Won-Ho Hahn

Serum cystatin C during 30 postnatal days is dependent on the postconceptional age in neonates.

BackgroundCystatin C (CysC) is a promising endogenous marker for renal function. However, the reference serum CysC level is not sufficiently studied in neonates. This study was conducted to investigate the reference level of serum CysC for neonates, including very low birth weight infants according to the postconceptional age (PCA).MethodsSerum CysC levels were measured in 883 blood samples (246 neonates including 127 premature infants). Infants with symptoms or signs of acute kidney injury, systemic illness, congenital anomaly, or renal pathology were excluded. CysC levels were analyzed for association between subgroups dichotomized by postnatal age and PCA.ResultsReference ranges of serum CysC were determined and a decreasing trend of CysC levels was observed as PCA increased, except for the first 3 postnatal days. CysC levels were negatively correlated with gestational age at birth, and PCA (P < 0.001), while positively correlated with postnatal age and serum creatinine (P < 0.001).ConclusionThe reference level of serum CysC was determined according to postnatal age and PCA. As the reference CysC level was dependent on gestational age and PCA, consideration of these parameters is warranted when assessing CysC levels in neonates.

Recent Advances of Oral Rehydration Therapy (ORT)

Diarrheal disease is one of the leading causes of worldwide morbidity and mortality, especially in children. It causes loss of body fluid, which may lead to severe dehydration, electrolyte imbalance, shock and even to death. The mortality rate from acute diarrhea has decreased over the last few decades. This decline, especially in developing countries is largely due to the implantation of the standard World Health Organization-oral rehydration solution (WHO-ORS). However, the use of standard ORS has been limited by its inability to reduce fecal volume or diarrhea duration. Subsequently, this has led to various attempts to modify its compositions. And these modifications include the use of reduced osmolarity ORS, polymer-based ORS and zinc supplementation. Some of these variations have been successful and others are still under investigation. Therefore, further trials are needed to progress toward the ideal ORS. In this article, we briefly reviewed the pathophysiologic basis of the ORS, followed by the standard WHO-ORS and several modifications to improve the ORS.

Toll-like receptor 1 gene polymorphisms in childhood IgA nephropathy: a case-control study in the Korean population

Toll‐like receptors (TLRs) are innate immune mediators that stimulate nuclear factor kappa B and the inflammatory cytokines. TLR1 is expressed in renal tubular epithelial cells when the kidney is injured, but the role of TLR1 gene in glomerulonephritis has not been clearly elucidated. We aimed to investigate the association of TLR1 polymorphisms with immunoglobulin A nephropathy (IgAN) in children. One hundred and ninety pediatric patients with biopsy‐proven IgAN and 283 healthy control subjects were enrolled. Two single nucleotide polymorphisms of TLR1 gene [rs4833095 (missense, Asn248Ser) and rs5743557 (promoter, −414C/T)] were selected and genotyped by direct sequencing. For rs4833095, the C/T genotype in the codominant model (vs. the T/T genotype) [odds ratio (OR) = 2.11, 95% confidence interval (CI): 1.21–3.69, P = 0.009] and the genotype containing C allele (C/T and C/C) in the dominant model (vs. the T/T genotype) (OR = 1.97, 95% CI: 1.16–3.34, P = 0.012) were associated with an increased risk of IgAN. For rs5743557, the T/T genotype in the codominant model (vs. the C/C genotype) (OR = 1.74, 95% CI: 1.02–2.96, P = 0.041) appeared to be associated with IgAN risk. In haplotype analysis, the CT haplotype revealed an association with IgAN (codominant model, OR = 1.38, 95% CI: 1.06–1.80, P = 0.017; dominant model, OR = 1.76, 95% CI: 1.16–2.67, P = 0.008). After Bonferroni correction, the association of the genotypes of rs4833095 and the CT haplotype with IgAN risk remained significant. These findings suggest that TLR1 gene polymorphisms may affect IgAN susceptibility in Korean children.

The Clinical Significance of Serum Cystatin Cin Critically Ill Newborns With Normal Serum Creatinine

The aim of this study is to evaluate the clinical significance of cystatin C(CysC) in the newborns who show normal serum creatinine (Cr) and who are in an intensive care unit.

Association of CTLA4, CD28 and ICOS gene polymorphisms with clinicopathologic characteristics of childhood IgA nephropathy in Korean population

Primary IgA nephropathy (IgAN) is the most common glomerular disease in children and adolescents who undergo renal biopsy because of isolated microscopic haematuria or haematuria associated with proteinuria (Coppo 2008). Some evidence suggests the importance of the abnormal T-cell response in the pathogenesis of IgAN, and co-stimulatory molecules such as cytotoxic T-lymphocyte antigen 4 (CTLA4), CD28 molecule and inducible costimulator (ICOS) have been found to be vital for naive T-cells to initiate and terminate immune responses (Carreno and Collins 2002; Carreno et al. 2005). In this study, we tested single nucleotide polymorphisms (SNPs) of CTLA4/CD28/ICOS genes, and they were found to be associated with pathophisipology of paediatric IgAN in Korean population. The best-characterized T-cell co-stimulatory pathway involves receptors such as the CD28 and CTLA4 (also known as CD152). In addition, the ICOS has been also defined recently as a new pathway (Keir and Sharpe 2005). The CD28/CTLA4/ICOS genes lie within the 300-kb region on human chromosome 2q33 and their expressions are differentially regulated; although CD28 is constitutively present on naive T-cells, whereas CTLA4 and ICOS are present only after activation (Collins et al. 2005). Moreover, all of these molecules were found to be expressed by regulatory T-cells for the development and maintenance (Keir and Sharpe 2005).

Linkage and association study of neurotrophins and their receptors as novel susceptibility genes for childhood IgA nephropathy.

Neurotrophins (NTs) and their receptors (NTRs) are known to be important for pathogenesis of various inflammatory diseases that occur in not only neuronal but also nonneuronal tissues, including kidney. Here, we investigated association between childhood IgA nephropathy (IgAN) and single nucleotide polymorphisms (SNPs) of genes encoding NTs [nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)] and NTRs [nerve growth factor receptor (NGFR) and neurotrophic tyrosine kinase receptor 1–3 (NTRK1–3)]. The genotyping data of 197 patients and 289 control subjects revealed significant association between NGF SNP rs11102930 and presence of IgAN. Patient subgroup analysis revealed that that the presence of nephrotic range proteinuria (>40 mg/m2/h) was associated with rs6334 of NTRK1 and rs11030104, rs7103411, rs7103873, and rs6484320 of BDNF. Significant genotype differences were observed in podocyte foot process effacement for rs1187321 and rs1187323 of NTRK2. Furthermore, some SNPs showed significantly different genotype distribution between patients with or without pathologically advanced disease markers, specifically in rs6334 of NTRK1. Our results suggest that SNPs of NTs and NTRs are associated with susceptibility, pathological advancement, podocyte foot process effacement, and development of proteinuria in childhood IgAN.

Polymorphisms of insulin-like growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) contribute to pathologic progression in childhood IgA nephropathy

Previous studies have suggested that insulin-like growth factor-1 (IGF-1) signaling might play an important role in renal fibrosis and regulation of the proliferation of mesangial cells and podocytes. We conducted the present study to investigate association between single nucleotide polymorphisms (SNPs) of IGF-1 (IGF-1) and IGF-1 receptor (IGF-1R) genes and childhood immunoglobulin (Ig) A nephropathy (IgAN). We analyzed five SNPs of IGF-1 and IGF-1R in 188 pediatric IgAN patients and in 263 healthy controls. We compared variations in SNPs in several sets of IgAN subgroups that were designated based on the presence of nephrotic range proteinuria (>40 mg/m2 per h), podocyte foot process effacement, and pathological progression. Genotyping of IgAN patients and controls revealed differences in IGF-1R rs2229765. Moreover, the rs2195239, rs978458, and rs1520220 SNPs of IGF-1 showed significant association with pathological progression. Thus, in the present study, we observed associations between the IGF-1/1R pathway, susceptibility to IgAN, and the pathologic progression of IgAN.

Polymorphisms of signal transducers and activators of transcription 1 and 4 (STAT1 and STAT4) contribute to progression of childhood IgA nephropathy

BACKGROUND Several experimental studies have suggested that signal transducers and activators of transcription 1 and 4 (STAT1 and STAT4) play important roles in the regulation of mesangial proliferation and renal fibrosis, and in the development of inflammation in several types of glomerulonephritis. METHODS The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the STAT1 and STAT4 genes and childhood IgA nephropathy (IgAN). RESULTS Genotyping of 170 childhood IgAN patients and 442 controls showed no significant differences in allele frequency. However, patient subgroup analysis revealed that development of proteinuria ( and >4mg/m(2)/h) was associated with STAT1 rs10199181 (dominant model, P=0.035) and high serum level of IgA with STAT1 rs6718902 (dominant model, P=0.035) and STAT1 rs2280232 (codominant model, P=0.014; dominant model, P=0.022). Furthermore, some SNP frequencies were significantly different between patients with pathologically mild and advanced disease; STAT1 rs6718902 (overdominant model, P=0.030), STAT1 rs10199181 (codominant model, P=0.023; dominant model, P=0.012; overdominant model, P=0.018), and STAT4 rs7561832 (dominant model, P=0.026; overdominant model, P=0.029). CONCLUSIONS Our results suggest that polymorphisms of STAT1 and STAT4 are associated with increased susceptibility, pathological advancement, and development of proteinuria in childhood IgAN.

Reference Intervals of Serum Procalcitonin Are Affected by Postnatal Age in Very Low Birth Weight Infants during the First 60 Days after Birth

Background: Procalcitonin (PCT) may be a more sensitive marker for neonatal bacterial infections than C-reactive protein (CRP). However, the reference intervals of serum PCT were not sufficiently studied in neonates older than 1 week of age, especially for very low birth weight infants. Objectives: This study investigated the reference level of serum PCT for neonates according to gestational age (GA) and postnatal age (PNA). Methods: Serum PCT was measured in 914 blood samples from 7-60 days after birth in 415 neonates including 184 premature infants. Infants with sepsis, congenital anomaly, or clinically evident intra-amniotic infections were excluded. Multivariate analysis of covariance was used to detect the interaction between GA and PNA. To compare subgroups dichotomized by GA and PNA, analysis of covariance was performed with clinical parameters as covariates to obtain an adjusted p value. Results: Serum PCT levels were negatively correlated with GA, PNA, birth weight, birth height, and platelet count, and positively correlated with white blood cell count, absolute neutrophil count, hematocrit, and serum CRP after logarithmic transformation. Reference intervals of serum PCT were established according to GA and PNA. High PCT levels were found in infants with GA ≤32 weeks and PNA 7-30 days. Conclusion: The reference levels of serum PCT were determined according to GA and PNA. As the reference PCT levels of infants with GA ≤32 weeks were affected by PNA, cautious interpretation of PCT levels in these infants is warranted.

Association Between Lymphotoxin Beta Receptor Gene Polymorphisms and IgA Nephropathy in Korean Children

Lymphotoxin beta receptor (LTBR) is essential for development and organization of the secondary lymphoid tissues. To investigate whether LTBR polymorphisms are associated with IgA nephropathy (IgAN) in Korean children, One hundred ninety nine patients with IgAN and 289 controls were recruited. Two promoter single nucleotide polymorphisms (SNPs) (rs3759333, -1387C/T and rs3759334, -1326A/G) and one coding SNP (rs2364480, Ala172Ala) in LTBR gene were selected and genotyped by direct sequencing. For analysis of data, SNPStats, SPSS 18.0, and Haploview version 4.2 were used. Multiple logistic regression models (codominant 1, codominant 2, dominant, and recessive models) were performed for odds ratio (OR), 95% confidence interval (CI), and p value. The rs3759334 was significantly associated with IgAN in codominant 1 (G/G vs. A/G, p = 0.025) and dominant (p = 0.017) models. The A alleles of rs3759334 and rs2364480 were related to risk of developing IgAN, respectively (rs3759334, p = 0.015; rs2364480, p = 0.041). Haplotypes CGC and TAA in LTBR gene were also associated with IgAN, respectively (CGC, p = 0.032 in codominant; TAA, p = 0.008 in codominant, p = 0.009 in dominant models). In conclusion, results suggest that LTBR gene polymorphisms may be associated with risk of IgAN in Korean children.