The global burden of chronic kidney disease: estimates, variability and pitfalls.

Chronic kidney disease (CKD) is currently defined by abnormalities of kidney structure or function assessed using a matrix of variables - including glomerular filtration rate (GFR), thresholds of albuminuria and duration of injury - and is considered by many to be a common disorder globally. However, estimates of CKD prevalence vary widely, both within and between countries. The reasons for these variations are manifold, and include true regional differences in CKD prevalence, vagaries of using estimated GFR (eGFR) for identifying CKD, issues relating to the use of set GFR thresholds to define CKD in elderly populations, and concerns regarding the use of one-off testing for assessment of eGFR or albuminuria to define the prevalence of CKD in large-scale epidemiological studies. Although CKD is common, the suggestion that its prevalence is increasing in many countries might not be correct. Here, we discuss the possible origins of differences in estimates of CKD prevalence, and present possible solutions for tackling the factors responsible for the reported variations in GFR measurements. The strategies we discuss include approaches to improve testing methodologies for more accurate assessment of GFR, to improve awareness of factors that can alter GFR readouts, and to more accurately stage CKD in certain populations, including the elderly.

Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate.

BACKGROUND: Cystatin C is increasingly used in glomerular filtration rate (GFR) estimation equations. The dependence of cystatin C results upon the analytical method has been a major source of controversy. METHODS: Cystatin C was measured with non-standardized turbidimetric Roche Generation 1 and standardized nephelometric Siemens assays in 3666 and additionally with standardized Roche Generation 2 and Siemens in 567 blood samples of the Berlin Initiative Study. Cystatin C-based GFR was assessed with CKD-EPIcys (Chronic Kidney Disease Epidemiology) and CAPA (Caucasian, Asian, Pediatric, Adult) equations and the impact of the assays on GFR estimation was determined. Equation performance compared to measured GFR was evaluated. RESULTS: Concordance of Roche Gen2 and Siemens was high with median difference of 0.003 ± 0.13 mg/L (limits of agreement: -0.12 to 0.12) and Passing Bablok correlation was essentially perfect. Roche Gen1 assay showed worse concordance with Siemens: median difference was 0.08 ± 0.13 mg/L (limits of agreement: -0.18 to 0.34) and correlation was inferior. Mean difference (± SD) of estimated GFRCKD-EPIcys was 0 ± 4 mL/min/1.73 m(2) for Gen2 and Siemens compared to -5 ± 8 with Gen1. Performance of GFR estimating equations was not influenced by the choice of Siemens or Gen2 assays. CONCLUSIONS: Standardization of Roche Gen2 assay improved accuracy of cystatin C measurement compared to Siemens. It suggests only negligible method bias and results in equal performance of both assays when estimating GFR indicating that successful calibration has led to major progress in cystatin C analysis.

Critical care and vitamin D status assessment: what about immunoassays and calculated free 25OH-D?

BACKGROUND: Interpretation of 25OH-D measurement during critical care (CC) may be problematic due to variations of binding protein concentrations (albumin, ALB, and vitamin D binding protein, VDBP). Determination of free 25OH-D concentration may thus be relevant in CC patients. The aim of this observational study was to evaluate effects of an acute hemodilution on vitamin D (VD) status. METHODS: Blood samples were obtained before (T1) and after a crystalloid load (T2) administered at anesthesia induction for minor surgery. 25OH-D was measured with LC-MS/MS and with 3 immunoassays (IA): DiaSorin Liaison, IDS iSYS and bioMérieux Vidas. VDBP was measured with the R&D Elisa and ALB on Cobas. Free 25OH-D was calculated using published formula. Accuracy of each 25OH-D IA was calculated as the percentage of IA values within 20% of their respective LC-MS/MS values. Performances of the three AI were compared with LC-MC/MS using Bland-Altman analysis. RESULTS: Twenty adults were included. Compared to T1 values, VDBP, ALB and LC-MS/MS values decreased in parallel by a mean of 23% at T2. IA values decreased less significantly (12, 14 and 15% for Liaison, iSYS and Vidas, respectively). IA-based calculated free 25OH-D significantly increased after dilution, while LC-MS/MS-based free values remained stable. At T1 and T2, bias were demonstrable for all IA. After hemodilution, bias would lead to overestimation for the three IA. Accuracy of IA decreased after dilution. CONCLUSIONS: Due to matrix effects, compared to LC-MS/MS, IA results were impacted by hemodilution. In CC patients, LC-MS/MS seems to be the best option to measure 25OH-D. Specific LC-MS/MS method should be developed to measure free 25OH-D.

Assessment of kidney function: Estimating GFR in children.

In a new study, Schwartz and colleagues have investigated the best way to estimate glomerular filtration rate (GFR) in children. Having already improved GFR estimation with the use of creatinine-based equations, the investigators now propose a more precise method for cystatin C measurement. The precision of a GFR equation will strongly depend on the analytical precision of the biological variables included.

A multicentric evaluation of IDMS-traceable creatinine enzymatic assays.

Chronic kidney disease definition is based on glomerular filtration rate (GFR) estimations which are derived from creatinine-based equations. The accuracy of GFR estimation is thus largely dependent of those of serum creatinine assays. International recommendations highlight the need for traceable creatinine assays. The French Society of Clinical Biochemistry conducted a study for measuring accuracy of creatinine enzymatic methods. This evaluation involved 25 clinical laboratories. Creatinine was measured in serum pools ranging from 35.9±0.9 µmol/L to 174.5±3.1 µmol/L (IDMS determination) using 12 creatinine enzymatic methods. For all creatinine values greater than 74.4±1.4 µmol/L, the bias and imprecision did not exceed 5% and 5.9%, respectively. For the lowest value (35.9±0.9 µmol/L), the bias ranged from -1.8 to 9.9% (with one exception). At this level, the imprecision ranged from 1.9 to 7.8%. The true performances of the assays (couples of bias and relative standard deviation), were evaluated using Monte-Carlo simulations. Most of the assays fall within the maximum Total Error of 12% at all concentrations. This study demonstrates substantial improvements in the calibration, traceability and precision of the enzymatic methods, reaching the NKDEP recommendations. Moreover, most of these assays allowed accurate creatinine measurements for creatinine levels lower than 40 µmol/L.

Performance of iohexol determination in serum and urine by HPLC: validation, risk and uncertainty assessment.

BACKGROUND: Determination of glomerular filtration rate plays an important role in nephrological practice. Iohexol is a reference marker for glomerular filtration rate determination. It is available and safe. The aim of this study was to develop a simple, efficient and easy to use analytical method for the quantification of iohexol in serum and urine by high performance liquid chromatography and to thoroughly validate this method. METHODS: The HPLC method was inspired from the method published by Krutzen. The e.noval software V2.0 (Arlenda, Liège, Belgium) was used to compute all validation results. RESULTS: The validation results indicate that the method will give accurate and reliable results for serum values ranging from 12.95 to 1295 microg/ml and for urine values ranging from 86.0 to 4144 microg/ml. In routine practice, iohexol concentrations found in plasma after injection range from 40 to 600 microg/ml. The expected urinary values are much wider. One should not hesitate to dilute urine samples to fit with the validated range over 5000 microg/ml. CONCLUSION: This is the first time that a reference method for the determination of GFR is validated with such a rigorous and thorough protocol. Contrary to other GFR markers, iohexol is now strongly validated from an analytical point of view.