BACKGROUND: Although the present diagnosis of acute kidney injury (AKI) involves measurement of acute increases in serum creatinine (SC) and reduced urine output (UO), measurement of UO is underutilized for diagnosis of AKI in clinical practice. The purpose of this investigation was to conduct a systematic literature review of published studies that evaluate both UO and SC in the detection of AKI to better understand incidence, healthcare resource use, and mortality in relation to these diagnostic measures and how these outcomes may vary by population subtype.
METHODS: The systematic literature review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Data were extracted from comparative studies focused on the diagnostic accuracy of UO and SC, relevant clinical outcomes, and resource usage. Quality and validity were assessed using the National Institute for Health and Care Excellence (NICE) single technology appraisal quality checklist for randomized controlled trials and the Newcastle-Ottawa Quality Assessment Scale for observational studies.
RESULTS: A total of 1729 publications were screened, with 50 studies eligible for inclusion. A majority of studies (76%) used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to classify AKI and focused on the comparison of UO alone versus SC alone, while few studies analyzed a diagnosis of AKI based on the presence of both UO and SC, or the presence of at least one of UO or SC indicators. Of the included studies, 33% analyzed patients treated for cardiovascular diseases and 30% analyzed patients treated in a general intensive care unit. The use of UO criteria was more often associated with increased incidence of AKI (36%), than was the application of SC criteria (21%), which was consistent across the subgroup analyses performed. Furthermore, the use of UO criteria was associated with an earlier diagnosis of AKI (2.4-46.0 h). Both diagnostic modalities accurately predicted risk of AKI-related mortality.
CONCLUSIONS: Evidence suggests that the inclusion of UO criteria provides substantial diagnostic and prognostic value to the detection of AKI.

Sarcopenia is an important prognostic factor, but its optimal screening methods remain challenging. Several new indices developed based on serum creatinine (Cr) and cystatin C (CysC) have been proposed to be diagnostic biomarkers for sarcopenia screening.
This review aimed to evaluate the diagnostic accuracy of serum Cr- and CysC-based indices for sarcopenia diagnosis.
We systematically searched MEDLINE, EMBASE, SCIE and SCOPUS from inception to 2 April 2023. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random-effects model was used to synthesise the pooled sensitivity, specificity and area under the curves of the summary receiver operating characteristic (SROC-AUC).
We retrieved 936 publications and included 16 studies with 5,566 participants (mean age ranged: 51.0-78.4 years, 50.2% men). The prevalence of sarcopenia ranged from 7.8 to 69.5%. All included studies presented a moderate to high risk of bias. The serum Cr- and CysC-based indices showed moderate diagnostic accuracy for sarcopenia (pooled sensitivity: 0.67, 95% CI 0.57-0.75; pooled specificity: 076, 95% CI 0.67-0.83; pooled SROC-AUC: 0.78, 95% CI 0.74-0.81). The Cr/CysC ratio is the most widely studied index, followed by the Cr × eGFRcys index. Overall, both indicators had satisfactory and comparable performance in screening sarcopenia.
Serum Cr- and CysC-based indices showed moderate diagnostic accuracy for sarcopenia. The most studied indices-the Cr/CysC ratio and Cr × eGFRcys index-had comparable diagnostic accuracy for evaluating sarcopenia and may serve as surrogate markers for sarcopenia. However, further validation is required to verify these findings.

UNASSIGNED: The effectiveness of N-acetylcysteine (NAC) in treating contrast-induced nephropathy (CIN) has been the subject of conflicting meta-analyses, but the strength of the evidence for these correlations between NAC use and CIN has not been measured overall.
UNASSIGNED: To evaluate the data from randomized clinical studies (RCTs) that examined the relationships between NAC use and CIN in meta-analyses.
UNASSIGNED: Between the creation of the database and April 2023, searches were made in PubMed, Cochrane Library, EMBASE, and Web of Science. N-acetylcysteine, contrast-induced nephropathy, or contrast-induced renal disease were among the search keywords used, along with terms including systematic review and meta-analysis. The Assessment of Multiple Systematic Reviews, version 2, which assigned grades of extremely low, low, moderate, or high quality to each meta-analysis\'s scientific quality, was used to evaluate each meta-analysis. The confidence of the evidence in meta-analyses of RCTs was evaluated using the Grading of Recommendation, Assessment, Development and Evaluations method, with evidence being rated as very low, low, moderate, or high.
UNASSIGNED: In total, 493 records were screened; of those, 46 full-text articles were assessed for eligibility, and 12 articles were selected for evidence synthesis as a result of the screening process. Based on the pooled data, which was graded as moderate-quality evidence, it can be concluded that NAC can decrease CIN (OR 0.72, 95% CI 0.65-0.79, p < 0.00001) and blood levels of serum creatinine (MD -0.09, 95% CI -0.17 to -0.01, p = 0.03). In spite of this, there were no associations between NAC and dialysis requirement or mortality in these studies.
UNASSIGNED: The results of this umbrella review supported that the renal results were enhanced by NAC. The association was supported by moderate-quality evidence.
UNASSIGNED: [https://clinicaltrials.gov/], identifier [CRD42022367811].

Urinary ascites represents a scarcely observed pseudo-acute kidney injury in clinical settings. Protracted or missed diagnosis may hold grave ramifications for patient outcomes.
We reported a case involving an elderly female patient experiencing pseudo-acute kidney injury accompanied by ascites, wherein her renal dysfunction persisted despite medical intervention and hemodialysis. Urinary ascites was identified via a methylene blue test and by contrasting creatinine levels in serum and ascites. This patient\'s kidney function was multiple typified by a marked elevation in serum creatinine/Cystatin C ratio (> 2 L/dL), potentially serving as a clue for the clinical diagnosis of pseudo-acute kidney injury engendered by urinary ascites.
This case suggested the potential diagnostic value of an asynchronous increase in serum creatinine and serum CysC (or an increased ratio of blood creatinine to blood CysC) in patients with pseudo-acute kidney injury.

Premature infants are at high risk for acute kidney injury (AKI) and current diagnostic criteria are flawed. The objective of this study was to determine the diagnostic accuracy of urine and serum biomarkers not currently used in routine clinical practice to predict AKI in premature infants.
A systematic review was performed that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA). Data were extracted on the diagnostic accuracy of AKI biomarkers using serum creatinine or urine output as the reference standard. Quality and validity were assessed using modified Standards for Reporting Diagnostic Accuracy (STARD) criteria.
We identified 1024 articles, with 15 studies (791 infants) eligible for inclusion. Twenty-seven biomarkers were identified including serum cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin, kidney injury molecule-1, epidermal growth factor, and protein S100-P. However, many were only reported by one study each. A meta-analysis could only be conducted on uNGAL (288 infants from 6 studies) using a hierarchical, random-effects logistic-regression model. uNGAL had a summary sensitivity of 77% (95% CI 58-89%), specificity of 76% (95% CI 57-88%) and AUC-SROC of 0.83 (95% CI 0.80-0.86) for the diagnosis of AKI. By utilising uNGAL, the post-test probability of AKI increased to 52% (95% CI 37-66%) with a positive test and decreased to 9% (95% CI 5-16%) with a negative test if the pre-test probability was 25%.
uNGAL shows promise as a diagnostically accurate biomarker for AKI in premature infants.

OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes) definition of acute kidney injury (AKI) is frequently used in studies to examine the epidemiology of AKI. This definition is variably interpreted and applied to routinely collected health care data. The aim of this study was to examine this variation and to achieve consensus in how AKI should be defined for research using routinely collected health care data.
UNASSIGNED: Scoping review via searching Medline and EMBASE for studies using health care data to examine AKI by using the KDIGO creatinine-based definition. An international panel of experts formed to participate in a modified Delphi process to attempt to generate consensus about how AKI should be defined when using routinely collected laboratory data.
UNASSIGNED: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for scoping reviews was followed. For the Delphi process, 2 rounds of questions were distributed via internet-based questionnaires to all participants with a prespecified cutoff of 75% agreement used to define consensus.
RESULTS: The scoping review found 174 studies that met the inclusion criteria. The KDIGO definition was inconsistently applied, and the methods for application were poorly described. We found 58 (33%) of papers did not provide a definition of how the baseline creatinine value was determined, and only 34 (20%) defined recovery of kidney function. Of 55 invitees to the Delphi process, 35 respondents participated in round 1, and 25 participated in round 2. Some consensus was achieved in areas related to how to define the baseline creatinine value, which patients should be excluded from analysis of routinely collected laboratory data, and how persistent chronic kidney disease or nonrecovery of AKI should be defined.
CONCLUSIONS: The Delphi panel members predominantly came from the United Kingdom, the United States, and Canada, and there were low response rates for some questions in round 1.
CONCLUSIONS: The current methods for defining AKI using routinely collected data are inconsistent and poorly described in the available literature. Experts could not achieve consensus for many aspects of defining AKI and describing its sequelae. The KDIGO guidelines should be extended to include a standardized definition for how AKI should be defined when using routinely collected data.

BACKGROUND: 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 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.
CONCLUSIONS: 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.

Serum creatinine (Cr) is a biosynthetic product of creatine phosphate metabolism in muscles and is closely related to total muscle mass, but it is not easily affected by diet. Several studies have tried to explore the role of serum Cr levels in amyotrophic lateral sclerosis (ALS), but the results were inconsistent. Therefore, our study aims to explore the differences of serum Cr levels between ALS patients and controls and whether serum Cr at baseline is an independent predictor of survival. Methods: We searched all the related studies that probed into the association between Serum Cr levels and ALS based on PubMed, EMBASE and Cochrane library from October 1952 to February 2019. The quality of the included studies was evaluated by using Newcastle-Ottawa Scale (NOS), and all the statistical analysis of this meta-analysis was performed by Stata version 12.0. Results: Eight studies with a total of 11377 ALS patients and 937 controls were included. Among them, five studies indicated that ALS patients had lower serum Cr levels (SMD = -0.78, 95%CI [-0.97, -0.60]) compared to controls, and three studies showed that higher serum Cr levels in ALS patients were related to lower overall mortality (HR 0.89, 95%CI [0.80, 0.99]). Conclusion: The levels of serum Cr in ALS patients are significantly lower than those in controls, and they are inversely related to overall mortality in ALS patients. Therefore, the serum Cr, an easily accessible serological factor, may serve as a prognostic biomarker.

OBJECTIVE: To review systematically current literature on kidney function changes during pregnancy, in order to estimate the extent of adaptation over the course of both healthy physiological and complicated singleton pregnancies, and to determine healthy pregnancy reference values.
METHODS: PubMed (NCBI) and EMBASE (Ovid) electronic databases were searched, from inception to July 2017, for studies on kidney function during uncomplicated and complicated pregnancies. Included studies were required to report a non-pregnant reference value of kidney function (either in a non-pregnant control group or as a prepregnancy or postpartum measurement) and a pregnancy measurement at a predetermined and reported gestational age. Kidney function measures assessed were glomerular filtration rate (GFR) measured by inulin clearance, GFR measured by creatinine clearance and serum creatinine level. Pooled mean differences between pregnancy measurements and reference values were calculated for predefined intervals of gestational age in uncomplicated and complicated pregnancies using a random-effects model described by DerSimonian and Laird.
RESULTS: Twenty-nine studies met the inclusion criteria and were included in the analysis. As early as the first trimester, GFR was increased by up to 40-50% in physiological pregnancy when compared with non-pregnant values. Inulin clearance in uncomplicated pregnancy was highest at 36-41 weeks, with a 55.6% (53.7; 95% CI, 44.7-62.6 mL/min) increase when compared with non-pregnant values, and creatinine clearance was highest at 15-21 weeks\' gestation, with a 37.6% (36.6; 95% CI, 26.2-46.9 mL/min) increase. Decrease in serum creatinine level in uncomplicated pregnancy was most prominent at 15-21 weeks, with a 23.2% (-0.19; 95% CI, -0.23 to -0.15 mg/dL) decrease when compared with non-pregnant values. Eight studies reported on pregnancies complicated by a hypertensive disorder. Meta-regression analysis showed a significant difference in all kidney function parameters when comparing uncomplicated and hypertensive complicated pregnancies.
CONCLUSIONS: In healthy pregnancy, GFR is increased as early as the first trimester, as compared with non-pregnant values, and the kidneys continue to function at a higher rate throughout gestation. In contrast, kidney function is decreased in hypertensive pregnancy. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

BACKGROUND: N-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.
OBJECTIVE: To determine the effect of NAC on kidney function.
METHODS: A systematic review and meta-analysis.
METHODS: Prospective studies, with administration of NAC, in the absence of any other change in kidney function (such as contrast administration or surgery).
METHODS: Adult 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.
METHODS: Serum creatinine and/or cystatin C measurements before and after NAC administration.
METHODS: An 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.
RESULTS: The 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.
CONCLUSIONS: Possible heterogeneity and publication bias and lack of mechanistic data.
CONCLUSIONS: This 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.
BACKGROUND: This review is registered with PROSPERO, CRD42017055984.
BACKGROUND: La N-acétylcystéine (NAC) est un antioxydant capable de régénérer le glutathion et principalement utilisé pour traiter les cas de surdose d’acétaminophène. La NAC pourrait également s’avérer efficace comme traitement préventif de l’insuffisance rénale aiguë iatrogénique ou pour ralentir la progression de l’insuffisance rénale chronique. Cette substance a fait l’objet de plusieurs études dans ce contexte, mais les résultats demeurent mitigés. Notamment, il reste toujours à rapporter adéquatement une justification de l’effet protecteur de la NAC sur la base d’un mécanisme biologique. Parmi les rapports contradictoires, certaines données montreraient que la NAC abaisse artificiellement les valeurs de créatinine sérique mesurées sans améliorer la fonction rénale, potentiellement par interférence de l’essai. À la lumière de ces résultats divergents, une revue systématique de la littérature sera effectuée pour déterminer si la NAC produit un effet sur la fonction rénale mesurée par la créatinine sérique.
OBJECTIVE: Mesurer l’effet de l’administration de NAC sur la fonction rénale.
UNASSIGNED: Une revue systématique de la littérature et une méta-analyse.
UNASSIGNED: Les études prospectives avec administration de NAC sans autres changements dans la fonction rénale; l’administration d’un produit de contraste ou une intervention chirurgicale, par exemple.
UNASSIGNED: Des adultes, volontaires sains ou atteints de néphropathie chronique, ayant reçu de la NAC. Seront exclues les populations dont la fonction rénale est faible ou inexistante; notamment, les cas d’insuffisance rénale terminale.
UNASSIGNED: Des mesures de la créatinine sérique et/ou de la cystatine C faites avant et après l’administration de NAC.
UNASSIGNED: Un documentariste spécialisé assistera les recherches dans les bases de données MEDLINE, EMBASE et Cochrane CENTRAL afin de répertorier tous les types d’essais, y compris les essais contrôlés à répartition aléatoire, et toutes les études de cohorte prospectives faisant état d’une variation de la créatinine sérique à la suite de l’administration de NAC. À l’aide de critères d’inclusion prédéfinis, deux réviseurs seront indépendamment chargés de trier les titres et abrégés des études répertoriées lors de la revue de la littérature. Ils devront ensuite extraire les données des textes des études qui auront été retenues. Une analyse des effets aléatoires sera utilisée pour calculer la moyenne pondérée des écarts pour les variations observées dans les mesures de créatinine en présence de NAC. La qualité des essais aléatoires sera évaluée à l’aide de l’outil Cochrane sur le risque de biais, et celle des études observationnelles sera mesurée avec l’échelle de Newcastle-Ottawa.
UNASSIGNED: Le principal résultat d’intérêt est la fonction rénale telle que rapportée soit par un changement dans les mesures de créatinine sérique et/ou de la cystatine C dans les essais à répartition aléatoire, soit en comparant les valeurs mesurées avant et après l’administration d’une dose de NAC.
UNASSIGNED: L’hétérogénéité des données, de possibles biais de publication et un manque de données mécanistiques.
CONCLUSIONS: Cette revue systématique offrira une synthèse des données probantes actuelles sur l’effet de la NAC sur les mesures de créatinine sérique. Ces résultats fourniront des lignes directrices aux cliniciens et serviront de bases solides pour les recherches futures dans ce domaine.