Ameliorating Effect of Gemigliptin on Renal Injury in Murine Adriamycin-Induced Nephropathy.

Background. Previous studies have shown the antiapoptotic and anti-inflammatory potential of DPP-IV inhibitor in experimental models of renal injury. We tested whether DPP-IV inhibitor (gemigliptin) ameliorates renal injury by suppressing apoptosis, inflammation, and oxidative stress in mice with adriamycin nephropathy. Methods. Mice were treated with normal saline (control), gemigliptin (GM), adriamycin (ADR), or adriamycin combined with gemigliptin (ADR+GM). Apoptosis, inflammation, and oxidative stress were analyzed via western blotting, real-time PCR, light microscopy, and immunofluorescence. Results. In the ADR+GM group, urine albumin creatinine ratio decreased significantly compared with that in the ADR group on day 15. Glomerulosclerosis index and tubulointerstitial injury index in mice with adriamycin-induced nephropathy decreased after gemigliptin treatment. ADR group showed higher levels of apoptosis, inflammation, and oxidative stress-related molecules compared with the control group. The upregulation of these molecules was significantly reduced by gemigliptin. In the ADR group, the staining intensities of WT-1 and nephrin reduced, but these changes were ameliorated in the ADR+GM group. Conclusion. We demonstrated that gemigliptin ameliorates nephropathy by suppressing apoptosis, inflammation, and oxidative stress in mice administered adriamycin. Our data demonstrate that gemigliptin has renoprotective effects on adriamycin-induced nephropathy.

Elevated serum immunoglobulin E level as a marker for progression of immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin E (IgE) has traditionally been associated with anaphylaxis and atopic disease. Previous studies reported that serum IgE levels are elevated in nephrotic syndrome and suggested IgE levels as a prognostic indicator in glomerular diseases. The aim of this study was to explore the association between serum IgE levels and renal outcome in patients with immunoglobulin A nephropathy (IgAN). METHODS: We included 117 patients with biopsy-proven IgAN. Renal progression was defined if a patient meets one of these criteria: (1) a negative value of delta estimated glomerular filtration rate (mL/min/1.73 m(2)/mo) or (2) a rise in serum creatinine to an absolute level of ≥ 1.3 mg/dL (male) or 1.2 mg/dL (female). We defined delta changes in serum creatinine, estimated glomerular filtration rate, and proteinuria as a difference of values during the follow-up period. RESULTS: A total of 117 patients with IgAN were included. The serum IgE level was significantly high in the renal progressive group compared with the nonprogressive group. Sex and history of gross hematuria were significantly different between the high-IgE group and the low-IgE group. Regression analysis showed that a male sex, initial proteinuria, and change of proteinuria were significantly associated with serum IgE levels. CONCLUSION: The serum IgE level is potentially associated with disease progression and pathogenesis of IgAN.

Long-term clinical outcomes of korean patient with Crohn's disease following early use of infliximab.

BACKGROUND/AIMS: Several recent studies have reported that the early use of infliximab (IFX) improves the prognosis of Crohn's disease (CD). However, no data are available from Asian populations, as the forementioned studies have all been conducted in Western countries. The aim of the current study was to evaluate the impact of early use of IFX on the prognosis of Korean patients with CD. METHODS: Patients with a diagnosis of CD established between July 1987 and January 2012 were investigated in 12 university hospitals in Korea. Because insurance coverage for IFX treatment began in August 2005, patients were assigned to either of 2 groups based on diagnosis date. The first group included patients diagnosed from July 1987 to December 2005, and the second from January 2006 to January 2012. We compared the cumulative probabilities of operation and reoperation between the two groups using the Kaplan-Meier method and a log-rank test. RESULTS: Of the 721 patients investigated, 443 (61.4%) comprized the second group. Although the cumulative probabilities of immunosuppressant (P<0.001) and IFX use (P<0.001) after diagnosis were significantly higher in the second group, there were no significant differences in cumulative probabilities of operation (P=0.905) or reoperation (P=0.418) between two groups. CONCLUSIONS: The early use of IFX did not reduce CD-related surgery requirements in Korean patients with CD. These study results suggest that the early use of IFX may have little impact on the clinical outcome of CD in Korean patients in the setting of a conventional step-up algorithm.

Non-invasive epigenetic detection of fetal trisomy 21 in first trimester maternal plasma.

BACKGROUND: Down syndrome (DS) is the most common known aneuploidy, caused by an extra copy of all or part of chromosome 21. Fetal-specific epigenetic markers have been investigated for non-invasive prenatal detection of fetal DS. The phosphodiesterases gene, PDE9A, located on chromosome 21q22.3, is completely methylated in blood (M-PDE9A) and unmethylated in the placenta (U-PDE9A). Therefore, we estimated the accuracy of non-invasive fetal DS detection during the first trimester of pregnancy using this tissue-specific epigenetic characteristic of PDE9A. METHODOLOGY/PRINCIPAL FINDINGS: A nested, case-control study was conducted using maternal plasma samples collected from 108 pregnant women carrying 18 DS and 90 normal fetuses (each case was matched with 5 controls according to gestational weeks at blood sampling). All pregnancies were singletons at or before 12 weeks of gestation between October 2008 and May 2009. The maternal plasma levels of M-PDE9A and U-PDE9A were measured by quantitative methylation-specific polymerase chain reaction. M-PDE9A and U-PDE9A levels were obtained in all samples and did not differ between male and female fetuses. M-PDE9A levels did not differ between the DS cases and controls (1854.3 vs 2004.5 copies/mL; P = 0.928). U-PDE9A levels were significantly elevated in women with DS fetuses compared with controls (356.8 vs 194.7 copies/mL, P<0.001). The sensitivities of U-PDE9A level and the unmethylation index of PDE9A for non-invasive fetal DS detection were 77.8% and 83.3%, respectively, with a 5% false-positive rate. In the risk assessment for fetal DS, the adjusted odds ratios of U-PDE9A level and UI were 46.2 [95% confidence interval: 7.8-151.6] and 63.7 [95% confidence interval: 23.2-206.7], respectively. CONCLUSIONS: Our findings suggest that U-PDE9A level and the unmethylation index of PDE9A may be useful biomarkers for non-invasive fetal DS detection during the first trimester of pregnancy, regardless of fetal gender.

Association between MTHFR 1298A>C polymorphism and spontaneous abortion with fetal chromosomal aneuploidy.

PROBLEM Polymorphisms in genes involved in folate metabolism are commonly associated with defects in folate-dependent homocysteine metabolism, which can result in DNA hypomethylation and chromosome nondisjunction. This prospective study aimed to investigate the associations between MTHFR 677C>T, MTHFR 1298A>C, MTR 2756A>G, MTRR 66A>G, and CBS 844ins68 polymorphisms and spontaneous abortion (SA) with fetal chromosomal aneuploidy. METHOD OF STUDY Subjects included 33 SA with normal fetal karyotype, 24 SA with fetal chromosomal aneuploidy and 155 normal controls. Polymorphisms were genotyped by PCR-RFLP and QF-PCR analysis. RESULTS The frequencies of MTHFR 1298AC and combined 1298AC/CC genotypes were higher in SA with fetal chromosomal aneuploidy than in controls. The 1298C allele frequency was also significantly higher in SA with fetal chromosomal aneuploidy than in controls. Moreover, the 1298C allele frequency was higher in SA with fetal chromosomal aneuploidy than in SA with normal fetal karyotype. The combined 1298AC/CC genotype was significantly associated with the risk of SA with fetal chromosomal aneuploidy compared with that of the 1298AA genotype (adjusted OR = 2.93, 95% CI: 1.11-7.69). There was no association between SA with fetal chromosomal aneuploidy and other polymorphisms. CONCLUSIONS Our findings indicate that MTHFR 1298A>C polymorphism may be an independent risk factor for SA with fetal chromosomal aneuploidy.