Measurements of serum cystatin C concentrations underestimate renal dysfunction in pediatric patients with chronic kidney disease.

BACKGROUND: In our clinical experience, cystatin C (CysC) concentrations are not as high as expected in patients with chronic kidney disease (CKD) and high-stage renal dysfunction. We therefore investigated whether measurements of serum CysC result in an underestimation of renal dysfunction in pediatric patients with CKD. METHODS: Glomerular filtration rate (GFR) was estimated from serum creatinine (Cr) concentration, using the equation Cr-GFR (%) = [0.30 × body length (m)/serum Cr] × 100; and from serum CysC concentration, using the equation Cys-GFR (%) = (0.70/serum CysC) × 100. We investigated the relationship between GFR estimated by these 2 equations. Patients aged 2-12 years were assorted into 5 groups, based on GFR-Cr categories of <12.5, ≥12.5 to <25, ≥25 to <50, ≥50 to <75, and ≥75%, and GFR-CysC/GFR-Cr ratios were compared in these 5 groups. RESULTS: The median GFR-CysC/GFR-Cr ratio in groups of patients with GFR-Cr of <12.5, ≥12.5 to <25, ≥25 to <50, ≥50 to <75, and ≥75% were 2.28, 1.48, 1.22, 1.18 and 0.98, respectively, with statistically significant differences between any two groups (p < 0.001). CONCLUSION: Measurements of serum CysC concentrations lead to underestimation of renal dysfunction in pediatric patients with CKD.

Reference serum cystatin C levels in Japanese children.

BACKGROUND: Single measurements of serum cystatin C (cysC) concentration have generally been used to determine glomerular filtration rate (GFR) in adults. Since GFR varies to some extent among children, we attempted to determine reference serum cysC concentrations for Japanese children. METHODS: Serum cysC concentrations were determined by a latex particle-enhanced turbidimetric immunoassay in children who did not present with kidney disease or infectious disease, and the relationship between age and serum cysC level was assessed. RESULTS: We found that reference serum cysC levels gradually decreased during the first year after birth, thereafter becoming constant. Mean serum cysC concentration in children aged 1 year (0.76 ± 0.10 mg/L) was slightly higher than in children aged ≥2 years (0.70 ± 0.09 mg/L). CONCLUSION: Our reference values will be applicable for screening renal function in Japanese children.

Reference serum creatinine levels determined by an enzymatic method in Japanese children: relationship to body length.

BACKGROUND: It is necessary to set the standard serum creatinine (Cr) values for the medical care of pediatric chronic kidney disease patients. The estimated glomerular filtration rate (eGFR, ml/min/1.73 m(2)) = kappa x body length (cm)/serum Cr value (mg/dl) determined by the Jaffe method devised by Schwartz has been used clinically. However, enzymatic methods have recently been used to measure Cr instead of the Jaffe method, making it necessary to reevaluate the coefficient kappa of the above equation. Following transformation of the above formula, the normal serum Cr level should be proportional to body length: normal serum Cr value (mg/dl) = k x body length (m). METHODS: Serum Cr values were measured by an enzymatic method in children who did not present with kidney disease or infectious disease, and the relationship between the body length and serum Cr level was determined by linear regression analysis. RESULTS: We found a regression equation capable of estimating the reference value of serum Cr from body length. In children aged 1-12 years, body length (m) x 0.30 yielded a value similar to the reference serum Cr level. CONCLUSION: There have been no previous reports of the determination of reference serum Cr levels by enzymatic methods in Japanese children. Our formula will be applicable for screening of renal function in Japanese children.

Identification of EGFR expression status association with metastatic lymph node density (ND) by expression microarray analysis of advanced gastric cancer.

Metastatic lymph node density (ND) has been reproducibly proven to be a prognostic factor in gastric cancer. The molecular mechanisms that underlie this aggressiveness are underexplored. Here, we aimed to identify molecules associated with this unique phenotype. Tumor specimens from patients with stage III gastric cancer with high or low ND (n = 4 for both) were compared at the mRNA level using Affymetrix microarray (harboring 54,675 genes). The expression data were prioritized, and genes that correlated with ND were selected. Ultimately, the EGFR was validated as such a candidate molecule in patients with primary advanced gastric cancer who underwent standard treatment (n = 167). Expression data of the microarray were prioritized based on gene expression ratio and frequency of gene expression. The first priority genes to be selected were genes that are known to be amplified in cancer, which included NKX2.1, CHST9, CTNND2, SLC25A27, FGFR2, EGFR, and PTGER1. Of these genes, the EGFR gene was of particular interest. EGFR expression in primary gastric cancer was examined using immunohistochemistry (IHC). The Student's t-test elucidated a significant difference in EGFR expression between IHC 2+/3+ and IHC 1+ according to ND (P = 0.0035). The Chi-square test also indicated a significant difference between high and low levels of EGFR immunohistochemical staining (IHC2+/3+ and IHC1+, respectively) and ND status (P = 0.0023). According to the least squares method, as ND increased, the risk that EGFR staining levels changed from IHC 1+ to IHC 2+ also increased. In this study, we determined that high EGFR expression may underlie the aggressive mechanism of advanced gastric cancer with high ND.