Ultrasensitive Silicon Nanowire Biosensor with Modulated Threshold Voltages and Ultra-Small Diameter for Early Kidney Failure Biomarker Cystatin C.

Acute kidney injury (AKI) is a frequently occurring severe disease with high mortality. Cystatin C (Cys-C), as a biomarker of early kidney failure, can be used to detect and prevent acute renal injury. In this paper, a biosensor based on a silicon nanowire field-effect transistor (SiNW FET) was studied for the quantitative detection of Cys-C. Based on the spacer image transfer (SIT) processes and channel doping optimization for higher sensitivity, a wafer-scale, highly controllable SiNW FET was designed and fabricated with a 13.5 nm SiNW. In order to improve the specificity, Cys-C antibodies were modified on the oxide layer of the SiNW surface by oxygen plasma treatment and silanization. Furthermore, a polydimethylsiloxane (PDMS) microchannel was involved in improving the effectiveness and stability of detection. The experimental results show that the SiNW FET sensors realize the lower limit of detection (LOD) of 0.25 ag/mL and have a good linear correlation in the range of Cys-C concentration from 1 ag/mL to 10 pg/mL, exhibiting its great potential in the future real-time application.

Establishment of muscle mass-based indications for the cystatin C test in renal function evaluation.

Background: We aimed to suggest muscle mass-based criteria for using of the cystatin C test for the accurate estimated glomerular filtration rate (eGFR). Materials and methods: We recruited 138 Korean subjects and evaluated eGFRcr (derived from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) based on creatinine) was compared to eGFRcys based on cystatin C as the reference value. The skeletal muscle mass index (SMI) by bioelectrical impedance analysis (BIA) was used as representative of muscle mass. Calf circumference (CC) was also evaluated. We defined the patients by eGFRcr as those with values of eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2 as the detection of hidden renal impairment (DHRI). Cut-off values were determined based on muscle mass for the cases of DHRI suggesting the criteria of cystatin C test in renal function evaluation. Results: We confirmed significant negative correlation between %difference of eGFRcr from eGFRcys and SMI (r, -0.592 for male, -0.484 for female) or CC (r, -0.646 for male, -0.351 for female). SMI of 7.3 kg/m2 for males and 5.7 kg/m2 for females were suggested to be significant cutoffs for indication of cystatin C test. We also suggested CC would be valuable for cystatin C indication. Conclusion: We suggested the muscle mass-based objective criteria relating to SMI and CC that would indicate the use of cystatin C to evaluate renal function test in sarcopenic cases. Our results highlight the importance of muscle mass-based selection of renal function.

Serum Cystatin C as a predictor of acute kidney injury in neonates: a meta-analysis

Abstract Objective: The objective of this meta-analysis is to evaluate the diagnostic value of serum Cystatin C in acute kidney injury (AKI) in neonates Sources: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang Database were searched to retrieve the literature related to the diagnostic value of Cystatin C for neonatal AKI from inception to May 10, 2021. Subsequently, the quality of included studies was determined using the QUADAS-2 tool. Stata 15.0 statistical software was used to calculate the combined sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Additionally, meta-regression analysis and subgroup analysis contributed to explore the sources of heterogeneity Summary of the findings: Twelve articles were included. The pooled sensitivity was 0.84 (95%CI: 0.74-0.91), the pooled specificity was 0.81 (95%CI: 0.75-0.86), the pooled PLR was 4.39 (95%CI: 3.23-5.97), the pooled NLR was 0.19 (95%CI: 0.11-0.34), and the DOR was 22.58 (95%CI: 10.44-48.83). The area under the receiver operating characteristic curve (AUC) was 0.88 (95%CI: 0.85-0.90). No significant publication bias was identified (p > 0.05).

Beta-2-Microglobulin is an Independent Risk Factor for Asymptomatic Carotid Atherosclerosis in Patients with Primary Aldosteronism.

AIM: To identify the association between serum beta-2-microglobulin (B2M) or cystatin C (CysC) and asymptomatic carotid atherosclerosis in patients with primary aldosteronism (PA). METHODS: In this cross-sectional study, 265 subjects were enrolled, including 83 patients with PA, 91 with essential hypertension (EH), and 91 normotensive (NT) controls. B2M, CysC, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured, and the aldosterone-to-renin ratio (ARR) was calculated. Carotid intima-media thickness (cIMT), increased cIMT, and presence of carotid plaque or carotid stenosis ＜50% in the carotid artery were measured via ultrasonography to evaluate the degree of asymptomatic carotid atherosclerosis. RESULTS: CIMT increased in the NT, EH, and PA groups (0.60 (0.50, 0.80) mm vs. 0.80 (0.60, 1.00) mm vs. 0.90 (0.70, 1.10) mm, P＜0.01), so as the prevalence of increased cIMT and presence of carotid plaque (both P＜0.05). The B2M and CysC levels exhibited the same trend (B2M: 1.60±0.34 mg/L, 1.80±0.41 mg/L, 1.98±0.64 mg/L, P＜0.05; CysC: 0.76±0.12 mg/L, 0.88±0.17 mg/L, 0.94±0.23 mg/L, P＜0.05). B2M, CysC, PAC, and ARR were all positively associated with cIMT (all P＜0.01) in the PA group. After adjusting for potential confounders, B2M, PAC, but not CysC or ARR were independently associated with increased cIMT and presence of carotid plaque and carotid stenosis ＜50%, respectively. The receiver operating characteristic (ROC) curve analysis revealed that B2M and PAC demonstrated significant predictive ability for increased cIMT and presence of carotid plaque and carotid stenosis ＜50%. CONCLUSION: B2M is an independent risk factor for asymptomatic carotid atherosclerosis in patients with PA.

Serum Cystatin C as a predictor of acute kidney injury in neonates: a meta-analysis.

OBJECTIVES: The objective of this meta-analysis is to evaluate the diagnostic value of serum Cystatin C in acute kidney injury (AKI) in neonates. SOURCES: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang Database were searched to retrieve the literature related to the diagnostic value of Cystatin C for neonatal AKI from inception to May 10, 2021. Subsequently, the quality of included studies was determined using the QUADAS-2 tool. Stata 15.0 statistical software was used to calculate the combined sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Additionally, meta-regression analysis and subgroup analysis contributed to explore the sources of heterogeneity. SUMMARY OF THE FINDINGS: Twelve articles were included. The pooled sensitivity was 0.84 (95%CI: 0.74-0.91), the pooled specificity was 0.81 (95%CI: 0.75-0.86), the pooled PLR was 4.39 (95%CI: 3.23-5.97), the pooled NLR was 0.19 (95%CI: 0.11-0.34), and the DOR was 22.58 (95%CI: 10.44-48.83). The area under the receiver operating characteristic curve (AUC) was 0.88 (95%CI: 0.85-0.90). No significant publication bias was identified (p > 0.05). CONCLUSIONS: Serum Cystatin C has a good performance in predicting neonatal AKI; therefore, it can be used as a candidate biomarker after the optimal level is determined by large prospective studies.

Predictive value of kidney injury markers for early DGF in kidney transplant recipients / 器官移植

Objective To evaluate the predictive values of serum neutrophil gelatinase-associated lipocalin (NGAL), urine NGAL, serum cystatin C (Cys-C) and serum creatinine (Scr) for early delayed graft function (DGF) in kidney transplant recipients. Methods Clinical data, blood and urine samples of 159 kidney transplant recipients were collected. All recipients were divided into the DGF group (n=42) and immediate graft function (IGF) group (n=117) according to the incidence of DGF. Clinical data of all recipients were analyzed. The changes of serum NGAL, urine NGAL, Cys-C and Scr levels were statistically compared between two groups. The predictive values of different markers for early DGF were assessed. Results Among 159 kidney transplant recipients, DGF occurred in 42 cases with an incidence rate of 26.4%. There were statistically significant differences in donor age, cold ischemia time of donor kidney and complement-dependent cytoxicity (CDC) between the two groups(all P < 0.05). Within postoperative 2 weeks, the serum NGAL levels in the DGF group were higher than those in the IGF group (all P < 0.05). The Cys-C, Scr and urine NGAL levels in the DGF group were higher compared with those in the IGF group within 3 weeks after kidney transplantation(all P < 0.001). Serum NGAL, urine NGAL, Cys-C and Scr levels had certain predictive values for early DGF in kidney transplant recipients. Cys-C yielded the highest predictive value with a cut-off value of 4.73 mg/L, sensitivity of 0.833, specificity of 0.812 and area under the curve (AUC) of 0.895. Conclusions Cys-C has higher predictive value for early DGF in kidney transplant recipients compared with serum NGAL, urine NGAL and Scr.

Cystatin C level is associated with the recovery of renal function in cancer patients after onset of acute kidney injury.

BACKGROUND: The risk of injury to the kidney can be significantly exacerbated by the presence of tumors and the effects of related treatments. Kidney injury associated with cancer is common in multiple myeloma, tumor lysis syndrome, hematopoietic stem cell therapy, and chemotherapy. Cancer patients are at increased risk of infection, sepsis, tumor lysis syndrome, drug-related toxicity, and other comorbidities, leading to a significantly increased risk of acute kidney injury (AKI). This study retrospectively analyzed the clinical data of AKI in cancer patients and explored the predictive value of Cystatin C (CysC) in the prognosis of cancer patients with AKI. METHODS: Cancer patients attending the Fifth People's Hospital of Shenyang from April 2014 to March 2019 were enrolled according to inclusion and exclusion criteria. Cancer patients with AKI were divided into two groups according to the changes in renal function during the follow-up period: a renal function recovery group and a nonrecovery group. The differences in baseline data of the two groups were compared. Logistic univariate and multivariate regression analyses were conducted to determine the risk of renal function failure. RESULTS: A total of 3,127 cases were included. Among them, 659 cases (21.1%) had AKI, and 2,468 cases had no AKI. Among the 659 AKI patients, 473 (71.8%) patients' renal function recovered, while 186 (28.2%) did not. Logistic univariate and multivariate regression analyses indicated that age [odds ratio (OR) =1.133, 95% confidence interval (CI): 1.064-1.219], diabetes (OR =1.226, 95% CI: 1.093-1.385), chronic kidney disease (CKD) (OR =1.347, 95% CI: 1.108-1.624), hematological malignancies (OR =1.174, 95% CI: 1.063-1.311), chemotherapy (OR =1.119, 95% CI: 1.055-1.304), systolic blood pressure (OR =1.108, 95% CI: 1.062-1.267), serum creatinine (Scr) (OR =1.262, 95% CI: 1.105-1.446), and CysC (OR =1.416, 95% CI: 1.251-1.739) were related to the failure of renal function to recover after AKI. CONCLUSIONS: Baseline CysC level is associated with the occurrence of AKI in cancer patients and a failure to recover renal function during follow-up.

Pressure overload promotes cystatin C secretion of cardiomyocytes to regulate the MAPK signaling pathway and mediate cardiac hypertrophy.

BACKGROUND: This study aimed to compare serum cystatin C (CysC) levels between hypertensive and non-hypertensive patients, and to explore the correlation between serum CysC and left ventricular hypertrophy (LVH). We also investigated the effects of pressure overload on cardiac expression and secretion of CysC, and explored the direct effect of CysC on the hypertrophy of primary cardiomyocytes. METHODS: Serum CysC was compared in patients with hypertension (634 patients) and those without hypertension (411 patients), and the correlation between serum CysC levels and LVH was explored. A transverse aortic constriction (TAC) mouse model and a mechanical stretch model of primary cardiomyocytes and fibroblasts were developed to compare cardiac expression and secretion of CysC under pressure overload. After intervention with exogenous CysC, we compared the cross-sectional area of primary cardiomyocytes, cardiac hypertrophy-associated gene expression, and phosphorylation of the MAPK signaling pathway. RESULTS: In chronic kidney disease (CKD) stage 1 patients, serum CysC was higher in hypertensive patients independent of renal function. Serum CysC elevation was an independent predictor of LVH after correction for endogenous creatinine clearance rate (eCCr), left ventricular ejection fraction (LVEF), and NT-proBNP. Cardiac levels of CysC in TAC mice were elevated. CST3 gene expression was upregulated, and both intracellular and culture supernatant CysC levels increased after mechanical stretch of primary cardiomyocytes. After intervention with exogenous CysC, the cross-sectional area of primary cardiomyocytes increased, as well as the gene expression of Nppa, Nppb, and Myh7, and the phosphorylation of ERK, p38, and TAK1. CONCLUSIONS: Serum CysC levels were higher in hypertensive patients, and serum CysC elevation was an independent predictor of LVH after correction for eCCr. Pressure overload induced greater cardiomyocyte secretion of CysC. Exogenous CysC can enter cardiomyocytes, having a pro-hypertrophic effect on primary cardiomyocytes through regulation of the MAPK signaling pathways.

Evaluation of Serum Cystatin C as an Early Biomarker of Acute Kidney Injury in Patients with Acute Pancreatitis.

INTRODUCTION: Acute pancreatitis (AP) is an inflammatory process of pancreas with varying degree of involvement of regional tissues. The aim of this study was to investigate the potential use of serum cystatin C (Cys-C) for the early and accurate diagnosis of acute kidney injury (AKI) in patients of AP. MATERIALS AND METHODS: This was a prospective study conducted in 1 year. Total of 215 cases of AP fulfilling the inclusion criteria were enrolled in this study. Patients suffering from chronic pancreatitis, neoplasm, chronic liver disease, and chronic kidney disease were excluded from the study. Diagnosis of AP was based on the Atlanta classification 2012. All patients were classified into a non-AKI group (n = 152) and an AKI group (n = 38) according to the dynamic changes in serum creatinine levels. Serum Cys-C was measured by particle-enhanced immune nephelometric assay. RESULTS: By univariate logistic regression analysis, body mass index (BMI) (OR = 1.44, 95% CI: 1.23-1.68; p < 0.001), blood urea (OR = 1.15, 95% CI: 1.06-1.23; p < 0.001), Cys-C (OR = 1.04, 95% CI: 1.01-1.07; p < 0.05), serum calcium (OR = 0.59, 95% CI: 0.41-0.86; p < 0.05), and serum lactate dehydrogenase (LDH) (OR = 1.001, 95% CI: 1.0-1.001; p < 0.05) were the significant indicators for AKI in patients with AP. Using multivariate logistic regression analysis, urinary albumin and Cys-C were independent and significant indicators of AKI in patients with AP (OR = 1.026, 95% CI: 1.01-1.07; p < 0.01). Receiver operating characteristic (ROC) curve of serum Cys-C, for AKI in patient with AP could be identified with a sensitivity of 92.06% at specificity of 96.0% [area under the curve (AUC) = 0.96, 95% CI: 0.92-0.98] by baseline serum Cys-C (cutoff value = >32.32 mg/L). CONCLUSION: Increase of baseline serum Cys-C was associated with AKI in patients with AP. HOW TO CITE THIS ARTICLE: Patel ML, Shyam R, Bharti H, Sachan R, Gupta KK, Parihar A. Evaluation of Serum Cystatin C as an Early Biomarker of Acute Kidney Injury in Patients with Acute Pancreatitis. Indian J Crit Care Med 2020;24(9):777-782.

Effect of terlipressin on renal function in cirrhotic patients with acute upper gastrointestinal bleeding.

BACKGROUND: Renal dysfunction is a serious morbidity in cirrhotic patients with acute upper gastrointestinal bleeding (AUGIB). Terlipressin is the first-line treatment choice for acute variceal bleeding and hepatorenal syndrome (HRS). This study aimed to assess the effect of terlipressin on renal function in patients with liver cirrhosis and AUGIB. METHODS: We retrospectively reviewed 40 cirrhotic patients with AUGIB treated with terlipressin by an attending physician between January 2016 and June 2018. We analyzed the change of renal function parameters, including cystatin C (CysC) and creatinine (Cr), during the use of terlipressin and after terlipressin was stopped. We also identified the factors associated with renal function improvement in patients without active bleeding during the use of terlipressin. RESULTS: During the use of terlipressin, CysC value was significantly reduced (1.3±0.8 vs. 1.1±0.7, P=0.001); Cr value was reduced, but the reduction was not statistically significant (68.8±24 vs. 65.5±23, P=0.817); the rate of CysC reduction was significantly higher in patients treated with terlipressin than those treated with somatostatin/octreotide (73.1% vs. 0%, P=0.005); the rate of Cr reduction was not significantly different between patients treated with terlipressin and somatostatin/octreotide (61.5% vs. 20%, P=0.148); no factor associated with CysC reduction was identified; higher hemoglobin, red blood cell, and platelet and lower prothrombin time and international normalized ratio at baseline were significantly associated with Cr reduction. After terlipressin was stopped, neither CysC nor Cr value was significantly reduced (P=0.852 and P=0.296). CONCLUSIONS: Terlipressin may be beneficial on preventing renal function impairment in cirrhotic patients with AUGIB.

Research progress on molecular markers related to the donor kidney injury from organ donation after citizen's death / 器官移植

Shortage of donor kidney is a major problem in renal transplantation. Accurate evaluation of donor kidney function may reduce the organ rejection rate and save more patients with uremia. Compared with pathological examination, detection of circulating molecular markers is more convenient in clinical application. In this article, the research progress on the markers of kidney injury, such as serum creatinine, serum cystatin C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), mitochondrial DNA (mtDNA), kidney injury molecule-1(KIM-1) and interleukin -18 (IL-18), were briefly reviewed.

The value of cystatin C and urinary and serum neutrophil gelatinase-associated lipocalin during the perioperative period of renal transplantation.

BACKGROUND: The perioperative management of renal transplantation is complex. Our research aimed to study the clinical value of cystatin-C (Cys-C) and urinary and serum neutrophil gelatinase-associated lipocalin (NGAL) during the perioperative period of renal transplantation. METHODS: We collected the clinical information of 47 renal transplantation patients. Urine and serum samples were collected daily until the second week and then weekly until discharge to determine serum NGAL (s-NGAL), urine NGAL (u-NGAL), serum creatinine (s-Cr), and Cys-C levels. Receiver-operating characteristic (ROC) analysis was used, and the area under the curve (AUC) was compared to evaluate the accuracy of the diagnosis of delayed graft function (DGF). Multivariable analysis was used to find the association between the markers and renal function at discharge. RESULTS: In our research, the value of Cys-C, serum NGAL, and urine NGAL were higher in DGF group. In the ROC analysis, Cys-C had the highest AUC (0.939) compared with s-NGAL (0.909), u-NGAL (0.856), and s-Cr (0.747). Multivariable analysis showed that Cys-C levels in the first week after the operation and cold ischemia time were independently associated with estimated glomerular filtration rate (eGFR) at discharge (P<0.05). CONCLUSIONS: Our results showed that Cys-C, serum NGAL, and urine NGAL could reflect renal function sensitively. Cys-C had the highest sum of sensitivity and specificity at 4.77 mg/L, with a sensitivity of 0.818 and specificity of 0.889. The Cys-C level during the first week after the operation was independently associated with eGFR at discharge and could predict the short-term prognosis of renal transplantation patients.

Serum and Urinary NGAL and Cystatin C Levels as Diagnostic Tools for Acute Kidney Injury and Chronic Kidney Disease: A Histobiochemical Comparative Study.

BACKGROUND: High global incidence of acute kidney injury (AKI) is an observable complication in critically ill patients. Long-term disease and medication complexity contribute to devastating chronic kidney disease (CKD), diminishing quality of life. OBJECTIVES: To establish new biomarkers to guide patient care and facilitate novel therapeutics development. METHODS: Serum and urinary levels of creatinine, CysC, and NGAL were estimated in 86 renal patients and compared with healthy controls for AKI and CKD categorization. Creatinine and CysC measurements were used to estimate GFR. Kidney biopsies were prepared for light microscopy for further characterization. Patients' demographic data were used in group association studies. RESULTS: Thirty-six patients met the criteria for AKI and 50 for CKD. Both mean serum and urine creatinine levels were significantly elevated by 2.8 and 2.6, respectively, from baseline in 48 h in the AKI group but not CKD group. Mean serum Cystatin C (CysC) values were higher than controls but similar in both disease states, while urine levels were slightly higher in CKD patients, and remained steady by the end of the follow-up (EF-Up). Further, a significant 2.9-fold and 5.5-fold (p=0.001) increase in serum NGAL in AKI and CKD, respectively, and a dramatic 7.1-factor reduction in AKI group, but no appreciable change in the CKD group from admission to EF-Up were observed. Similarly, urine NGAL level for AKI and CKD increased 3.2-fold and 6-fold respectively, on admission, which decreased moderately with the AKI group (2.5-fold) but increased by a factor of 1-8 (10.7- fold; p=0.001) at EF-Up. ROC assessment curve revealed relatively higher NGAL performance at good predictive values than CysC (p < 0.009). CONCLUSION: Our data demonstrated creatinine elevation by a factor > 2 in 48 h in AKI group but not CKD group, which returned close to normal levels by the EF-Up, an indication of abrupt renal injury in AKI, compared with a persistent effect in the CKD group. Both serum and urine NGAL sensitivity and specificity provided powerful discriminative tool between AKI and CKD by reduction in the AKI group and an increase in the CKD group by the EF-UP, thus, contributing in establishing the basis for AKI and CKD classification. CysC, however, displayed less sensitivity than NGAL, indicating effects by enigmatic non-specific factors.

Comparison of the new and traditional CKD-EPI GFR estimation equations with urinary inulin clearance: A study of equation performance.

BACKGROUND: Diagnosis, prognostication and treatment in chronic kidney disease is often informed by an estimate of the glomerular filtration rate (GFR). Commonly used GFR estimation (eGFR) equations are based on serum creatinine (Cr) concentrations and display suboptimal precision and accuracy. Newer equations incorporating additional endogenous markers such as ß-Trace Protein (BTP), ß2-Microglobulin (B2M) and cystatin C (cysC) have been developed but require validation. METHODS: This prospective cohort study evaluated the performance of 6 eGFR equations developed by the chronic kidney disease - epidemiology collaboration group (CKD-EPI) against urinary inulin clearance GFR in patients recruited from outpatient nephrology clinics. RESULTS: Mean biases were negligible and similar between equations. The eGFR-EPI Cr/cysC had the best precision and accuracy of all the equations and the best agreement with inulin mGFR when classifying participants into GFR categories. The BTP and B2M equations displayed the worst precisions and accuracies and showed the least consistent performance across levels of GFR. Thus, the eGFR-EPI Cr/cysC is the least biased, most precise and has the highest accuracy as compared to other eGFR-EPI equations. CONCLUSIONS: The BTP and B2M equations are the worst performing of the eGFR-EPI equations, and no benefit is observed with the addition of BTP or B2M to Cr/cysC.

Intracerebroventricular administration of Cystatin C ameliorates disease in SOD1-linked amyotrophic lateral sclerosis mice.

Cystatin C (CysC) is a major protein component of Bunina bodies, which are a pathological hallmark observed in the remaining motor neurons of patients with amyotrophic lateral sclerosis (ALS). Dominant mutations in the SOD1 gene, encoding Cu/Zn superoxide dismutase (SOD1), are causative for a subset of inherited ALS cases. Our previous study showed that CysC exerts a neuroprotective effect against mutant SOD1-mediated toxicity in vitro; however, in vivo evidence of the beneficial effects mediated by CysC remains obscure. Here we examined the therapeutic potential of recombinant human CysC in vivo using a mouse model of ALS in which the ALS-linked mutated SOD1 gene is expressed (SOD1G93A mice). Intracerebroventricular administration of CysC during the early symptomatic SOD1G93A mice extended their survival times. Administered CysC was predominantly distributed in ventral horn neurons including motor neurons, and induced autophagy through AMP-activated kinase activation to reduce the amount of insoluble mutant SOD1 species. Moreover, PGC-1α, a disease modifier of ALS, was restored by CysC through AMP-activated kinase activation. Finally, the administration of CysC also promoted aggregation of CysC in motor neurons, which is similar to Bunina bodies. Taken together, our findings suggest that CysC represents a promising therapeutic candidate for ALS.

Study on Combined Determination Plasma NGAL,Cys C and Urinary NAG/Crea for the Diagnosis of Early Diabetic Nephropathy / 现代检验医学杂志

Objective To investigate the value of plasma neutrophil gelatinase-associated lipocalin (NGAL),cystatin C (Cys C) and the ratio of urinary N-acetyl-beta-D-glucosaminidase to creatinine (NAG/Crea) combined determination in the diagnosis of early diabetic nephropathy.Methods Collected 67 cases of patients with type 2 diabetes hospitalized in the First Affiliated Hospital of Kunming Medical University from December 2016 to February 2017.According to the value of UALB/Crea was divided into two groups:Diabetic urinary microalbumin normal group (UALB/Crea＜30 mg/gCrea) had 35 patients and early diabetic nephropathy group (namely the trace albuminuria group,UALB/Crea 30 ～ 300 mg/gCrea) had 32 patients.Other selected 20 normal volunteers as control group,compared with a medical group to gather all the staff of the clinical data,using automatic biochemical analyzer detected the plasma NGAL,Cys C and urine NAG/Crea,and adopted the receiver-operating characteristic (ROC) curve of the detection index was analyzed.Results ①Plasma NGAL,Cys C and urinary NAG/Crea of diabetic nephropathy patients was significantly higher than those of healthy control group (Z=-5.740 ～-5.386,P＜0.05).②The areaunder receiver operating characteristic (ROC) curve of plasma NGAL,Cys C and urine NAG/Crea were 0.858,0.911 and 0.714.Conclusion Plasma NGAL,Cys C and urinary NAG/Crea combined determination have a higher value for early diagnosis of diabetic nephropathy.

Deviations from the expected relationship between serum FGF23 and other markers in children with CKD: a cross-sectional study.

BACKGROUND: High levels of fibroblast growth factor-23 (FGF23) are associated with mortality. In chronic kidney disease (CKD), FGF23 levels rise as renal function declines. We analyzed the contribution of laboratory values to the variance of FGF23 levels in relationship to a curve of expected FGF23 levels for a given GFR. METHODS: Following approval by the research ethics boards, we measured FGF23, CysC eGFR, creatinine, urea, albumin, calcium, phosphate, vitamin D metabolites, PTH, alkaline phosphatase, CRP, and venous gases in 141 pediatric CKD patients (45, 37, 32, 13 and 14 CKD stages I, II, III, IV, and V, respectively). Data were expressed as median (25th, 75th percentile). RESULTS: FGF23 correlated significantly with CysC, CysC eGFR, PTH, 1.25 (OH)2 vitamin D, phosphate, and pH. The correlation of the latter three remained significant in the multivariate analysis. We calculated a formula for the expected FGF23 value for a given level of eGFR which reads Y = 1295 * e-0.07247*X + 38.35. Deviation by more than 20% from the curve also depended on phosphate, 1.25 (OH)2 vitamin D and pH. CONCLUSIONS: Our data emphasize the importance of phosphate and 1.25 (OH)2 vitamin D levels. The impact of acidosis on FGF23 warrants further studies.

Correlation of serum cystatin C and N-terminal pro-brain natriuretic peptide with severity of coronary heart disease / 中国基层医药

Objective To investigate the correlation of serum cystatin C(CysC) and N-terminal brain natriuretic peptide (NT-proBNP) levels with severity of coronary heart disease.Methods 240 patients with coronary artery disease were selected.According to coronary angiography,they were divided into four groups:52 cases of non-CAD group,coronary single vessel disease group (73 cases),62 cases of double vessel disease,53 cases of triple vessel disease group.The serum CysC,NT-proBNP levels were determined and compared among the four groups.The relationship between CysC,NT-proBNP levels and severity of coronary artery disease was analyzed.Results The CysC,NT-proBNP levels in the single coronary vessel disease group,double vessel disease group and multivessel disease group were higher than non-CHD group,the differences were statistically significant(t=2.019,3.870,7.449,P=0.046,0.000,0.000;t=6.068,15.365,24.851,P=0.000,0.000,0.000);and with the crown pulse lesion count increased,the serum CysC,NT-proBNP levels increased gradually,the differences were statistically significant(t=2.080,3.070,P=0.039,0.000;t=10.953,12.078,P=0.000,0.000).Coronary artery disease severity was positively correlated with CysC,NT-proBNP levels (r1=0.562,r2=0.503).Conclusion The severity of coronary artery disease is closely related to the levels of CysC,NT-proBNP,which has some predictive value for coronary artery disease,patients with high CysC,NT-proBNP levels should be given high priority.

Clinical Significance of Combined Detection of Serum Lp-PLa2, Hcy and CysC for the Diagnosis of Hypertensive Disorder Complicating Pregnancy / 现代检验医学杂志

Objeetive To investigate the clinical significance of combined detection of lipoprotein associated serum phospholipase A2 (Lp-PLa2),homocysteine (Hcy) and cystatin C (CysC) in the diagnosis of hypertensive disorders complicating pregnancy (HDCP).Methods From January 2013 to May 2016 in Changan Hospital,selected 113 cases of pregnancy induced hypertension patients as the observation group,and were divided into three group A,B and C (group A:55 cases of HDCP patients,group B:32 cases of mild preeclampsia and group C for patients with severe preeclampsia 26 cases).At the same period,selected 50 cases of normal college pregnancy as control group,serum Lp-PLa2 (enzyme-linked immunosorbent assay),Hcy (cyclophorase method) and CysC (particle enhanced turbidimetric method),the test results were analyzed and compared.Results Serum Lp-PLa2,Hcy and CysC test results in the control group,the observation group A,observation group B and observation group C increased significantly,in the observation group C increased most obviously.Compared with the control group,the serum levels of Lp-PLa2,Hcy and CysC in the observation group were significantly higher,the difference was statistically significant (F=8.102,7.231 and 6.926,all P＜0.05).Pearson correlation analysis showed that there was a positive correlation between serum Lp-PLa2,Hcy and CysC and blood pressure (r=0.71,0.69,0.63,all P＜0.05).The abnormal rate of serum Lp-PLa2,Hcy and CysC for three joint detection was higher than that of single detection,and the difference was statistically significant (x2 =6.725,P＜0.001).The abnormal rate of serum Lp-PLa2,Hcy and Cys single test results increased with the exacerbation of HDCP,and the difference was statistically significant (x2=9.351,P＜0.000).Conclusion Serum Lp-PLa2,Hey,CysC and pregnancy would be closely related to the occurrence and development of hypertension syndrome,so combined detection of HDCP can improve the detection rate of abnormal results,and it has important clinical significance for early diagnosis and prognosis of HDCP.

Significance of combined detection of serum Cys-C and Hcy in the diagnosis of early renal injury in children ;with diabetes / 中国糖尿病杂志

Objective To investigate the combined detection of serum cystatin C (Cys‐C ) and homocysteine (Hcy) for the diagnosis of early renal damage in diabetic children. Methods Data of 97 cases of diabetic children were collected in our hospital. According to the levels of 24 hUAER ,diabetic children were divided into <30 mg group (n=34) ,30~299 mg group (n=42) ,and ≥300 mg group (n=21). 40 cases of healthy children were selected as control group (NC). Laboratory indexes were compared among different groups. The critical values of Cys‐C and Hcy in early diagnosis of renal damage were calculated by receiver operating curve (ROC). Results The levels of Cys‐C and Hcy in <30 mg group were significantly higher than in NC group [Cys‐C (1.04 ± 0.26 ) vs(0.79 ± 0.21 ) mg/L ,Hcy (13.09 ± 2.15) vs(8.57 ± 1.24)μmol/L ,respectively ,P< 0.05]. When Cys‐C cutoff point took 1.02 mg/L ,the diagnosis sensitivity for diabetic nephropathy diagnosis was 86.09% and the specificity was 83.28% ,the maximum diagnostic index reached 1.6937 ,ROC area under the curve was 0.841.When Hcy threshold took 13.00 μmol/L ,the sensitivity was 83.98% and the specificity was 79.24% ,with the maximum diagnostic index 1.6322 and ROC area 0.795.Cys‐C combined with Hcy had a sensitivity of 92.38% and a specificity of 89.17% ,with the maximum diagnostic index 1.764 and ROC area 0.928. Conclusion Cys‐C combined with Hcy detection for early diagnosis of renal injury in diabetic children has important clinical value.