serum Cr and CysC levels and GFR were 0.8±0.2 mg/dL, 1.1±0.3 mg/L, and 73.4±25.5 mL/min, respectively. Significant and severe renal impairment were noted in 28 (31.5%) and 2 (2.2%) patients, respectively. GFR was well correlated with serum Cr, CysC, and e-GFRMDRD, while it was not correlated with e-GFRC&G. In multivariate analysis, only CysC was significantly correlated with GFR (β, 45.620; 95% CI, 23.042-68.198; P<0.001). Serum CysC level was the only independent predictor for significant renal impairment.
Significant renal dysfunction was not rare in patients with cirrhotic ascites, even their serum Cr level is normal. Serum CysC is a useful marker for detecting significant renal dysfunction in these patients.
Ascites; Creatitine; Cystatin C; Liver cirrhosis; Renal dysfunction
Background and aims: Diagnosis of moderately impaired renal function is of particular importance in patients with cirrhosis of the liver. Whereas patients with a markedly impaired glomerular filtration rate can be diagnosed easily by elevated serum creatinine concentrations, moderately reduced renal function may be missed by this conventional parameter. Recently, cystatin C has been suggested as a sensitive marker of renal function, independent of sex or muscle mass. Therefore, the aim of this study was to investigate the value of serum cystatin C concentration for the detection of moderately impaired renal function.
Methods: Ninety seven inhospital patients with cirrhosis and a 24 hour creatinine clearance of at least 40 ml/min were investigated and divided into group 1 (creatinine clearance ≥70 ml/min; n=55) and group 2 (creatinine clearance 40–69 ml/min; n=42).
Results: Serum cystatin C concentrations (mean (SD): 1.31 (0.51) v 1.04 (0.34) mg/l (p=0.008)) and creatinine concentrations (1.03 (0.52) v 0.86 (0.22) mg/100 ml (p=0.03)) were higher in group 2 than in group 1; there was no significant difference in urea concentrations. Receiver-operator characteristics (ROC) revealed a differential diagnostic advantage of cystatin C over creatinine and urea. At cut off concentrations of 1.0 mg/l, 0.9 mg/100 ml, and 28 mg/100 ml, respectively, cystatin C, creatinine, and urea exhibited 69%, 45%, and 44% sensitivity (p<0.05). As patients with a small muscle mass or reduced physical activity could be particularly prone to overestimation of their renal function, separate analyses were performed for the subgroups of female and Child-Pugh class C patients, respectively. In both groups, discrimination between patients with moderately impaired and normal renal function was best with cystatin C. In female patients, sensitivity of cystatin C (77.8%) was superior (p<0.05) to that of creatinine (38.9%) and urea (41.2%). In Child-Pugh C patients, the ROC curve was significantly better for cystatin C than for creatinine.
Conclusions: Serum cystatin C determination could be a valuable tool in patients with cirrhosis, particularly with Child-Pugh class C or in female patients, for early diagnosis of moderately impaired renal function.
creatinine clearance; urea; creatinine; glomerular filtration rate