Dong-Jin Oh

Assessment of Fluid Shifts of Body Compartments using Both Bioimpedance Analysis and Blood Volume Monitoring

Fluid shifts are commonplace in chronic hemodialysis patients during the intra- and interdialytic periods. In this study, we evaluated fluid shifts of body compartments using both bioimpedance spectroscopy and blood volume monitoring from the start to the end of hemodialysis. 24 stable hemodialysis patients were included on the study. Relative change of blood volume was progressively reduced from the start to the end of hemodialysis (1 hr, -7.22±3.23%; 2 hr, -9.78±4.69%; 3 hr, -12.88±5.65%; 4 hr, -15.41±6.54%, respectively). Mean % reduction of intracellular fluid was not significantly different to that of extracellular fluid at the end of hemodialysis (Δ ICF, -6.58±5.34% vs. Δ ECF, -7.07±5.12%). Mean % fluid reduction of arms, legs and trunk was -11.98±6.76%, -6.43±4.37% and -7.47±4.56%, respectively at the end of hemodialysis. There were 3 characteristic patterns in blood-volume change. Similar amounts of fluid were removed from the extracellular and intracellular compartments during hemodialysis, with the arms showing the greatest loss in terms of body segments. The pattern of blood volume change measured by blood volume monitoring may be useful for more accurate determination of dry-weight and for correcting volume status in hemodialysis patients.

Profile of human β-defensins 1,2 and proinflammatory cytokines (TNF-α, IL-6) in patients with chronic kidney disease.

Background/Aim: Our aim was to determine whether altered human β-defensin (HBD), pro-inflammatory cytokines including interleukin (IL)-6 and tumor necrotic factor (TNF)-α could increase the risk of developing and exacerbation of chronic kidney disease (CKD), especially for patients with diabetic nephropathy (DN). Methods: Serum samples were obtained from 338 CKD patients and 88 sex, age-matched healthy controls. The concentrations of HBD-1 were assayed using an RIA kit. Serum levels of HBD-2, IL-6 and TNF-α were assayed using an ELISA kit. Results: Serum levels of HBD-1, IL-6 and TNF-α were significantly higher in CKD patients compared to healthy controls (P<0.05). HBD-1 levels were inversely related to estimated glomerular filtration rate (eGFR), which was the coefficient factor (β = -0.357, P = 0.035) explaining the variability in HBD-1 in CKD. Diabetic nephropathy (DN) patients at stage 3-5 had significantly higher serum HBD-1 levels than non DN patients (P=0.00). Conclusion: Our data support the view that there is increased inflammation in CKD and DN. The inverse correlation between eGFR and serum HBD-1 which we observed is suggestive of a relationship between innate immunity and renal function and should be further investigated.

IGF-1 is an Independent Risk Factor for Anemia in Diabetic Pre-dialysis Patients

Background We investigated whether the presence of diabetes mellitus (DM) was related to the degree of the anemia in predialytic patients with renal failure and what was the most relevant factor for anemia in patients with chronic kidney disease (CKD) from DM (DM-CKD). Methods Seventy seven patients (47 predialytic patients with long-term type 2 DM (DM-CKD) and 30 predialytic patients whose disease was due to other causes (non DM-CKD)) were enrolled in this study. The blood hemoglobin (Hb) and hematocrit, and the creatinine, ferritin, vitamin B12, folate, iron, LDH, albumin, hs-CRP, intact-PTH, erythropoietin, leptin and Insulin-like growth factor I (IGF-1) levels were measured using standard methods. The estimated GFR was calculated using the abbreviated MDRD equation. Results The two groups did not significantly differ as to age, gender, the serum creatinine level and the inflammatory status. The Hb level was significantly lower in the DM-CKD patients than that in the non DM-CKD patients (8.5±1.7 g/dL vs 9.6±1.6 g/dL, respectively, p=0.01). The Hb level was significantly lower in the DM-CKD patients who were being treated with ACE inhibitors (the DM-ACE patients) than that in the non DM-CKD patients who were being treated with ACE inhibitors (the non DM-ACE patients) (8.5±1.5 g/dL vs 10.8±1.6 g/dL, respectively, p=0.001). Multiple regression analysis indicated that serum IGF-1 concentration was independently associated with the Hb level (β=0.425, p=0.02) in the DM-CKD patients. Conclusions The Hb concentration was significantly lower in the DM-CKD patients than that in the non DM-CKD patients. It was independently associated with the serum IGF-1 concentration in the DM-CKD patients.

Role of IL-1α in Cisplatin-Induced Acute Renal Failure in Mice

Background/Aims For unknown reasons, caspase-1 -/- mice, protected against cisplatin-induced acute renal failure (ARF), are deficient in interleukin (IL)-1α. We thus asked whether IL-1α deficiency underlies the mechanism of protection against cisplatin-induced ARF in these mice. Methods Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice to produce a cisplatin-induced model of ARF. IL-1α was measured in control vehicle- and cisplatin-treated wild-type animals. We also examined whether IL-1α -/- mice were similarly protected against cisplatin-induced ARF. Additionally, infiltration of CD11b- and CD49b-positive cells, as markers of macrophages, natural killer, and natural killer T cells (pan-NK cells), was investigated in wild-type and IL-1α -/- mice. Results Compared with vehicle-treated mice, renal IL-1α increased in cisplatin-treated wild-type mice beginning on day 1. IL-1α -/- mice were shown to be protected against cisplatin-induced ARF. No significant difference in the infiltration of neutrophils or CD11b- and CD49b-positive cells were observed between wild-type and IL-1α -/- mice. Conclusions Mice deficient in IL-1α are protected against cisplatin-induced ARF. The lack of IL-1α may explain, at least in part, the protection against cisplatin-induced ARF observed in caspase-1 -/- mice. Investigation of the protective mechanism (s) in IL-1α -/- mice in cisplatin-induced ARF merits further study.

The Relation Between Hypoalbuminemia and Compliance and Intima-media Thickness of Carotid Artery in Continuous Ambulatory Peritoneal Dialysis Patients

The aim of this study was to identify the main factor affecting compliance and intimamedia thickness of the elastic common carotid artery in continuous ambulatory peritoneal dialysis patients. Increased intima-media thickness and decreased arterial compliance are associated with elevated risk of cardiovascular disease. This study included 20 patients and 20 age- and sex- matched healthy control subjects. The compliance and intima-media thickness of the right common carotid artery within 1 cm to the bifurcation were measured three times using high-resolution B-mode echocardiography. Blood samples were obtained to measure levels of hemoglobin, phosphorus, total calcium, total CO2, serum albumin, C-reactive protein, serum total cholesterol, LDL- and HDL-cholesterol and triglycerides. We found that the compliance of common carotid artery was lower in the patient group than in the control group. In the patient group, the compliance of common carotid artery was positively correlated with serum albumin concentration, and intima-media thickness of common carotid artery was negatively correlated with serum albumin levels. Stepwise regression analysis showed that serum albumin concentration was independently related to the compliance of common carotid artery, suggesting hypoalbuminemia can independently give deleterious effects on the arterial wall in continuous ambulatory peritoneal dialysis patients.

The ratio of osteoprotegerin to fetuin-a is independently associated with vascular stiffness in hemodialysis patients.

Background: The aim of the present study was to compare levels of fetuin-A, osteoprotegerin (OPG), and heat shock protein (HSP)70 according to the stage of chronic kidney disease (CKD), as well as to evaluate the association between serum fetuin-A, OPG, and HSP70 concentrations with respect to vascular stiffness and calcification in hemodialysis (HD) patients. Methods: We measured fetuin-A, OPG, and HSP70 in 35 healthy controls, 35 patients with stage 3 CKD, 35 patients with stage 4 CKD, and 81 HD patients. Using these data, we studied the association of fetuin-A, OPG, and HSP70 with clinical, biochemical, and vascular measures in HD patients. Results: Levels of OPG and HSP70 were higher and fetuin-A was lower in HD patients than in healthy controls. The cardio-ankle vascular index (CAVI) showed a positive correlation with OPG (r = 0.248, p = 0.040) and the OPG/fetuin-A ratio (r = 0.260, p = 0.031). The ankle-brachial index (ABI) showed a negative correlation with OPG (r = -0.245, p = 0.031) and the OPG/fetuin-A ratio (r = -0.267, p = 0.018). Intima-media thickness (IMT) showed a positive correlation with OPG (r = 0.273, p = 0.014) and the OPG/fetuin-A ratio (r = 0.269, p = 0.015). On stepwise multiple linear regression analyses, only the logarithmic function of the OPG/fetuin-A ratio was independently associated with CAVI (β = 13.325, SE = 6.247, p = 0.038). Conclusions: Our results demonstrate that OPG and the OPG/fetuin-A ratio are correlated with increased vascular stiffness and IMT in HD patients. In addition, the OPG/fetuin-A ratio was independently associated with vascular stiffness in HD patients.

Reduction of natural killer and natural killer T cells is not protective in cisplatin-induced acute renal failure in mice

Aims:  A recent report showed that fractalkine (CX3CL1), which functions as both a potent chemoattractant and adhesion molecule for monocytes and natural killer (NK) cells was significantly increased in cisplatin‐induced acute renal failure (CisARF) in mice. Therefore, we developed the hypothesis that increased CX3CL1 expression in CisARF initiates NK cell infiltration in the kidney. The aim of the present study was to determine the role of NK cells in CisARF in mice.

Association of serum albumin and homocysteine levels and cardio-ankle vascular index in patients with continuous ambulatory peritoneal dialysis

Background The cardio-ankle vascular index (CAVI) is a newly developed arteriosclerotic measurement that has been proposed as an alternative to aortic pulse-wave velocity (PWV). The present study used the CAVI to identify the main factors associated with arteriosclerosis in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods Fifteen CAPD patients were enrolled in the study. The CAVI is independent of the pressure and vascular reflection between the heart valve and the ankle. Serum albumin, uric acid, total calcium, phosphorus, lipid levels, high-sensitivity C-reactive protein and homocysteine concentrations in CAPD patients were measured using standard methods. Total body fat mass, truncal and non-truncal fat mass and lean body mass were measured using dual energy X-ray absorptiometry with a Lunar DPX-L scanner. Results CAPD patients had a mean CAVI of 9.37±3.16 m/sec, which was higher than the general population. The CAVI was negatively correlated with the serum albumin concentration (r=-0.548; p=0.034). Stepwise regression analysis showed that both the serum albumin concentration (β=-0.643, p=0.013) and the serum homocysteine level (β=0.486, p=0.004) were independently associated with the CAVI. Conclusions An increase in CAVI was independently associated with both serum albumin and homocysteine level.

Serum osteoprotegerin level is associated with degree of arteriovenous fistula stenosis in patients with hemodialysis.

AIMS Vascular access dysfunction caused by stenosis is a major complication for hemodialysis (HD) patients. However, the relevant humoral mediators of arteriovenous (AV) access stenosis are still under investigation. The aim of the present study was to evaluate the association between serum fetuin-A, osteoprotegerin (OPG), and heat shock protein (Hsp) 70 concentration with arteriovenous fistula (AVF) patency in HD patients. METHODS Serum fetuin-A, OPG and Hsp70 concentrations were measured in 64 HD patients. Using these data, we studied the association of fetuin-A, OPG and Hsp70 with the degree of AVF stenosis using ultrasonography in HD patients. RESULTS The degree of AVF stenosis was positively correlated with OPG levels (r = 0.411, p = 0.001) and OPG/fetuin-A ratio (r = 0.375, p = 0.002). The levels of OPG and OPG/fetuin-A ratio were statistically higher in the group of AVF stenosis ≥ 11.5%. Stepwise linear regression analyses independently predicted the degree of AVF stenosis on the logarithmic function of the OPG (β = 8.775, standard error = 0.493, p = 0.034) and OPG/fetuin-A ratio (β = 10.325, standard error = 3.247, p = 0.018). CONCLUSIONS Our data demonstrated that OPG and the OPG/fetuin-A ratio correlated with the degree of AVF stenosis in HD patients. In addition, OPG and the OPG/fetuin-A ratio were the most important predictors of the degree of AVF stenosis in HD patients.

Successfully treated multicentric Castleman's disease with renal thrombotic microangiopathy using rituximab and corticosteroid.

Thrombotic microangiopathy (TMA) is a rare renal complication accompanied with Castlemans disease. We report the first case of TMA combined plasma cell type multicentric Castlemans disease (MCD) which was successfully treated with rituximab and corticosteroid. A previously healthy 60-year-old Korean man was admitted due to acute renal failure, thrombocytopenia, and multiple lymphadenopathies. The result of lymph node biopsy was plasma cell type Castlemans disease and TMA was revealed by kidney biopsy. After treatment with rituximab, prednisolone and temporary hemodialysis, complete remission was achieved. The combination of corticosteroid and rituximab was associated with improvement for this patient.