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Background: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from several European medical centres., Methods: Three thousand four hundred eight measurements of GFR (mGFR) using plasma clearance of exogenous substances were performed in 2218 children aged 2-17 years. Validated equations included Schwartz-2009 CR /2012 CR/CYS/CR+CYS , FAS CR/CYS/CR+CYS , LMR CR , Schwartz-Lyon CR , Berg CYS , CAPA CYS , CKD-EPI CYS , Andersen CR+CYS and arithmetic means of the best single-marker equations in explorative analysis. Five metrics were used to compare the performance of the GFR equations: bias, precision and three accuracy measures including the percentage of GFR estimates (eGFR) within ± 10% (P 10 ) and ± 30% (P 30 ) of mGFR., Results: Three of the cystatin C equations, Berg CYS , CAPA CYS and CKD-EPI CYS , exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPI CYS had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-Lyon CR had the best performance but was inaccurate at mGFR < 30 mL/min/1.73 m 2 and in underweight patients. Arithmetic means of the best creatinine and cystatin C equations above improved bias compared to the existing composite creatinine+cystatin C equations., Conclusions: The present study strongly suggests that cystatin C should be the primary biomarker of choice when estimating GFR in children with decreased GFR. Arithmetic means of well-performing single-marker equations improve accuracy further at most mGFR levels and have practical advantages compared to composite equations.

Introduction: Reporting estimated glomerular filtration rate (eGFR) instead of serum concentrations is advised in current guidelines. Most creatinine-based eGFR equations for children require height, a parameter not readily available to laboratories. Combining height-dependent creatinine- and cystatin C-based eGFR improves performance. Recently, a height-independent creatinine-based eGFR equation has been developed., Aim: To compare the combination of height-independent creatinine- and cystatin C-based equations with a combination of equations using anthropometric data., Methods: Retrospective analysis of 408 pediatric inulin clearance studies with simultaneous height, creatinine, cystatin C and urea measurements. eGFR calculation using the recalibrated Schwartz crea (height-dependent), FASage (height-independent) and the Schwartz cys equation. The means (Schwartz crea +Schwartz cys )/2 and (FASage+Schwartz cys )/2 were compared with the CKiD3 equation incorporating cystatin C, creatinine, urea, height and gender in terms of %prediction error and accuracy., Results: All three single parameter equations performed similarly (P 30 accuracy around 80%). (FASage+Schwartz cys )/2 (P 30 89.2%) and (Schwartz crea +Schwartz cys )/2 (P 30 89.0%), performed comparably to CKiD3 (P 30 90.0%). If the difference between the creatinine- and the cystatine C based eGFR was <40%, P 30 accuracy of the mean exceeded 90%., Conclusion: Combining the height-independent FASage and Schwartz Cys equations substantially improves accuracy and performs comparably to height-dependent equations. This allows laboratories to directly report eGFR in children., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background Guidelines recommend estimation of glomerular filtration rate (eGFR) prior to iodine contrast media (CM) examinations. It is also recommended that absolute eGFR in mL/min, not commonly used relative GFR (adjusted to body surface area; mL/min/1.73 m 2 ), should be preferred when dosing and evaluating toxicity of renally excreted drugs. Purpose To validate the absolute Lund-Malmö equation (LM-ABS) in comparison with the absolute Cockcroft-Gault (CG) equation and the relative equations, revised Lund-Malmö (LM-REV), MDRD, and CKD-EPI, after converting relative estimates to absolute values, and to analyze change in eGFR classification when absolute instead of relative eGFR was used. Material and Methods A total of 3495 plasma clearance of iohexol to measure GFR (mGFR) served as reference test. Bias, precision, and accuracy (percentage of estimates ±30% of mGFR; P 30 ) were compared overall and after stratification for various mGFR, eGFR, age, and BMI subgroups. Results The overall P 30 results of CG/LM-ABS/LM-REV/MDRD/CKD-EPI were 62.8%/84.9%/83.7%/75.3%/75.6%, respectively. LM-ABS was the most stable equations across subgroups and the only equation that did not exhibit marked overestimation in underweight patients. For patients with relative eGFR 30-44 and 45-59 mL/min/1.73 m 2 , 36% and 58% of men, respectively, and 24% and 32% of women, respectively, will have absolute eGFR values outside these relative eGFR intervals. Conclusion Choosing one equation to estimate GFR prior to contrast medium examinations, LM-ABS may be preferable. Unless absolute instead of relative eGFR are used, systematic inaccuracies in assessment of renal function may occur in daily routine and research on CM nephrotoxicity may be flawed.

Background: No comprehensive systematic review of the accuracy of glomerular filtration rate (GFR) measurement methods using renal inulin clearance as reference has been published., Study Design: Systematic review with meta-analysis of cross-sectional diagnostic studies., Setting & Population: Published original studies and systematic reviews in any population., Selection Criteria for Studies: Index and reference measurements conducted within 48 hours; at least 15 participants studied; GFR markers measured in plasma or urine; plasma clearance calculation algorithm verified in another study; tubular secretion of creatinine had not been blocked by medicines., Index Tests: Endogenous creatinine clearance; renal or plasma clearance of chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA), diethylenetriaminepentaacetic acid (DTPA), iohexol, and iothalamate; and plasma clearance of inulin., Reference Test: Renal inulin clearance measured under continuous inulin infusion and urine collection., Results: Mean bias <10%, median bias <5%, the proportion of errors in the index measurements that did not exceed 30% (P30) ≥80%, and P10 ≥50% were set as requirements for sufficient accuracy. Based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the quality of evidence across studies was rated for each index method. Renal clearance of iothalamate measured GFR with sufficient accuracy (strong evidence). Renal and plasma clearance of 51Cr-EDTA and plasma clearance of iohexol were sufficiently accurate to measure GFR (moderately strong evidence). Renal clearance of DTPA, renal clearance of iohexol, and plasma clearance of inulin had sufficient accuracy (limited evidence). Endogenous creatinine clearance was an inaccurate method (strong evidence), as was plasma clearance of DTPA (limited evidence). The evidence to determine the accuracy of plasma iothalamate clearance was insufficient. With the exception of plasma clearance of inulin, only renal clearance methods had P30 >90%., Limitations: The included studies were few and most were old and small, which may limit generalizability. Requirements for sufficient accuracy may depend on clinical setting., Conclusions: At least moderately strong evidence suggests that renal clearance of 51Cr-EDTA or iothalamate and plasma clearance of 51Cr-EDTA or iohexol are sufficiently accurate methods to measure GFR., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The performance of creatinine-based glomerular filtration rate (GFR) estimating equations may vary in subgroups defined by GFR, age and body mass index (BMI). This study compares the performance of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with the revised Lund-Malmö equation (LM Revised), a new equation that can be expected to handle changes in GFR across the life span more accurately., Methods: The study included 3495 examinations in 2847 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 52 mL/min/1.73 m²). Bias, precision [interquartile range (IQR)] and accuracy [percentage of estimates ±10% (P₁₀) and ±30% (P₃₀) of mGFR] were compared., Results: The overall results of LM Revised/MDRD/CKD-EPI were: median bias 2%/8%/11%, IQR 12/14/14 mL/min/1.73 m², P₁₀ 40%/35%/35% and P₃₀ 84%/75%/76%. LM Revised was the most stable equation in terms of bias, precision and accuracy across mGFR, age and BMI intervals irrespective of gender. MDRD and CKD-EPI overestimated mGFR in patients with decreased kidney function, young adults and elderly. All three equations overestimated mGFR and had low accuracy in patients with BMI <20 kg/m², most pronounced among men., Conclusions: In settings similar to the investigated cohort LM Revised should be preferred to MDRD and CKD-EPI due to its higher accuracy and more stable performance across GFR, age and BMI intervals.

Plasma cystatin C is increasingly used as a marker of glomerular filtration rate. Most assays for cystatin C are based on turbidimetric or nephelometric detection and studies of other rapid methods are limited. This study aimed to develop and compare differently configured immunoassays for quantification of plasma cystatin C, using recombinant cystatin C and two cystatin C-specific antibodies. Method 1 was a two-step sandwich assay with polyclonal antibody as capture and europium chelate-labeled monoclonal antibody as tracer. Method 2 was a one-step heterogeneous competitive assay using immobilized polyclonal antibody and europium-labeled cystatin C. Method 3 was a one-step homogeneous competitive assay with europium-labeled polyclonal antibody as donor and cyanine 5-labeled cystatin C as acceptor. All three assays were evaluated with plasma samples and their performance was compared to a conventional particle-enhanced turbidimetric immunoassay (PETIA). Method 3 was the easiest to perform, with incubation at ambient temperature for 10 min and 20 μL of sample, while methods 1 and 2 had washing steps, took 40 min and 15 min at 37°C, respectively, but used only 10 μL of 100- or 10-fold diluted sample, respectively. The working ranges for methods 1, 2 and 3 were 0.0005-0.2, 0.05-1.0 and 0.25-20mg/L, respectively. Kinetics for method 3 was the fastest with >95% binding completion and for method 2 the slowest with 60% binding completion. All three methods showed good correlation to PETIA, but produced higher cystatin C levels than PETIA. Methods 1 and 3 offered the most favorable performance characteristics and especially method 3 enabled rapid and simple measurement of circulating cystatin C., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To evaluate the clinical performance in a paediatric population of the Lund-Malmö creatinine-based glomerular filtration rate (GFR) prediction equations, primarily developed for adults., Material and Method: Iohexol clearance was used as the gold standard in 85 paediatric Caucasian patients (0.3-17 years; 37 F/48 M). One Lund-Malmö equation was based on age and gender (LM) and one included lean body mass (LM-LBM). Comparisons focused on correlation (adjusted R2), bias (median percent error) and accuracy (proportions of predicted GFR differing < or = 30% from measured GFR) (mL/min/1.73 m2). The performances were compared with those of the Modification of Diet in Renal Disease (MDRD) Study equation, a dedicated paediatric creatinine equation, Counahan-Barratt (CB) and a cystatin C-based equation., Results: The MDRD equation performed poorly with a median bias of 96%. Of the remaining equations, only the LM-LBM produced significant bias (+10% in median) according to line of identity regression analysis. The LM equation yielded marginally higher accuracy (76%) than the LM-LBM equation (74%) and the CB (73%), but lower than the cystatin C-based equation (82%). However, the estimated accuracy figures for these four equations were generally imprecise and none of the differences compared with the LM equation was statistically significant., Conclusion: In contrast to most creatinine-based GFR prediction equations, the LM equation performs adequately for both children and adults. This may be due to the unique model-building principles used when the LM equation was established. Further validation in a larger paediatric population is necessary.

The aim of this study was to establish creatinine growth curves separately for males and females that can be used to adjust childhood levels of serum creatinine to corresponding adult levels. Linear regression with fractional polynomials of age as independent variable was used to construct creatinine growth curves for a reference cohort (n = 83,157 samples from Belgium and Sweden, age 2–40 years). Adjusted creatinine obtained from the growth curves was used to improve accuracy of estimated glomerular filtration rate (eGFR) based on the Lund–Malmö revised (LMR) equation in children. The LMR equation based on creatinine values adjusted to age 18 years was validated against measured GFR (mGFR) in a separate cohort of 4005 children from four different European countries. Validation metrics included median bias, precision, and accuracy expressed as percentage of estimates within ±30% (P30) of mGFR. Remarkable improvements in bias and accuracy were observed; P30 increased from 56% to 74% after creatinine adjustments in children with mGFR <75 mL/min/1.73 m2 (n = 932), while P30 was relatively unchanged (89–90%) at mGFR ≥75 mL/min/1.73 m2 (n = 3073). The suggested approach with adjusted creatinine makes LMR applicable in children irrespective of their renal function. [ABSTRACT FROM AUTHOR]

Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved. Methods In a cross-sectional analysis covering the years 2003–17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n  = 8365) and in patients with low likelihood of CKD (six community cohorts, n  = 6759). Comparisons were made with the Lund–Malmö revised equation (LMR) and the Full Age Spectrum equation. Results 7In patients aged 18–39 years old, CKD-EPI overestimated GFR with 5.0–16 mL/min/1.73 m2 in median in both cohort types at mGFR levels <120 mL/min/1.73 m2. LMR had greater accuracy than CKD-EPI in the CKD cohorts (P30, the percentage of estimated GFR within 30% of mGFR, 83.5% versus 76.6%). CKD-EPI was generally the most accurate equation in the community cohorts, but all three equations reached P30 above the Kidney Disease Outcomes Quality Initiative benchmark of 90%. Conclusions None of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated. [ABSTRACT FROM AUTHOR]

Background Validation studies comparing glomerular filtration rate (GFR) equations based on standardized creatinine and cystatin C assays in the elderly are needed. The Icelandic Age, Gene/Environment Susceptibility-Kidney cohort was used to compare two pairs of recently developed GFR equations, the revised Lund–Malmö creatinine equation (LMRCr) and the arithmetic mean of the LMRCr and Caucasian, Asian, Paediatric and Adult cystatin C equations (MEANLMR+CAPA), as well as the Full Age Spectrum creatinine equation (FASCr) and its combination with cystatin C (FASCr+Cys), with the corresponding pair of Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPICr and CKD-EPICr+Cys). Methods A total of 805 individuals, 74–93 years of age, underwent measurement of GFR (mGFR) using plasma clearance of iohexol. Four metrics were used to compare the performance of the GFR equations: bias, precision, accuracy [including the percentage of participants with estimated GFR (eGFR) within 30% of mGFR (P30)] and the ability to detect mGFR <60 mL/min/1.73 m2. Results All equations had a P30 >90%. LMRCr and FASCr yielded significantly higher precision and P30 than CKD-EPICr, while bias was significantly worse. LMRCr, FASCr and CKD-EPICr showed similar ability to detect mGFR <60 mL/min/1.73 m2 based on the area under the receiver operating characteristic curves. MEANLMR+CAPA, FASCr+Cys and CKD-EPICr+Cys all exhibited consistent improvements compared with the corresponding creatinine-based equations. Conclusion None of the creatinine-based equations was clearly superior overall in this community-dwelling elderly cohort. The addition of cystatin C improved all of the creatinine-based equations. [ABSTRACT FROM AUTHOR]

Estimating glomerular filtration rate (GFR) in adults by using the average of values obtained by a cystatin C- (eGFRcystatin C) and a creatinine-based (eGFRcreatinine) equation shows at least the same diagnostic performance as GFR estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparison of eGFRcystatin C and eGFRcreatinine plays a pivotal role in the diagnosis of Shrunken Pore Syndrome, where low eGFRcystatin C compared to eGFRcreatinine has been associated with higher mortality in adults. The present study was undertaken to elucidate if this concept can also be applied in children. Using iohexol and inulin clearance as gold standard in 702 children, we studied the diagnostic performance of 10 creatinine-based, 5 cystatin C-based and 3 combined cystatin C-creatinine eGFR equations and compared them to the result of the average of 9 pairs of a eGFRcystatin C and a eGFRcreatinine estimate. While creatinine-based GFR estimations are unsuitable in children unless calibrated in a pediatric or mixed pediatric-adult population, cystatin C-based estimations in general performed well in children. The average of a suitable creatinine-based and a cystatin C-based equation generally displayed a better diagnostic performance than estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparing eGFRcystatin and eGFRcreatinine may help identify pediatric patients with Shrunken Pore Syndrome. [ABSTRACT FROM AUTHOR]

Unlabelled: Creatinine-based equations to estimate glomerular filtration rate (GFR) are increasingly used in radiological practice and in studies on contrast medium-induced acute kidney injury (CIAKI). Their use is recommended in guidelines and contrast medium textbooks to identify patients at risk of CIAKI or nephrogenic systemic fibrosis. There is also an increased interest in cystatin C-based equations. Adopting GFR equations requires local creatinine and cystatin C assay calibrations to equal those used in developing the equations to avoid overestimation or underestimation of renal function. Methods should preferably be traceable to international standards, and assay traceability should be defined in CIAKI studies. Absolute GFR (mL/min) should be used when dosing contrast media and relating the dose to CIAKI instead of commonly used relative GFR (mL/min/1.73 m(2)) estimates. Accuracy of creatinine and cystatin C equations (percentage of GFR estimates within 30% of measured GFR) ranges between 75% and 85%. Equations combining creatinine and cystatin C may reach 90%, an accuracy similar to clearance methods (used as a reference test when developing and validating equations) when compared to the gold standard, renal clearance of inulin. The local laboratory or nephrology experts should be consulted in matters of method calibration and choice of GFR equation.Key Points: • Traceability of creatinine/cystatin C assays used in GFR equations must be defined. • Absolute, not relative, GFR should be used when dosing contrast media. • Consult the local laboratory or nephrologist to choose the proper GFR equation. [ABSTRACT FROM AUTHOR]

Background: The recently established international cystatin C calibrator makes it possible to develop non-laboratory specific glomerular filtration rate (GFR) estimating (eGFR) equations. This study compares the performance of the arithmetic mean of the revised Lund-Malmö creatinine and CAPA cystatin C equations (MEANLM-REV+CAPA), the arithmetic mean of the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) creatinine and cystatin C equations (MEANCKD-EPI), and the composite CKD-EPI equation (CKD-EPICREA+CYSC>) with the corresponding single marker equations using internationally standardized calibrators for both cystatin C and creatinine. Methods: The study included 1200 examinations in 1112 adult Swedish patients referred for measurement of GFR (mGFR) 2008–2010 by plasma clearance of iohexol (median 51 mL/min/1.73 m2 ). Bias, precision (interquartile range, IQR) and accuracy (percentage of estimates  ± 30% of mGFR; P30) were compared. Results: Combined marker equations were unbiased and had higher precision and accuracy than single marker equations. Overall results of MEANLM-REV+CAPA/ MEANCKD-EPI/CKD-EPICREA+CYSC were: median bias –2.2%/– 0.5%/–1.6%, IQR 9.2/9.2/8.8 mL/min/1.73 m2 , and P30 91.3%/91.0%/91.1%. The P30 figures were about 7–14 percentage points higher than the single marker equations. The combined equations also had a more stable performance across mGFR, age and BMI intervals, generally with P30   ≥  90% and never  < 80%. Combined equations reached P30 of 95% when the difference between eGFRCREA and eGFRCYSC was  < 10% but decreased to 82% at a difference of   ≥  40%. Conclusions: Combining cystatin C and creatinine assays improves GFR estimations with P30   ≥  90% in adults. Reporting estimates of both single and combined marker equations in clinical settings makes it possible to assess the validity of the combined equation based on the agreement between the single marker equations. [ABSTRACT FROM AUTHOR]

Objective. GFR-prediction equations based upon cystatin C and creatinine have better diagnostic performance in estimating GFR than equations based upon only one of the two markers. The present work concerns in what way a comparison between separate estimations of GFR based upon cystatin C (eGFRcystatin C) or creatinine (eGFRcreatinine) can be used to evaluate the diagnostic performance of a combined cystatin C- and creatinine-based estimation of GFR. Methods. The difference between eGFRcystatin C and eGFRcreatinine was compared with measured GFR (iohexol clearance) and a combined cystatin C- and creatinine-based estimation of GFR in a Swedish-Caucasian cohort of 857 adult patients. Results. A difference between eGFRcystatin C and eGFRcreatinine of ≥ 40% indicated a markedly reduced diagnostic performance of the combined cystatin C- and creatinine-based estimation of GFR. Conclusion. Comparison of the agreement between eGFRcystatin C and eGFRcreatinine can be used to evaluate the diagnostic performance of combined cystatin C- and creatinine-based estimations of GFR. If 'threshold values' for discordance are exceeded, it must be considered whether the clinical context requires the use of an invasive gold standard method to measure GFR. In some clinical contexts either creatinine or cystatin C are known to be invalidated as markers of GFR and in these situations the use of only the cystatin C- or the creatinine-based GFR estimate should be considered when the 'threshold values' are exceeded. [ABSTRACT FROM AUTHOR]

Objective. GFR-prediction equations based upon cystatin C and creatinine have better diagnostic performance in estimating GFR than equations based upon only one of the two markers. The present work concerns in what way a comparison between separate estimations of GFR based upon cystatin C (eGFRcystatin C) or creatinine (eGFRcreatinine) can be used to evaluate the diagnostic performance of a combined cystatin C- and creatinine-based estimation of GFR. Methods. The difference between eGFRcystatin C and eGFRcreatinine was compared with measured GFR (iohexol clearance) and a combined cystatin C- and creatinine-based estimation of GFR in a Swedish-Caucasian cohort of 857 adult patients. Results. A difference between eGFRcystatin C and eGFRcreatinine of ≥ 40% indicated a markedly reduced diagnostic performance of the combined cystatin C- and creatinine-based estimation of GFR. Conclusion. Comparison of the agreement between eGFRcystatin C and eGFRcreatinine can be used to evaluate the diagnostic performance of combined cystatin C- and creatinine-based estimations of GFR. If 'threshold values' for discordance are exceeded, it must be considered whether the clinical context requires the use of an invasive gold standard method to measure GFR. In some clinical contexts either creatinine or cystatin C are known to be invalidated as markers of GFR and in these situations the use of only the cystatin C- or the creatinine-based GFR estimate should be considered when the 'threshold values' are exceeded. [ABSTRACT FROM AUTHOR]

Objective. To increase the accuracy of estimated GFR (eGFR) from creatinine overall and at measured GFR ≥≥90 mL/min per 1.73 m2 by revising the Lund-Malmöö (LM) equations, to elaborate on more complex forms to improve the LM and CKD-EPI equations further, and to assess benefits of adding lean body mass (LBM). Material and methods. Swedish Caucasians ( n == 850, 376 women; median 60, range 18--95 years) referred for GFR measurement (plasma iohexol-clearance: median 55, range 5--173 mL/min/1.73 m2) constituted the Lund-Malmöö Study cohort. Bias, precision, accuracy, expressed as median absolute percentage difference and percentage of estimates ±±10% (P10) and ±±30% (P30) of measured GFR, and classification ability with respect to five GFR stages were compared with the original LM, CKD-EPI and MDRD equations. Results. LM Revised overall performed better than LM Original without LBM due to increased accuracy at measured GFR ≥≥90 mL/min/1.73 m2. Further extensions of the CKD-EPI or LM equations did not substantially improve overall performance. In particular, the performance of LM Revised at measured GFR ≥≥90 mL/min/1.73 m2 could not be improved further without decreasing accuracy and classification ability at lower GFR-levels. Adding LBM to the equations had no strong effect on accuracy. Conclusion. Comparisons with the CKD-EPI and MDRD equations suggest that the LM equations are superior for the present Swedish population, due to markedly higher accuracy of the LM equations at measured GFR <30 mL/min/1.73 m2. However, the LM equations cannot be recommended for use in general clinical practice until validated in other populations. [ABSTRACT FROM AUTHOR]

Objective. To compare the recently developed CKD-EPI equation to estimate GFR in adult Swedish-Caucasians with the MDRD equation. Material and methods. Swedish-Caucasians ( N == 850, 376 females; median age 60, range 5--95 years) referred for plasma iohexol-clearance (median 55, range 5--223 mL/min/1.73 m2) constituted the Lund-Malmöö Study cohort. Bias, precision (interquartile range, IQR, of the differences between estimated and measured GFR), accuracy expressed as percentage of estimates ±±10% (P10) and ±±30% (P30) of measured GFR, and classification ability for five GFR stages <15, 15--29, 30--59, 60--89 and ≥≥90 mL/min/1.73 m2 were compared. Results. Overall there were no important differences between the equations; CKD-EPI/MDRD median values of bias ++5.4%/++3.4%, IQR both 14 mL/min/1.73 m2, P10 36%/34%, P30 both 80%, and correctly classified GFR stages 68%/67%. P30 for the CKD-EPI equation was substantially higher than for MDRD at GFR ≥≥90 mL/min/1.73 m2 (93% versus 79%). The MDRD equation performed better in the GFR interval 30--89 mL/min/1.73 m2, while accuracy was limited for both equations at GFR <30 mL/min/1.73 m2 (P30 <75% in both females and males). The CKD-EPI/MDRD equations caused a ++22%/++14% bias in the 18--39 year interval and the MDRD equation a ++18% bias ≥≥80 years. Both equations performed poorly in males with BMI <20 kg/m2 (CKD-EPI/MDRD median bias ++36%/46%). Conclusion. Overall the recently developed CKD-EPI equation performed well but was not superior to the MDRD equation. The CKD-EPI equation may be preferred in screenings of general populations and in the elderly. None of the equations appeared reliable among patients with markedly decreased GFR, young adults and underweight males. [ABSTRACT FROM AUTHOR]

Objective. To demonstrate how patients’ probability of having chronic kidney disease (CKD) stage 3–5 (measured GFR <60 mL/min/1.73 m2) can be predicted from a specific value of estimated glomerular filtration rate (eGFR). Material and methods. The probability of CKD stage 3–5 was predicted from a logistic regression model ( n = 850) using three different eGFR prediction equations: Lund-Malmö, MDRD and CKD-EPI. Population weighting was used to illustrate how this probability varies in three different populations: original sample (55% true prevalence of CKD stage 3–5), a screening (6.7% prevalence) and a CKD population (84% prevalence). Results. All three eGFR-equations had high classification ability (area under the receiver-operating-characteristic curve = 97%). The probability of CKD stage 3–5 increased with decreasing eGFR, varied substantially among the populations studied and to some extent between the eGFR-equations. Using the Lund-Malmö equation as illustration, the probability of CKD stage 3–5 is > 90% only when eGFR is <38 mL/min/1.73 m2 in a screening population, whereas it is > 90% already when eGFR is <51 mL/min/1.73 m2 in a CKD population. Conversely, the probability of CKD stage 3–5 is <10% if eGFR > 59 mL/min/1.73 m2 in a screening population, whereas it is <10% only when eGFR is > 88 mL/min/1.73 m2 in a CKD population. Conclusion. Instead of reporting diagnostic accuracy as sensitivity, specificity, and predictive values, actual eGFR supplemented with the probability that it represents a true GFR <60 mL/min/1.73 m2 may be more valuable for physicians. Clinical (pre-test) probability in the population must be considered when predicting this probability. [ABSTRACT FROM AUTHOR]

Knowledge of glomerular filtration rate (GFR) is required to detect and follow impairment of renal function, to allow correct dosage of drugs cleared by the kidneys, and for the use of nephrotoxic contrast media. Correct determination of GFR requires invasive techniques, which are expensive, slow and not risk-free. Therefore, GFR-prediction equations based solely upon cystatin C or creatinine and anthropometric data or upon cystatin C, creatinine and anthropometric data have been developed. The combined prediction equations display the best diagnostic performance, but in several easily identifiable clinical situations (e.g. abnormal muscle mass, treatment with large doses of glucocorticoids) prediction equations based upon either cystatin C or creatinine are better than the combined equations. In Lund, where cystatin C has been used as a GFR-marker in the clinical routine since 1994, a strategy based upon this knowledge has therefore been developed. This comprises simultaneous use of a cystatin C-based and a creatinine-based GFR-prediction equation. If the GFRs predicted agree, the mean value is used as a reliable GFR-estimate. If the GFRs predicted do not agree, clinical data is evaluated to identify reasons for not using one of the two prediction equations and the GFR predicted by the other one is used. If no reasons for the difference in predicted GFRs are found, an invasive gold standard determination of GFR is performed. If the GFRs predicted agree for a patient, the creatinine value is reliably connected to a specific GFR and can be used to follow changes in GFR of that patient. [ABSTRACT FROM AUTHOR]

Purpose: To test various ways of combining creatinine and cystatin C in equations to predict glomerular filtration rate (GFR). Material and methods: Performance of the following expressions to predict GFR was compared with measured GFR (iohexol clearance, mL/min/1.73m2) in 857 patients: (i) Lund-Malmo creatinine equation, (ii) Grubb cystatin C equation, (iii) arithmetic mean of (1) and (2), (iv) geometric mean of (1) and (2), (v) linear regression on (1) and (2), (vi) regression on (1) and cystatin C, and (vii) regression on creatinine, cystatin C, age and gender. Results: For the entire cohort median percent error (bias) was <5% for all expressions, though all expressions tended to underestimate (−8.3 to −15.8%) GFR at levels ≥90 mL/min/1.73m2. The five expressions combining creatinine and cystatin C significantly improved correlation and accuracy ( p<0.001) within 15 and 30% of measured GFR compared with the equations based on the separate analytes and with no significant difference between the five expressions. In a subgroup of patients with neurological disease and muscle atrophy the cystatin C equation performed better than the expressions combining creatinine and cystatin C. Conclusion: Simply calculating the arithmetic mean of predicted GFR based on separate creatinine and cystatin C equations performs equally well as more complex equations. Reporting GFR based on separate creatinine and cystatin C equations, and their arithmetic mean also has the definite advantage that the physician can choose the estimated GFR, most appropriate depending on the clinical setting and patient characteristics. [ABSTRACT FROM AUTHOR]

Objective. New proposed definitions of chronic kidney disease necessitate the development and use of simple and accurate methods for estimating glomerular filtration rate (GFR). Plasma cystatin C has been shown to be a more reliable GFR marker than creatinine and formulae for estimating GFR have been reported. The purpose of this study was to validate a cystatin C-based GFR prediction equation in a different population from the derivation set but using the cystatin C assay of a single laboratory, and to compare the results with that of the creatinine-based Modification of Diet in Renal Disease (MDRD) Study equation. Material and methods. A newly presented formula based on plasma cystatin C and gender and the MDRD formula based on creatinine for estimation of GFR were validated in an unselective patient material. Single sample iohexol clearance was used as the GFR reference method in 406 consecutive patients with GFR varying from normal to poor renal function. The creatinine assay used was standardized to express true plasma creatinine. Results. Median bias (1.1%) and accuracy (79.1% of the estimates within ±30% of iohexol clearance) of the cystatin C formula were close to the derivation set. The accuracy was significantly higher than that of the original four-variable MDRD equation (73.2%; median bias 9.8%). However, the accuracy did not differ significantly from that of the re-expressed MDRD formula (79.6%; median bias 3.2%) based on true creatinine. Both formulae performed with a low bias and acceptable accuracy up to a GFR of 90 ml/min/1.73 m2. Conclusions. GFR estimation based on plasma cystatin C performed equally well in the validation as in the derivation set, and was as accurate as the re-expressed MDRD creatinine-based equation. [ABSTRACT FROM AUTHOR]