N-Acetylcysteine Interference With Creatinine Measurement: An In Vitro Analysis.
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SUBMITTER: McCudden C
PROVIDER: S-EPMC8258456 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundN-acetylcysteine (NAC) is an antioxidant which can regenerate glutathione and is primarily used for acetaminophen overdose. It is also a potential therapy to prevent iatrogenic acute kidney injury or slow the progression of chronic kidney disease. It has been considered in this context by many studies with mixed results. Notably, a biological-mechanism rationale for a protective effect of NAC has never been adequately reported. Among conflicting reports, there appears to be evidence that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, a systematic review of the literature will be conducted to determine whether there is an effect of NAC on kidney function measured with serum creatinine.ObjectiveTo determine the effect of NAC on kidney function.DesignA systematic review and meta-analysis.SettingsProspective studies, with administration of NAC, in the absence of any other change in kidney function (such as contrast administration or surgery).PatientsAdult humans aged 18 years old or more, either healthy volunteers or with chronic kidney disease, were administered with NAC. Populations having little to no kidney function such as in end-stage kidney disease will be excluded.MeasurementsSerum creatinine and/or cystatin C measurements before and after NAC administration.MethodsAn information specialist will assist in searching MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify all study types including randomized controlled trials, and prospective cohort studies reporting change in serum creatinine after NAC administration. Two reviewers will independently screen the titles and abstracts of the studies obtained from the search using predefined inclusion criteria and will then extract data from the full texts of selected studies. The weighted mean difference will be calculated for change in creatinine with NAC, using random-effects analysis. Quality assessment will be done with the Cochrane Risk of Bias tool for randomized trials and the Newcastle-Ottawa Scale for observational studies.ResultsThe outcome of interest is kidney function as reported by either change in serum creatinine and/or serum cystatin C measurement for randomized trials or comparing baseline (pre-NAC dose) values and those following the NAC dose.LimitationsPossible heterogeneity and publication bias and lack of mechanistic data.ConclusionsThis systematic review will provide a synthesis of current evidence on the effect of NAC on serum creatinine measurement. These findings will provide clinicians with guidelines and serve as a strong research base for future studies in this field.Systematic review registrationThis review is registered with PROSPERO, CRD42017055984.
| S-EPMC6156188 | biostudies-literature
Project description:BackgroundSerum creatinine is a widely used biomarker for evaluating renal function. Sarcosine oxidase enzymatic (SOE) analysis is currently the most widely used method for the detection of creatinine. This method was negatively interfered with by calcium dobesilate, causing pseudo-reduced results. The aim of this study was to explore a new method to alleviate the negative interference of this drug on creatinine detection.MethodWe formulated eight drug concentrations and 12 creatinine concentrations from serum. The SOE method, the new method, and the Jaffe method were used for detection in five systems. Creatinine biases were analyzed under the conditions with or without the interference of calcium dobesilate, at consistent or inconsistent creatinine concentrations. Creatinine concentrations were also analyzed at three medical decision levels (MDLs).ResultsCalcium dobesilate had negative interference in creatinine SOE analysis. With the increase in calcium dobesilate concentrations, the negative bias increases. The new BG method showed an anti-negative interference effect. In the Roche system, the BG method reduced the negative bias from -71.11% to -16.7%. In the Abbott system, bias was reduced from -45.15% to -2.74%. In the Beckman system, the bias was reduced from -65.36% to -7.58%. In the Siemens system, the bias was reduced from -58.62% to -7.58%. In the Mindray system, the bias was reduced from -36.29% to -6.84%.ConclusionThe new method alleviated the negative interference of calcium dobesilate in creatinine SOE detection. The negative bias could be reduced from -60% or -70% to less than -20%.
| S-EPMC8418471 | biostudies-literature
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.
| S-EPMC5837547 | biostudies-literature
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.
| S-EPMC7879108 | biostudies-literature
Project description:Most patients are discharged early (within 24?hours) after coronary angiography (CAG) and may miss identification the late (24-48?hours) increase in serum creatinine (SCr), whose characteristics and prognosis have been less intensively investigated.We prospectively recruited 3065 consecutive patients with SCr measurement, including only1344 patients with twice SCr measurement (both early and late). The late contrast-induced acute kidney injury (CI-AKI) was defined as significantly increase in SCr (?0.3?mg/dL or ?50%) not in early phase, but only in late phase after the procedure, and the early CI-AKI experienced a significantly increase in early phase.Overall, CI-AKI developed in 134 patients (10%), and the incidence of late and early CI-AKI were 3.6% and 6.4%, respectively. There were no difference in age, renal, and heart function, contrast volume among patients with late and early CI-AKI. With mean follow-up period of 2.45 years, long-term mortality (3 years, 29.7% and 35.6%, respectively, P?=?.553) was similar for patients with late and early CI-AKI. Cox analysis showed that both late (adjusted HR 2.05; 95% CI, 1.02-4.15) and early (adjusted HR 2.68; 95% CI, 1.57-4.59) CI-AKI was significantly associated with long-term mortality (all P?<?.001).Only late increase in SCr, as late CI-AKI, accounted for about one-third of CI-AKI incidence and has similar good predictive value for long-term mortality with that of an early increase, early CI-AKI, among patients with SCr measured twice, supporting the importance of late repeating SCr measurement after CAG, even without an early significant increase in SCr.
| S-EPMC5815667 | biostudies-literature
Project description:The double-slit experiment strikingly demonstrates the wave-particle duality of quantum objects. In this famous experiment, particles pass one-by-one through a pair of slits and are detected on a distant screen. A distinct wave-like pattern emerges after many discrete particle impacts as if each particle is passing through both slits and interfering with itself. Here we present a temporally- and spatially-resolved measurement of the double-slit interference pattern using single photons. We send single photons through a birefringent double-slit apparatus and use a linear array of single-photon detectors to observe the developing interference pattern. The analysis of the buildup allows us to compare quantum mechanics and the corpuscular model, which aims to explain the mystery of single-particle interference. Finally, we send one photon from an entangled pair through our double-slit setup and show the dependence of the resulting interference pattern on the twin photon's measured state. Our results provide new insight into the dynamics of the buildup process in the double-slit experiment, and can be used as a valuable resource in quantum information applications.
| S-EPMC4001097 | biostudies-literature
Project description:BACKGROUND:A falsely high cerebrospinal fluid (CSF) total protein (TP) result measured by pyrogallol red (PGR) method was suspected to be caused by preparation of the collection site with povidone-iodine (PVP-iodine) solution. METHODS:CSF TP was evaluated for interference in samples with different final concentrations of PVP-iodine (up to 0.25% PVP and 0.025% iodine) or iodine alone (up to 0.025% iodine) using three methods: PGR, modified biuret and benzethonium chloride (BZTC). Interference exceeding ±20% of the baseline value is considered clinically significant according to the criterion defined by the College of American Pathologists. RESULTS:There were positive interference with the PGR method and negative inference for the BZTC method in CSF samples spiked with PVP-iodine. The PVP-iodine (up to 0.25% PVP and 0.025% iodine) did not cause a clinically significant interference with the modified biuret method. PVP alone without iodine caused a positive interference with the PGR method but did not interfere with the modified biuret or the BZTC method. When the samples were spiked with iodine alone, none of the three methods was affected (change<20%) by iodine concentration up to 0.025%. CONCLUSIONS:Contamination of CSF specimens with PVP-iodine can lead to interference with CSF TP measurements using PGR or BZTC methods.
| S-EPMC4305459 | biostudies-literature
Project description:The Hong-Ou-Mandel (HOM) experiment was a benchmark in quantum optics, evidencing the non-classical nature of photon pairs, later generalized to quantum systems with either bosonic or fermionic statistics. We show that a simple modification in the well-known and widely used HOM experiment provides the direct measurement of the Wigner function. We apply our results to one of the most reliable quantum systems, consisting of biphotons generated by parametric down conversion. A consequence of our results is that a negative value of the Wigner function is a sufficient condition for non-gaussian entanglement between two photons. In the general case, the Wigner function provides all the required information to infer entanglement using well known necessary and sufficient criteria. The present work offers a new vision of the HOM experiment that further develops its possibilities to realize fundamental tests of quantum mechanics using simple optical set-ups.
| S-EPMC3866653 | biostudies-literature
Project description:We here used the technology of RNA interference or selective treatment of the ESR1 and cDNA microarrays to reconstruct a network between genes known to be disregulated in ER-positive breast cancer diseases. Therefor single genes of high importance were silenced and the effect of this pertubation was measured with cDNA microarrays. Keywords: Network Reconstruction, RNAi, siRNA, Interaction Network human ER-positive breast cancer cell line was cultivated as described and transfection with chemically synthesized siRNAs was performed according to standard HiPerFect transfection protocol by Qiagen (Hilden, Germany) At least 4 cDNA-microarrays were hybridized in dye-swap method for the silencing of every gene of interest. To minimize off-target effects we used at least two different siRNAs per gene.
| S-ECPF-GEOD-12291 | biostudies-other
Project description:BackgroundThe Jaffe and enzymatic methods are the two most common methods for measuring serum creatinine. The Jaffe method is less expensive than the enzymatic method but is also more susceptible to interferences. Interferences can lead to misdiagnosis but interferences may vary by patient population. The overall risk associated with the Jaffe method depends on the probability of misclassification and the consequences of misclassification. This study assessed the risk associated with the Jaffe method in an outpatient population. We analyzed the discordance rate in the estimated glomerular filtration rate based on serum creatinine measurements obtained by the Jaffe and enzymatic method.MethodsMethod comparison and risk analysis. Five hundred twenty-nine eGFRs obtained by the Jaffe and enzymatic method were compared at four clinical decision limits. We determined the probability of discordance and the consequence of misclassification at each decision limit to evaluate the overall risk.ResultsWe obtained 529 paired observations. Of these, 29 (5.5%) were discordant with respect to one of the decision limits (i.e. 15, 30, 45 or 60 ml/min/1.73m2). The magnitude of the differences (Jaffe result minus enzymatic result) were significant relative to analytical variation in 21 of the 29 (72%) of the discordant results. The magnitude of the differences were not significant relative to biological variation. The risk associated with misclassification was greatest at the 60 ml/min/1.73m2 decision limit because the probability of misclassification and the potential for adverse outcomes were greatest at that decision limit.ConclusionThe Jaffe method is subject to bias due to interfering substances (loss of analytical specificity). The risk of misclassification is greatest at the 60 ml/min/1.73m2 decision limit; however, the risk of misclassification due to bias is much less than the risk of misclassification due to biological variation. The Jaffe method may pose low risk in selected populations if eGFR results near the 60 ml/min/1.73m2 decision limit are interpreted with caution.
| S-EPMC4657986 | biostudies-literature