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Protein-energy wasting (PEW) is associated with mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. The correct diagnosis of PEW is extremely important in order to predict clinical outcomes. However, it is unclear which parameters should be used to diagnose PEW. Therefore, this retrospective observational study investigated the relationship between mortality and nutritional parameters in ESRD patients on maintenance hemodialysis. A total of 144 patients were enrolled. Nutritional parameters, including body mass index, serum albumin, dietary intake, normalized protein catabolic rate (nPCR), and malnutrition inflammation score (MIS), were measured at baseline. Fifty-three patients died during the study. Survivors had significantly higher nPCR (1.10 +/- 0.24 g/kg/day vs. 1.01 +/- 0.21 g/kg/day; p = 0.048), energy intake (26.7 +/- 5.8 kcal/kg vs. 24.3 +/- 4.2 kcal/kg; p = 0.009) and protein intake (0.91 +/- 0.21 g/kg vs. 0.82 +/- 0.24 g/kg; p = 0.020), and lower MIS (5.2 +/- 2.3 vs. 6.1 +/- 2.1, p = 0.039). In multivariable analysis, energy intake 5 (HR 2.146, 95% CI 1.173-3.928; p = 0.013) were independent variables associated with all-cause mortality. These results suggest that higher MIS and lower energy intake are harmful to ESRD patients on maintenance hemodialysis. Optimal energy intake could reduce mortality in these patients.

Endoplasmic reticulum (ER) stress is increasingly identified as modulator of fibrosis. Losartan, an angiotensin II receptor blocker, has been widely used as the first choice of treatment in chronic renal diseases. We postulated that anti-fibrotic effect of losartan is mediated through inhibition of ER stress via SIRT1 (silent mating type information regulation 2 homolog 1) hemeoxygenase-1 (HO-1)/thioredoxin pathway. Renal tubular cells, tunicamycin (TM)-induced ER stress, and unilateral ureteral obstruction (UUO) mouse model were used. Expression of ER stress was assessed by Western blot analysis and immunohistochemical stain. ER stress was induced by chemical ER stress inducer, tunicamycin, and non-chemical inducers such as TGF-β, angiotensin II, high glucose, and albumin. Losartan suppressed the TM-induced ER stress, as shown by inhibition of TM-induced expression of GRP78 (glucose related protein 78) and p-eIF2α (phosphospecific-eukaryotic translation initiation factor-2α), through up-regulation of SIRT1 via HO-1 and thioredoxin. Losartan also suppressed the ER stress by non-chemical inducers. In both animal models, losartan reduced the tubular expression of GRP78, which were abolished by pretreatment with sirtinol (SIRT1 inhibitor). Sirtinol also blocked the inhibitory effect of losartan on the UUO-induced renal fibrosis. These findings provide new insights into renoprotective effects of losartan and suggest that SIRT1, HO-1, and thioredoxin may be potential pharmacological targets in kidney diseases under excessive ER stress condition.

Background. In end-stage renal disease patients with hepatitis B surface antigen (HBsAg), the risk of hepatic dysfunction after immunosuppression represents a large barrier in renal transplantation. Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. We retrospectively investigated the outcome of HBsAg-positive renal transplantation recipients after lamivudine had become available. Methods. From July 1994 to August 2000, seventeen HBsAg-positive patients (M: F = 15: 2) received renal allografts (13:4 = living: cadaveric donors). Liver function tests at the time of transplantation were normal in all patients. Pre-transplant liver biopsies performed in 15 patients demonstrated minimal inflammatory histology, except in three patients showing pathological and clinical signs of active hepatitis. Lamivudine was started pre-operatively in these three subjects. Another seven patients were treated with lamivudine for postoperative hepatic dysfunction. The remaining seven patients did not develop hepatic dysfunction after transplantation. Results. Lamivudine was initially effective in decreasing serum HBV DNA titres, and in normalizing hepatic enzymes. Lamivudine was well tolerated without significant side effects for 35.5 ±8.9 months after initiation of treatment. HBV DNA became negative in nine patients but remained positive in one patient. Among the nine patients with initial negative conversion of HBV DNA, two developed transient positive conversion of HBV DNA and two demonstrated persistent positive conversion. Among the patients with normal liver histology in the pre-transplant period, 41.6% (5/12) developed liver pathology progression after immunosuppression. All 17 patients had functioning grafts, except for one patient who developed relapsed IgA nephropathy. Conclusions. Our data showed relatively favourable outcomes in hepatitis B-positive renal transplant recipients receiving lamivudine treatment, even though two patients developed lamivudine resistance.

The epithelial-mesenchymal transition (EMT) is a novel mechanism that promotes renal fibrosis. Transforming growth factor-β (TGF-β), angiotensin II, aldosterone, high glucose, and urinary albumin are well-known causes of EMT and renal fibrosis. We examined whether and how activation of AMP-activated protein kinase (AMPK) suppressed EMT induced by the above agents in tubular epithelial cells. All experiments were performed using HK-2 cells. Protein expression was measured by Western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry. Exposure of tubular cells to TGF-β (10 ng/ml), angiotensin II (1 μM), aldosterone (100 nM), high glucose (30 mM), and albumin (5 mg/ml) for 5 days induced EMT, as shown by upregulation of α-smooth muscle actin and downregulation of E-cadherin. ROS and NADPH oxidase 4 (Nox4) expression were increased, and antioxidants such as tiron and N-acetylcysteine inhibited EMT induction. Metformin (the best known clinical activator of AMPK) suppressed EMT induction through inhibition of ROS via induction of heme oxygenase-1 and endogenous antioxidant thioredoxin. An AMPK inhibitor (compound C) and AMPK small interfering RNA blocked the effect of metformin, and another AMPK activator [5-aminoimidazole-4-carboxamide-1β riboside (AICAR)] exerted the same effects as metformin. In conclusion, AMPK activation might be beneficial in attenuating the tubulointerstitial fibrosis induced by TGF-β, angiotensin II, aldosterone, high glucose, and urinary albumin.

This study sought to identify specific enzyme(s) involved in the biochemical cascade of inhibition of renin secretion through Ca(2+)-calmodulin mediation with the use of inhibitors of protein kinase and phosphatases. Inhibition of renin secretion mediated by Ca(2+)-calmodulin was induced by incubating rat renal cortical slices in K(+)-rich depolarizing medium, producing > 50% inhibition. This inhibition was completely blocked by the calmodulin antagonist calmidazolium. The inhibitor of protein kinase with broad specificity, K-252a, blocked the inhibition of renin secretion. Neither KN-62, a specific inhibitor of Ca(2+)-calmodulin-dependent protein kinase II (CaMK II), nor specific inhibitors of protein phosphatase 2B (PP2B), cyclosporin A and FK-506, blocked the inhibition. On the other hand, all four known inhibitors specific for myosin light chain kinase (MLCK), with different chemical structures and mechanisms of inhibition (ML-9, ML-7, KT-5926 and wortmannin), almost completely protected renin secretion against the inhibition by Ca2+. In particular, ML-9 reversively protected > 77% secretion against the inhibition both in K(+)-rich medium alone and in combination with the calcium ionophore A-23187 in a concentration-dependent manner. Together, these findings from our present study provide the first evidence, albeit indirect in nature, for the possibility that activation of Ca(2+)-calmodulin-dependent MLCK at the downstream of Ca2+ influx into juxtaglomerular (JG) cells leads to phosphorylation of 20-kDa regulatory myosin light chain (MLC20). Through interaction with actin, the phosphorylated MLC20 may play an important role in the inhibitory stimulus-secretion coupling of renin.

Objective To evaluate and compare the pharmacokinetics and tolerability of a single oral dose of mirodenafil in volunteer patients with severe renal impairment and healthy volunteers. Methods and materials This open-label, single-dose, parallel group clinical study enrolled a total 12 volunteers (6 healthy volunteers and 6 volunteer patients with severe renal impairment). Each volunteer was orally administered 50 mg mirodenafil and serial blood samples were obtained after drug administration to determine the plasma concentration of mirodenafil using LC-MS/MS. The measured individual plasma concentrations were used to calculate the pharmacokinetic parameters using noncompartmental methods. Tolerability was also assessed using measurements of vital signs, clinical chemistry tests, and interviews. Results All of the volunteers completed the study with no serious adverse events (AEs). A total of 4 AEs were reported, but all were of mild or moderate intensity and not considered to be related to the study drug. The geometric mean (95% CI) of the terminal half-life (t1/2β) and the apparent clearance (CL/F) values of mirodenafil were 2.2 (1.4 - 3.4) h and 127.2 (95.1 - 170.2) l/h in the volunteer patients, and 3.0 (2.1 - 4.4) h and 136.1 (74.4 - 249.2) l/h in the healthy volunteers, respectively. The geometric mean of the AUC0-t of the volunteer patients was 8% higher and the geometric mean for clearance was 7% lower compared with the healthy volunteers. However, the geometric mean of the Cmax of the volunteer patients was 38% higher than that of the healthy volunteers. Conclusions A single oral 50-mg dose of mirodenafil was well tolerated. Exposure (AUC0-t) to mirodenafil was similar in both healthy volunteers and volunteer patients with severe renal impairment and healthy volunteers.

The role of spleen tyrosine kinase (Syk) in high glucose-induced intracellular signal transduction has yet to be elucidated. We investigated whether Syk is implicated in high glucose-induced transforming growth factor-β1 (TGF-β1) up-regulation in cultured human proximal tubular epithelial cells (HK-2 cell). High glucose increased TGF-β1 gene expression through Syk, extracellular signal-regulated kinase (ERK), AP-1 and NF-κB. High glucose-induced AP-1 DNA binding activity was decreased by Syk inhibitors and U0126 (an ERK inhibitor). Syk inhibitors suppressed high glucose-induced ERK activation, whereas U0126 had no effect on Syk activation. High glucose-induced NF-κB DNA binding activity was also decreased by Syk inhibitors. High glucose increased nuclear translocation of p65 without serine phosphorylation of IκBα and without degradation of IκBα, but with an increase in tyrosine phosphorylation of IκBα that may account for the activation of NF-κB. Both Syk inhibitors and Syk-siRNA attenuated high glucose-induced IκBα tyrosine phosphorylation and p65 nuclear translocation. Depletion of p21-activated kinase 2 (Pak2) by transfection of Pak2-siRNA abolished high glucose-induced Syk activation. In summary, high glucose-induced TGF-β1 gene transcription occurred through Pak2, Syk and subsequent ERK/AP-1 and NF-κB pathways. This suggests that Syk might be implicated in the diabetic kidney disease.

Different cell types in the kidney, including those in tubules, glomeruli, and interstitium, have been proposed as candidate adult renal stem cells, raising controversy about the very existence of such cells. In this study, we sought to clarify the location and nature of adult renal stem cells and to address their reparative role in native kidney disease.The expression of the stem cell marker CD133 was analyzed in 31 normal fetal and adult human kidneys by immunohistochemical methods. Co expression of CD133 with Ki-67 and tubule specific markers was also examined. Seventeen cases of pauci-immune glomerulonephritis were evaluated for CD133 and Ki-67 expression, and this was correlated with the patients' renal prognosis.CD133 was expressed in S-shaped bodies of fetal kidneys and co-expressed with Ki-67. It was highly expressed in mature tubules of fetal and adult kidneys without Ki-67 co-expression. CD133+ cells were most abundant in the S3 segment of proximal tubules and co-expressed with the distal tubule marker, suggesting multipotency. Most tubular CD133+ cells in normal adult kidneys exhibited pathologic features of acute and chronic injury. In pauci-immune glomerulonephritis, tubular CD133 and Ki-67 co-expression tended to be higher in cases where renal function recovered.These results suggest that adult renal stem cells reside predominantly in the S3 segment of the proximal tubule, where they remain mitotically silent under normal conditions, but can be induced by cellular injury. These results also suggest a potential role for adult renal stem cells in recovery from native human kidney disease.

Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in solid organ transplant recipients. Endothelin-1 (ET-1) is implicated in the pathogenesis of atherosclerosis and is one of the potential therapeutic targets. This study was conducted to evaluate the effect of mycophenolic acid (MPA), an immunosuppressant for the transplant recipients, on tumor necrosis factor-alpha (TNF-alpha)-induced ET-1 production in aortic endothelial cells.In cultured human aortic endothelial cells, TNF-alpha increased ET-1 through AP-1 and NF-kappaB, whereas MPA attenuated it by reducing both AP-1 and NF-kappaB DNA-binding activities. TNF-alpha increased ET-1 via c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), but not extracellular signal-regulated kinase. N-acetylcysteine that downregulated TNF-alpha-induced reactive oxygen species (ROS) inhibited JNK activation, but not p38 MAPK. N-acetylcysteine, SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated TNF-alpha-induced DNA-binding activities of both AP-1 and NF-kappaB. MPA inhibited JNK and p38 MAPK activations as well as ROS generation. N-acetylcysteine, SP600125, SB203580 and MPA had no effect on either TNF-alpha-induced IkappaBalpha degradation or p65 nuclear translocation, but attenuated p65 Ser276 phosphorylation.MPA attenuated TNF-alpha-induced ET-1 production through inhibitions of ROS-dependent JNK and ROS-independent p38 MAPK that regulated NF-kappaB as well as AP-1. These findings suggest that MPA could have an effect of amelioration of atherosclerosis.

Fatty acid-bearing albumin [FA(+) albumin] exerts more deleterious effects in tubular cells than albumin alone. We investigated the effect of FA(+) albumin on the vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of L-carnitine, since it was known to modulate intracellular fatty acid concentration.Activation of AP-1 and NF-kappaB was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinase was examined by Western blot analysis. VCAM-1 mRNA and protein expression were measured by Northern blot analysis and cell ELISA.FA(+) albumin induced VCAM-1 expression via activation of AP-1 and NF-kappaB, which was mediated through activation of c-Src kinase, followed by MAP kinases (p38, ERK 1/2, JNK-1) and IkappaB kinase and IkappaB-alpha, respectively. Inhibitors of protein kinase C and tyrosine kinase, anti-oxidants and intracellular calcium chelator suppressed the FA(+) albumin-induced activation of c-Src kinase. L-Carnitine suppressed the FA(+) albumin-induced VCAM-1 expression via inhibition of c-Src kinase.VCAM-1 expression with activation of c-Src kinase-AP-1/NFkappaB pathways might be one of the possible mechanisms that linked FA(+) albumin to tubulointerstitial injury. L-Carnitine might be beneficial in attenuating FA(+) albumin-induced tubular injury.

Background/Aims: It is not clear whether a sublethal dose of myoglobin induces some pathophysiological changes in tubular cells, potentially affecting tubular injury or tubular regeneration. We investigated the effect of a low dose of myoglobin on vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of losartan and simvastatin on myoglobin-induced VCAM-1 expression and the signaling pathways. Methods: Activation of nuclear factor (NF)-ĸB and activator protein (AP)-1 was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinases was examined by Western blot analysis. VCAM-1 mRNA and protein were measured by Northern blot analysis and cell ELISA. Results: A sublethal dose of myoglobin (100 µg/ml) induced VCAM-1 expression via activation of AP-1 and NF-ĸB, which was mediated through activation of c-Src kinase, followed by mitogen-activated protein kinases (p38, ERK 1/2, JNK-1) and the IĸB kinase – IĸB-α. Inhibitors of protein kinase C and tyrosine kinase, antioxidants and intracellular calcium chelator suppressed myoglobin-induced activation of c-Src kinase. Losartan and simvastatin suppressed myoglobin-induced VCAM-1 expression via inhibition of c-Src kinase. Conclusion: VCAM-1 expression via c-Src kinase-AP-1/NF-ĸB pathways might be one of the possible mechanisms linking myoglobin to tubular injury. Losartan and simvastatin might be beneficial in attenuating myoglobin-induced tubular injury.

Beraprost sodium, an orally active prostaglandin I2 analog with vasodilatory, cytoprotective, antiplatelet, antithrombotic, and anti-inflammatory effects, 120 μg daily for 8 weeks, decreased plasma D-dimer, a marker of intravascular coagulation, and von Willebrand factor, a marker for endothelial injury, in 100 chronic peritoneal dialysis patients. Total cholesterol, triglycerides, high-density lipoprotein, apolipoprotein A1, apolipoprotein B, albumin, prealbumin, fibrinogen, troponin-T, and high-sensitivity C-reactive protein levels were not changed. Three patients complained of headache and 1 patient experienced facial flushing; however, no serious adverse effects were observed. These results suggest that beraprost sodium is effective in partially reversing the thrombogenic coagulation profile and endothelial injury in chronic peritoneal dialysis patients.

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.

Background: The ratio of bioimpedance in the right leg (rl-RBI) may be helpful in adjusting dry body weight (DBW) in new hemodialysis (HD) patients. Methods: rl-RBI was calculated as follows: rl-RBI = impedance at 50 kHz/impedance at 500 kHz, as measured by bioimpedance spectroscopy (BIS). Theoretically, rl-RBI is inversely related to extracellular water. A reference range of rl-RBI was obtained from 137 chronic but stable HD patients already achieving DBW. In 34 new HD patients (females:males = 16:18; age 49 ± 12 years), DBW(s) were stepwise adjusted under the guidance of rl-RBI by modifying the amount of ultrafiltration. Results: The target range of rl-RBI was defined as 1.106–1.150. rl-RBI before the first HD was 1.115 ± 0.027. At the study endpoint, when the target range of rl-RBI was achieved, pretibial pitting edema and pulmonary edema were resolved without any episode of muscle cramping or intradialytic hypotension. Along with an increase in rl-RBI, pre-HD blood pressure tended to decrease at systole (p = 0.072) and diastole (p = 0.005). The cardiothoracic ratio also decreased significantly (p = 0.004). Conclusion: The measurement of rl-RBI by BIS is worthy of further evaluation as an objective and applicable index for determining DBW in new HD patients.

Sulodexide, a standardized extractive glycosaminoglycan containing 80% “fast moving” heparin and 20% dermatan sulfate, decreased plasma D-dimer, a marker of intravascular coagulation, and fibrinogen levels in chronic peritoneal dialysis patients. Blood levels of von Willebrand factor, lipid, and high-sensitivity C-reactive protein were not significantly changed. No bleeding episodes were reported. These results suggest that sulodexide was effective in partially reversing the thrombogenic coagulation profile without increasing the risk of bleeding.

Despite substantial advances in dialysis techniques and machines, acute kidney injury (AKI) requiring renal replacement therapy (RRT) is still associated with up to 60% in-hospital mortality. However, there is little information on whether RRT overcomes the significant morbidity and mortality of AKI. What is most important in the treatment of AKI is that RRT is not a cause-specific therapy but life-supportive management. This review discusses the indications of, proper initiation of, and optimal prescription for RRT to improve the survival of critically ill patients with AKI.

Background/Aim: Endothelial dysfunction due to reduced nitric oxide (NO) availability precedes the development of atherosclerosis. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is not only a cause of endothelial dysfunction, but also a predictor of the cardiovascular outcome in end-stage renal disease (ESRD) patients on hemodialysis (HD). α-Lipoic acid (ALA), a strong antioxidant, increases NO-mediated vasodilation in diabetic patients. We investigated whether ALA could decrease the plasma level of ADMA in diabetic ESRD patients on HD. Methods: Fifty patients undergoing HD three times per week were randomized to a treatment group receiving ALA 600 mg/day for 12 weeks or a control group. We measured the plasma levels of cholesterol, albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, hemoglobin A1c, and ADMA in both groups at baseline and at 12 weeks. Results: In the control group, the levels of total cholesterol, serum albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, hemoglobin A1c, and ADMA did not change. In the treatment group, the plasma levels of ADMA decreased significantly from a median of 1.68 (range 0.45–3.78) µM to a median of 1.31 (range 0.25–3.19) µM (p = 0.001). Conclusion: Considering that ADMA is an independent risk factor for cardiovascular outcome in ESRD patients, ALA may have the potential of a beneficial effect in them, in part by decreasing the plasma level of ADMA.

Ginkgo biloba extract decreased plasma D-dimer concentration, a marker of intravascular coagulation, in chronic peritoneal dialysis patients. Blood levels of fibrinogen, von Willebrand factor, hs-CRP, albumin and liver enzyme levels were not significantly changed. No bleeding episode was reported. These results suggest that Ginkgo biloba extract was effective in partially reversing the thrombogenic coagulation profile without increasing the risk of bleeding.

Hemodialysis (HD) and continuous venovenous hemodiafiltration (CVVHDF) have been adopted as forms of renal replacement therapy (RRT) in patients with acute renal failure (ARF). Although CVVHDF has many advantages, previous studies reported no definite improvement in survival rate compared to HD.In this retrospective study, 148 intensive care unit patients underwent HD (70 males, 25 females; mean age 45 +/- 17 years) or CVVHDF (42 males, 11 females; mean age 52 +/- 18 years). The severity of illness was estimated at the initiation of RRT and on the third day of RRT and presented using the APACHE III scoring system. The number of organ failures was checked at the initiation of RRT.The survival rate was 46% in the HD group and 21% in the CVVHDF group (p = 0.002). CVVHDF was applied to the more severely ill patients, who had longer periods using a ventilator (p = 0.002) and/or vasopressor (p0.001), higher numbers of organ failures (p0.001) and higher initial APACHE III scores (p0.001). Among patients with APACHE III scores103, the survival rate was 13% in the CVVHDF group and 0% in the HD group. In patients with kidney failure and failure of two other organs, the survival rate was 9% in the HD group and 36% in the CVVHDF group (p = 0.035).The mortality rate in the CVVHDF group was higher than that in the HD group, which may have been because CVVHDF was applied to the more severely ill patients. In contrast, CVVHDF may give a chance of survival to patients with APACHE III scores103 and may be more useful than HD in patients with failure of three or more organs.

Background: C-reactive protein (CRP) is known to have a direct proinflammatory effect in endothelial cells. However, little is known about the effect of CRP in intrinsic renal cells. We investigated the effects of CRP on the nuclear factor-ĸB (NF-ĸB) activation and monocyte chemoattractant protein-1 (MCP-1) gene expression in human mesangial cells and also examined whether intracellular calcium and reactive oxygen species (ROS) were involved in the CRP- induced NF-ĸB activation. Methods: NF-ĸB binding activity and MCP-1 mRNA expression were measured by electrophoretic mobility shift assay and Northern blot analysis, respectively.Intracellular calcium was monitored by confocal microscopy using calcium sensitive dye, Fluo-3 and intracellular ROS production was determined, using 2′,7′-dichlorofluorescin diacetate. Results: CRP increased NF-ĸB binding activity in a dose-dependent manner (12.5–100 µg/ml), which was induced within 1 h after incubation and peaked around 3 h. CRP also increased the MCP-1 mRNA expression via activation of NF-ĸB. Both intracellular calcium and ROS was induced by CRP. Calcium chelator, BAPTA-AM and anti-oxidants such as N-acetylcysteine and tiron suppressed CRP-induced NF-ĸB activation. Conclusion: CRP exerted a proinflammatory effect in human mesangial cells by inducing MCP-1 gene expression via NF-ĸB activation, which was mediated, at least in part, through intracellular calcium and ROS.

Background This study was performed to evaluate the effects of acute systemic inflammation on peritoneal solute transport rate (PSTR) in chronic peritoneal dialysis (CPD) patients. Methods A baseline standard peritoneal equilibration test (PET) was performed on each patient every 6 months, and blood concentration of high-sensitivity C-reactive protein (hs-CRP) was assayed every 2 months in our peritoneal dialysis clinic. Acute systemic inflammation was defined as a greater than 10-fold increase in hs-CRP concentration compared with baseline value, in the absence of peritonitis, and returning to baseline level in 2 months. In patients with acute systemic inflammation, PET and hs-CRP concentration assays were performed during inflammation and after recovery. Ten patients with acute systemic inflammation were enrolled in the inflammation group and 42 other patients served as controls. Results There were no significant changes in hs-CRP and dialysate-to-plasma ratio of creatinine (D/Pcreat) in the control group during the study period. In the inflammation group, median hs-CRP levels at baseline, during acute inflammation, and at recovery were 2.3 mg/L (range 0.3 – 4.5 mg/L), 39.2 mg/L (range 15.1 – 117.4 mg/L), and 3.7 mg/L (range 0.9 – 8.9 mg/L), respectively. Median D/Pcreat increased significantly from baseline (0.64; range 0.55 – 0.98) to time of acute inflammation (0.72; range 0.60 – 0.96) ( p < 0.05). The D/Pcreat at recovery was 0.67 (range 0.52 – 0.94), which decreased significantly from time of acute inflammation ( p < 0.05). There was no correlation between changes in log (hs-CRP) and changes in D/Pcreat. Conclusion We have shown here that acute systemic inflammation is associated with a temporary increase in PSTR in CPD patients.

Despite substantial advances in dialytic techniques and machines, acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with up to 60% in-hospital mortality. But, there is no full detail of definite RRT to overcome the significant morbidity and mortality of AKI. What is most important in the treatment for AKI is that RRT is not a cause-specific therapy but a Life-supportive management. This review discusses the indications of, proper initiation of, and optimal prescription for RRT to improve the survival of the patients with AKI. (Korean J Med 2012;82:17-21)

A new staging system for multiple myeloma (MM) has utilized serum concentrations of beta2-microglobulin (Sbeta2M) and albumin as important prognostic factors for survival. Since Sbeta2M is an indicator of glomerular filtration rate, we compared the prognostic values of Sbeta2M and 24-hr urinary creatinine clearance (Ccr) in patients with MM. We retrospectively reviewed the records of 170 MM patients from January 1996 to November 2003 whose 24-hr urinary Ccr was available at the time of diagnosis. We found that pretreatment Sbeta2M was inversely related to Ccr (Spearman's correlation coefficient=-0.787). In univariate analysis, the hazard ratio (HR) of death was 1.043 (p0.001) for Sbeta2M and 0.985 (p0.001) for Ccr. Multivariate analysis showed that Sbeta2M (HR 1.030, p=0.010) and Ccr (HR 0.993, p=0.059) were significant prognostic factors in patients' survival. In conclusion, 24-hr urinary Ccr may be utilized for staging of patients with MM.

In the new staging system of multiple myeloma (MM) by South West Oncology Group (SWOG), the concentration of serum β2 microglobulin (β2m) and serum albumin were focused as the most important prognostic factors for survival. However, serum concentration of β2m has been known as an indicator of glomerular filtration rate. The aim of this study was to compare the prognostic value of the level of β2m with that of creatinine clearance (Ccr) in patients with multiple myeloma. Retrospectively, from January 1, 1996 to November 30, 2003, we reviewed 176 MM patients (M: F 110:66 mean age: 58.5±11.0) whose 24-hour urinary creatinine clearance was available at the time of diagnosis. We collected clinical data such as hemoglobin, serum creatinine, calcium, albumin, β2m, creatinine clearance before chemotherapies, and patients’ survival time. Pretreatment β2m was inversely related to Ccr (Spearman’s correlation coefficient = −0.781, P We could propose another new staging system with β2m replaced by Ccr in SWOG staging system. The stages were defined as: stage 1, Ccr ≥ 80ml/min; stage 2, 50< Ccr In conclusion, Ccr could be more important prognostic factor than the level of β2m in patients of MM and we propose that Ccr should be reassessed as the component of staging system of MM.