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The Immunohistochemical Evaluation of Solid Pseudopapillary Tumors of the Pancreas and Pancreatic Neuroendocrine Tumors Reveals ERO1Lβ as a New Biomarker.
Xie, J, Zhu, Y, Chen, H, Shi, M, Gu, J, Zhang, J, Shen, B, Deng, X, Zhan, X, Peng, C
Medicine. 2016;(2):e2509
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Abstract
Solid pseudopapillary tumor of the pancreas (SPTP) is a class of low-grade malignant tumors that carry a favorable prognosis after surgery. Our group has reported that dysfunctions in the endoplasmic reticulum (ER) protein processing pathway may play a role in tumor development. However, alterations of this pathway in other pancreatic tumors had not been well investigated. In this study, we collected 35 SPTP and pancreatic neuroendocrine tumor (PNET) specimens and described the clinicopathological features of them. We performed immunohistochemistry (IHC) for 6 representative proteins (ERO1Lβ, TRAM1, GRP94, BIP, P4HB, and PDIA4) involved in the ER pathway in both SPTP and PNET specimens. We compared the IHC scoring results of tumors and matched normal pancreas tissues and demonstrated that these proteins were downregulated in SPTP specimens. Five of these proteins (TRAM1, GRP94, BIP, P4HB, and PDIA4) did not display significant changes between PNET and normal pancreas tissue. However, ERO1Lβ was upregulated in PNET tissues compared to the normal tissues, which could be used as a pathological biomarker in the future.
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Association of urinary injury biomarkers with mortality and cardiovascular events.
Sarnak, MJ, Katz, R, Newman, A, Harris, T, Peralta, CA, Devarajan, P, Bennett, MR, Fried, L, Ix, JH, Satterfield, S, et al
Journal of the American Society of Nephrology : JASN. 2014;(7):1545-53
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Abstract
Kidney damage is a common sequela of several chronic pathologic conditions. Whether biomarkers of kidney damage are prognostic for more severe outcomes is unknown. We measured three urinary biomarkers (kidney injury molecule-1 [KIM-1], IL-18, and albumin) in 3010 individuals enrolled in the Health, Aging and Body Composition (Health ABC) study and used Cox proportional hazards models to investigate the associations of urinary KIM-1/creatinine (cr), IL-18/cr, and albumin/cr (ACR) with all-cause mortality and cardiovascular disease (CVD). Multivariable models adjusted for demographics, traditional CVD risk factors, and eGFR. Mean age of participants was 74 years, 49% of participants were men, and 41% of participants were black. During the median 12.4 years of follow-up, 1450 deaths and 797 CVD outcomes occurred. Compared with the lowest quartile, successive quartiles had the following adjusted hazard ratios (HRs; 95% confidence intervals [95% CIs]) for mortality: KIM-1/cr: (1.21; 1.03 to 1.41), (1.13; 0.96 to 1.34), and (1.28; 1.08 to 1.52); IL-18/cr: (1.02; 0.88 to 1.19), (1.16; 0.99 to 1.35), and (1.06; 0.90 to 1.25); ACR: (1.08; 0.91 to 1.27), (1.24; 1.06 to 1.46), and (1.63; 1.39 to 1.91). In similar analyses, only ACR quartiles associated with CVD: (1.19; 0.95 to 1.48), (1.35; 1.08 to 1.67), and (1.54; 1.24 to 1.91). Urinary KIM-1 had a modest association with all-cause mortality but did not associate with CVD, and urinary IL-18 did not associate with either outcome. In contrast, albuminuria strongly associated with all-cause mortality and CVD. Future studies should evaluate reasons for these differences in the prognostic importance of individual kidney injury markers.
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Nonalbuminuric proteinuria as a biomarker for tubular damage in early development of nephropathy with type 2 diabetic patients.
Kim, SS, Song, SH, Kim, IJ, Kim, WJ, Jeon, YK, Kim, BH, Kwak, IS, Lee, EK, Kim, YK
Diabetes/metabolism research and reviews. 2014;(8):736-41
Abstract
AIM: The aim of this study was to evaluate the association between urinary nonalbumin protein (NAP) and urinary tubular markers in early diabetic nephropathy. METHODS Urinary NAP was measured in 118 patients with type 2 diabetes with estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m². Urine levels of tubular markers [kidney injury molecule (KIM)-1, neutrophil gelatinase-assoicated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP)] were measured by using an Enzyme-linked immunosorbent assay (ELISA). Patients were divided into three groups according to urinary NAP values. RESULTS The urine levels of KIM-1, NGAL and L-FABP were significantly higher in the third tertile group than in the first tertile group (all p < 0.001). There was a significant positive correlation between NAP and each tubular marker (KIM-1, NGAL and L-FABP) in univariate analysis (all p < 0.001). Urinary NAP was positively correlated with all urinary tubular markers after adjustment for age, duration of diabetes, systolic blood pressure, eGFR, low-density lipoprotein cholesterol, HbA1c and albumin-to-creatinine ratio (KIM-1 r = 0.170, p < 0.001; NGAL r = 0.142, p < 0.015 and L-FABP r = 0.262, p < 0.001). In normoalbuminuric patients (n = 58), urinary NAP was also significantly correlated with NGAL and L-FABP in multivariate regression analyses (r = 0.302, p = 0.030 and r = 0.430, p = 0.001). CONCLUSIONS These findings suggest that urinary NAP reflects tubular damage in the early-stage type 2 diabetic nephropathy (eGFR ≥ 60 mL/min/1.73 m²). We suggest that urinary NAP could be used as a biomarker for tubular damage in clinical practice.
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Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury.
Belcher, JM, Sanyal, AJ, Peixoto, AJ, Perazella, MA, Lim, J, Thiessen-Philbrook, H, Ansari, N, Coca, SG, Garcia-Tsao, G, Parikh, CR, et al
Hepatology (Baltimore, Md.). 2014;(2):622-32
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Abstract
UNLABELLED Acute kidney injury (AKI) is common in patients with cirrhosis and associated with significant mortality. The most common etiologies of AKI in this setting are prerenal azotemia (PRA), acute tubular necrosis (ATN), and hepatorenal syndrome (HRS). Accurately distinguishing the etiology of AKI is critical, as treatments differ markedly. However, establishing an accurate differential diagnosis is extremely challenging. Urinary biomarkers of kidney injury distinguish structural from functional causes of AKI and may facilitate more accurate and rapid diagnoses. We conducted a multicenter, prospective cohort study of patients with cirrhosis and AKI assessing multiple biomarkers for differential diagnosis of clinically adjudicated AKI. Patients (n = 36) whose creatinine returned to within 25% of their baseline within 48 hours were diagnosed with PRA. In addition, 76 patients with progressive AKI were diagnosed by way of blinded retrospective adjudication. Of these progressors, 39 (53%) patients were diagnosed with ATN, 19 (26%) with PRA, and 16 (22%) with HRS. Median values for neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and albumin differed between etiologies and were significantly higher in patients adjudicated with ATN. The fractional excretion of sodium (FENa) was lowest in patients with HRS, 0.10%, but did not differ between those with PRA, 0.27%, or ATN, 0.31%, P = 0.54. The likelihood of being diagnosed with ATN increased step-wise with the number of biomarkers above optimal diagnostic cutoffs. CONCLUSION Urinary biomarkers of kidney injury are elevated in patients with cirrhosis and AKI due to ATN. Incorporating biomarkers into clinical decision making has the potential to more accurately guide treatment by establishing which patients have structural injury underlying their AKI. Further research is required to document biomarkers specific to HRS.