Dataset Information

A Systematic Review of the Effect of N-Acetylcysteine on Serum Creatinine and Cystatin C Measurements.

ABSTRACT:

Introduction

N-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.

Methods

A 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).

Results

Six 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 ?mol/L [95% confidence interval {CI} -5.6 to 0.0]; P = 0.05). This was greater with non-Jaffe methods (WMD, -3.24 ?mol/L [95% CI -6.29 to -0.28]; P = 0.04) than Jaffe (WMD, -0.51 ?mol/L [95% CI -7.56 to 6.53]; P = 0.89) and in particular with intravenous (WMD, -31.10 ?mol/L [95% CI -58.37 to -3.83]; P = 0.03) compared with oral NAC (WMD, -2.5 ?mol/L [95% CI -5.32 to 0.32]; P = 0.08). There was no change in cystatin C after NAC administration.

Discussion

NAC 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.

SUBMITTER: Huang JW

PROVIDER: S-EPMC7879108 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

A Systematic Review of the Effect of N-Acetylcysteine on Serum Creatinine and Cystatin C Measurements.

Huang Johnny W JW Lahey Brianna B Clarkin Owen J OJ Kong Jennifer J Clark Edward E Kanji Salmaan S McCudden Christopher C Akbari Ayub A J W Chow Benjamin B Shabana Wael W Hiremath Swapnil S

Kidney international reports 20201203 2

<h4>Introduction</h4>N-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 systema ...[more]

PMID: 33615065

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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.

Project description:Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR.Using cross-sectional analyses, we developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5352 participants from 13 studies. These equations were then validated in 1119 participants from 5 different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials.Mean measured GFRs were 68 and 70 ml per minute per 1.73 m(2) of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine-cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml per minute per 1.73 m(2) with the combined equation, as compared with 3.7 and 3.4 ml per minute per 1.73 m(2) with the creatinine equation and the cystatin C equation (P=0.07 and P=0.05), respectively. Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m(2), respectively [P=0.001 and P<0.001]), and the results were more accurate (percentage of estimates that were >30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P<0.001 for both comparisons]). In participants whose estimated GFR based on creatinine was 45 to 74 ml per minute per 1.73 m(2), the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m(2) or greater than or equal to 60 ml per minute per 1.73 m(2) (net reclassification index, 19.4% [P<0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m(2) as having a GFR of 60 ml or higher per minute per 1.73 m(2).The combined creatinine-cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

Project description:BackgroundSerum cystatin C (SCysC) and serum creatinine (SCr) are two biomarkers used in common practice to estimate the glomerular filtration rate (GFR). For SCysC and SCr to be used in a given population, normal values need to be determined to better assess patients. This study aimed to determine SCysC and SCr reference intervals (RIs) in a Cameroonian adult population and factors susceptible of influencing them.MethodsWe carried-out a cross-sectional study from November 2016 to May 2017 in Yaoundé, Cameroon. Participants were Cameroonians aged 18 years and above, residing inside the country and found in good health at study inclusion. SCysC and SCr were determined by particle-enhanced turbidimetric immunoassay standardized against the ERM-DA471/IFCC reference material and by the IDMS reference modified Jaffe kinetic method, respectively. RIs were determined using the 2.5th and 97.5th percentiles and their respective 90% confidence intervals (CIs). The quantile regression served to identify potential factors likely influencing SCysC and SCr values.ResultsWe included 381 subjects comprising 49.1% females.. RIs for SCysC varied between 0.57 (90%CI: 0.50-0.60) and 1.03 mg/L (90%CI: 1.00-1.10) for females, and from 0.70 (90%CI: 0.60-0.70) to 1.10 mg/L (90%CI: 1.10-1.20) for males. Concerning SCr, its RIs ranged from 0.58 (90%CI: 0.54-0.61) to 1.08 mg/dL (90%CI: 1.02-1.21) for females, and from 0.74 (90%CI: 0.70-0.80) to 1.36 mg/dL (90%CI: 1.30-1.45) for males. Men had significantly higher SCysC and SCr values than women (p < 0.001). Likewise, subjects aged 50 years and above had higher SCysC values in comparison to younger age groups (p < 0.001), which was not the case for SCr values (p = 0.491). Moreover, there was a positive and significant correlation between SCysC and SCr in women (ρ = 0.55, p < 0.001), in men (ρ = 0.39, p < 0.001) and globally (ρ = 0.58; p < 0.001). Furthermore, the sex influenced both biomarkers' values across all quantile regression models while age and body surface area (BSA) influenced them inconsistently.ConclusionThis study has determined serum cystatin C and serum creatinine reference intervals in an adult Cameroonian population, whose interpretations might take into account the patient's sex and to a certain extent, his/her age and/or BSA.

Project description:BackgroundWe recently published and validated the new serum creatinine (Scr)-based full-age-spectrum equation (FAS crea ) for estimating the glomerular filtration rate (GFR) for healthy and kidney-diseased subjects of all ages. The equation was based on the concept of normalized Scr and shows equivalent to superior prediction performance to the currently recommended equations for children, adolescents, adults and older adults.MethodsBased on an evaluation of the serum cystatin C (ScysC) distribution, we defined normalization constants for ScysC ( Q cysC = 0.82 mg/L for ages <70 years and Q cysC = 0.95 mg/L for ages ≥70 years). By replacing Scr/ Q crea in the FAS crea equation with ScysC/ Q cysC , or with the average of both normalized biomarkers, we obtained new ScysC-based (FAS cysC ) and combined Scr-/ScysC-based FAS equations (FAS combi ). To validate the new FAS cysC and FAS combi we collected data on measured GFR, Scr, ScysC, age, gender, height and weight from 11 different cohorts including n = 6132 unique white subjects (368 children, aged ≤18 years, 4295 adults and 1469 older adults, aged ≥70 years).ResultsIn children and adolescents, the new FAS cysC equation showed significantly better performance [percentage of patients within 30% of mGFR (P30) = 86.1%] than the Caucasian Asian Paediatric Adult Cohort equation (P30 = 76.6%; P < 0.0001), or the ScysC-based Schwartz equation (P30 = 68.8%; P < 0.0001) and the FAS combi equation outperformed all equations with P30 = 92.1% (P < 0.0001). In adults, the FAS cysC equation (P30 = 82.6%) performed equally as well as the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI cysC ) (P30 = 80.4%) and the FAS combi equation (P30 = 89.9%) was also equal to the combined CKD-EPI equation (P30 = 88.2%). In older adults, FAS cysC was superior (P30 = 88.2%) to CKD-EPI cysC (P30 = 84.4%; P < 0.0001) and the FAS combi equation (P30 = 91.2%) showed significantly higher performance than the combined CKD-EPI equation (P30 = 85.6%) (P < 0.0001).ConclusionThe FAS equation is not only applicable to all ages, but also for all recommended renal biomarkers and their combinations.

Dataset Information

A Systematic Review of the Effect of N-Acetylcysteine on Serum Creatinine and Cystatin C Measurements.

Introduction

Methods

Results

Discussion

Publications

A Systematic Review of the Effect of N-Acetylcysteine on Serum Creatinine and Cystatin C Measurements.

Similar Datasets

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