Predictive value of serum neutrophil gelatinase-associated lipocalin and cystatin C as markers for contrast nephropathy in patients undergoing coronary angiography

Contrast induced-nephropathy is a more frequent and potentially serious complication after coronary angiography. Very few biomarkers exist for monitoring contrast induced-nephropathy. Recently, serum neutrophil gelatinase-associated lipocalin [NGAL] represents a novel biomarker for early identification of acute kidney injury. The present work aimed to test the hypothesis that NGAL could represent an early biomarker for kidney injury and to assess the relation ship between NGAL and serum creatinine and cystatin C, in patients with normal serum creatinine undergoing percutaneous coronary angiography. The study was performed on thirty non-diabetic patients with normal serum creatinine, undergoing coronary angiography due to corollary artery disease. All patients were mateched for age and body mass index. following full clinical examination, fasting blood sample were withdrawn for estimation of blood glucose. glycosylated hemoglobin, lipid profile. creatinine as well as NGAL and cystatin C before coronary angiography. Another blood samples were taken 4 and 24 hours after coronary angiography for all patients for evaluation of serum creatinine, NUGL and cystatin C. There was a significant increase in serum NGAL level 4 hours and 24 hours after coronary interventions when compared to the baseline value before coronary- angiography Before coronary angiography, serum NGAL was positively correlated with serum creatinine, and cystatin C. in multiple regression analysis, serum creatinine was the only predictor of serum NGAL. Serum NGAL, 4 hour after coronary angiography, correlated with serum ereatinine only in simple and multiple regression analysis. On the other hand, serum cystatin C level increased significantly only 24 hour after coronary angiography compared to the baseline value before coronary angiography. In a simple regression analysis serum cystain C correlated positively to systolic and diastolic blood pressure, Serum creatinine and serum NGAL, before Coronary angiography. In multiple regression analysis, serum creatinine and systolic blood pressure were the predictors of serum cystatin C. Serum NGAL and cystatin C could be valuable in the detection of acute renal impairment after coronary angiography. However current diagnostic methods such as. Serum creatinine or cystatin C measurements only respond after renal function has deteriorated. Therefore, the presence of new early markers for renal injury such as NGAL, can initiate proper management of acute renal failure within hours rather than days of the insult

Utilidad de las ecuaciones basadas en la concentración sérica de cistatina C en el estudio de la función renal / Usefulness of equations based on serum cystatin C concentration in the study of renal function

La creatinina sérica es un marcador poco sensible para identificar reducciones leves del índice de filtración glomerular (IFG); por ello resulta de gran importancia clínica disponer de métodos alternativos para estimar la función renal. Con este objetivo estudiamos la función renal de 41 pacientes -grupo completo y divididos según la creatinina sérica (menor o igual 1.2 mg/dl o mayores)- usando el clearance de creatinina modificado con cimetidina (Clcrc) como aproximación al IFG, las ecuaciones de Larsson y Hoek que incluyen el uso de cistatina C sérica y las tradicionales fórmulas de Cockroft-Gault y MDRD abreviada. En el grupo completo de pacientes y especialmente en aquellos con creatinina sérica menor o igual 1.2 mg/dl - con reducción de la función renal: Clcrc: 62.01 mas o menos 17.33 ml/min/1.73 m2-, las ecuaciones de Larsson y Hoek mostraron mejores correlaciones y menores diferencias promedio respecto a las fórmulas basadas en la creatinina sérica. La ecuación MDRD abreviada mostró buen rendimiento sólo en el grupo con evidente alteración de la función renal (creatinina sérica > 1.2 mg/dl). Concluimos que en pacientes con diferentes estadios de función renal, las fórmulas que emplean la cistatina C sérica detectan la reducción del IFG más precozmente respecto a aquellas basadas en la creatinina sérica.

Serum creatinine is an insensitive marker to identify early changes in glomerular filtration rate (GFR), for this reason alternative methods to estimate renal function result of great clinical importance. Forty-one patients were studied using creatinine clearance modified with cimetidina (Clcrc) as surrogate of GFR, cystatin C-based equations (i.e. Larsson and Hoek formulas), Cockroft-Gault and MDRD abbreviated equations. In the whole group, as well as in those patients with serum creatinine less than or equal to 1.2 mg/dl -but reduced renal function: Clcrc 62.01 more or less 17.33 ml/min/1.73 m2-, Larsson and Hoek equations showed higher correlations and lower bias than creatinine-based formulas. Abbreviated MDRD equation showed good performance just in those patients with evident alteration of renal function (serum creatinine > 1.2 mg/dl). We concluded that in patients with different stages of renal function, cystatin C-based equations detect reduction of renal function earlier than the serum creatinine-based formulas.

Evaluation of serum cystatin C as a marker for detection of early renal function impairment in children with chronic liver disease

Evaluation of renal failure is essential in patients with decompensated liver cirrhosis, because a significant proportion of them manifest reduced glomerular filtration rate [GFR]. Careful assessment of GFR is critically important for prognosis because the indicators of renal function are sensitive markers of severity of liver dysfunction in cirrhosis and are better predictors of patient survival than estimating hepatic dysfunction. Plasma creatinine concentrations and calculated creatinine clearance are of limited values as GFR markers in patients with chronic liver diseases [CLD] especially liver cirrhosis. Recently, assessment of serum cystatin C concentrations was proposed as a possible indicator of early GFR changes in such patients. The aim of this work was to study the utility of measurement of serum cystatin C level as a marker of early detection of renal impairment in patients with CLD and to assess its correlation to the severity of liver dysfunction. This study was conducted on 30 children [17 males and 13 females] with CLD. Their ages ranged from 2 to 16 years. Twenty healthy children with matched age and sex were chosen as a control group. They were selected from those admitted to the Hepatology Unit of Pediatric Department, Tanta University Hospitals. In this study all patients were subjected to the following: full clinical history, through physical examination, abdominal ultrasonography, histopathological assessment of liver biopsy and laboratory investigations. The latter included complete blood count, liver function tests, complete urine analysis, blood urea, serum creatinine, creatinine clearance [CrCI], hepatitis markers as well as measurement of serum cystatin concentrations by particle induced immunonephelometry. Control children were subjected to the whole previous investigations except liver biopsy. Severity of liver dysfunction in studied patients was classified into grades A, B and C according to modified Child-Pugh' classification. This study showed that mean CrCl values were significantly reduced in patients [77.03 +/- 17.4 ml/min/1.73m[2]] compared to controls [86.7 +/- 9.2 ml/min/1.73m[2]]. Mean CrCI values were impaired in 3 [10%] patients. All of them had ascites. Serum cystatin C levels were significantly higher in the studied patients [1.02 +/- 0.55mg/L] compared to controls [0.38 +/- 0.10mg/L], and significantly higher in grade C patients [1.35 +/- 0.65mg/L] than in those with grades B [0.92 +/- 0.46 mg/L] and A [0.73 +/- 0.29 mg/L]. Serum cystatin C levels were high in 10 [30%] patients of whom 70% [7/10] had ascites. Regarding ascitic patients, there was a significant reduction in CrCl values in ascitic compared to non-ascitic patients. Furthermore, there was a significant increase in serum cystatin C levels in ascitic compared to non-ascitic patients. Serum cystatin C correlated significantly with CrCI and severity of CLD as assessed by its correlation with liver function tests and Child's scores. ROC curve plots demonstrated that the area under the curve [AUC] of cystatin C [0.92] was greater than that of CrCI [0.76] and serum creatinine [0.58]. Therefore, sensitivity, specificity and diagnostic accuracy of cystatin C were higher than those of CrCl and both were better than those of serum creatinine. The positive and negative predictive values of serum cystatin C were higher than those of CrCl and serum creatinine. From this study, we can conclude that serum cystatin C is more accurate and simple than serum creatinine and creatinine clearance as a marker of GFR changes for prediction of early renal impairment in patients with CLD. Furthermore, serum cystatin C concentration was significantly high in patients with CLD that was correlated with the severity of liver dysfunction. Measurement of serum cystatin C may be recommended or at least added to serum creatinine in the routine assessment of early GFR changes in patients with CLD. However, further prospective comparative studies on a large scale with a gold standard method for measuring GFR are required to evaluate serum cystatin C concentration in different stages of renal impairment In children with CLD

Urinary creatinine and serum cystatin C in asthmatic children treated with inhaled corticosteroid and beta 2 agonist

L-arginine, an amino acid involved in the production of urea, creatinine and nitric oxide [NO] that is known to play an important role as an inflammatory mediator in the airways. Inhaled corticosteroids and beta [2] agonists are the most frequently prescribed medications in the management of chronic asthma. Current guidelines emphasis their complementary role. Although many patients use both drugs, there is little information on the effectiveness of their combination. In the present study we investigated the effect of a combination of glucocorticoids and beta [2] -agonists inhaled by asthmatics on the metabolism of L-arginine. Sixty-six children with mild-to moderate asthma were enrolled in this study and treated with different regimens of inhaled drugs but fifty three children only completed the study [Twenty one with inhaled beta [2] agonist [salmeterol], 15 with inhaled corticosteroid [fluticasone propionate], and 17 with a combination of inhaled salmeterol and fluticasone propionate]. Fifteen healthy-matched children served as a control group. Pulmonary function tests [forced expiratory volume in one second [FEV[1]], peak expiratory flow rate [PEFR]], methacholine challenge tests, serum cystatin C, 24 hours urinary measurement of urea, creatinine, nitrates, and urinary osmolality were performed before and after three months of the inhaled drug therapy. The results of this study demonstrated: [1] Non significant differences in serum cystatin C and urinary urea, creatinine, nitrates, osmolality were noted in asthmatic children vs control group. [2] non significant differences in serum cystatin C level and urine osmolality were observed in different groups before and after therapy. [3] compared to that before therapy, children treated by the combination of corticosteroid and beta [2] agonist had a significant higher level of urinary creatinine [p=0.0001] and a higher creatinine/urea ratio [c/u ratio] [p=0.0001] with significantly lower levels of urinary urea [p=0.002], and urinary nitrates [p=0.0001]. [4] in children treated by the combination of corticosteroid and beta [2] -agonist, there were a significant positive correlations between urinary creatinine and both FEV[1] [r= +0.699, p<0.01] and methacholine provocative dose causing a 20% fall in FEV[1] [R= +0.695, P< 0.01]. Also there were significant positive correlations between c/u ratio and both FEV[1] [r= +0.821, p = <0.01] and methacholine provocative dose causing a 20% fall in FEV[1] [r= +0.850, p< 0.01]. [5] in children treated with corticosteroid alone, only urinary nitrates was significantly lower after treatment as compared to that before treatment. [6] in children treated with beta [2] agonist alone, no significant differences in urinary urea, creatinine, nitrates and c/u ratio as compared to that before therapy. In asthmatic children, treatment with a combination of inhaled corticosteroid and beta [2] -agonist had a beneficial augmenting influence on the metabolism of L-arginine with better improvement of lung functions and bronchial hyperreactivity than treatment with either corticosteroid or beta [2] -agonist alone. Also creatininuria and urinary c/u ratio can be used as a simple and noninvasive parameters for assessment of response to treatment in these children. Also our results demonstrated normal serum cystatin C concentrations in asthmatic children in between attacks and remained unaffected by a therapy with inhaled corticosteroid, beta [2] agonist or a combination of both

Effects of Magnesium Sulfate on Supraceliac Aortic Unclamping in Experimental Dogs

Intravascular administration of magnesium (Mg) causes vasodilation and increases renal blood flow. The aim of this study was to investigate the renal effect of Mg following unclamping of the supraceliac aorta. Mongrels were divided into two groups, control (group C, n=7) and Mg group (group Mg, n=7). In group Mg, 30 mg/kg MgSO4 was injected as a bolus immediately prior to unclamping the supraceliac aorta and thereafter as an infusion (10 mg/kg/hr). The group C received an equivalent volume of saline solution. Systemic hemodynamics, renal artery blood flow, renal cortical blood flow (RCBF), renal vascular resistance, and renal function were compared. Following the aortic unclamping, cardiac output and RCBF were less attenuated, and the systemic and renal vascular resistance was elevated to a lesser degree in the group Mg compared to the group C. There was no significant difference in the plasma renin activity, serum creatinine and Cystatin-C between the two groups. The present study shows that Mg infusion improves systemic hemodynamics and RCBF after aortic unclamping. However, we did not observe any improvement in renal function when Mg was administered after supraceliac aortic unclamping.

Serum cystatin C as a new marker of glomerular filtration rate [GFR]

Cystatin C is a 13 KD basic protein that is a member of the cystatin super-family of cysteine protease inhibitors. The cystatin C gene seems to be a house keeping gene, which is compatible with a stable production rate of cystatin C by most cells. This protein is freely filtered through the glomerulus and almost completely reabsorbed and catabolized by proximal tubular cells. Because of these characteristics cystatin C is assumed to be a better marker of glomerular filtration rate than other markers. 115 new cases of renal disease aged between 14 and 88 years and 121 healthy subjects, aged between 11 and 78 years were studied. In all of the subjects serum cystatin C and creatinine were determined and creatinine clearance was determined only in patients. Cystatin C was determined by a particle-enhanced turbidimetric assay and creatinine was measured by Jaffe's method. In addition, to assess the diagnostic efficiency of serum cystatin C in comparison to that of serum creatinine and creatinine clearance in predicting changes in GFR, we performed Tc99m - DTPA clearance on 53 subjects including controls and patients. A linear relationship was found between Tc99m - DTPA clearance and Y serum cystatin C [r= 0.712, p-value <0.001], 1/serum creatinine [r= 0.709, p-value< 0.001] and creatinine clearance [r= 0.777, p- value <0.001]. Diagnostic accuracy in the identification of reduced GFR measured as area under the receiver-operating characteristic plot was 0.878 +/- 050 [Mean +/- SE] for Scystatin C, 0.866 +/- 0.051 for creatinine and 0.866 +/- 0.051 for creatinine clearance. The serum cystatin C reference values [mean +/- 1.96 SD] determined was 0.83 -0.88 mg/L. A cutoff cystatin C concentration of 0.82 mg/L had 92% sensitivity and 79% specificity for detecting abnormal GFR. There was no significant correlation between cystatin C and age [p- value <0.219] and weight [p- value <0.193]. This study demonstrates that serum cystatin C has an increased diagnostic accuracy for reduced GFR when compared with serum creatinine and creatinine clearance. Hence, cystatin C seems to be an alternative for the estimation of GFR

Serum cystatin-C: a sensitive marker for early detection of reduction in glomerular fitration rate

The aim of the present study was to evaluate the diagnostic value of serum cystatin-C [Cys-C] as a serum marker of glomerular filtration rate [GFR] in patients with various renal diseases with a wide range of renal function as well as to compare between serum Cys-C, creatinine and beta 2-microglobulin [beta 2m] as indicators of GFR. The study included 63 patients [39 males and 24 females aged between 17 and 75 years]. Serum Cys-C was measured by automated particle- enhanced turbidimetry, serum creatinine by Synchron CX-7 autoanalyzer, serum beta 2m by enzymognost beta 2m assay and GFR by 99m Tc-labeled diethylenetriamine pentaacetic acid [99m TcDTPA] clearance. The results demonstrated that serum Cys-C significantly increased in patients with reduced GFR [less than 80ml/min], while serum creatinine and serum beta 2m were significantly increased at a later stage of renal insufficiency at GFR [less than 40ml/min]. The sensitivity and diagnostic accuracy of Cys-C were better than that of serum creatinine and beta 2m

Serum cystatin C as a marker of renal affection in diabetic renal disease

This study aimed to assess clinical usefulness of measurement of serum cystatin C as a marker of renal affection in different stages of diabetic renal disease. The study included 40 patients with either types of diabetes mellitus [DM] at different stages of diabetic nephropathy [DN] as well as 20 healthy subjects matched for age and sex as controls. All the participants were investigated for renal function tests [S creatinine, urea, creatinine clearance], urine strip testing for microalbuminuria [Micral test], quantitative 24 hour urinary protein assessment, renal isotope scan by TC99 DTPA to assess GFR and finally an assessment of S cystatin C level by particle enhanced turbidimetric immunoassay [PETIA] technique