Serum cystatin C concentration compared with other markers of glomerular filtration rate in the old old

OBJECTIVES: To assess serum cystatin C, compared with other markers of renal function, as a marker of renal function in the old old (aged 85 and older). DESIGN: A cross-sectional analysis of data obtained in medically stable people aged 70 and older in a geriatric ward at a university hospital. SETTING: University hospital in Belgium. PARTICIPANTS: Forty-eight patients (17 men, 31 women) mean age +/- standard deviation 84.4 +/- 6.3 without acute illness or overt malignancy 7 days after admission were included. Twenty-five patients were aged 85 and older. MEASUREMENTS: Blood samples and 24-hour urine collections were obtained from each patient to determine serum creatinine, serum cystatin C levels, serum albumin, and creatinine clearance. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault formula and the Modification of Diet in Renal Study Group (MDRD) formula. On the same day, clearance of 51chromium ethylenediamine tetraacetic acid was performed in all patients as the criterion standard of GFR. RESULTS: Serum creatinine (r=0.68), serum cystatin C (r=0.62), urinary creatinine clearance (r=0.57), the Cockcroft-Gault formula (r=0.82), and the MDRD-formula (r=0.65) correlated significantly with GFR (P <.0001). Regression analysis showed that serum cystatin C and serum creatinine were comparable markers of renal function (Y=0.442 +/- 0.007 x GFR and Y=0.494 +/- 0.01 x GFR respectively). Receiver operating characteristic analysis showed a similar area under the curve for serum cystatin C and serum creatinine (P=.5) in detecting renal impairment (GFR <80 mL/min). The Cockcroft-Gault formula provides a good estimation of GFR when the GFR is less than 60 mL/min (Y=1.11 +/- 1.04 x GFR). When the GFR is greater than 60 mL/min, the Cockcroft-Gault formula underestimates GFR (Y=11.01 +/- 0.66 x GFR). In patients aged 85 and older, a slight decrease in GFR (51.8 +/- 21.3 mL/min vs 65.2 +/- 34.3 mL/min in patients aged 70-84; P=.10) is observed. This is reflected by a nonsignificant increase in serum cystatin C (P=.06), whereas serum creatinine is identical in both groups (P=.88). CONCLUSION: Serum cystatin C, serum creatinine, the Cockcroft-Gault formula, the MDRD formula, and urinary creatinine clearance are comparable markers of renal function in the overall older population. The Cockcroft-Gault formula underestimates renal function in older people with GFR greater than 60 mL/min. In our study, serum cystatin C was not superior to serum creatinine in the detection of renal impairment.     

Simple cystatin C formula compared to sophisticated CKD-EPI formulas for estimation of glomerular filtration rate in the elderly

Despite the fact that the serum creatinine level is notoriously unreliable for the estimation of glomerular filtration rate (GFR) in the elderly, the serum creatinine concentration and serum creatinine-based formulas, such as the Modification of Diet in Renal Disease study equation (MDRD) are the most commonly used markers to estimate GFR. Recently, serum cystatin C-based formulas, the newer creatinine formula (the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI creatinine formula), and an equation that uses both serum creatinine and cystatin C (CKD-EPI creatinine and cystatin formula) were proposed as new GFR markers. The aim of our study was to compare the MDRD formula, CKD-EPI creatinine formula, CKD-EPI creatinine and cystatin formula, and simple cystatin C formula (100/serum cystatin C) against (51) Cr-EDTA clearance in the elderly. A total of 317 adult Caucasian patients aged >65 years were enrolled. In each patient, (51) Cr-EDTA clearance, serum creatinine, and serum cystatin C were determined, and the GFR was calculated using the MDRD formula, CKD-EPI formulas, and simple cystatin C formula. Statistically significant correlations between (51) Cr-EDTA clearance and all formulas were found. In the receiver operating characteristic (ROC) curve analysis with a cut-off of GFR 45 mL/min/1.73 m(2), a higher diagnostic accuracy was achieved with the equation that uses both serum creatinine and cystatin C (CKD-EPI creatinine and cystatin formula) than the MDRD formula (P < 0.013) or CKD-EPI creatinine formula (P < 0.01), but it was not higher than that achieved for the simple cystatin C formula (P = 0.335). Bland and Altman analysis for the same cut-off value showed that the creatinine formulas underestimated and the simple cystatin C formula overestimated measured GFR. All equations lacked precision. The accuracy within 30% of estimated (51) Cr-EDTA clearance values differ according to the stage of CKD. Analysis of the ability to correctly predict GFR below and above 45 mL/min/1.73 m(2) showed a high prediction for all formulas. Our results indicate that the simple cystatin C formula, which requires just one variable (serum cystatin C concentration), is a reliable marker of GFR in the elderly and comparable to the creatinine formulas, including the CKD-EPI formulas.     

Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy

OBJECTIVE: To determine whether serum cystatin C is more accurate than serum creatinine in the detection of diabetic nephropathy, also after adjustment for age. METHODS: Forty-one patients with type 1 and 82 patients with type 2 diabetes were evaluated with serum creatinine, serum cystatin C, and (51)Cr-EDTA clearance (reference method). Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. Statistical estimations were performed both without and with age adjustment created by z-scores for (51)Cr-EDTA clearance, creatinine, and cystatin C. The cut-off levels for glomerular filtration rate (GFR) ((51)Cr-EDTA clearance) were 60 and 80 mL min(-1) 1.73 m(-2), respectively, in absolute values and 80, 90 and 95% CIs, respectively, in age-adjusted values (z-scores). RESULTS: Estimations without age adjustment showed significantly (P = 0.0132) closer correlation for cystatin C (r = 0.817) versus (51)Cr-EDTA clearance as compared with creatinine (r = 0.678). However, when using age-adjusted values, the correlation for cystatin C and creatinine, respectively, versus (51)Cr-EDTA clearance did not differ. When comparing the diagnostic utilities for serum cystatin C versus serum creatinine in manifest renal impairment (GFR < 60 mL min(-1) 1.73 m(-2) or z-scores <-1.28 SD), there were no significant differences between the two markers whether age adjusted or not. However, for diagnosing mild nephropathy (GFR < 80 mL min(-1) 1.73 m(-2) or z-score -0.84 SD), serum cystatin C is significantly more useful. CONCLUSIONS: Serum cystatin C performed better compared with serum creatinine even when measured enzymatically, to detect mild diabetic nephropathy. However, serum creatinine was as efficient as serum cystatin C to detect advanced diabetic nephropathy.     

Serum cystatin C concentration as a marker of glomerular filtration rate in patients with various renal diseases

OBJECTIVE: The present study was undertaken to evaluate clinical application of serum cystatin C as a new marker of glomerular filtration rate (GFR) in patients with various renal diseases. PATIENTS AND METHODS: A total of 140 patients were enrolled in the study. We measured the serum cystatin C levels and compared them with creatinine clearance (Ccr) and inulin clearance (Cin) as an indicator of GFR. RESULTS: There was a significant positive correlation between serum cystatin C and creatinine levels (r=0.928). Serum cystatin C was inversely correlated with creatinine clearance. Moreover, the reciprocal serum cystatin C level was positively correlated with Cin (r=0.882). The receiver-operating characteristic curve of serum cystatin C and creatinine demonstrated that the diagnostic accuracy of the serum cystatin C level is superior to that of creatinine in identifying individuals with reduced GFR. CONCLUSION: These results indicated that measurement of serum cystatin C is useful to estimate GFR, and in particular, to detect a mild reduction of GFR in patients with renal diseases.     

The accuracy of cystatin C and commonly used creatinine-based methods for detecting moderate and mild chronic kidney disease in diabetes.

BACKGROUND: The accuracy of measuring serum cystatin C levels for detecting various stages of chronic kidney disease (CKD) in diabetes is still unclear. METHODS: In a cross-sectional study of 251 subjects, a reference glomerular filtration rate (GFR) was measured using (99c)Tc-DTPA plasma clearance (iGFR). Multivariate analysis was used to identify independent clinical and biochemical associations with serum cystatin C and iGFR levels. The diagnostic accuracy of cystatin C and commonly used creatinine-based methods of measuring renal function (serum creatinine, the MDRD four-variable and Cockcroft-Gault formulae) for detecting mild and moderate CKD was also compared. RESULTS: In the entire study population the same five variables, age, urinary albumin excretion rates, haemoglobin, history of macrovascular disease and triglyceride levels were independently associated with both cystatin C and iGFR levels. A serum cystatin C level cut-off > 82.1 nmol/l (1.10 mg/l) had the best test characteristics as a screening tool for detecting moderate CKD (< 60 ml/min per 1.73 m(2)) when compared with creatinine-based methods. At the upper threshold for mild CKD (< 90 ml/min per 1.73 m(2)), cystatin C also had greater diagnostic accuracy than creatinine, but had similar diagnostic accuracy when compared with creatinine-based formulae for predicting renal function. CONCLUSIONS: This study suggests that the clinical and biochemical parameters associated with serum cystatin C levels are closely linked to those associated with GFR and highlights the potential usefulness of screening for moderate or mild CKD in subjects with diabetes by simply measuring serum cystatin C levels.     

Cystatin C blood level as a risk factor for death after heart surgery.

AIMS: Pre-operative renal dysfunction is a known risk factor for mortality and morbidity after heart surgery. Despite limited accuracy, serum creatinine is widely used to estimate glomerular filtration rate (GFR). Cystatin C is more accurate for assessing GFR. The aim of the present study was to assess associations between GFR estimated from serum cystatin C levels before heart surgery and hospital mortality, hospital morbidity, and 1 year mortality. METHODS AND RESULTS: In a prospective single-centre observational study, clinical risk factors for morbidity and mortality were recorded and serum creatinine and cystatin C levels were measured in patients admitted for heart surgery. Hospital mortality and morbidity and 1 year mortality were recorded. Over an 8 month period, 499 patients were screened, among whom 376 (74.5%) were included in the study. Hospital mortality was 5.6% (21 patients) and 1 year mortality was 10.2%. Hospital morbidity, defined by a length of stay above the 75th percentile, was 22.1% (83 patients). In the multivariable analysis, GFR estimated from serum cystatin C, but not GFR estimated from serum creatinine, was an independent risk factor for hospital morbidity/mortality (odds ratio per 10 mL/min of GFR decrease, 1.20 (1.07-1.34), P = 0.001) and for 1 year mortality (hazards ratio per 10 mL/min of GFR decrease, 1.26 (1.09-1.46), P = 0.002). CONCLUSION: Pre-operative GFR estimation from serum cystatin C may provide a better risk assessment than pre-operative GFR estimation from serum creatinine in patients scheduled for heart surgery.     

Estimation of Glomerular Filtration Rate in Elderly Chronic Kidney Disease Patients: Comparison of Three Novel Sophisticated Equations and Simple Cystatin C Equation

Estimating glomerular filtration rate (GFR) in elderly patients is a problem, since they are poorly represented in studies developing GFR equations. Serum cystatin C is a better indicator of GFR than serum creatinine in elderly patients. Therefore the aim of our study was to compare frequently used serum cystatin C based GFR equations with a gold standard (⁵¹CrEDTA clearance) in elderly chronic kidney disease (CKD) patients. 106 adult Caucasian patients, older than 65 years (58 women, 48 men; mean age 72.5 years), were included. In each patient ⁵¹CrEDTA clearance, serum creatinine (IDMS traceable method) and serum cystatin C (immunonephelometric method) were determined. GFR was estimated using the Simple cystatin C, CKD‐EPI cystatin C, CKD‐EPI creatinine‐cystatin C and BIS2 equation. Mean serum creatinine of our patients was 141.4 ± 41.5 μmol/L, mean serum cystatin C 1.79 ± 0.6 mg/L, mean ⁵¹CrEDTA clearance was 52.2 ± 15.9 mL/min per 1.73 m². Statistically significant correlations between ⁵¹CrEDTA clearance and all formulas were found (P < 0.0001). In the receiver operating characteristic (ROC) curve analysis (cut‐off for GFR 45 mL/min per 1.73 m²) no significant differences in diagnostic accuracy between all the before mentioned equations were found. Bland‐Altman analysis for the same cut‐off showed that CKD‐EPI creatinine‐cystatin C and BIS2 equation underestimated and CKD‐EPI cystatin C and Simple cystatin C equation overestimated measured GFR. All equations lacked precision. Analysis of ability to correctly predict patient's GFR below or above 45 mL/min per 1.73 m² showed similar ability for all equations (P = 0.24–0.89). All equations are equally accurate for estimating GFR in elderly Caucasian CKD patients. For daily practice Simple cystatin C equation is most practical.     

Serum creatinine in patients with advanced liver disease is of limited value for identification of moderate renal dysfunction: are the equations for estimating renal function better?

BACKGROUND: The Cockcroft-Gault formula (CGF) is used to estimate the glomerular filtration rate (GFR) based on serum creatinine (Cr) levels, age and sex. A new formula developed by the Modification of Diet in Renal Disease (MDRD) Study Group, based on the patient's Cr levels, age, sex, race and serum urea nitrogen and serum albumin levels, has shown to be more accurate. However, the best formula to identify patients with advanced liver disease (ALD) and moderate renal dysfunction (GFR 60 mL/min/1.73 m2 or less) is not known. The aim of the present study was to compare calculations of GFR, using published formulas (excluding those requiring urine collections) with standard radionuclide measurement of GFR in patients with ALD. METHODS: Fifty-seven consecutive subjects (40% women) with a mean age of 50 years (range 16 to 67 years) underwent 99m-technetium-diethylenetriamine pentaacetic acid (99mTc-DTPA) (single injection) radionuclide measurement of GFR. To calculate GFR, three formulas were used: the reciprocal of Cr multiplied by 100 (100/Cr), the CGF and the MDRD formulas. Pearson's correlation coefficient (r) and Bland-Altman analyses of agreement were used to analyze the association between 99mTc-DTPA clearance and the three equations for GFR. RESULTS: The mean 99mTc-DTPA clearance was 83 mL/min/1.73 m2 (range 28 mL/min/1.73 m2 to 173 mL/min/1.73 m2). Mean calculated GFRs by 100/Cr, the CGF and the MDRD formula were 106 mL/min/1.73 m2, 98 mL/min/1.73 m2 and 86 mL/min/1.73 m2, respectively. Regression analysis showed good correlation between radionuclide GFR and calculated GFR with r(100/Cr)=0.74, r(CGF)=0.80, r(MDRD)=0.87, all at P > or = 0.0001. The MDRD formula provided the least bias. The Bland-Altman plot showed best agreement between GFR calculated by the MDRD formula and 99mTc-DTPA clearance, with only 3 mL/min/1.73 m2 overestimation. There was higher variability between radionuclide GFR and calculated GFR by the CGF and by 100/Cr. Although there was no difference in precision, GFR calculated by the MDRD formula had the best overall accuracy. The sensitivity and specificity for detection of moderate renal dysfunction by the MDRD formulas were 73% and 87%, respectively. CONCLUSIONS: Among the Cr-based GFR formulas, the MDRD formula showed a larger proportion of agreement with radionuclide GFR in patients with ALD. In clinical practice, the MDRD is the best formula for detection of moderate renal dysfunction among those with ALD.     

胱抑素C在评估慢性心力衰竭患者肾功能不全中的价值

目的观察慢性心力衰竭（CHF）患者的血清胱抑素C（Cys-C）、血清肌酐（Scr）、肾小球率过滤（eGFR）水平,评估Cys-C在CHF患者肾功能不全中的诊断价值。方法选取我院住院88例CHF的患者测定Cys-C、Scr,计算eGRF（简化MDRD公式）,根据eGFR水平将患者分成4组：GRF正常组、GRF轻度下降组、GRF中度下降组、GRF重度下降及肾衰竭组,比较4组间Cys-C、Scr的差异并进行Cys-C、Scr与GRF的相关性分析。结果 4组患者的血清Cys-C水平分别为（0.93±0.18）,（1.08±0.22）,（1.58±0.59）,（2.7±0.86）mg/L,差异有显著统计学意义（P〈0.01）,血清Cys-C与GRF显著相关,相关系数为0.62（P〈0.01）。结论 Cys-C可以作为肾小球滤过率的判断指标,有助于慢性心力衰竭患者肾功能不全的早期诊断。     

Calculated glomerular filtration rate is a useful screening tool to identify scleroderma patients with renal impairment

OBJECTIVES: Although it only occurs in a minority of patients, renal involvement is a life-threatening complication of scleroderma (SSc). We have investigated the utility of two formulae to calculate glomerular filtration rate (GFR) in a population of SSc patients. METHODS: Twenty-six patients (20 female, 6 male, median age 58 yr, age range 12-80 yr) satisfied our criteria for inclusion in a retrospective comparison of measured and calculated GFR. GFR was measured using (51)Cr-EDTA. The modified Cockcroft and Gault formula and equation 7 from the Modification of Diet in Renal Disease (MDRD) were used to calculate GFR. RESULTS: Eighteen out of 19 patients analysed with a serum creatinine concentration less than the upper limit of the normal range had a measured GFR outside the normal range. Three patients with a normal creatinine concentration had a measured GFR <60 ml/min and in each of these the calculated GFR was also abnormal. All patients with a measured GFR <60 ml/min were identified using both the MDRD and the modified Cockcroft and Gault formula to calculate GFR. The greatest correlation between measured and calculated GFR was seen when the MDRD formula, which employs demographic and serum variables, was used in patients with body surface area (BSA) >1.4 m(2) who were not taking Iloprost (r=0.91). Use of the Cockcroft and Gault formula to calculate creatinine clearance with a correction factor for GFR, the inclusion of patients taking Iloprost and the inclusion of patients with BSA <1.4 m(2) were all associated with a lower degree of correlation. CONCLUSION: Serum creatinine is a poor marker of renal function in SSc patients. Calculating GFR from demographic and serum variables is a simple technique to identify SSc patients who have abnormal renal function. The authors recommend the use of the MDRD formula.     

Prediction of Glomerular Filtration Rate from Serum Creatinine,Age, Sex and Body Weight

ABSTRACT. Trollfors B, Alestig K, Jagenburg R (Department of Infectious Diseases, Regional Hospital, University of Umeå, Umeå, and Departments of Infectious Diseases and Clinical Chemistry, Östra Hospital, University of Göteborg, Göteborg, Sweden). Prediction of glomerular filtration rate from serum creatinine, age, sex and body weight. Acta Med Scand 1987; 221:495–8. The accuracy and precision of estimates of glomerular filtration rate (GFR) from serum creatinine, age, sex and body weight using the methods proposed by Cockroft and Gault and by Siersbaeck-Nielsen et al. were determined in 234 subjects on 574 occasions. The two methods gave almost identical estimates of GFR. As reference for determination of GFR plasma clearance of ⁵¹Cr-EDTA as described by Bröchner-Mortensen was used. The estimates of GFR gave a systematic deviation of about 10 ml/min and a precision of about ±15 ml/min (1 SD) in the GFR range between 30 and 90 ml/min.     

胱抑素与老年肌酐正常肾损害患者肾小球滤过率的相关性研究

目的探讨在血清肌酐正常的老年肾损害患者中,胱抑素(cystatinC,Cys-C)对肾小球滤过率(GFR)评价的意义。方法对2002-11~2003-12泸州医学院附属医院86例有肾损害但血清肌酐(Scr)正常的老年患者,应用乳胶颗粒增强比浊法测定血清中Cys-C浓度,并采用CockCroft-Cault公式计算内生肌酐清除率(Ccr)。分别比较Cys-C与Scr和Ccr的相关性。结果56例Cys-C升高超过正常,占56.1%;比较Ccr≤59mL/min和Ccr>59mL/min两组间的Cys-C质量浓度发现,当Ccr≤50mL/min时,97.1%的患者Cys-C超过正常,在Ccr>59mL/min时,已有44.2%患者Cys-C超过正常。血清Cys-C与Scr存在高度的正直线相关(r=0.89,P<0.01);Cys-C与Ccr存在高度的负直线相关(r=-0.87,P<0.01)。结论在老年患者中,Cys-C比Scr和Ccr更敏感地反映早期肾小球滤过率的下降。     

Serum cystatin C versus serum creatinine in the estimation of glomerular filtration rate in rhabdomyolysis

Cystatin C has emerged as a possible, usable surrogate marker of renal function. We present a case that illustrates the clinical utility of cystatin C in the setting of acute kidney injury secondary to rhabdomyolysis. An African American male whose baseline cystatin C and serum creatinine levels taken a month prior to admission were compared against their daily values during his admission and at follow up. On admission, the patient's reduction in glomerular filtration rate (GFR) from baseline was much less when calculated with cystatin C than with serum creatinine. His clinical recovery was more reflective of the higher GFR with cystatin C than what would be assumed with his serum creatinine, which at its worst was 5 ml/min/1.73 m(2). The patient was eventually discharged from the hospital with a GFR of 40 ml/min by cystatin C despite his GFR by the MDRD equation being 12. Cystatin C may be a more accurate marker of the both the amount of injury and the rate of resolution of acute kidney injury than serum creatinine in rhabdomyolysis.     

Renal dysfunction in falciparum--malaria is detected more often when assessed by serum concentration of cystatin C instead of creatinine

OBJECTIVES: To estimate the frequency of renal dysfunction in falciparum malaria by serum concentration of cystatin C, a new sensitive indicator of the glomerular filtration rate (GFR). METHODS: Retrospective study of stored sera and patient files. Assessment of renal function by serum concentration of creatinine and cystatin C and comparison of the results from both indicators of GFR. RESULTS: A total of 108 adult patients with falciparum malaria were included in the study. Concentration of creatinine and cystatin C correlated well (r = 0.706; P < 0.001). Elevated cystatin C was more frequent than elevated creatinine (54.6%vs. 20.4%; P < 0.001). Patients older than 50 years developed renal dysfunction more often (P < 0.05) than younger ones. Results from cystatin C and creatinine were concordant in 63 (58.3%) and contradictory in 45 (41.6%) cases. Four (3.7%) patients had elevated creatinine but normal cystatin C levels, hence 63 patients (58.3%) showed elevation of at least one indicator of GFR. The frequency of elevated cystatin C and elevated creatinine was unrelated to body weight, gender or bilirubin level. CONCLUSIONS: The prevalence of impaired renal function in patients with falciparum malaria seems to have been underestimated in the past. Using a sensitive marker, 55% of the patients have a reduced GFR.     

Bestimmung der glomerul?ren Filtrationsrate bei chronischer Niereninsuffizienz

The estimated glomerular filtration rate (GFR) formulas in chronic kidney disease (CKD) EPI and modification of diet in renal disease (MDRD) are important for diagnosing CKD as they increase the sensitivity of isolated serum creatinine measurement; however, they do have limitations in accuracy (often less than 30%) and tend to underestimate true kidney function. In a recent meta-analysis the CKD-EPI formula showed a better accuracy in predicting cardiovascular mortality and end-stage renal disease compared to the MDRD formula. In special clinical situations kidney function should not only be estimated by these formulas but confirmed by creatinine clearance or cystatin C measurement. For prognostic evaluation extended parameters other than the CKD stage are needed.     

Estimation of the glomerular filtration rate in elderly inpatients: comparison of four methods

PURPOSE: High variability has been observed in the estimation of the glomerular filtration rate (GFR) in older patients, according to the formula used and no single formula has been recommended to date. The aim of this study was to quantify the precision and accuracy of the GFR estimated by means of three formulas and the measurement of cystatin C. METHODS: This prospective study was conducted in an acute care geriatric unit. Participants were patients, aged 70 years and over, having a possible 24-hour urine collection. The GFR was estimated using the Cockroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD), and the Creatinine Clearance (Cl-Cr) formulas. The serum level of cystatin C was also measured. RESULTS: Eighty-one patients were included in the study. CG formula underestimated the GFR by a mean difference of 8.65 ml/min, compared with MDRD formula. Cl-Cr underestimated the GFR by a mean difference of 7.56 ml/min, compared with CG formula, and by a mean difference of 16.79 ml/min, compared with the MDRD formula. The degree of discrepancy between CG and Cl-Cr estimates, and between Cl-Cr and MDRD estimates decreased as the estimated GFR approached normal values. MDRD best matched the measurement of cystatin C, followed by CG and Cl-Cr (Kappa coefficient=0.43, 0.22 and 0.16, respectively). CONCLUSION: Our study confirms the high variability of GFR in older patients and particularly in those with abnormal renal function, depending on the formula used. Serum cystatine C level and MDRD formula appear to be the most concordant estimates of GFR in this population.     

Plasma cystatin C determinations in a healthy elderly population

Plasma cystatin C measurement has been previously shown to be a better indicator of changes in glomerular filtration rate (GFR) than plasma creatinine. The available literature on reference intervals for cystatin C concentration encompasses only paediatric and adult populations up to 60 years of age, therefore we set out to determine an elderly reference range. Blood was taken from 401 subjects (65-101 years) and cystatin C and creatinine concentrations measured using commercially available methodologies. The availability of height and weight measurements allowed the additional calculation of predicted creatinine clearances using the Cockcroft and Gault formulae. Whilst no notable gender difference in cystatin C values was observed (female, 1.48 mg/l; male, 1.53 mg/l), concentrations rose with increasing age (60-79 years, 1.39 mg/l; >80 years, 1.70 mg/l). Conversely, there was a significant (P<0.0001) gender difference in creatinine values (female, 99 micromol/l; male, 120 micromol/l) but none between age groups (60-79 years, 105 micromol/l; >80 years, 113 micromol/l). Calculated GFR determinations resulted in a predicted creatinine clearance range of 21-81 ml/min per 1.73 m2 (n=361). There was no significant difference between gender (male, 18-88 ml/min per 1.73 m2; female, 24-69 ml/min per 1.73 m2), but a very significant 20% decrease in predicted GFR per decade. Sex-related reference intervals for creatinine were established (female, 66-149 micromol/l; male, 71-204 micromol/l); whilst age-related reference intervals were established for both cystatin C (60-79 years, 0.93-2.68 mg/l; >80 years, 1.07-3.35 mg/l) and predicted creatinine clearance (60-79 years, 27-89 ml/min per 1.73 m2; >80 years=18-55 ml/min per 1.73 m2). Plasma cystatin C measurement offers a simple, more sensitive screening assay for early changes in GFR and reflects the decreasing GFR that occurs with increasing age.     

Pitfalls of using estimations of glomerular filtration rate in an intensive care population

Background: Accurate knowledge of the glomerular filtration rate (GFR) is imperative in the intensive care unit (ICU) as renal status is important for medical decisions, including drug dosing. Aims: Recently, an estimation of GFR (eGFR) was suggested as a method of estimating GFR. How well this formula predicts GFR in unwell patients with normal initial serum creatinine concentrations has not been examined. Methods: The accuracy of the eGFR (before and after adjustment for actual body surface area (BSA)) was compared with measured and with estimated creatinine clearance using the Cockcroft Gault (CG) formula adjusted for total and lean body weight. Results: A total of 237 observations was recorded in 47 subjects. These were initially analysed independently, and then using the first observation only. Overall the mean difference between measured creatinine clearance and eGFR was ?12 mL/min (95% confidence interval (CI) ?20 to ?3), between measured creatinine clearance and CG +17 mL/min (95% CI 9–24), between measured creatinine clearance and CG adjusted for ideal body weight +12 mL/min (95% CI 4–21) and between measured creatinine clearance and eGFR ‘unadjusted’ for BSA 5 mL/min (95% CI ?2–13). Conclusions: Using either eGFR or CG formulae to estimate renal function in ICU subjects with normal serum creatinine concentrations is inaccurate. Although correcting for BSA improves the eGFR, this requirement to measure height and weight removes a major attraction for its use. We suggest that eGFR should not be automatically calculated in the ICU setting.     

Creatinine‐based estimation of glomerular filtration rate in patients with a Fontan circulation

Background: Patients with a Fontan circulation are at risk of renal dysfunction. We analyzed cross‐sectional data in pediatric and adult Fontan patients in order to assess the accuracy of commonly used serum creatinine‐based methods in estimating glo‐ merular filtration rate (GFR). Methods: A total of 124 Fontan patients (58 children, 66 adults) were enrolled across three study centers. Measurement of GFR (mGFR) using in vivo ^99mTc‐DTPA clear‐ ance was performed. Various serum creatinine‐based equations were used to calcu‐ late estimated GFR (eGFR). Results: Mean mGFR was 108 ± 28 mL/min/1.73 m² in children and 92 ± 20 mL/ min/1.73 m² in adults. Fourteen children (25%) and 28 adults (45%) had an mGFR <90 mL/min/1.73 m² . There was no significant correlation between mGFR and eGFR (Schwartz) in children (r = 0.22, P = .1), which substantially overestimated mGFR (bias 50.8, 95%CI: 41.1‐60.5 mL/min/1.73 m² , P < .0001). The Bedside Schwartz equation also performed poorly in the children (r = 0.08, P = .5; bias 5.9, 95%CI: −2.9‐14.6 mL/ min/1.73 m² , P < .0001). There was a strong correlation between mGFR and both eGFR (CKD‐EPI) and eGFR (MDRD) in adults (r = 0.67, P < .0001 in both cases), how‐ ever, both methods overestimated mGFR (eGFR(CKD‐EPI):bias 23.8, 95%CI: 20‐27.6 mL/min/1.73 m² , P < .0001; eGFR (MDRD):bias 16.1, 95%CI: 11.8‐20.4 mL/ min/1.73 m² , P < .0001). None of the children with an mGFR <90 mL/min/1.73 m² had an eGFR (Schwartz) <90 mL/min/1.73 m² . Sensitivity and specificity of eGFR (CKD‐EPI) and eGFR (MDRD) for mGFR <90 mL/min/1.73 m² in adults were 25% and 92% and 39% and 100%, respectively. Conclusions: This study identifies the unreliability of using creatinine‐based equa‐ tions to estimate GFR in children with a Fontan circulation. The accuracy of formulas incorporating cystatin C should be further investigated and may aid noninvasive sur‐ veillance of renal function in this population.     

Kidney function and systolic blood pressure new insights from cystatin C: data from the Heart and Soul Study

BACKGROUND: Control of hypertension is paramount in treating chronic kidney disease. The relationship between kidney function and blood pressure (BP) components has been studied in persons with diagnosed CKD, diabetes, or hypertension. Whether kidney function in the normal range is associated with systolic BP (SBP), diastolic BP (DBP), and pulse pressure is unclear. METHODS: We evaluated the association between kidney function and each BP component using cystatin C and 24-h creatinine clearance (CrCl) among 906 participants in the Heart and Soul Study. RESULTS: We observed that SBP was linearly associated with cystatin C concentrations (1.19+/-0.55 mm Hg increase per 0.4 mg/L cystatin C, P=.03) across the range of kidney functions. In contrast, using CrCl, SBP was significantly associated with kidney function only in subjects with CrCl<60 mL/min (6.4+/-2.13 mm Hg increase per 28 mL/min, P=.003) but not >60 mL/min (0.36+/-0.77 mm Hg per 28 mL/min, P=.64). Slopes differed significantly (for spline term P=.001). We found that DBP was not associated with cystatin C (0.34+/-0.40 mm Hg per 0.4 mg/L cystatin, P=.39) or CrCl (0.62+/-0.44 mm Hg per 28 mL/min clearance, P=.16). Pulse pressure was linearly associated with cystatin C (1.28+/-0.55 mm Hg per 0.4 mg/L cystatin, P=.02) and with CrCl<60 mL/min (7.27+/-2.16 mm Hg per 28 mL/min, P=.001). CONCLUSIONS: Both SBP and pulse pressure were significantly associated with kidney function across a wide range of cystatin C concentrations, even in subjects with presumably normal kidney function, by creatinine-based measures. Cystatin C may provide new insights into the association of CKD and hypertension, a relationship that may be an underappreciated barrier to hypertension control.