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DPP-4 inhibitors (gliptins) have shown better glycaemic control even in more feeble cases such as elderly people, patients with high cardiovascular and hypoglycaemic risk and individuals with renal impairment. However, the plasma concentrations of selected drugs has to be estimated to correlate those results with various uncertainties during clinical studies. A simple and sensitive LC-QTOF/MS method was developed and validated to measure the human plasma concentrations of vildagliptin, saxagliptin, sitagliptin, linagliptin and teneligliptin, using pioglitazone as an internal standard. Chromatographic separation of five gliptins was achieved on a Zorbax Eclipse Plus C-18 column Rapid Resolution HD (50 × 2.1 mm, 1.8 μm) using a mobile phase consisting of 20 mM ammonium formate and acetonitrile in gradient mode. Detection was performed with positive ion electrospray ionization mass spectrometry using target ions in selective ion mode. Simpler protein precipitation was employed for sample extraction from human plasma. The low recovery of gliptins observed due to non-specific binding to glass was surpassed by using polypropylene. The mean recovery was found to be 96.82 ± 1.03% (VIL), 94.32 ± 0.74% (SAX), 95.37 ± 2.09% (SIT), 91.67 ± 3.14% (LIN) and 93.29 ± 1.03% (TEN) respectively. The proposed method will serve as an excellent tool for various clinical studies like therapeutic drug monitoring, pharmacokinetics, toxicological and protein binding studies.

Background30%–40% of post-cardiac surgery patients develop acute kidney injury (AKI). AKI diagnosis uses raised serum creatinine levels which can take several days to rise.AimTo systematically review the diagnostic value of novel blood biomarkers of AKI in children post-cardiac surgery, and identify those worthy of future research and inclusion into clinical practise.MethodMedline, EMBASE, CENTRAL and Web of Science were searched in October 2016 using the search strategy: AKI, cardiac surgery and biomarker. Two independent reviewers assessed the eligibility of the reports in Endnote based on predefined inclusion criteria (novel biomarker, clear definition of AKI, cardiac surgery in children [<18 year]) and exclusion criteria (no plasma/serum biomarker studied, no patients without AKI, non-English reports) at title, abstract and full paper screening stages. Eligible papers had data extracted into a custom-designed Excel spreadsheet and risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. When possible meta-analysis was performed using MedCalc v16 where reports (n 3) on the same biomarker had an AUROC and 95% CI or standard error.ResultsOf 3898 independent reports found, 21 met the inclusion criteria. 2 biomarkers had enough reports (n 3) to warrant independent comparison; Cystatin C [n=7] and plasma neutrophil gelatinase-associated lipocalin (pNGAL) [n=7]. Cystatin C had enough data to perform a meta-analysis ([n=5]; pooled AUROC=0.79 [95% CI: 0.73–0.85); I2=55%). pNGAL had conflicting evidence for its efficacy (AUROC range: 0.45–0.95). All other reported biomarkers showed varied performance, notably a combination of urine NGAL+Cystatin C showed good discrimination (AUROC=0.90). QUADAS analysis showed low risk of bias in all studies (score >8) as well as uncertainty bias due to lack of reporting on examiner blinding and participant withdrawals.ConclusionCystatin C may be a useful early diagnostic marker of AKI yet there is currently insufficient research for using any novel biomarker of AKI diagnosis after paediatric cardiac surgery. Large, multicentre studies with homogenous methodology should be undertaken to address this and to identify how they evaluate patient outcomes.

AimThere is a high incidence of acute kidney injury (AKI) after cardiac surgery in children, which is associated with significant morbidity and mortality. Serum creatinine (sCr), currently used as an indicator of renal function, only responds to significant kidney injury and following a time delay, resulting in missed and late diagnoses of AKI post-cardiac surgery. Novel biomarkers may provide a more sensitive and timely diagnosis of AKI. The aim of this study was to systematically review the diagnostic value of novel urinary biomarkers of AKI in children undergoing cardiac surgery.MethodsThe databases Medline, EMBASE, Cochrane CENTRAL and Web of Science were systematically searched for studies assessing the diagnostic value of any non-creatinine biomarker in identifying AKI in children (<18 years) undergoing any form of cardiac surgery. Screening for eligibility was performed independently by two authors. Random effects meta-analyses were performed where at least three separate studies reported an area under the receiver operator characteristics curve (AUROC) with a 95% confidence interval (CI) or standard error, for a single biomarker.ResultsTwenty-five citations were included in the final review. Neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) were the most frequently studied biomarkers, and were the only ones with sufficient data for a meta-analysis. A summary of the pooled AUROC values (with 95% CI) and study heterogeneity (I2) for NGAL, NGAL corrected for urine creatinine (NGAL-uCr) and IL-18 are summarised in the table. There was significant clinical and methodological heterogeneity between included studies, as evidenced by the high I2values.Abstract G448(P) Table 1Pooled AUROC (95% CI)l2NGAL0.80 (0.74 to 0.87)81%NGAL-uCr0.80 (0.71 to 0.90)88%IL-180.74 (0.67 to 0.80)72%Many other biomarkers were only reported in a single, or a few, studies which meant there were insufficient for a meta-analysis. These displayed a wide range of diagnostic utility.ConclusionNGAL, NGAL-uCr and IL-18 are modest discriminators of AKI when measured within 24 hours of surgery, although other biomarkers (such as KIM-1 and L-FABP) are promising candidates for further research. Larger studies are required to determine biomarker diagnostic/prognostic performance in predicting AKI, and its complications, in children after cardiac surgery.