Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury

Succar, Lena; Pianta, Timothy J; Davidson, Trent; Pickering, John W.; Endre, Z. H.

doi:10.1016/j.kint.2017.02.030

Cited by 32 publications

(31 citation statements)

References 30 publications

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“…Third, patients with cirrhosis and AKI may lie on an AKI–CKD spectrum, and the presence of clinical or subclinical CKD may modify biomarker profiles . We were unable to examine for more definitive signs of CKD as renal biopsies and imaging were not universally performed, nor were we able to clearly determine the cause or chronicity of renal dysfunction .…”

Section: Discussionmentioning

confidence: 99%

External Validation of a Pretransplant Biomarker Model (REVERSE) Predictive of Renal Recovery After Liver Transplantation

et al. 2019

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In patients with end-stage liver disease, the ability to predict recovery of renal function following liver transplantation (LT) remains elusive. However, several important clinical decisions depend on whether renal dysfunction is recoverable after LT. We used a cohort of patients undergoing LT to independently validate a published pre-LT model predictive of post-transplant renal recovery (Renal Recovery Assessment at Liver Transplant [REVERSE]: high osteopontin [OPN] and tissue inhibitor of metalloproteinases-1 [TIMP-1] levels, age < 57, no diabetes). Serum samples pre-LT and 4-12 weeks post-LT (n = 117) were analyzed for kidney injury proteins from three groups of recipients: (1) estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m 2 prior to and after LT (irreversible acute kidney injury [AKI]), (2) eGFR < 30 mL/minute/1.73 m 2 prior to LT and >50 mL/minute/1.73 m 2 after LT (reversible AKI [rAKI]) (3) eGFR > 50 mL/minute/1.73 m 2 prior to and after LT (no AKI). In patients with elevated pre-LT serum levels of OPN and TIMP-1, recovery of renal function correlated with decreases in the level of both proteins. At 4 weeks post-LT (n = 77 subset), the largest decline in OPN and TIMP-1 was seen in the rAKI group. Validation of the REVERSE model in this independent data set had high area under the curve (0.78) in predicting full post-LT renal recovery (sensitivity 0.86, specificity 0.6, positive predictive value 0.81, negative predictive value 0.69). Our eGFR findings were confirmed using measured GFR. Conclusion: The REVERSE model, derived from an initial training set combining plasma biomarkers and clinical characteristics, demonstrated excellent external validation performance characteristics in an independent patient cohort using serum samples. Among patients with kidney injury pre-LT, the predictive ability of this model may prove beneficial in clinical decision-making both prior to and following transplantation. (Hepatology 2019;70:1349-1359).A cute kidney injury (AKI) is common among patients with decompensated liver disease awaiting liver transplantation (LT) alone and is associated with a 7-fold increase in mortality. (1) Pretransplant renal dysfunction, particularly if not reversible after LT, is also an important predictor of chronic kidney disease (CKD), morbidity, and mortality after LT. (2)(3)(4)(5) Accurate assessment of reversibility of pre-LT renal injury is important for several reasons. First, identification of patients with

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Section: Discussionmentioning

confidence: 99%

External Validation of a Pretransplant Biomarker Model (REVERSE) Predictive of Renal Recovery After Liver Transplantation

et al. 2019

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“…Animals were humanely euthanised under anaesthesia. The animal models, creatinine assays and histopathology are described in S6 and S7 Files [58]. PLOS ONE…”

Section: Animalsmentioning

confidence: 99%

Selection and validation of reference genes for normalisation of gene expression in ischaemic and toxicological studies in kidney disease

et al. 2020

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Normalisation to standard reference gene(s) is essential for quantitative real-time polymerase chain reaction (RT-qPCR) to obtain reproducible and comparable results of a gene of interest (GOI) between subjects and under varying experimental conditions. There is limited evidence to support selection of the commonly used reference genes in rat ischaemic and toxicological kidney models. Employing these models, we determined the most stable reference genes by comparing 4 standard methods (NormFinder, qBase+, BestKeeper and comparative ΔCq) and developed a new 3-way linear mixed-effects model for evaluation of reference gene stability. This new technique utilises the intra-class correlation coefficient as the stability measure for multiple continuous and categorical covariates when determining the optimum normalisation factor. The model also determines confidence intervals for each candidate normalisation gene to facilitate selection and allow sample size calculation for designing experiments to identify reference genes. Of the 10 candidate reference genes tested, the geometric mean of polyadenylate-binding nuclear protein 1 (PABPN1) and betaactin (ACTB) was the most stable reference combination. In contrast, commonly used ribosomal 18S and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were the most unstable. We compared the use of PABPN1×ACTB and 2 commonly used genes 18S and GAPDH on the expression of 4 genes of interest know to vary after renal injury and expressed by different kidney cell types (KIM-1, HIF1α, TGFβ1 and PECAM1). The less stable reference genes gave varying patterns of GOI expression in contrast to the use of the least unstable reference PABPN1×ACTB combination; this improved detection of differences in gene expression between experimental groups. Reduced within-group variation of the now more accurately normalised GOI may allow for reduced experimental group size particularly for comparison between various models. This objective selection of stable reference genes increased the reliability of comparisons within and between experimental groups.

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“…and can be categorized by the rapid decline in the kidney function and extensive tubular damage. It has a very high mortality rate and is reported to cause multiple organ damages ( Succar et al, 2017 ). Different reports suggest that elevated level of inflammatory cytokines and intracellular reactive oxygen species (ROS) mediated mechanisms are involved with the AKI associated cytotoxicity ( Burmeister et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Mangiferin Ameliorates Cisplatin Induced Acute Kidney Injury by Upregulating Nrf-2 via the Activation of PI3K and Exhibits Synergistic Anticancer Activity With Cisplatin

et al. 2018

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Occurrence of oxidative stress is the principal cause of acute kidney injury induced by cisplatin. Mangiferin, a naturally occurring antioxidant molecule, is found to ameliorate several oxidative stress mediated pathophysiological conditions including cancer. Cisplatin induced cytotoxicity was measured in NKE cells by MTT assay and microscopic analysis. Induction of oxidative stress and regulation of proapoptotic molecules were subsequently investigated by using different spectrophotometric analyses, FACS and immunocytochemistry. Induction of nephrotoxicity was determined by analyzing different serum biomarkers and histological parameters in vivo using swiss albino mice. Activation of NF-κB mediated pro-inflammatory and caspase dependent signaling cascades were investigated by semi-quantitative RT-PCR and immunoblotting. Mangiferin was found to ameliorate cisplatin induced nephrotoxicity in vitro and in vivo by attenuating the induction of oxidative stress and upregulating Nrf-2 mediated pro-survival signaling cascades via the activation of PI3K. Additionally, mangiferin showed synergistic anticancer activity with cisplatin in cancer cell lines (MCF-7 and SKRC-45) and EAC cell induced solid tumor bearing experimental mice. The ameliorative effect of mangiferin is primarily attributed to its anti-oxidant and anti-inflammatory properties. It acts differentially in normal tissue cells and tumor cells by modulating different cell survival regulatory signaling molecules. For the first time, the study reveals a mechanistic basis of mangiferin action against cisplatin induced nephrotoxicity. Since Mangiferin shows synergistic anticancer activity with cisplatin, it can be considered as a promising drug candidate, to be used in combination with cisplatin.

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Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury

Cited by 32 publications

References 30 publications

External Validation of a Pretransplant Biomarker Model (REVERSE) Predictive of Renal Recovery After Liver Transplantation

External Validation of a Pretransplant Biomarker Model (REVERSE) Predictive of Renal Recovery After Liver Transplantation

Selection and validation of reference genes for normalisation of gene expression in ischaemic and toxicological studies in kidney disease

Mangiferin Ameliorates Cisplatin Induced Acute Kidney Injury by Upregulating Nrf-2 via the Activation of PI3K and Exhibits Synergistic Anticancer Activity With Cisplatin

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