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

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

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

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

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

INTRODUCTIONClinical practice guidelines recommend using creatinine-based equations to estimate glomerular filtration rates (GFRs). While these equations were formulated for Caucasian-American populations and have adjustment coefficients for African-American populations, they are not validated for other ethnicities. The Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) recently developed a new equation that uses both creatinine and cystatin C. We aimed to assess the accuracy of this equation in estimating the GFRs of participants (healthy and with chronic kidney disease [CKD]) from a multiethnic Asian population.

METHODSSerum samples from the Asian Kidney Disease Study and the Singapore Kidney Function Study were used. GFR was measured using plasma clearance of 99mTc-DTPA. GFR was estimated using the CKD-EPI equations. The performance of GFR estimation equations were examined using median and interquartile range values, and the percentage difference from the measured GFR.

RESULTSThe study comprised 335 participants (69.3% with CKD; 38.5% Chinese, 29.6% Malays, 23.6% Indians, 8.3% others), with a mean age of 53.5 ± 15.1 years. Mean standardised serum creatinine was 127 ± 86 μmol/L, while mean standardised serum cystatin C and mean measured GFR were 1.43 ± 0.74 mg/L and 67 ± 33 mL/min/1.73 m2, respectively. The creatinine-cystatin C CKD-EPI equation performed the best, with an estimated GFR of 67 ± 35 mL/min/1.73 m2.

CONCLUSIONThe new creatinine-cystatin C equation estimated GFR with little bias, and had increased precision and accuracy in our multiethnic Asian population. This two-biomarker equation may increase the accuracy of population studies on CKD, without the need to consider ethnicity.

Adult ; Aged ; Biomarkers ; blood ; urine ; China ; ethnology ; Creatinine ; blood ; Cystatin C ; blood ; Female ; Glomerular Filtration Rate ; Healthy Volunteers ; Humans ; India ; ethnology ; Malaysia ; ethnology ; Male ; Middle Aged ; Models, Statistical ; Prospective Studies ; Renal Insufficiency, Chronic ; blood ; urine ; Reproducibility of Results

OBJECTIVE: To detect the levels of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (Cys-C ) in blood and the level of kidney injury molecule 1 (KIM-1) in urine in elderly patients with renal calculi at diff erent times, and to explore the eff ect of percutaneous nephrostolithotomy (PCNL) combined with flexible ureteroscopy (FU) on early postoperative renal function. METHODS: A total of 46 patients with renal calculi were selected, and their blood or urine specimens were collected respectively at preoperative and postoperative 2, 12, 24, 48, and 72 h. The concentrations of NGAL, Cys-C, KIM-1 were detected. RESULTS: The levels of NGAL and Cys-C began to increase respectively at postoperative 2 and 12 h, and reached peak at postoperative 12 to 24 h. There was significant difference in the levels of NGAL and Cys-C between the postoperative 12 and 2 h or between postoperative 48 and 24 h (all P<0.05). The levels of NGAL and Cys-C began to decline and eventually returned to preoperative levels respectively at postoperative 48 and postoperative 72 h. The KIM-1 began to increase at postoperative 2 h and peaked at postoperative 24 h, which was significant difference between the postoperative 24 and 12 h or postoperative 48 and 24 h (both P<0.05). The level of KIM-1 began to decline and eventually returned to preoperative levels at postoperative 48 h. CONCLUSION After the combined treatment of percutaneous nephrostolithotomy with flexible ureteroscopy, the concentrations of NGAL, Cys-C and KIM-1 are significantly increased, suggesting injuries on renal function. The time of renal tubular injury and recovery is earlier than that of renal glomerulus.
Acute-Phase Proteins ; urine ; Aged ; Cystatin C ; blood ; urine ; Hepatitis A Virus Cellular Receptor 1 ; Humans ; Kidney ; physiopathology ; Kidney Calculi ; surgery ; Lipocalin-2 ; Lipocalins ; blood ; urine ; Membrane Glycoproteins ; blood ; urine ; Nephrostomy, Percutaneous ; Postoperative Period ; Proto-Oncogene Proteins ; blood ; urine ; Receptors, Virus ; blood ; Ureteroscopy

Spot urinary albumin to creatinine ratio (ACR) measurement has been suggested as a surrogate to 24-hr urine collection for the assessment of microalbuminuria, and cystatin C (cysC) is known as an advantageous marker for renal function. The aim of this study was to evaluate the clinical values of spot urinary ACR and serum cysC for the assessment of diabetic nephropathy instead of 24-hr urine microalbumin in children and adolescents with diabetes. A total of 113 children and adolescents (age 12-19 yr, M:F = 47:66) with type 1 or 2 diabetes were enrolled. We evaluated the validity of spot urine ACR and serum cysC, and then compared them to 24-hr urine microalbumin and creatinine clearance. Spot urine ACR was correlated with 24-hr urine albumin excretion (R2 = 0.828, P = 0.001) and creatinine clearance (R2 = 0.249, P = 0.017). The ROC curve analysis of serum cysC demonstrated higher diagnostic accuracy than that of serum creatinine (AUC 0.732 vs 0.615). Both the measurements of spot urine ACR and serum cysC might better predict the presence of diabetic nephropathy than 24-hr urine microalbumin in childhood diabetic patients.
Adolescent ; Albuminuria/*urine ; Child ; Creatinine/*urine ; Cystatin C/*blood ; Diabetes Mellitus, Type 1/*diagnosis ; Diabetes Mellitus, Type 2/*diagnosis ; Diabetic Nephropathies/*diagnosis ; Female ; Glomerular Filtration Rate ; Hemoglobin A, Glycosylated/analysis ; Humans ; Kidney Function Tests ; Male ; Predictive Value of Tests ; ROC Curve

Urinary biomarkers of acute kidney injury (AKI) have been revealed recently to be useful for prior prediction of AKI. However, it is unclear whether these urinary biomarkers can also detect recovery from established AKI. Urinary biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, were measured every 2 days for 8 days in 66 patients with AKI. At day 0, there were no significant differences in plasma creatinine, BUN, and urine cystatin C between AKI patients in the recovery (n = 33) and non-recovery (n = 33) groups. Plasma creatinine concentrations were significantly lower in the recovery group (3.0 +/- 2.0 mg/dL) than in the non-recovery group (5.4 +/- 1.9 mg/dL) on day 4 after AKI diagnosis (P < 0.001). In contrast, there were significant differences in urine NGAL between the two groups starting on day 0 (297.2 +/- 201.4 vs 407.6 +/- 190.4 ng/mL, P = 0.025) through the end of the study (123.7 +/- 119.0 vs 434.3 +/- 121.5 ng/mL, P < 0.001). The multiple logistic regression analysis showed that urine NGAL could independently predict recovery from AKI. Conclusively, this prospective observational study demonstrates that urine NGAL can be a highly versatile marker for early detection of the recovery phase in established AKI patients.
Acute Kidney Injury/*diagnosis/pathology ; Acute-Phase Proteins/urine ; Adolescent ; Adult ; Aged ; Biological Markers/*urine ; Creatinine/blood ; Cystatin C/urine ; Female ; Humans ; Lipocalins/urine ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Proto-Oncogene Proteins/urine ; ROC Curve ; Recovery of Function ; Young Adult