Hsp72 is an early and sensitive biomarker to detect acute kidney injury

Barrera‐Chimal, Jonatan; Pérez‐Villalva, Rosalba; Cortés‐González, Cesar; Ojeda-Cervantes, Marcos; Gamba, Gerardo; Morales‐Buenrostro, Luis E.; Bobadilla, Norma A.

doi:10.1002/emmm.201000105

Cited by 56 publications

(59 citation statements)

References 48 publications

(74 reference statements)

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“…Furthermore, HSP72 has been reported as an early and sensitive urinary biomarker of acute kidney injury in several studies . To our knowledge, this is the first study evaluating uHSP72 levels in DN in T2DM patients, in which uHSP72 levels were significantly increased in both micro‐ and macroalbuminuric diabetics compared with normoalbuminuric diabetics and healthy controls, indicating its positive association with disease progression.…”

Section: Discussionmentioning

confidence: 68%

NLRP3 expression and urinary HSP72 in relation to biomarkers of inflammation and oxidative stress in diabetic nephropathy patients

et al. 2017

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Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. Nod-like receptors nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome displays a considerable role in the chronic inflammatory state observed in diabetic patients. Urinary heat shock protein 72 (uHSP72) is a sensitive and specific biomarker for the early detection of acute kidney injury. The aim of this study was to evaluate NLRP3 relative gene expression, its correlation with inflammatory and oxidative stress markers, and to assess the value of uHSP72 in the early detection of DN in type 2 diabetic patients with different degrees of DN. Forty-five type 2 diabetic patients: 15 normoalbuminuric, 15 microalbuminuric, 15 macroalbuminuric, in addition to 15 healthy controls were enrolled in this study. Clinical examination and routine laboratory investigations were performed. NLRP3 mRNA expression was assessed by real time polymerase chain reaction. Serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin 1β (IL-1β), and uHSP72 levels were estimated by enzyme-linked immunosorbent assay. Serum chitotriosidase (CHIT1) activity was examined. NLRP3 mRNA relative expression, serum levels of 8-OHdG, IL-1β, and uHSP72, in addition to CHIT 1 activity were significantly increased in the macroalbuminuric patient group as compared to control and the other two diabetic groups. Also, a significant positive correlation was documented between the previously mentioned parameters and urinary albumin/creatinine ratio, serum creatinine, and HbA1c. Multiple linear regression analysis using urinary albumin/creatinine ratio as dependent variable confirmed that uHSP72 and NLRP3 mRNA relative expression were the independent predictors of DN (β were 0.432 and 0.448 respectively, P < 0.001). Receiver operating characteristic analyses revealed that both NLRP3 mRNA relative expression and uHSP72 levels were useful biomarkers discriminating DN patients from patients with type 2 diabetes mellitus (AUC were 0.957 and 0.983, respectively). uHSP72 may be considered as a novel potential diagnostic biomarker for the early detection of DN. Moreover, these data support the pivotal role of NLRP3 in the development and progression of DN. © 2017 IUBMB Life, 69(8):623-630, 2017.

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Section: Discussionmentioning

confidence: 68%

NLRP3 expression and urinary HSP72 in relation to biomarkers of inflammation and oxidative stress in diabetic nephropathy patients

et al. 2017

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“…All procedures were performed according to the manufacturer's instructions. Because we recently showed that heat-shock protein 72 (Hsp72) is a sensitive biomarker of AKI [31], urinary Hsp72 levels were analyzed by using a commercially available high-sensitivity ELISA (ADI-EKS-715; Assay Designs, Ann Arbor, Mich., USA). Briefly, samples and standards were added to wells coated with a mouse monoclonal antibody.…”

Section: Methodsmentioning

confidence: 99%

Mineralocorticoid Receptor Blockade Reduced Oxidative Stress in Renal Transplant Recipients: A Double-Blind, Randomized Pilot Study

et al. 2013

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Background: Previous experimental studies from our laboratory have demonstrated that aldosterone plays a central role in renal ischemic processes. This study was designed to evaluate the effect of mineralocorticoid receptor blockade in renal transplant recipients from living donors. Methods: 20 adult kidney transplant recipients from living donors were included in a double-blind, randomized, placebo-controlled clinical pilot study that compared spironolactone and placebo. Placebo or spironolactone (25 mg) was administered 1 day before and 3 days posttransplantation. Renal function and urinary kidney injury molecule-1, interleukin-18, and heat shock protein 72 as well as urinary hydrogen peroxide (H₂O₂) levels were quantified. Results: No significant differences were seen between the groups studied regarding age, gender, indication for kidney transplantation, residual renal function, renal replacement therapy, or warm and cold ischemia periods. In contrast, spironolactone administration significantly reduced the oxidative stress assessed by the urinary H₂O₂ excretion, in spite of no differences in renal function or reduction in tubular injury biomarkers. Conclusions: The findings of this exploratory study strongly suggest that aldosterone promotes oxidative stress and that the administration of spironolactone reduces the production of urinary H₂O₂ as a result of lesser formation of surrogate reactive oxygen species secondary to the ischemia-reperfusion phenomenon.

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“…21,22 Similarly, HSP70 may indicate early diabetic kidney injury because it has been shown in experimental models of acute kidney injury and gentamicin-induced renal tubular injury in Human Kidney tubular cell line (HK-2) that uHSP70 is a useful marker for early detection of proximal tubular cell injury. 23,24 DN is a consequence of exposure to consistent high plasma glucose concentration and various other metabolic factors such as advanced glycosylated end products (AGEs), oxidative stress, growth factors, and cytokines.…”

Section: Discussionmentioning

confidence: 99%

Higher urine heat shock protein 70/creatinine ratio in type 1 diabetes mellitus

et al. 2016

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Insidious progressive renal damage caused by type 1 diabetes mellitus (T1DM) begins in childhood before it becomes manifest in adult ages. Heat shock proteins (HSPs) regulate the cell response to any hazardous factors to prevent cell structure. The aim of the study is to determine whether urine levels of HSPs increase in diabetic children with time and indicate a progressive renal injury in T1DM. Thirty-three patients with T1DM and 24 healthy children were enrolled in the study. Renal function was normal in all patients. Urine levels of HSP27, HSP40, HSP60, HSP70, and HSP90 were measured by enzyme-linked immunosorbent assay at two consecutive years (2012 and 2013). The results were evaluated as urine HSP/creatinine ratios (uHSP/Cr). Mean urine HSP27/Cr, HSP40/Cr, HSP60/Cr, HSP70/Cr, HSP90/Cr in patient group were significantly higher than in controls in 2012 (uHSP27/Cr 460.12 ± 217.64 versus 270.02 ± 136.83 pg/mgCr; uHSP40/Cr 180.89 ± 118.59 versus 99.44 ± 62.49 pg/mgCr; uHSP60/Cr 114.40 ± 64.91 versus 70.50 ± 43.70 pg/mgCr; uHSP70/Cr 41.17 ± 28.42 versus 16.47 ± 7.32 pg/mgCr; uHSP90/Cr 175.64 ± 102.22 versus 107.61 ± 75.85 pg/ mgCr) (p50.05). In 2013, uHSP70/Cr level increased significantly (51.08 ± 27.72 pg/mgCr; p ¼ 0.001), whereas uHSP60/Cr level decreased and uHSP27/Cr, uHSP40/Cr, uHSP90/Cr levels remained stable (p40.05). Area under the curve (AUC) for uHSP70/Cr (0.957) was significantly higher than the others. Using a cutoff 22.59 pg/mgCr for uHSP70/Cr to predict of diabetic damage, sensitivity and specificity were 85% and 96%, respectively. Our results suggest that uHSP70/Cr increases over time and may indicate early phases of progressive kidney damage in diabetic children. ARTICLE HISTORY

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Hsp72 is an early and sensitive biomarker to detect acute kidney injury

Cited by 56 publications

References 48 publications

NLRP3 expression and urinary HSP72 in relation to biomarkers of inflammation and oxidative stress in diabetic nephropathy patients

NLRP3 expression and urinary HSP72 in relation to biomarkers of inflammation and oxidative stress in diabetic nephropathy patients

Mineralocorticoid Receptor Blockade Reduced Oxidative Stress in Renal Transplant Recipients: A Double-Blind, Randomized Pilot Study

Higher urine heat shock protein 70/creatinine ratio in type 1 diabetes mellitus

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