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Background: Serum phosphorus concentrations are associated with an increased risk of cardiovascular disease (CVD) and mortality in patients with renal insufficiency. This association has also been reported in Western individuals without chronic kidney disease (CKD). Objective: It is unclear, however, whether this correlation occurs in Korean individuals without CKD, who usually ingest less phosphorus than do Western individuals. Design: We reviewed the findings in 402 healthy Korean adults with a mean (±SD) age of 50.8 ± 8.5 y (n = 257 men and 145 women) and a glomerular filtration rate of 83.5 ± 14.1 mL/min, who underwent health screening with electron-beam computed tomography (EBCT). The study population was separated into 4 groups on the basis of the coronary calcium concentration (Agatston score: 0, >0 to ≤10, >10 to ≤100, and >100). Mean serum phosphorus concentrations, measured ≥10 y before EBCT, were compared. Results: Multivariate analysis showed that age (P = 0.001), male sex (P = 0.002), family history of CVD (P = 0.006), serum glucose (P = 0.003), and serum phosphorus >3.6 mg/dL (P = 0.008) were significant factors influencing the coronary calcification group with an Agatston score >100, when those with an Agatston score of 0 were considered as the reference group. Compared with the group with a serum phosphorus concentration ≤3.3 mg/dL, the OR of an Agatston score >100 in individuals with a serum phosphorus concentration >3.6 to ≤3.9 mg/dL was 3.89 (95% CI: 1.43, 10.63; P = 0.008) and in those with a serum phosphorus concentration >3.9 mg/dL was 3.17 (95% CI: 1.19, 8.41; P = 0.021). Conclusion: A lower concentration of serum phosphorus within the normal range could be associated with less calcification of the coronary artery in Koreans with normal renal function. [ABSTRACT FROM AUTHOR]

The epithelial-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress induced by urinary protein, particularly albumin, play an important role in tubulointerstitial injury. However, signaling pathways regulating both albumin-induced EMT and ER stress are not precisely known. We postulated that reactive oxygen species (ROS), c-Src kinase, and mammalian target of rapamysin (mTOR) would act as upstream signaling molecules. We further examined the effect of imatinib mesylate on these processes. All experiments were performed using HK-2 cells, a human proximal tubular cell line. Protein and mRNA expression were measured by Western blot analysis and real-time PCR, respectively. Exposure of tubular cells to albumin (5 mg/ml) for up to 5 days induced EMT in a time-dependent manner, as shown by conversion to the spindle-like morphology, loss of E-cadherin protein, and upregulation of α-smooth muscle actin mRNA and protein. Albumin also induced ER stress as evidenced by phosphorylation of eukaryotic translation initiation factor-2α and increased expression of GRP78 mRNA and protein. Albumin induced ROS, c-Src kinase, and mTOR as well. Antioxidants, c-Src kinase inhibitor (PP2), and mTOR inhibitor (rapamycin) suppressed the albumin-induced EMT and ER stress. Antioxidants and PP2 inhibited the albumin-induced c-Src kinase and mTOR, respectively. Imatinib suppressed the albumin-induced EMT and ER stress via inhibition of ROS and c-Src kinase. Imatinib also inhibited the albumin-induced mRNA expression of MCP-1, VCAM-1, transforming growth factor (TGF)-β1, and collagen I (α1). In conclusion, the ROS-c-Src kinase-mTOR pathway played a central role in the signaling pathway that linked albumin to EMT and ER stress. Imatinib might be beneficial in attenuating the albumin-induced tubular injury. [ABSTRACT FROM AUTHOR]

Background: Many studies have been performed in kidney transplant recipients to test whether hyperuricemia plays a role in decreased kidney function, but the results have been controversial. We conducted a retrospective cohort study to assess the predictors of hyperuricemia and how uric acid (UA) influences glomerular filtration rate (GFR) changes. Methods: 556 patients who underwent kidney transplantation between January 1, 1990 and February 24, 2009, were included. Serum UA levels were routinely recorded every 3 months after transplantation. Hyperuricemia was defined as serum UA ≥6.0 mg/dl for women, and ≥7.0 mg/dl for men. A time-dependent covariate Cox model was used to assess the association of serial changes of estimated GFR (eGFR) and UA. Results: Multivariate analysis indicated that male gender, eGFR, and transplant duration were associated with higher mean UA levels. A time-dependent covariate Cox model indicated that initial eGFR level (hazard ratio: 1.001; p = 0.035) and previous UA level (hazard ratio: 1.454; p < 0.001) affected the subsequent eGFR level. Conclusions: Our results indicated a predictive relationship between UA and eGFR based on the results of a time-dependent covariate Cox model that elevated serum UA precedes a graft dysfunction in kidney transplant recipients. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Arterial blood gas analysis (ABGA) is a useful test that estimates the acid-base status of patients. However, numerically reported test results make rapid interpretation difficult. To overcome this problem, we have developed an algorithm that automatically interprets ABGA results, and assessed the validity of this algorithm for applications in clinical laboratory services. Methods: The algorithm was developed based on well-established guidelines using three test results (pH, PaCO2 and [HCO3 2]) as variables. Ninety-nine ABGA test results were analysed by the algorithm. The algorithm's interpretations and the interpretations of two representative web-based ABGA interpretation programs were compared with those of two experienced clinicians. Results: The concordance rates between the interpretations of each of the two clinicians and the algorithm were 91.9% and 97.0%, respectively. The web-based programs could not issue definitive interpretations in 15.2% and 25.3% of cases, respectively, but the algorithm issued definitive interpretations in all cases. Of the 10 cases that invoked disagreement among interpretations by the algorithm and the two clinicians, half were interpreted as compensated acid-base disorders by the algorithm but were assessed as normal by at least one of the two clinicians. In no case did the algorithm indicate a normal condition that the clinicians assessed as an abnormal condition. Conclusions: The interpretations of the algorithm showed a higher concordance rate with those of experienced clinicians than did two web-based programs. The algorithm sensitively detected acid-base disorders. The algorithm may be adopted by the clinical laboratory services to provide rapid and definitive interpretations of test results. [ABSTRACT FROM AUTHOR]

Background: Many studies have been performed in kidney transplant recipients to test whether hyperuricemia plays a role in decreased kidney function, but the results have been controversial. We conducted a retrospective cohort study to assess the predictors of hyperuricemia and how uric acid (UA) influences glomerular filtration rate (GFR) changes. Methods: 556 patients who underwent kidney transplantation between January 1, 1990 and February 24, 2009, were included. Serum UA levels were routinely recorded every 3 months after transplantation. Hyperuricemia was defined as serum UA ≥6.0 mg/dl for women, and ≥7.0 mg/dl for men. A time-dependent covariate Cox model was used to assess the association of serial changes of estimated GFR (eGFR) and UA. Results: Multivariate analysis indicated that male gender, eGFR, and transplant duration were associated with higher mean UA levels. A time-dependent covariate Cox model indicated that initial eGFR level (hazard ratio: 1.001; p = 0.035) and previous UA level (hazard ratio: 1.454; p < 0.001) affected the subsequent eGFR level. Conclusions: Our results indicated a predictive relationship between UA and eGFR based on the results of a time-dependent covariate Cox model that elevated serum UA precedes a graft dysfunction in kidney transplant recipients. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The occurrence of disasters to a queueing system causes all customers to be removed if any are present. Although there has been much research on continuous-time queues with disasters, the discrete-time Geo/Geo/1 queue with disasters has appeared in the literature only recently. We extend this Geo/Geo/1 queue to the GI/Geo/1 queue. We present the probability generating function of the stationary queue length and sojourn time for the GI/Geo/1 queue. In addition, we convert our results into the Geo/Geo/1 queue and the GI/M/1 queue. [ABSTRACT FROM AUTHOR]

Aim: i.v. iron therapy is more effective in maintaining adequate iron status in haemodialysis (HD) patients than oral iron therapy (OIT). However, data on lower doses of i.v. iron therapy are insufficient. Methods: A non-randomized, open-label study was performed to compare the efficacy of low-dose (≤50 mg/week of iron sucrose) i.v. iron therapy (LD-IVIT) with OIT in HD patients with 100–800 µg/L serum ferritin levels over 4 months. Results: Eighty-nine patients in the LD-IVIT group (40 men, 49 women; aged 61 ± 13 years) and 30 patients in the oral iron therapy group (17 men, 13 women; aged 59 ± 7 years) were evaluated. After 4 months of each treatment, serum ferritin levels increased from 398 ± 137 to 529 ± 234 µg/L in the LD-IVIT group ( P < 0.01) but decreased from 351 ± 190 to 294 ± 175 µg/L in the OIT group ( P < 0.01). In the LD-IVIT group, transferrin saturation (from 28% ± 11% to 30% ± 14%, P = 0.49), weekly doses of recombinant human erythropoietin (from 5822 ± 2354 to 5636 ± 2306 IU/week, P = 0.48) and haemoglobin (from 101 ± 9 to 103 ± 9 g/L, P = 0.15) levels remained stable. Conclusion: LD-IVIT may be one of the regimens that may be considered for maintaining iron status in HD patients. However, efficacy of LD-IVIT should be verified by further randomized study. [ABSTRACT FROM AUTHOR]

Background: Although several previous studies have reported that kidney donors are not at increased risk for adverse effects, some donors have been found to progress to chronic kidney disease (CKD). We retrospectively evaluated the risk factors for estimated glomerular filtration rate (GFR) from abbreviated Modification of Diet in Renal Disease (MDRD) equation (MDRD-GFR) of less than 60 mL/min per 1.73 m2 in kidney donors. Methods: Of the 756 individuals who underwent open donor nephrectomy between 27 June 1990 and 30 April 2001, 104 had follow-up records for 50 months or more. MDRD-GFR of 60 mL/min per 1.73 m2 at final follow up divided these individuals into a normal group ( n = 78) and a CKD-GFR group ( n = 26). We compared several clinical parameters between the two groups at baseline and follow up to evaluate the risk factors for MDRD-GFR of less than 60 mL/min per 1.73 m2 in kidney donors. Results: The CKD-GFR group was significantly older than the normal group at baseline (47 ± 12 vs 41 ± 11 years old, P = 0.02). Hypertension was more prevalent in the CKD-GFR group at baseline (15% vs 2%, P = 0.005). Binary logistic regression analysis showed that age (Odds ratio (OR) 1.06, 95% confidence interval (CI) 1.01–1.10) and hypertension (OR 7.91, 95% CI 1.13–55.2) at baseline were independent risk factors for MDRD-GFR of less than 60 mL/min per 1.73 m2. At final follow up, the prevalence rates of hypertension (31% vs 8%, P = 0.006) and proteinuria (15% vs 0%, P = 0.003) were significantly higher in the CKD-GFR group. Conclusion: Older kidney donors and those with hypertension were significantly more likely to have a MDRD-GFR of less than 60 mL/min per 1.73 m2. [ABSTRACT FROM AUTHOR]

Backgrounds: Immunological staining of the transplanted kidney for C4d in peritubular capillaries (C4dPTC) has emerged as a useful method to detect antibody-mediated rejection in situ. In this retrospective study, we evaluated the prevalence of C4dPTC deposition in allograft renal biopsies diagnosed of IgA nephropathy (IgAN) and analysed its clinical significance. Method: Sixty-six biopsy specimens of post-transplant IgAN, which were obtained to evaluate azotemia and/or heavy proteinuria, were examined by immunohistochemical staining of the paraffin sections with polyclonal antibody for C4d. Results: C4d was stained positively in peritubular capillaries in 16 (24%) of the 66 cases. The C4dPTC-negative (n=50) and C4dPTC-positive groups (n=16) were not different in recipient gender, age, donor age, type of donor (living vs. cadaveric), interval from transplantation to graft biopsy (41.6± 21.8 vs. 48.3±26.1 months) and post-biopsy follow-up period (60.3±23.3 vs. 56.9±25.4 months). During the follow-up period, 12 of 50 (24%) although the incidence of graft failure was not different by the C4d deposition in peritubular capillaries, intervals from renal biopsy to graft failure tended to be shorter in C4dPTC-positive cases than C4dPTC-negative cases. In Kaplan–Meier analysis, the renal allograft function of the C4dPTC-positive group deteriorated more rapidly than that of the C4dPTC-negative group (p<0.05). Histologically, the C4dPTC-positive group had findings suggestive of acute cellular rejection more commonly than the C4dPTC-negative group (p<0.01). Conclusions: Evidence of humoral rejection, as demonstrated by C4dPTC deposition, was concurrently present in significant portions of post-transplant IgAN biopsy specimens and was associated with more rapid deterioration of renal function. These results suggest that C4dPTC positivity needs to be determined at the time of biopsy even in cases of post-transplant glomerulonephritis and immunosuppression may need to be modified accordingly. [ABSTRACT FROM AUTHOR]

Background. Glomerular endothelial cells play a role in the pathogenesis of glomerulonephritis by producing chemotactic factors. We investigated the role of NF-κB and AP-1 in tumour necrosis factor α (TNF-α) induced monocyte chemoattractant protein 1 (MCP-1) production in cultured human glomerular endothelial cells (HGEC). We also examined whether or not these processes could be modified by glucocorticoid. Methods. MCP-1 protein and mRNA levels were measured by ELISA and northern blot. NF-κB and AP-1 binding activity were assessed by electrophoretic mobility shift assay. Cytosolic IκBα and nuclear p65 protein were evaluated by western blot. For specific inhibition of NF-κB or AP-1, we used a decoy oligodeoxynucleotide. Results. TNF-α (10 ng/ml) increased MCP-1 mRNA expression in HGEC and also the release of MCP-1 protein into culture media. These effects could be partially inhibited by dexamethasone (10 nM). TNF-α induced MCP-1 production appeared to be NF-κB and AP-1 interdependent, based on the following results. (i) TNF-α increased NF-κB and AP-1 binding activity. (ii) Both NF-κB decoy oligodeoxynucleotide and AP-1 decoy oligodeoxynucleotide partially suppressed TNF-α induced MCP-1 mRNA expression. On the other hand, dexamethasone decreased TNF-α induced DNA-binding activity of AP-1 without an effect on the DNA-binding activity of NF-κB, cytosolic IκBα degradation or p65 nuclear translocation. Conclusions. These data demonstrate that while TNF-α induced MCP-1 production is mediated by the cooperative action of NF-κB and AP-1 in HGEC, dexamethasone represses TNF-α induced MCP-1 production via suppression of AP-1 binding activity. [ABSTRACT FROM AUTHOR]

Background/Aims: Accurate measurement of glomerular filtration rate (GFR) is critical for the management of kidney transplant recipients. Comparison of creatinine and cystatin C in renal transplant recipients gave conflicting results. We aimed to compare the performance of creatinine- and cystatin C-based equations and creatinine clearance in 102 early postoperative Korean renal transplant patients. Methods: We measured 51Cr-EDTA clearance using a 2-compartment model and considered this the reference GFR. Then, we estimated GFR using 13 creatinine- and 7 cystatin C-based equations. Serum creatinine value was calibrated to isotope-dilution mass spectrometry (IDMS). Results: The mean reference GFR was 76.77 ± 17.01 ml/min/1.73 m2. The IDMS-traceable MDRD (IDMS-MDRD) equation had the highest accuracy (94.12 within 30% of the reference; 99.02 within 50% of the reference) with a bias of 0.33 ml/min/1.73 m2 and a precision of 12.57 ml/min/1.73 m2. The Mayo Clinic equation also performed well (92.16% within 30% of the reference; 99.02% within 50% of the reference; bias: –0.19 ml/min/1.73 m2). As for cystatin C-based equations, the Filler equation had the least bias (0.03 ml/min/1.73 m2) but low accuracy (78.43% within 30% of the reference). Conclusions: We conclude that the IDMS-MDRD equation provided the best estimate of GFR in our early postoperative Korean renal transplant patients. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]