Air pollution and hemorrhagic fever with renal syndrome in South Korea: an ecological correlation study

Background : The effects of air pollution on the respiratory and cardiovascular systems, and the resulting impacts on public health, have been widely studied. However, little is known about the effect of air pollution on the occurrence of hemorrhagic fever with renal syndrome (HFRS), a rodent-borne infectious disease. In this study, we evaluated the correlation between air pollution and HFRS incidence from 2001 to 2010, and estimated the significance of the correlation under the effect of climate variables. Methods : We obtained data regarding HFRS, particulate matter smaller than 10 μm (PM10) as an index of air pollution, and climate variables including temperature, humidity, and precipitation from the national database of South Korea. Poisson regression models were established to predict the number of HFRS cases using air pollution and climate variables with different time lags. We then compared the ability of the climate model and the combined climate and air pollution model to predict the occurrence of HFRS. Results : The correlations between PM10 and HFRS were significant in univariate analyses, although the direction of the correlations changed according to the time lags. In multivariate analyses of adjusted climate variables, the effects of PM10 with time lags were different. However, PM10 without time lags was selected in the final model for predicting HFRS cases. The model that combined climate and PM10 data was a better predictor of HFRS cases than the model that used only climate data, for both the study period and the year 2011. Conclusions : This is the first report to document an association between HFRS and PM10 level.This work was supported by a grant from the Korean Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A084001).Peer Reviewe

The Bilirubin Level is Negatively Correlated with the Incidence of Hypertension in Normotensive Korean Population

Reactive oxygen species have been known to be an important factor in the pathogenesis of hypertension. Bilirubin, one of the metabolites of heme degraded by heme oxygenase, is a potent anti-oxidant. We verified the effect of serum bilirubin level on the incidence of hypertension in normotensive subjects. We grouped 1,208 normotensive subjects by the criterion of the highest quintile value of serum bilirubin, 1.1 mg/dL. The incidence of hypertension was higher in group 1 with bilirubin less than 1.1 mg/dL than in group 2 with bilirubin 1.1 mg/dL or more (186/908 vs. 43/300, p=0.018). The relative risk for hypertension was 0.71 (95% confidence interval, 0.51-0.99), p=0.048 in group 2 compared to group 1 by Cox's proportional hazard model. Among the groups stratified by gender, smoking, and liver function status, the group 2 showed a lower risk of hypertension in females and in non-smokers. In conclusion, a mild increase within the physiological range of serum bilirubin concentration was negatively correlated with the incidence of hypertension. The effect of bilirubin on the development of hypertension was more evident in females and in non-smokers

Recombinant uteroglobin prevents the experimental crescentic glomerulonephritis

Recombinant uteroglobin prevents the experimental crescentic glomerulonephritis.BackgroundAlthough uteroglobin is known to have an immunomodulatory property and prevents the deposition of immune-complexes on the glomeruli of mice, the therapeutic potential of uteroglobin is uncertain in glomerulonephritis. To test the hypothesis that uteroglobin can prevent glomerulonephritis, we have studied the effects of recombinant uteroglobin on the development of experimental crescentic glomerulonephritis that is induced by anti-glomerular basement membrane (anti-GBM) antibodies.Methods and ResultsGlomerulonephritis was induced by the intravenous injection of rabbit anti-GBM globulin antibodies into mice (C57BL/6), and renal injury was evaluated 7, 14, and 21 days afterward. Recombinant uteroglobin or phosphate-buffered saline (PBS) were given intravenously to mice for 3 days after anti-GBM antibody injection. Proteinuria was significantly reduced in mice treated with recombinant uteroglobin compared with disease-control mice at 7 and 14 days after an anti-GBM antibody injection, although the serum creatinine concentration was similar in both groups. The amount of proteinuria was similar in recombinant uteroglobin-treated and normal control mice. By histologic analysis, mesangial matrix expansion, mesangial proliferation, and cellular crescents representing crescentic glomerulonephritis were markedly attenuated by injection of recombinant uteroglobin. The in vitro proliferative responses of mesangial cells to lipopolysaccharide (LPS) were blunted by the addition of recombinant uteroglobin in a dose-dependent manner. The preventive effects exerted by recombinant uteroglobin treatment were based on the inhibition of antibodies and complement-3 deposition on the glomeruli.ConclusionThis study demonstrates the preventive effects of recombinant uteroglobin in an experimental model of crescentic glomerulonephritis, and suggests the therapeutic implications of uteroglobin for human chronic glomerulonephritis

The Prevalence of Chronic Kidney Disease (CKD) and the Associated Factors to CKD in Urban Korea: A Population-based Cross-sectional Epidemiologic Study

Chronic kidney disease (CKD) is a worldwide problem. This study was designed to survey the prevalence and risk factors for CKD in Korea. The 2,356 subjects were selected in proportion to age, gender, and city. Subjects 35 yr of age or older were selected from 7 cities. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) Study equation, with albuminuria defined as a urine albumin to creatinine ratio of 30 mg/g or more. The overall prevalence of CKD was 13.7%. The prevalences of CKD according to stage were 2.0% stage 1, 6.7% stage 2, 4.8% stage 3, 0.2% stage 4, and 0.0% stage 5. The prevalences of microalbuminuria and macroalbuminuria were 8.6% and 1.6%, respectively. The prevalence of eGFR less than 60 mL/min/1.73 m(2) was 5.0%. Age, body mass index (BMI), hypertension, diabetes mellitus, systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting blood glucose were independent factors related to the presence of CKD. In conclusions, Korea, in which the prevalence of CKD is increasing, should prepare a policy for early detection and appropriate treatment of CKD. The present data will be helpful in taking those actions.Moranne O, 2009, J AM SOC NEPHROL, V20, P164, DOI 10.1681/ASN.2008020159Chin HJ, 2008, NEPHROL DIAL TRANSPL, V23, P2810, DOI 10.1093/ndt/gfn132Zhang LX, 2008, AM J KIDNEY DIS, V51, P373, DOI 10.1053/j.ajkd.2007.11.009BRODSKY J, 2008, AM J KIDNEY DIS S, V51, pS239Imai E, 2007, AM J KIDNEY DIS, V50, P927, DOI 10.1053/j.ajkd.2007.09.004Coresh J, 2007, JAMA-J AM MED ASSOC, V298, P2038Kwan BCH, 2007, CLIN J AM SOC NEPHRO, V2, P992, DOI 10.2215/CJN.04221206Iseki K, 2007, HYPERTENS RES, V30, P167Madan P, 2007, NEPHROL DIAL TRANSPL, V22, P440, DOI 10.1093/ndt/gfl572IMAI E, 2007, CLIN EXP NEPHROL, V11, P156Kuo HW, 2007, AM J KIDNEY DIS, V49, P46, DOI 10.1053/j.ajkd.2006.10.007CHIN HJ, 2007, KOREAN J NEPHROL, V26, P195Ma YC, 2006, J AM SOC NEPHROL, V17, P2937, DOI 10.1681/ASN.2006040368Li ZY, 2006, CLIN CHIM ACTA, V366, P209, DOI 10.1016/j.cca.2005.10.011*KOR SOC NEPHR, 2006, KOREAN J NEPHROL, V25, pS425Fried LF, 2005, J AM SOC NEPHROL, V16, P3728, DOI 10.1681/ASN.2005040384Viktorsdottir O, 2005, NEPHROL DIAL TRANSPL, V20, P1799, DOI 10.1093/ndt/gfh914Shlipak MG, 2005, NEW ENGL J MED, V352, P2049, DOI 10.1056/NEJMoa043161Domrongkitchaiporn S, 2005, J AM SOC NEPHROL, V16, P791, DOI 10.1681/ASN.2004030208Foley RN, 2005, J AM SOC NEPHROL, V16, P489Coresh J, 2005, J AM SOC NEPHROL, V16, P180Go AS, 2004, NEW ENGL J MED, V351, P1296, DOI 10.1056/NEJMoa041031Wasen E, 2004, J INTERN MED, V256, P70John R, 2004, AM J KIDNEY DIS, V43, P825, DOI 10.1053/j.ajkd.2003.12.046Hunsicker LG, 2004, J AM SOC NEPHROL, V15, P1363, DOI 10.1097/01.ASN.0000126069.68755.99Fox CS, 2004, JAMA-J AM MED ASSOC, V291, P844Chadban SJ, 2003, J AM SOC NEPHROL, V14, pS131, DOI 10.1097/01.ASN.0000070152.11927.4ACoresh J, 2003, AM J KIDNEY DIS, V41, P1, DOI 10.1053/ajkd.2003.50007SAMAK MJ, 2003, CIRCULATION, V108, P2154Ramirez SPB, 2002, J AM SOC NEPHROL, V13, P1907, DOI 10.1097/01.ASN.0000018406.20282.C8Ko GTC, 2001, BRIT J NUTR, V85, P239Levey AS, 1999, ANN INTERN MED, V130, P461Iseki K, 1996, KIDNEY INT, V49, P8001

Clinicopathologic Characteristics of IgA Nephropathy with Steroid-responsive Nephrotic Syndrome

Nephrotic syndrome is an unusual manifestation of IgA Nephropathy (IgAN). Some cases respond to steroid treatment. Here we describe a case-series of IgAN patients with steroid-responsive nephrotic syndrome. Twelve patients with IgAN with steroid-responsive nephrotic syndrome were evaluated and followed up. All patients presented with generalized edema. Renal insufficiency was found in two patients. The renal biopsy of eight patients revealed wide foot process effacement in addition to the typical features of IgAN. They showed complete remission after steroid therapy. Seven relapses were reported in five patients; six of the relapsed cases responded to steroid therapy. Compared with steroid-non-responsive patients, the patients with steroid-responsive nephrotic syndrome had shorter symptom duration, more weight gain, more proteinuria, and lower histologic grade than did those that had steroid-non-responsive nephrotic syndrome at presentation. None of the responders progressed to end stage renal disease, whereas five (38%) non-responders required dialysis or renal transplantation. Patients with IgAN who have steroid-responsive nephrotic syndrome likely have both minimal change disease and IgAN. The clinical features of sudden onset of generalized edema, initial heavy proteinuria and initial severe hypoalbuminemia might help identify the subset of patients, especially in low grade IgAN

Improvement in Erythropoieis-stimulating Agent-induced Pure Red-cell Aplasia by Introduction of Darbepoetin-α When the Anti-erythropoietin Antibody Titer Declines Spontaneously

Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-α. The patient developed progressive, severe anemia after the use of erythropoietin-α. As the anemia did not improve after the administration of either other erythropoietin-α products or erythropoietin-β, all ESAs were discontinued. Oxymetholone therapy failed to improve the transfusion-dependent anemia and a rechallenge with ESAs continuously failed to obtain a sustained response. However, her anemia improved following reintroduction of darbepoetin-α at 3 yr after the initial diagnosis. Interestingly, anti-erythropoietin antibodies were still detectable, although their concentration was too low for titration. In conclusion, darbepoetin-α can improve ESA-induced PRCA when the anti-erythropoietin antibody titer declines and its neutralizing capacity is lost

Detection of Hantaan Viral Antigens in Renal Tissues from a Patient with Korean Hemorrhagic Fever in Convalescent Phase

A case of a patient with Korean hemorrhagic fever (KHF) who showed typical clinical manifestations is described for the purpose of reporting the detection of Hantaan viral antigens in renal tissues. The pathophysiologic mechanisms of renal damage are not well known, and several mechanisms including direct renal injury by the virus itself have been proposed to explain the renal lesions and the clinical manifestations. We detected Hantaan viral antigens in renal tissues from a KHF patient in the convalescent phase by the immunohistochemical method using the monoclonal antibodies to Hantaan viral envelope glycoproteins (G1, G2). The immunostainings demonstrated Hantaan viral antigens in the renal tubular epithelial cells, the intraluminal desquamated tubular cells, the infiltrated cells in the interstitium, and the capillary endothelial cells in the interstitium and glomeruli. The presence of viral antigens in renal tissues may support the hypothesis that direct renal injury by the virus is one of the pathophysiologic mechanisms of renal damage in KH

Interleukin-10 Promoter Polymorphism is Associated with the Predisposition to the Development of IgA Nephropathy and Focal Segmental Glomerulosclerosis in Korea

The roles of interleukin-10 (IL-10) have been emphasized in several models of glomerulonephritis (GN). Three biallelic polymorphisms within the IL-10 promoter region, at positions -1,082, -819, and -592 from the transcription initiation site, were shown to affect the level of IL-10 production. To investigate the effect of IL-10 promoter polymorphisms on the predisposition to development of GN in Korea, IL-10 promoter polymorphisms were assayed by polymerase chain reaction followed by restriction fragment length polymorphism in 108 patients with IgA nephropathy (IgAN), 49 focal segmental glomerulosclerosis (FSGS), and 100 healthy controls. In comparison with the control, the frequency of -1,082*G alleles were lower in IgAN and the frequencies of -592*C and -819*C were lower in FSGS, respectively. As for the haplotype, GCC haplotype was less frequent among IgAN than the control and ATA haplotype was more frequent among FSGS than the control (p<0.05). The frequency of intermediate producer genotypes (GCC/ACC and GCC/ATA) were lower among IgAN or FSGS than the control. Our findings suggested that IL-10 promoter polymorphism predisposed to the development of IgAN and FSGS in Korean patients

Association of Angiotensin II Type 2 Receptor Gene A1818T Polymorphism with Progression of Immunoglobulin A Nephropathy in Korean Patients

We determined the relationship between the progression of immunoglobulin A nephropathy (IgAN) and the A1818T polymorphism in intron 2 of Angiotensin II type 2 receptor (AT2R) gene, which might play protective roles in the pathogenesis of IgAN. Patients with biopsy-proven IgAN were recruited from the registry of the Progressive REnal disease and Medical Informatics and gEnomics Research (PREMIER) which was sponsored by the Korean Society of Nephrology. A1818T polymorphism of AT2R gene was analyzed with PCR-RFLP method and the association with the progression of IgAN, which was defined as over 50% increase in baseline serum creatinine level, was analyzed with survival analysis. Among the 480 patients followed for more than 10 months, the group without T allele had significantly higher rates of progression of IgAN than the group with T allele (11.4% vs. 3.9%, p=0.024), although there were no significant differences in the baseline variables such as initial serum creatinine level, the degree of proteinuria, and blood pressure. In the Cox's proportional hazard model, the hazard ratio of disease progression in the patients with T allele was 0.221 (95% confidence interval for Exp(B): 0.052-0.940, p=0.041) compared to that of without T allele. In conclusion, A1818T polymorphism of AT2R gene was associated with the progression of IgAN