Biomarkers ; urine ; Child ; Child, Preschool ; Cystatin C ; Cystatins ; urine ; Cytomegalovirus Infections ; pathology ; urine ; Female ; Humans ; Kidney ; pathology ; Male ; TATA Box Binding Protein-Like Proteins ; urine ; alpha-Macroglobulins ; urine

Changes in renal function are one of the most common manifestations of severe illness. There is a clinical need to intervene early with proven treatments in patients with potentially deleterious changes in renal function. Unfortunately progress has been hindered by poor definitions of renal dysfunction and a lack of early biomarkers of renal injury. In recent years, the definitional problem has been addressed with the establishment of a new well-defined diagnostic entity, acute kidney injury (AKI), which encompasses the wide spectrum of kidney dysfunction, together with clearer definition and sub-classification of the cardio-renal syndromes. From the laboratory have emerged new biomarkers which allow early detection of AKI, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C. This review describes the new concepts of AKI and the cardio-renal syndromes as well as novel biomarkers which allow early detection of AKI. Panels of AKI biomarker tests are likely to revolutionise the diagnosis and management of critically ill patients in the coming years. Earlier diagnosis and intervention should significantly reduce the morbidity and mortality associated with acute kidney damage.
Acute Kidney Injury/*diagnosis ; Biological Markers/analysis/blood/urine ; Cystatin C/blood/urine ; Heart Failure/complications/etiology ; Humans ; Kidney Diseases/complications/*diagnosis/etiology ; Lipocalins/blood/urine ; Syndrome

PURPOSE: In children, 24-hour urine collections are unreliable for evaluating glomerular filtration rate (GFR) because of the difficulty of regulating voiding and the daily variation of urinary creatinine up to 25%. Additionally, creatinine clearance (Ccr) based on urinary creatinine is considered inaccurate. The purpose of this study was to compare estimated GFR determined using Ccr, formulas with serum cystatin C and creatinine, and 99mTc-mercaptoacetyltriglycine (MAG3) dynamic renal scintigraphy. METHODS: This retrospective study included 101 patients (age, <18 years) who visited Chung-Ang University Hospital between July 2011 and August 2012. GFR was estimated using 24-hour urinary creatinine, five formulas with serum creatinine and cystatin C, and 99mTc-MAG3 renal scan. RESULTS: Of the 101 patients, glomerular renal diseases were present in 60 patients (59.4%) and non-glomerular diseases were present in 41 patients (40.6%). There was a significant correlation between estimated GFR determined using 99mTc-MAG3 renal scan and Ccr (r=0.389, P<0.001). The correlation values between estimated GFR determined using 99mTc-MAG3 renal scan and each formula of Schwartz, Counahan-Barratt, Cockcroft-Gault, Filler and Lepage, and Bokencamp were 0.265 (P=0.007), 0.128 (P=0.044), 0.230 (P=0.021), 0.356 (P<0.001), and 0.355 (P<0.001), respectively. 99mTc-MAG3 renal scan was correlated with estimated-GFR by all formulas in decreased renal function. CONCLUSION: Estimated GFRs determined using serum creatinine and cystatin C, and 99mTc-MAG3 renal scan correlated well with estimated GFR determined using Ccr. 99mTc-MAG3 renal scan may be replaced for evaluation of renal function with convenience in patients with renal disease and decreased renal function in childhood.
Child* ; Creatinine ; Cystatin C ; Glomerular Filtration Rate* ; Humans ; Radionuclide Imaging* ; Retrospective Studies ; Technetium Tc 99m Mertiatide ; Urine Specimen Collection

BACKGROUNDAcute renal failure (ARF) after liver transplantation is associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of early effective prognostic factors. Recent studies indicated that serum levels of cystatin C and beta2-microglobulin (beta2 MG) as well as urinary beta2 MG and N-acetyl-beta-D-glucosaminidase (NAG) would increase in patients with early and mild renal impairment. In this study, these factors were detected during the different stages in patients who accepted orthotopic liver transplantation (OLT), and their feasibilities to predict early ARF after OLT were also analyzed.

METHODSSixty patients with normal blood urea nitrogen (BUN) and serum creatinine (SCr) who received modified piggyback liver transplantation without veno-venous bypass were prospectively studied. Blood samples were drawn from patients for the determination of serum beta2 MG (n = 60), SCr (n = 60) and serum Cystatin C (n = 39) at following 5 intervals: before operation (T0), 20 minutes before anhepatic phase (T1), 25 minutes in anhepatic (T2), 60 minutes after reperfusion (T3) and at the end of operation (T4). Urinary beta2 MG (n = 60) and NAG (n = 60) were also examined at following 3 intervals: before operation (T0), 60 minutes after reperfusion (T3) and at the end of operation (T4). According to the Rimola A criteria of ARF in 24 hours after operation, all the patients were divided into two groups: ARF group and non-ARF group. The data were statistically analyzed to evaluate the feasibiliy of regarding these factors as prognostic factors for early ARF after liver transplantation in patients with normal SCr and BUN before operation.

RESULTSTen of sixty cases showed ARF (16.7%). The Logistic regression analysis showed that the levels of serum and urinary beta2 MG as well as serum cystatin C before operation were correlated with early ARF after liver transplantation (P < 0.05), while only serum levels of cystatin C and Cr at the end of operation correlated with early ARF (P < 0.05, P < 0.01) after liver transplantation. The serum beta2 MG, Cystatin C, SCr and urinary beta2 MG levels in ARF group were much more higher than that in non-ARF group (P < 0.05, P < 0.01). There were significant differences between the correct and false predictive positive ratios of serum cystatin C, serum and urinary beta2 MG levels before operation (P < 0.05, P < 0.01), while only SCr showed significant difference between these groups at the end of operation (P < 0.01).

CONCLUSIONSThe results revealed that there was potential renal damage among those patients who demonstrated normal SCr and BUN before operation, and that liver transplantation could aggravate this damage and causing ARF. Here we provided the prognostic values of serum Cystatin C, beta2 MG, urinary beta2 MG and NAG in patients with early acute renal failure after liver transplantation.

Acetylglucosaminidase ; urine ; Acute Kidney Injury ; blood ; diagnosis ; urine ; Adult ; Blood Urea Nitrogen ; Cystatin C ; blood ; Female ; Humans ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Postoperative Complications ; blood ; diagnosis ; urine ; Predictive Value of Tests ; Prognosis ; beta 2-Microglobulin ; analysis ; blood ; urine

OBJECTIVE: To evaluate the early predictive and diagnostic significance of the acute kidney injury (AKI) associated biomarkers for patients in the intensive care unit (ICU).
 METHODS: From January to June, 2014, relevant clinical data of participants were collected upon admission to the intensive care unit (ICU) in Affiliated Hospital of Zunyi Medical College. Levels of serum cystatin C (sCys C), neutrophil gelatinase-associated lipocalin (sNGAL), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1), interleukin-18 (uIL-18), and N-acetyl-beta-D-glucosaminidase (uNAG) were detected by enzyme linked immune sorbent assay (ELISA), and compared between AKI and non-AKI patients. Diagnostic significance of these biomarkers was evaluated by a receiver operating characteristic (ROC) curve and the area under the ROC curve.
 RESULTS: A total of 176 patients were enrolled in this study. Among them, 71 patients were diagnosed as AKI, in which 57 patients hospitalized with AKI and 14 developed AKI after 24 h hospitalization. The renal replacement therapy ratio was increased with the progress of clinical stage for AKI. AKI mortality rate was 18.8% (46.5% of the total number of deaths). The levels of sCys C, sNGAL, uNGAL, and uIL-18 in AKI patients were increased compared with those in the non-AKI patients (P<0.05). With the progress of AKI, sCys C, and uNGAL levels were also elevated. In 14 patients who suffered from AKI 24 h after hospitalization, the average levels of sCys C, uNGAL, uIL-18, and uKIM-1 were significantly increased (P<0.05). Sensitivity and specificity of the uNGAL, sCys C, and uIL-18 in AKI diagnosis were 97.2%, 76.1%, 54.9% and 93.3 %, 96.2%, 78.1%, respectively. The areas under the ROC curve of uNGAL, sCys C, and uIL-18 were 0.99, 0.90, and 0.69, respectively.
 CONCLUSION uNGAL, sCys C and uIL-18 can be used to predict and diagnose AKI, and to evaluate the AKI clinical stage.
Acetylglucosaminidase ; urine ; Acute Kidney Injury ; blood ; diagnosis ; urine ; Acute-Phase Proteins ; urine ; Biomarkers ; blood ; urine ; Case-Control Studies ; Cystatin C ; blood ; Enzyme-Linked Immunosorbent Assay ; Hepatitis A Virus Cellular Receptor 1 ; Humans ; Intensive Care Units ; Interleukin-18 ; urine ; Lipocalin-2 ; Lipocalins ; blood ; urine ; Membrane Glycoproteins ; urine ; Proto-Oncogene Proteins ; blood ; urine ; ROC Curve ; Receptors, Virus ; Sensitivity and Specificity

BACKGROUND: Cystatin C (cysC) is said to be an ideal marker for glomerular filtration rate (GFR), independent of external factors such as age, nutrition and inflammation. The authors compared the accuracy and precision of cysC-based and creatinine (Cr)-based GFR estimates using Cr51-EDTA GFR method as a reference. METHODS: Serum concentrations of cysC and Cr were measured in adults over 17 yr (n=170) and children below 17 yr (n=79) who had had GFR estimated by Cr51-EDTA method. CysC-based GFR was estimated by the formula of Thierry [CysC-based GFR estimates (mL/min/1.73 m2)=78 x (1/cysC, in mg/L)+4] and Cr-based GFR by the formula of modified Modification of Diet in Renal Disease [MDRD II, Cr-based GFR estimates (mL/min/1.73 m2)=186 x (Scr)(-1.154) x (Age)(-0.203) x 0.742 (for a female patient) x 1.212 (for a black patient). RESULTS: In comparison with Cr51-EDTA GFR, in children below 17 yr, the bias +/- standard deviation (SD) of cysC-based and Cr-based GFR estimates were 7.5 +/- 6.1 and 106.5 +/- 98.2, respectively, in the range of below 90 of Cr51-EDTA GFR (mL/min/1.73 m2), and 33.7 +/- 33.0 and 174.4 +/- 18.8 in the range of over 90. In adults over 17 yr, the respective figures were 13.1 +/- 11.0 and 17.4 +/- 29.8 in below 90, and 21.2 +/- 20.1 and 83.6 +/- 108.8 in over 90 of Cr51-EDTA GFR. CONCLUSIONS: CysC-based GFR estimates show acceptable ranges of biases over the whole age and GFR ranges. CysC-based GFR estimates is considered to be the marker for GFR, which could be used without limitation of age and GFR ranges.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological Markers/urine ; Child ; Chromium Radioisotopes/diagnostic use ; Creatinine/*urine ; Cystatin C ; Cystatins/*urine ; Edetic Acid/diagnostic use ; Female ; Glomerular Filtration Rate/*physiology ; Humans ; Male ; Middle Aged ; Organometallic Compounds/diagnostic use

OBJECTIVETo investigate the value of serum cystatin C (Cys-C), urinary Cys-C, urinary retinol binding protein (RBP) and urinary neutrophil gelatinase-associated lipocalin (NGAL) in the early assessment of multiple myeloma (MM) and their characteristic changes in different pathological types of renal impairment.

METHODSAccording to glomerular filtration rate (eGFR), the patients were divided into two groups, of which marked group A with normal renal function, the other marked group B with abnormal renal function. Sixty healthy subjects were chosen as control. Detection of the serum Cys-C, urinary RBP, urinary Cys-C, urinary NGAL, serum creatinine (Scr), urinary microalbumin (MAU) and urinary α1-microglobulin (α1-MG) were performed. Renal biopsy was carried out for patients who had abnormal serum Cys-C, urinary Cys-C, urinary RBP, urinary NGAL and were willing to accept further test.

RESULTSCompared with healthy controls, the serum Cys-C, urinary RBP, urinary Cys-C, urinary NGAL of group A were significantly higher than that of healthy controls. Six group A patients received renal biopsy, and varying degrees of renal damage were discovered. The serum Cys-C, urinary RBP, urinary Cys-C and urinary NGAL positive rate were 66.7%, 66.7%, 66.7% and 83.3%, respectively. Of twenty-four cases received biopsy after abnormal examination results were shown, six turned out to be amyloidosis, twelve cast nephropathy (CN) and 6 monoclonal immunoglobulin deposition disease (MIDD). Compared with MIDD and amyloidosis, the urinary Cys-C and NGAL of the CN group are significantly higher (P < 0.05). Compared with CN and amyloidosis, urinary RBP of MIDD is significantly higher (P = 0.043). Compared with MIDD and CN, the MAU of amyloidosis is significantly higher (P = 0.006).

CONCLUSIONCompared with the conventional indicators, serum Cys-C, urinary Cys-C, RBP and NGAL are more sensitive in early assessment of MM patients with renal damage. The MAU is higher in amyloid, the urinary Cys-C and urinary NGAL are significantly elevated in CN, the urinary RBP is significantly elevated in MIDD.

Acute-Phase Proteins ; urine ; Adult ; Aged ; Case-Control Studies ; Cystatin C ; blood ; urine ; Female ; Humans ; Kidney ; pathology ; Kidney Diseases ; blood ; diagnosis ; urine ; Kidney Function Tests ; Lipocalin-2 ; Lipocalins ; urine ; Male ; Middle Aged ; Multiple Myeloma ; blood ; pathology ; urine ; Proto-Oncogene Proteins ; urine ; Retinol-Binding Proteins ; urine

PURPOSE: Cystatin-C is produced at a constant rate, and has been known to be unaffected by non-renal factors. However, there are limited data on its superiority to serum creatinine as a marker of renal function in ESRD population. The aims of our study were to compare serum cystatin-C and serum creatinine with estimated GFR in ESRD patients at the initiation of dialysis, whether the non-renal factors may influence on serum cystatin-C levels, and whether serum cystatin-C may be a useful marker of the start of dialysis. METHODS: This study was cross-sectional about 163 ESRD patients. We measured serum cystatin-C and serum creatinine levels at the initiation of dialysis, and determined GFR from 24 hour urine collection [G (Ccr)], Cockcroft-Gault [G (C&G)], and the modification of diet in renal disease [G (MDRD)] formula. We considered age, gender, body weight and diabetic nephropathy as non-renal factors. RESULTS: The mean serum cystatin-C was 5.0+/-0.9 mg/dL, serum creatinine 11.4+/-5.9 mg/dL, G (Ccr) 5.0+/-2.9 mL/min/1.73m2, G (C&G) 7.5+/-3.1 mL/min/1.73m2, G (MDRD1) 5.7+/-2.9 mL/min/1.73m2, and G (MDRD2) 5.5+/-2.5 mL/min/1.73m2. We found significant correlation between estimated GFR and serum cystatin-C. However, comparing to serum creatinine, serum cystatin-C had no merits in estimating renal function and in predicting urgent hemodialysis. In the multivariate linear regression models, serum cystatin-C had no significant correlation with gender, body weight, and diabetic nephropathy, but decreased with the age. CONCLUSION: Serum cystatin-C is not superior to serum creatinine for estimating renal function and predicting urgent hemodialysis in ESRD patients. Besides, serum cystatin-C seems to be influenced by non-renal factors, age.
Age Factors ; Body Weight ; Creatinine ; Cystatin C ; Diabetic Nephropathies ; Dialysis* ; Diet ; Humans ; Kidney Failure, Chronic ; Kidney Function Tests ; Linear Models ; Renal Dialysis ; Urine Specimen Collection

OBJECTIVETo investigate the clinical significance of serum Cyst-C and urinary microalbumin in early renal impairment in children with Henoch-Schonlein purpura (HSP).

METHODSForty-eight children with HSP and who had normal serum creatinine level and 31 healthy children were enrolled. Contents of serum Cyst-C and urinary microalbumin were measured using ELISA and immunoturbidimetry, respectively. Urinary routine examination was performed in children with HSP. The contents of serum Cyst-C and urinary microalbumin were re-examined one month after treatment (recovery phase).

RESULTSThe contents of serum Cyst-C (2.24+/- 0.81 mg/L) and urinary microalbumin (20.04+/- 10.32 mg/L) in the HSP group at the acute phase were significantly higher than those in the control (0.85+/- 0.20 and 2.30+/- 1.38 mg/L respectively; P< 0.01). Serum Cyst-C (1.70+/- 0.30 mg/L) and urinary microalbumin contents (13.20+/- 8.16 mg/L) were significantly reduced at the recovery phase compared with those at the acute phase in the HSP group (P< 0.01). The proportion of urinary routine abnormality (33.3%) was significantly lower than that of urinary microalbumin (68.8%) and serum Cyst-C abnormalities (72.9%) in the HSP group (P< 0.01).

CONCLUSIONSSerum Cyst-C and urinary microalbumin may serve as indexes in the assessment of early renal impairment in children with HSP.

Adolescent ; Albuminuria ; etiology ; Child ; Child, Preschool ; Creatine ; blood ; Cystatin C ; blood ; Female ; Glomerular Filtration Rate ; Humans ; Kidney Diseases ; diagnosis ; etiology ; Male ; Purpura, Schoenlein-Henoch ; blood ; complications ; urine

This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m2 estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m2 estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.
Aged ; Albuminuria/urine ; *Biological Markers/blood/urine ; Creatinine/blood/urine ; *Cystatin C/blood/urine ; Diabetes Mellitus, Type 2/*blood/physiopathology/*urine ; Diabetic Nephropathies/*blood/physiopathology/*urine ; Female ; Glomerular Filtration Rate ; Humans ; Kidney Function Tests ; Male ; Middle Aged ; ROC Curve ; Retrospective Studies