Kidney biomarkers in MCPA-induced acute kidney injury in rats: Reduced clearance enhances early biomarker performance

Wunnapuk, Klintean; Liu, Xin; Gobé, Glenda C.; Endre, Zoltán H.; Peake, Philip W.; Grice, Jeffrey E.; Roberts, Michael S.; Buckley, Nicholas A.

doi:10.1016/j.toxlet.2014.01.018

Cited by 11 publications

(11 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In critically ill patients with AKI, OPN levels were high and correlated with RR in serial measurements, remarkably similar to our cohorts . In addition, OPN may be an earlier marker of AKI compared to other markers such as cystatin C . Its expression is up‐regulated in nephrons after acute injury and is associated with regeneration of renal tubular epithelia after acute tubular necrosis .…”

Section: Discussionsupporting

confidence: 83%

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

et al. 2019

View full text Add to dashboard Cite

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

show abstract

Section: Discussionsupporting

confidence: 83%

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

et al. 2019

View full text Add to dashboard Cite

show abstract

“…KIM-1 has been shown to be a sensitive biomarker for the detection of various kidney injuries induced by drugs [42], toxins [43], and ischemia [44], as well as early stages of repair. Peng et al demonstrated that KIM-1 in rat expression was the most sensitive in urine compared with other ischemic acute kidney injury markers such as monocyte chemoattractant protein-l (MCP-1) and cystatin C (Cys C) [40].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of the Segmental Renal Artery Clamping Technique on Ischemia-Reperfusion Injury in db/db Diabetic Mice

Liang

Zhu

Miao

et al. 2017

BioMed Research International

View full text Add to dashboard Cite

Renal ischemia-reperfusion (I/R) injury is inevitable in partial nephrectomy and other kidney surgeries, with a higher incidence in patients with renal insufficiency. This study aimed to investigate the protective effects of precise segmental renal artery clamping (SRAC) against renal I/R injury in db/db diabetic mice, compared with conventional renal artery clamping (RAC). Grape seed extract, a powerful free radical scavenger, was administered to diabetic mice for 4 weeks before operation in subgroups (30 mg/kg/d). The unilateral renal pedicle was ligatured, and I/R injury to the contralateral kidney was induced (ischemia for 30 min followed by reperfusion for 24 h). Blood glucose value, creatinine, blood urea nitrogen, and urine microalbumin/urine creatinine ratio increased gradually and showed no preoperative statistical differences among six subgroups. These parameters were significantly lower in the SRAC than in the RAC group 24 h postoperatively. Moreover, the nonischemic area in the SRAC group expressed less KIM-1 and TNF-α mRNA and also revealed minor histopathological damage induced by I/R. These findings suggest that SRAC effectively reduces early renal injury induced by I/R and accelerates the recovery of renal function in diabetic mice. Thus, SRAC may be an ideal technique in partial nephrectomy, especially for patients with diabetic nephropathy and other renal insufficiencies.

show abstract

“…Cisplatin, gentamicin, carbapenem, cyclosporine A, adriamycin, puromycin aminonucleoside, carboplatin, doxorubicin, bromoethylamine, paraquat [176], MCPA [177], glyphosate [178] Cisplatin [179], ifosfamide, methotrexate, gentamicin [175,180], contrast medium [181] β 2 -microglobulin Proximal tubular injury (reduced reabsorption); glomerular injury (leakage) Cadmium, cisplatin, puromycin aminonucleoside, carboplatin, gentamicin, cyclosporine, doxorubicin, bromoethylamine, contrast medium, paraquat [176], MCPA [177], glyphosate [178] Gentamicin and other aminoglycosides [172,182], vancomycin, contrast medium Gentamicin [180], cisplatin [179,183], contrast [185,186], paraquat poisoning [9] Interleukin-18 (IL-18)…”

Section: Figurementioning

confidence: 99%

“…Specific to proximal tubular injury; secreted in large quantities by dedifferentiated tubular cells Cisplatin, cyclosporine, gentamicin, cadmium, contrast medium, vancomycin carboplatin, doxorubicin, bromoethylamine, paraquat [176], MCPA [177], glyphosate [178] Paraquat poisoning [7], gentamicin [174,180], cisplatin [151,184] Neutrophil gelatinaseassociated lipocalin (NGAL)…”

Section: Contrast Medium Cisplatinmentioning

confidence: 99%

See 1 more Smart Citation

Role of biomarkers of nephrotoxic acute kidney injury in deliberate poisoning and envenomation in less developed countries

Mohamed

Endre

Buckley

2015

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

Acute kidney injury (AKI) has diverse causes and is associated with increased mortality and morbidity. In less developed countries (LDC), nephrotoxic AKI (ToxAKI) is common and mainly due to deliberate ingestion of nephrotoxic pesticides, toxic plants or to snake envenomation. ToxAKI shares some pathophysiological pathways with the much more intensively studied ischaemic AKI, but in contrast to ischaemic AKI, most victims are young, previously healthy adults. Diagnosis of AKI is currently based on a rise in serum creatinine. However this may delay diagnosis because of the kinetics of creatinine. Baseline creatinine values are also rarely available in LDC. Novel renal injury biomarkers offer a way forward because they usually increase more rapidly in AKI and are normally regarded as absent or very low in concentration, thereby reducing the need for a baseline estimate. This should increase sensitivity and speed of diagnosis. Specificity should also be increased for urine biomarkers since many originate from the renal tubular epithelium. Earlier diagnosis of ToxAKI should allow earlier initiation of appropriate therapy. However, translation of novel biomarkers of ToxAKI into clinical practice requires better understanding of non-renal factors in poisoning that alter biomarkers and the influence of dose of nephrotoxin on biomarker performance. Further issues are establishing LDC population-based normal ranges and assessing sampling and analytical parameters for low resource settings. The potential role of renal biomarkers in exploring ToxAKI aetiologies for chronic kidney disease of unknown origin (CKDu) is a high research priority in LDC. Therefore, developing more sensitive biomarkers for early diagnosis of nephrotoxicity is a critical step to making progress against AKI and CKDu in the developing world.

show abstract

Kidney biomarkers in MCPA-induced acute kidney injury in rats: Reduced clearance enhances early biomarker performance

Cited by 11 publications

References 58 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

Protective Effects of the Segmental Renal Artery Clamping Technique on Ischemia-Reperfusion Injury in db/db Diabetic Mice

Role of biomarkers of nephrotoxic acute kidney injury in deliberate poisoning and envenomation in less developed countries

Contact Info

Product

Resources

About