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Routine serum creatinine measurements: how well do we perform?

ABSTRACT: The first aim of the study was to investigate the accuracy and intra-laboratory variation of serum creatinine measurements in clinical laboratories in Flanders. The second purpose was to check the effect of this variation in serum creatinine concentration results on the calculated estimated glomerular filtration rate (eGFR) and the impact on classification of patients into a chronic kidney disease (CKD) stage.26 routine instruments were included, representing 13 different types of analyzers from 6 manufacturers and covering all current methodologies (Jaffe, compensated Jaffe, enzymatic liquid and dry chemistry methods). Target values of five serum pools (creatinine concentrations ranging from 35 to 934 ?mol/L) were assigned by the gold standard method (ID-GC/MS).Intra-run CV (%) (n?=?5) and bias (%) from the target values were higher for low creatinine concentrations. Especially Jaffe and enzymatic dry chemistry methods showed a higher error. The calculated eGFR values corresponding with the reported creatinine concentration ranges resulted in a different CKD classification in 47% of cases.Although most creatinine assays claim to be traceable to the gold standard (ID-GC/MS), large inter-assay differences still exist. The inaccuracy in the lower concentration range is of particular concern and may lead to clinical misinterpretation when the creatinine-based eGFR of the patient is used for CKD staging. Further research to improve harmonization between methods is required.

SUBMITTER: Hoste L

PROVIDER: S-EPMC4358903 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Routine serum creatinine measurements: how well do we perform?

Hoste Liesbeth L Deiteren Kathleen K Pottel Hans H Callewaert Nico N Martens Frank F

BMC nephrology 20150214

<h4>Background</h4>The first aim of the study was to investigate the accuracy and intra-laboratory variation of serum creatinine measurements in clinical laboratories in Flanders. The second purpose was to check the effect of this variation in serum creatinine concentration results on the calculated estimated glomerular filtration rate (eGFR) and the impact on classification of patients into a chronic kidney disease (CKD) stage.<h4>Methods</h4>26 routine instruments were included, representing 1 ...[more]

PMID: 25803560

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Project description:IntroductionN-acetylcysteine (NAC) is an antioxidant that can regenerate glutathione and is primarily used for acetaminophen overdose. NAC has been tested and used for preventing iatrogenic acute kidney injury or slowing the progression of chronic kidney disease, with mixed results. There are conflicting reports that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, we conducted a systematic review of the literature to determine whether there is an effect of NAC on kidney function as measured with serum creatinine and cystatin C.MethodsA literature search was conducted to identify all study types reporting a change in serum creatinine after NAC administration. The primary outcome was change in serum creatinine after NAC administration. The secondary outcome was a change in cystatin C after NAC administration. Subgroup analyses were conducted to assess effect of creatinine assay (Jaffe vs. non-Jaffe and intravenous vs. oral).ResultsSix studies with a total of 199 participants were eligible for the systematic review and meta-analysis. There was a small but significant decrease in serum creatinine after NAC administration overall (weighted mean difference [WMD], -2.80 μmol/L [95% confidence interval {CI} -5.6 to 0.0]; P = 0.05). This was greater with non-Jaffe methods (WMD, -3.24 μmol/L [95% CI -6.29 to -0.28]; P = 0.04) than Jaffe (WMD, -0.51 μmol/L [95% CI -7.56 to 6.53]; P = 0.89) and in particular with intravenous (WMD, -31.10 μmol/L [95% CI -58.37 to -3.83]; P = 0.03) compared with oral NAC (WMD, -2.5 μmol/L [95% CI -5.32 to 0.32]; P = 0.08). There was no change in cystatin C after NAC administration.DiscussionNAC causes a decrease in serum creatinine but not in cystatin C, suggesting analytic interference rather than an effect on kidney function. Supporting this, the effect was greater with non-Jaffe methods of creatinine estimation. Future studies of NAC should use the Jaffe method of creatinine estimation when kidney outcomes are being reported. Even in clinical settings, the use of an enzymatic assay when high doses of intravenous NAC are being used may result in underdiagnosis or delayed diagnosis of acute kidney injury.

Project description:BackgroundAcute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury. Snake envenomation is one of several causes of AKI in dogs and humans. Dogs are commonly envenomated by the European adder (Vipera berus) between April and October each year, but few studies exist examining serial serum creatinine (sCr) and symmetric dimethylarginine (SDMA) measurements and AKI biomarkers in these dogs. Novel urinary biomarkers could improve clinical outcome by allowing earlier diagnosis of and intervention in AKI. The aim of this study was to assess the presence of AKI in dogs envenomated by V. berus at 12, 24 and 36 h after bite, as well as 14 days later, using sCr, SDMA and a panel of urinary AKI biomarkers normalised to urine creatinine (uCr), compared to a group of healthy control dogs.ResultsThirty-five envenomated dogs and 35 control dogs were included. Serum creatinine did not exceed the upper reference limit at any time point in any dog after envenomation. Serum SDMA did not exceed 0.89 μmol/L in any dog. Compared to controls, urinary albumin/uCr, neutrophil gelatinase-associated lipocalin/uCr and monocyte chemotactic protein-1/uCr were significantly elevated 12 h (P < 0.0001, P < 0.0001, P = 0.01), 24 h (P < 0.001, P < 0.001, P = 0.002) and 36 h (P < 0.001, P < 0.001, P = 0.0008) after bite. Osteopontin/uCr was higher 24 and 36 h after bite (P < 0.0001), kidney injury molecule-1/uCr, interleukin-8/uCr and γ- glutamyl transferase/uCr were significantly higher 36 h after bite (P = 0.003, P = 0.0005, P = 0.001). Urinary cystatin C/uCr was not significantly different to controls at any timepoint. Biomarker/uCr ratios were not significantly different 14 days after envenomation compared to controls.ConclusionUrinary biomarker/Cr ratios are indicative of mild transient, non-azotaemic AKI in dogs envenomated by V. berus.

Project description:BackgroundA convenient method to estimate the creatinine generation rate and measures of creatinine clearance in hemodialysis patients using formal kinetic modeling and standard pre- and postdialysis blood samples has not been described.MethodsWe used data from 366 dialysis sessions characterized during follow-up month 4 of the HEMO study, during which cross-dialyzer clearances for both urea and creatinine were available. Blood samples taken at 1?h into dialysis and 30?min and 60?min after dialysis were used to determine how well a two-pool kinetic model could predict creatinine concentrations and other kinetic parameters, including the creatinine generation rate. An extrarenal creatinine clearance of 0.038?l/kg/24?h was included in the model.ResultsDiffusive cross-dialyzer clearances of urea [230?(SD 37 mL/min] correlated well (R2?=?0.78) with creatinine clearances [164?(SD 30)?mL/min]. When the effective diffusion volume flow rate was set at 0.791 times the blood flow rate for the cross-dialyzer clearance measurements at 1?h into dialysis, the mean calculated volume of creatinine distribution averaged 29.6?(SD 7.2) L], compared with 31.6?(SD 7.0)?L for urea (P?<?0.01). The modeled creatinine generation rate [1183?(SD 463)?mg/day] averaged 100.1?% (SD 29; median 99.3) of that predicted in nondialysis patients by an anthropometric equation. A simplified method for modeling the creatinine generation rate using the urea distribution volume and urea dialyzer clearance without use of the postdialysis serum creatinine measurement gave results for creatinine generation rate [1187?(SD 475) mg/day; that closely matched the value calculated using the formally modeled value, R2?=?0.971].ConclusionsOur analysis confirms previous findings of similar distribution volumes for creatinine and urea. After taking extra-renal clearance into consideration, the creatinine generation rate in dialysis patients is similar to that in nondialysis patients. A simplified method based on urea clearance and urea distribution volume not requiring a postdialysis serum creatinine measurement can be used to yield creatinine generation rates that closely match those determined from standard modeling.

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Routine serum creatinine measurements: how well do we perform?

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Routine serum creatinine measurements: how well do we perform?

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