Kidney injury molecule-1 expression in human kidney transplants with interstitial fibrosis and tubular atrophy

Nogare, Aline L.; Veronese, Francisco Veríssimo; Carpio, Virna Nowotny; Montenegro, Rosangela Munhoz; Pedroso, José Alberto Rodrigues; Pêgas, Karla Laís; Gonçalves, Luiz Felipe Santos; Manfro, Roberto Ceratti

doi:10.1186/s12882-015-0011-y

Cited by 23 publications

(13 citation statements)

References 27 publications

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“…A significant correlation between KIM-1 gene expression in samples of urine and tissue cells was found (p < 0.01). Nogare et al 52 also found that KIM-1 protein expression was increased in biopsies with interstitial fibrosis and tubule atrophy, compared with biopsies showing acute calcineurin inhibitor nephrotoxicity.…”

Section: Kim-1 and Kidney Transplantmentioning

confidence: 92%

Kidney injury molecule-1 in kidney disease

Chen

Wang

2016

Renal Failure

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Kidney injury molecule-1(KIM-1) is a type I membrane protein, comprising an extracellular portion and a cytoplasmic portion, which is expressed at very low levels in the normal kidney. The extracellular portion can cleave and rapidly enter tubule lumens after kidney injury, and can then be detected in the urine. It has been confirmed that the urine KIM-1 level is closely related to tissue KIM-1 level and correlated with kidney tissue damage. Not only is KIM-1 proven to be an early biomarker of acute kidney injury but it also has a potential role in predicting long-term renal outcome. This review summarizes the relationships between KIM-1 and kidney injury, especially in chronic kidney disease.

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Section: Kim-1 and Kidney Transplantmentioning

confidence: 92%

Kidney injury molecule-1 in kidney disease

Chen

Wang

2016

Renal Failure

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“…A clinical study showed that urinary KIM-1 could predict the development of graft loss after kidney transplantation [122]. Therefore, KIM-1 has been consistently demonstrated to be an early indicator of kidney injury and is considered a highly sensitive and specific urinary biomarker for monitoring drug-induced kidney injury [123][124][125][126].…”

Section: Urinary Biomarkers and Nephrotoxicitymentioning

confidence: 99%

“…Studies have revealed that urinary KIM-1 protein concentrations are significantly higher in patients with AKI [123,124], but increased KIM-1 expression can also be an early marker for identifying renal tubular damage. Nogare et al [125] have reported that KIM-1 protein expression is increased in biopsies with interstitial fibrosis and tubular atrophy, implying that KIM-1 can serve as a biomarker of chronic kidney injury (CKI) induced by CNIs. Thus, KIM-1 expression is significantly related to kidney function, which makes KIM-1 a sensitive and specific marker of both AKI and CKI.…”

Section: Urinary Biomarkers and Nephrotoxicitymentioning

confidence: 99%

Biomarkers for individualized dosage adjustments in immunosuppressive therapy using calcineurin inhibitors after organ transplantation

Tajima

Suetsugu

et al. 2018

Acta Pharmacol Sin

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Calcineurin inhibitors (CNIs), such as cyclosporine A and tacrolimus, are widely used immunosuppressive agents for the prevention of post-transplantation rejection and have improved 1-year graft survival rates by up to 90%. However, CNIs can induce severe reactions, such as acute or chronic allograft nephropathy, hypertension, and neurotoxicity. Because CNIs have varied bioavailabilities, narrow therapeutic ranges, and individual propensities for toxic effects, therapeutic drug monitoring is necessary for all CNIs. Identifying the genetic polymorphisms in drug-metabolizing enzymes will help to determine personalized dosage regimens for CNIs, as CNIs are substrates for CYP3A5 and P-glycoprotein (P-gp, MDR1). CNIs are often concomitantly administered with voriconazole or proton pump inhibitors (PPIs), giving rise to drug interaction problems. Voriconazole and PPIs can increase the blood concentrations of CNIs, and both are primarily metabolized by CYP2C19. Thus, it is expected that interactions between CNIs and voriconazole or PPI would be affected by CYP2C19 and CYP3A5 polymorphisms. CNI-induced acute kidney injury (AKI) is a serious complication of transplantations. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) are noninvasive urinary biomarkers that are believed to be highly sensitive to CNI-induced AKI. In this article, we review the adverse events and pharmacokinetics of CNIs and the biomarkers related to CNIs, including CYP3A5, CYP2C19, MDR1, NGAL, and KIM-1. We hope that these data will help to identify the optimal biomarkers for monitoring CNI-based immunosuppressive therapy after organ transplantation.

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“…In the past years, besides NGAL, several AKI and DGF biomarkers have been extensively investigated, including urinary KIM‐1, IL‐18, heat shock protein 72 (uHsp72), L‐FABP, calprotectin, CXCL9, CXCL10, CCL2, IL‐18, cystatin C, T‐cell immunoglobulin, and mucin domain‐3 (Tim‐3), tissue inhibitor of metalloproteinase 2 (TIMP‐2), insulin‐like growth factor‐binding protein 7 (IGFBP‐7) 57, 58, 59, 60, 61, 62, 63.…”

Section: Ngal and Other Candidate Biomarkers In Kidney Transplant Setmentioning

confidence: 99%

Neutrophil Gelatinase‐Associated Lipocalin as a Biomarker of Allograft Function After Renal Transplantation: Evaluation of the Current Status and Future Insights

et al. 2017

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Neutrophil gelatinase‐associated lipocalin (NGAL), a protein belonging to the lipocalin superfamily initially found in activated neutrophils, is expressed by several cell types, including kidney tubule. The increase in NGAL production and release from tubular cells in response to various insults has been proven to predict acute kidney injury (AKI). For this reason, it has emerged as a valuable noninvasive biomarker of AKI in clinical nephrology. Also in the renal transplant setting, different studies have indicated NGAL as a valuable tool, especially in the early postoperative period, since the currently available clinical and laboratory parameters remain poorly sensitive to monitor immediate posttransplant graft function. This is an analysis of the recent literature to assess the utility of plasma and urinary NGAL, exosomal mRNA for NGAL, and NGAL levels in the perfusate of machine‐perfused kidneys for the prediction of graft function recovery in the early postsurgery phase after renal transplantation. We found that NGAL appears as a promising troponin‐like biomarker to detect short‐term impairment of graft function after renal transplant, but there are still some limitations in its clinical application, essentially related to its low specificity. Moreover, comparing NGAL assayed in serum, urine, machine‐perfusate, or as exosomal mRNA, each one has shown limitations and benefits in terms of predictive performance for DGF, according to various existing studies, feasibly due to different cut‐off levels, designs and patient sample sizes.

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Kidney injury molecule-1 expression in human kidney transplants with interstitial fibrosis and tubular atrophy

Cited by 23 publications

References 27 publications

Kidney injury molecule-1 in kidney disease

Kidney injury molecule-1 in kidney disease

Biomarkers for individualized dosage adjustments in immunosuppressive therapy using calcineurin inhibitors after organ transplantation

Neutrophil Gelatinase‐Associated Lipocalin as a Biomarker of Allograft Function After Renal Transplantation: Evaluation of the Current Status and Future Insights

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