Il Hwan Oh

Etanercept induced organizing pneumonia in a patient with rheumatoid arthritis

TNF inhibitors are being used in a rapidly expanding number of rheumatoid arthritis (RA) patients due to their effectiveness and acceptable safety profiles. To date, concerns regarding the adverse effects of TNF inhibitors have focused on infections, hematologic malignancies, and demyelinating disorders. Recently, the development of autoantibodies and other autoimmunity has been increasingly reported. Here, we describe a 36-year-old RA patient in whom organizing pneumonia and systemic lupus erythematosus were detected during etanercept treatment.

Effects of sun exposure and dietary vitamin D intake on serum 25-hydroxyvitamin D status in hemodialysis patients.

BACKGROUND/OBJECTIVES Vitamin D deficiency is common in hemodialysis patients. The aim of this study was to identify whether or not sun exposure and dietary vitamin D intake have effects on serum 25-hydroxyvitamin D (25(OH)D) status in hemodialysis (HD) patients. The objective was to identify the main determinants of serum vitamin D status in the study subjects. SUBJECTS/METHODS A cross-sectional study of 47 HD patients (19 males and 28 females) was performed. We assessed serum 25(OH)D and 1,25(OH)2D levels between August and September 2012 and analyzed the prevalence of vitamin D deficiency in HD patients. To evaluate the determinants of serum 25(OH)D levels, we surveyed dietary vitamin D intake, degree of sun exposure, and outdoor activities. To compare biological variables, serum 25(OH)D was stratified as below 15 ng/ml or above 15 ng/ml. RESULTS Mean 25(OH)D and 1,25(OH)2D levels were 13.5 ± 5.8 ng/ml and 20.6 ± 11.8 pg/ml, respectively. The proportions of serum 25(OH)D deficiency (< 15 ng/ml), insufficiency (15-< 30 ng/ml), and sufficiency (≥ 30 ng/ml) in subjects were 72.4%, 23.4%, and 4.3%, respectively. Prevalence of vitamin D deficiency in female patients was 78.6%, whereas that in males was 63.2% (P = 0.046). Vitamin D intake and sun exposure time were not significantly different between the two stratified serum 25(OH)D levels. Dietary intake of vitamin D did not contribute to increased serum 25(OH)D levels in HD patients. The main effective factors affecting serum 25(OH)D status were found to be the sun exposure and active outdoor exercise. CONCLUSIONS Hypovitaminosis D is common in HD patients and is higher in females than in males. Sun exposure is the most important determinant of serum 25(OH)D status in HD patients.

Effects of dietary salt restriction on renal progression and interstitial fibrosis in adriamycin nephrosis.

Background/Aims: Although high salt intake is thought to accelerate renal progression in proteinuric kidney disease, it is not known whether strict dietary salt restriction could delay renal inflammation and interstitial fibrosis. Here, we sought to answer this question in a rat model of adriamycin-induced nephrotic syndrome. Methods: Adriamycin was administered via the femoral vein in a single bolus (7.5 mg/kg), and the rats were put on a sodium-deficient rodent diet. Rats with intact kidneys were studied for 5 weeks (experiment 1), and uninephrectomized rats were studied for 6 weeks (experiment 2). Results: In experiment 1, restricting salt intake improved renal tubulointerstitial histopathology in adriamycin-treated rats. Immunohistochemical and immunoblot results additionally showed that restricting dietary salt lowered adriamycin-induced expression of osteopontin, collagen III, and fibronectin. In experiment 2, salt restriction improved adriamycin-induced azotemia, although it did not affect proteinuria or blood pressure. Dietary salt restriction also reduced adriamycin-induced infiltration of ED1-positive cells and the upregulated expression of osteopontin and a-SMA. Massons trichrome and Sirius red staining revealed that salt restriction slowed Adriamycin-induced progression of renal interstitial fibrosis. Finally, qPCR revealed that adriamycin-induced expression of TNF-a, IκB-a, gp91phox, p47phox, and p67phox mRNA was blocked by salt restriction. Conclusion: Our findings demonstrate that strict dietary salt restriction delays the progress of renal inflammation and fibrosis in proteinuric kidney disease, most likely via relieving the reactive oxygen species-mediated NF-κB activation.

The Association of Normal Range Glycated Hemoglobin with Restrictive Lung Pattern in the General Population

Glycated hemoglobin (HbA1c) is an important diagnostic indicator of diabetes mellitus, and some authors have argued that it is related to impaired lung function in the diabetic population. However, there was rare study for association between lung function and HbA1c in the non-diabetic population. We investigated whether HbA1c below the diagnostic threshold is related to deficits in lung function. We analyzed biochemical and spirometry data from a nation-wide, population-based, case-control study (the KNHANES IV and V). Eligible as cases were all native Koreans aged 40 years or more with no medical illness. A total of 3670 participants were divided into 4 groups according to HbA1c (%) as follows: Group I (n = 842), ≥ 4.0 and ≤ 5.3; Group II (n = 833), > 5.3 and ≤ 5.5; Group III (n = 898), > 5.5 and ≤ 5.7; and Group IV (n = 1097), > 5.7 and ≤ 6.4. Group I had the greatest forced vital capacity (FVC, 96.3 ± 0.5% pred, P < 0.0001), forced expiratory volume per second (FEV1, 93.8 ± 0.5% pred, P < 0.0001) and FEV1/FVC (0.792 ± 0.003, P < 0.0001) compared with the other groups. Linear regression showed that HbA1c was closely related to FVC (β = -6.972154, P < 0.0001) and FEV1 (β = -5.591589, P < 0.0001), but not to FEV1/FVC. Logistic regression analysis revealed a significant association between HbA1c and a restrictive spirometric pattern (FVC < 80% pred., FEV1/FVC ≥ 0.70; OR = 3.772, 95% CI = 1.234-11.53), indicating that elevated HbA1c is closely associated with lung impairment in the non-diabetic population. In the healthy population, relatively high HbA1c level is associated with decrements of FVC and FEV1 and may be a reliable predictor of poor lung function, especially the restrictive pattern.

Evaluation of Urinary Indices for Albuminuria and Proteinuria in Patients with Chronic Kidney Disease

Background/Aims: Either protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) can be adopted for estimation of proteinuria in patients with chronic kidney disease (CKD). Estimated protein excretion rate (ePER) and estimated albumin excretion rate (eAER) may be superior to ACR and PCR. Reports show that urine albumin-to-protein ratio (APR) may be useful in detecting tubular proteinuria, but should be compared with urine protein electrophoresis (PEP). Methods: Both 24-h urine and spot urine were collected from 77 stable CKD patients for measurement of albumin, protein, and creatinine, and PEP. Based on MDRD and CKD-EPI equations, ePERMDRD, ePERCKD-EPI, eAERMDRD and eAERCKD-EPI were calculated to estimate daily proteinuria and albuminuria. Glomerular CKD was defined by clinical and/or pathological evidence. Results: ACR correlated significantly with PCR. However, microalbuminuria was present in patients without pathologic proteinuria. Twenty-four-hour urine albumin correlated better with eAERMDRD and eAERCKD-EPI than ACR, and 24-h urine protein correlated better with ePERMDRD and ePERCKD-EPI than PCR. APR significantly but not well correlated with the albumin fraction in urine PEP. The albumin fraction obtained from urine PEP was significantly higher in patients with glomerulopathy than those with non-glomerular CKD, whereas there were no differences in APR between groups. In contrast with APR, the albumin fraction in urine PEP was independently associated with glomerular CKD. Conclusions: Both PCR and ACR are useful in evaluation of proteinuria. In quantifying daily proteinuria and albuminuria, ePER and eAER are superior to PCR and ACR, respectively. Compared with APR, urine PEP is more useful in diagnosing glomerular proteinuria.

Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002–1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001–1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings.

Prognostic Significance of 1‐Year Serum Albumin Levels Within the Normal Range After Kidney Transplantation

Hypoalbuminemia is associated with poor outcomes in kidney transplantation (KT). However, what level is optimal in serum albumin is not clear for the long-term prognosis. To determine whether the long-term outcomes are different even between the normal ranges of serum albumin after KT, we analyzed data from 404 renal allograft recipients whose 1-year post-transplant serum albumin levels were within the normal limits (3.5-5.5 g/dL). During a follow-up of 122 ± 56 months, 97 graft losses, 20 patient deaths, and 50 cardiovascular (CV) events occurred. Based on 1-year serum albumin levels, the patients were divided into high normal (≥4.6 g/dL, n = 209) and low normal (<4.6 g/dL, n = 195) groups. Kaplan-Meier analyses revealed that the low normal group had poorer allograft survival (P = 0.01), patient survival (P < 0.001), and CV event-free survival (P < 0.001) than the high normal group. Cox regression analysis confirmed that 1-year serum albumin was inversely associated with the risk of graft loss (hazard ratio [HR] 0.414, 95% confidence interval [CI] 0.200-0.856), patient death (HR 0.097, 95% CI 0.019-0.484), and CV events (HR 0.228, 95% CI 0.074-0.702). In conclusion, a relatively low 1-year post-transplant serum albumin level within the normal limits (<4.6 g/dL) significantly predicts poor long-term outcomes.

A J‐Shaped Association Between Serum Uric Acid Level and Allograft Outcomes After Living Donor Kidney Transplantation

Hyperuricemia following kidney transplantation (KT) may contribute to a decline in allograft renal function, but be affected by KT-related confounding factors. Some studies have even suggested that a reduction in serum uric acid (UA) is associated with poor patient outcomes. Thus, we retrospectively analyzed the impact of serum UA on allograft outcomes in 281 KT recipients. KT recipients were divided into five groups according to serum UA level (mg/dL): Group I (n = 46), ≤ 5; Group II (n = 62), > 5 and ≤ 6; Group III (n = 70), > 6 and ≤ 7; Group IV (n = 53), > 7 and ≤ 8; Group V (n = 50), > 8. Regression analysis showed that serum UA level was significantly associated with future allograft function. In a Kaplan-Meier analysis, the dialysis-free survival of Group II recipients was better than that of the other groups (Group I, 140 ± 5 months; Group II, 208 ± 7 months; Group III, 148 ± 4 months; Group IV, 185 ± 12 months; Group V, 164 ± 11 months; P = 0.0164). In Cox proportional hazard models adjusting for estimated glomerular filtration rate, the relative risk of allograft loss still tended to be elevated in Group I (HR=3.417, 95% CI 1.138-10.258) and Group V (HR=2.793, 95% CI 1.108-7.041), using Group II as the reference. Our results suggest that there is a J-shaped association between serum UA levels and allograft outcomes in living donor KT recipients.

Effect of synergistic interaction between abnormal adiposity-related metabolism and prediabetes on microalbuminuria in the general population

Central obesity and related metabolic components are important risks for microalbuminuria. To describe the effects of interactions between central obesity and related metabolic components on microalbuminuria, we conducted a nation-wide, population-based interaction analysis using cardio-metabolic index (CMI) as a candidate indicator of central obesity and related abnormal lipid metabolism. We recruited native Koreans aged 20 years or older with no medical illness. A total of 5398 participants were divided into quintiles according to CMI with sex as a covariate factor. Participants in the highest CMI quintile had elevated blood pressure (BP), increased glycemic exposure, poor lipid profile, and increased urine albumin-to-creatinine ratio compared to other lower quintiles. Multiple logistic regression models adjusted for age, sex, systolic BP, and diastolic BP showed that CMI had an independent association with increased glycemic exposure and increased urine albumin-to-creatinine ratio. Our interaction analysis revealed a significant interaction between the highest CMI quintile and prediabetes with an increased risk of microalbuminuria (adjusted RERI = 0.473, 95% CI = 0.464–0.482; adjusted AP = 0.276, 95% CI = 0.156–0.395; adjusted SI = 2.952, 95% CI = 1.234–4.670). Our findings suggest a significant association between central obesity-related abnormal lipid metabolism and prediabetes, and their interaction may exert a synergistic effect on renal vascular endothelial dysfunction even before the appearance of full-blown diabetes mellitus. To confirm these findings, large population-based prospective studies are needed.

Alteration of Tight Junction Protein Expression in Dahl Salt-Sensitive Rat Kidney

Background/Aims: Altered pressure natriuresis is an important mechanism of hypertension, but it remains elusive at the molecular level. We hypothesized that in the kidney, tight junctions (TJs) may have a role in pressure natriuresis because paracellular NaCl transport affects interstitial hydrostatic pressure. Methods: To assess the association of salt-sensitive hypertension with altered renal TJ protein expression, Dahl salt-sensitive (SS) and salt-resistant (SR) rats were put on an 8% NaCl-containing rodent diet for 4 weeks. Systolic blood pressure (SBP) and urine NaCl excretion were measured weekly, and kidneys were harvested for immunoblotting and quantitative PCR analysis at the end of the animal experiments. Results: SBP was significantly higher in SS rats than in SR rats during the first to fourth weeks of the animal experiments. During the first and second week, urinary NaCl excretion was significantly lower in SS rats as compared with SR rats. However, the difference between the two groups vanished at the third and fourth weeks. In the kidney, claudin-4 protein and mRNA were significantly increased in SS rats as compared with SR rats. On the other hand, occludin protein and mRNA were significantly decreased in SS rats as compared with SR rats. The expression of claudin-2, claudin-7, and claudin-8 did not vary significantly between the two groups. Conclusions: In SS rats, SS hypertension was associated with differential changes in renal TJ protein expression. Both upregulation of claudin-4 and downregulation of occludin might increase paracellular NaCl transport in the kidney, resulting in impaired pressure natriuresis in SS rats.