Discrepant Results of Serum Creatinine and Cystatin C in a Urological Patient

Roij, K G E van; Horst, Henriëtte van der; Hubeek, Isabelle; Wijk, J. A. E. van; Bökenkamp, Arend

doi:10.1373/clinchem.2016.261925

Cited by 11 publications

(7 citation statements)

References 12 publications

(9 reference statements)

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“…This is in line with previous studies showing that the simple arithmetic means of existing single-marker equations tend to perform as well as more complex formulations that include both markers [21,43,44]. This approach also alerts the clinician to situations where one of the two GFR markers fails such as creatinine in spina bifida patients or cystatin C during high-dose glucocorticoid treatment [43,45,46].…”

Section: Discussionsupporting

confidence: 86%

Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children

et al. 2019

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Background Most validations of paediatric glomernlar filtration rate (GFR) estimating equations using standardized ceatinine (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-2009CR/2012CR/CYS/CR+CYS, FASCR/CYS/CR+CYS, LMRCR, Schwartz-LyonCR, BergCYS, CAPACYS, CKD-EPICYS, AndersenCR+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% (P10) and ± 30% (P30) of mGFR.Results Three of the cystatin C equations, BergCYS, CAPACYS and CKD-EPICYS, exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPICYS had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-LyonCR 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.

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Section: Discussionsupporting

confidence: 86%

Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children

et al. 2019

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“…However, if creatinine and cystatin C estimates differ by >40%, the eGFR values should be interpreted with caution [ 60 ]. In patients with chronic illnesses, larger discrepancies may be observed due to a reduction in muscle mass, administration of high-dose glucocorticoids, severe thyroid disease, reabsorption of filtered creatinine or heterophilic antibodies interfering with the antibody-based cystatin C assay [ 61 ]. A large discrepancy of >40% between a cystatin C– and creatinine-based eGFR is an important indication for measuring GFR using an exogenous biomarker unless the difference between the two estimates can be adequately explained [ 60 ].…”

Section: Discrepancies Between Creatinine-based and Cystatin C–based Egfrmentioning

confidence: 99%

Assessment of kidney function: clinical indications for measured GFR

Ebert

Bevc

Bökenkamp

et al. 2021

Clinical Kidney Journal

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In the vast majority of cases, glomerular filtration rate (GFR) is estimated using serum creatinine, which is highly influenced by age, sex, muscle mass, body composition, severe chronic illness and many other factors. This often leads to misclassification of patients or potentially puts patients at risk for inappropriate clinical decisions. Possible solutions are the use of cystatin C as an alternative endogenous marker or performing direct measurement of GFR using an exogenous marker such as iohexol. The purpose of this review is to highlight clinical scenarios and conditions such as extreme body composition, black race, disagreement between creatinine- and cystatin C-based estimated GFR (eGFR), drug dosing, liver cirrhosis, advanced chronic kidney disease and the transition to kidney replacement therapy, non-kidney solid organ transplant recipients, and living kidney donors where creatinine-based GFR estimation may be invalid. In contrast to the majority of literature on measured GFR (mGFR), this review does not include aspects of mGFR for research or public health settings but aims to reach practicing clinicians and raise their understanding of the substantial limitations of creatinine. While including cystatin C as a renal biomarker in GFR estimating equations has been shown to increase the accuracy of the GFR estimate, there are also limitations to eGFR based on cystatin C alone or the combination of creatinine and cystatin C in the clinical scenarios described above that can be overcome by measuring GFR with an exogenous marker. We acknowledge that mGFR is not readily available in many centres but hope that this review will highlight and promote the expansion of kidney function diagnostics using standardized mGFR procedures as an important milestone towards more accurate and personalized medicine.

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“…Still, the "Lund approach", which was proposed by Anders Grubb, compares a creatinine-and a cystatin C-based eGFR, and uses the average of both estimates [222], offers several advantages over the use of more complex equations. (i) It draws the clinician's attention to discrepant results of the two estimates, which can be a clue for yet unrecognized pathology [27,223]. (ii) In this situation, a motivated choice for one of the two equations may be more accurate than using the average.…”

Section: Combination Of Markersmentioning

confidence: 99%

Endogenous markers for kidney function in children: a review

Bakker

Gemke

Bökenkamp

2018

Critical Reviews in Clinical Laboratory Sciences

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Although glomerular filtration rate (GFR) in children can be measured using a gold-standard technique following injection of an exogenous marker, this invasive and cumbersome technique is not widely available and GFR is commonly estimated using serum levels of endogenous markers. Creatinine, urea, cystatin C, beta-trace protein, and beta-2 microglobulin are well-established endogenous markers of kidney function. These markers differ in site of production and effects of diet and medication, as well as renal-tubular handling and extra-renal elimination. For each marker, different methods are available for measurement. Importantly, the measurements of creatinine and cystatin C have recently been standardized with the introduction of international reference standards. In order to allow estimation of GFR from serum marker concentrations, different equations for estimated GFR (eGFR) have been developed in children, using simple or more complex regression strategies with gold standard GFR measurements as a dependent variable. As a rule, estimation strategies relying on more than one marker - either by calculating the average of single parameter equations or by using more complex equations incorporating several parameters - outperform eGFR estimations using only a single marker. This in-depth review will discuss the physiology, measurement and clinical use of creatinine, urea, cystatin C, beta-trace protein, and beta-2 microglobulin in children. It will also address the generation of eGFR equations in children and provide an overview of currently available eGFR equations for the pediatric age group.

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Discrepant Results of Serum Creatinine and Cystatin C in a Urological Patient

Cited by 11 publications

References 12 publications

Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children

Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children

Assessment of kidney function: clinical indications for measured GFR

Endogenous markers for kidney function in children: a review

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