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This study examined the characteristics of biochemical parameters, bone diseases, and vascular calcification in Korean patients with chronic kidney disease (CKD) not yet on dialysis. Serum levels of fibroblast growth factor 23 (FGF23), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D3 (25D), and 1,25-dihydroxyvitamin D3 (1,25D); lumbar spine, total hip, and femur neck bone mineral densities; and brachial-to-ankle pulse wave velocity (baPWV) representing vascular calcification were measured at baseline for 2,238 CKD patients in the KoreaN Cohort Study for Outcomes in Patients With CKD (KNOW-CKD). Increases in serum FGF23 and iPTH preceded changes in serum calcium and phosphate, similar to Western populations. However, the 25D and 1,25D levels decreased earlier than serum FGF23 or iPTH increased, with a decreased estimated glomerular filtration rate (eGFR) in Korean CKD patients. Vitamin D deficiency occurred in 76.7% of patients with CKD stage 1. Bone mineral densities were lowest in CKD stage 5 (lumbar spine, -0.64 ± 1.67; total hip, -0.49 ± 1.21; femur neck, -1.02 ± 1.25). Osteoporosis was more prevalent in patients with higher CKD stages. The mean baPWV, abdominal aortic calcification (AAC), and coronary calcium score also increased, with declined eGFR. In conclusion, a decline in serum vitamin D levels was observed in early CKD stages before significant increases of FGF23 and iPTH in the Korean CKD population compared with that in Western populations. Increased bone disease and vascular calcification occurred in early-stage CKD., Competing Interests: The authors have no potential conflicts of interest to disclose.

Background: Kidney is one of the major target organs in sepsis, while effective prevention of septic acute kidney injury has not yet been established. α-Lipoic acid (LA) has been known to exert beneficial effects against lipopolysaccharide (LPS)-induced damages in various organs such as heart, lung, and liver. We investigated the protective effect of LA on LPS-induced kidney injury., Methods: Two groups of rats were treated with LPS (20 mg/kg, i.p.), one of which being co-treated with LA (50 mg/kg), while the control group was treated with vehicle alone. Human renal proximal tubular epithelial cells (HK-2 cells) were cultured with or without LPS (10 μg/ml) in the presence or absence of LA (100 μg/ml) for 3 h prior to LPS treatment., Results: Serum creatinine level was increased in LPS-treated rats, which was attenuated by LA co-treatment. LPS treatment induced cleaved caspase-3 expression in the kidney, which was counteracted by LA. Terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells increased in the kidneys of LPS-treated rats compared with controls, which was counteracted by LA treatment. Protein expression of inducible nitric oxide synthase and cyclooxygenase-2 detected by immunoblotting and/or immunohistochemical staining, along with mRNA levels of pro-inflammatory cytokines detected by real-time polymerase chain reaction, was increased in the kidney with LPS administration, which was ameliorated with LA treatment. LA also protected LPS-induced tubular dysfunction, preserving type 3 Na(+)/H(+) exchanger and aquaporin 2 expressions in the kidney. Suppression of LPS-induced expression of cleaved caspase-3 by LA was also observed in HK-2 cells. Increased protein expression of phospho-extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinases by LPS treatment was attenuated by LA pretreatment, while p38 was not affected by either LPS or LA treatment. MitoTracker Red demonstrated LA prevented LPS-induced increment of mitochondrial oxidative stress, where concurrent 4',6-diamidino-2-phenylindole staining also revealed marked fragmentation and condensation of nuclei in HK-2 cells treated with LPS, which was prevented by LA., Conclusion: LA treatment attenuates LPS-induced kidney injury, such as renal tubular dysfunction, by suppression of apoptosis, and inflammation.

Potassium plays a key role in normal myocardial function, and current guidelines recommend that serum potassium levels be maintained from 4.0 to 5.0 mEq/L in patients with acute myocardial infarction (AMI). However, the impact of serum potassium levels on long-term mortality has not been evaluated. We retrospectively studied 1,924 patients diagnosed with AMI. The average serum potassium levels measured throughout the hospitalization were obtained and statistically analyzed. Patients were categorized into 5 groups to determine the relation between mean serum potassium and long-term mortality: <3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5 mEq/L. The long-term mortality was lowest in the group of patients with potassium levels of 3.5 to <4.0 mEq/L, whereas mortality was higher in the patients with potassium levels≥4.5 or <3.5 mEq/L. In a multivariate Cox-proportional regression analysis, the mortality risk was greater for serum potassium levels of >4.5 mEq/L (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.04 to 2.81 and HR 4.78, 95% CI 2.14 to 10.69, for patients with potassium levels of 4.5 to <5.0 mEq/L and ≥5.0, respectively) compared with patients with potassium levels of 3.5 to <4.0 mEq/L. The mortality risk was also higher for patients with potassium levels<3.5 mEq/L (HR 1.55, 95% CI 0.94 to 2.56). In contrast to the association with long-term mortality, there was no relation between serum potassium levels and the occurrence of ventricular arrhythmias. The results of the current analysis suggest that there is a need for change in our current concepts of the ideal serum potassium levels in patients with AMI., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The present study aimed to investigate the impact of high-sensitivity C-reactive protein (hs-CRP) and renal dysfunction on clinical outcomes in acute myocardial infarction (AMI) patients., Materials and Methods: The study involved a retrospective cohort of 8332 patients admitted with AMI. The participants were divided into 4 groups according to the levels of estimated glomerular filtration rate (eGFR) and hs-CRP: group I, no renal dysfunction (eGFR ≥60 mL·min(-1)·1.73 m(-2)) with low hs-CRP (≤2.0 mg/dL); group II, no renal dysfunction with high hs-CRP; group III, renal dysfunction with low hs-CRP; and group IV, renal dysfunction with high hs-CRP. We compared major adverse cardiac events (MACE) over a 1-year follow-up period., Results: The 4 groups demonstrated a graded association with increased MACE rates (group I, 8.8%; group II, 13.8%; group III, 18.6%; group IV, 30.1%; p<0.001). In a Cox proportional hazards model, mortality at 12 months increased in groups II, III, and IV compared with group I [hazard ratio (HR) 2.038, 95% confidence interval (CI) 1.450-2.863, p<0.001; HR 3.003, 95% CI 2.269-3.974, p<0.001; HR 5.087, 95% CI 3.755-6.891, p<0.001]., Conclusion: High hs-CRP, especially in association with renal dysfunction, is related to the occurrence of composite MACE, and indicates poor prognosis in AMI patients.

This study aimed to evaluate the effects of percutaneous coronary intervention (PCI) on short- and long-term major adverse cardiac events (MACE) in elderly (>75 yr old) acute myocardial infarction (AMI) patients with renal dysfunction. As part of Korea AMI Registry (KAMIR), elderly patients with AMI and renal dysfunction (GFR<60 mL/min) received either medical (n=439) or PCI (n=1,019) therapy. Primary end point was in-hospital death. Secondary end point was MACE during a 1 month and 1 yr follow-up. PCI group showed a significantly lower incidence of in-hospital death (20.0% vs 14.3%, P=0.006). Short-term and long-term MACE rates were higher in medical therapy group (31.9% vs 19.0%; 57.7% vs 31.3%, P<0.001), and this difference was mainly attributed to cardiac death (29.3% vs 17.6%; 51.9% vs 25.0%, P<0.001). MACE-free survival time after adjustment was also higher in PCI group on short-term (hazard ratio, 0.67; confidence interval, 0.45-0.98; P=0.037) and long-term follow-up (hazard ratio, 0.61, confidence interval, 0.45-0.83; P=0.002). In elderly AMI patients with renal dysfunction, PCI therapy yields favorable in-hospital and short-term and long-term MACE-free survival.

We report a case of Serratia marcescens peritonitis in a 45-year-old man with insulin-dependent diabetes mellitus undergoing continuous ambulatory peritoneal dialysis (CAPD). The patient presented with abdominal pain and cloudy dialysate. Empiric antibiotic therapy was initiated intraperitoneally with cefazolin and ceftazidime for 5 days. Cultures of the dialysate revealed S. marcescens, and the treatment was subsequently changed to gentamicin and ceftazidime. Oral ciprofloxacin was also added. The patient's abdominal pain and the dialysate white blood cell (WBC) count, however, did not improve. The indwelling CAPD catheter was therefore removed. This is an unusual case report in the Korean literature of S. marcescens peritonitis in a patient receiving CAPD.

Platelet dysfunction and associated hemorrhagic complications are often encountered in patients with chronic kidney disease. This study aimed to evaluate the prevalence and associations for abnormal bleeding time (BT) in patients with renal dysfunction. Hemoglobin, hematocrit, platelet, blood urea nitrogen, creatinine, and parathyroid hormone levels were determined in 1716 patients (55.18 ± 17.19 years, men 50.8%). For these patients, BTs were estimated using a platelet function analyzer-100. Glomerular filtration rates (GFRs) were estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. The study population was divided into six groups according to the estimated GFR (eGRF): group I, eGFR ≥ 90 ml/min/1.73 m(2); group II, 60 ≤ eGFR < 90 ml/min/1.73 m(2); group III, 30 ≤ eGFR < 60 ml/min/1.73 m(2); group IV, 15 ≤ eGFR < 30 ml/min/1.73 m(2); group V, eGFR < 15 ml/min/1.73 m(2); and group VI, undergoing regular hemodialysis. Renal insufficiency was defined as eGFR < 60 ml/min/1.73 m(2). To further investigate the role of inflammatory cytokines, nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) were measured in a 327-patient subset of the total patient population (52.82 ± 18.3 years, men 60.9%). Abnormal BT occurred in 11.8% of group I, 15.3% of group II, 29.1% of group III, 37.5% of group IV, 35.0% of group V, and 32.1% of group VI. By Pearson correlation coefficient, eGFR (r = -0.089), hemoglobin (r = -0.127), platelet (r = -0.054) were correlated with BT. Multivariate analysis revealed that age [odds ratio (OR), 1.013; 95% CI, 1.004-1.022], renal insufficiency (eGFR < 60 ml/min/1.73 m(2); OR, 2.271; 95% CI, 1.672-3.083), anemia (hemoglobin < 120 g/l; OR, 1.486; 95% CI, 1.089-2.027), and thrombocytopenia (platelet < 150 × 10(9)/l; OR, 1.445; 95% CI, 1.089-1.918) were independently associated with prolonged BT. Plasma levels of NO and TNF-α were increased in patients with renal insufficiency (eGFR < 60 ml/min/1.73 m(2)). Plasma levels of NO in renal insufficiency group were higher in prolonged BT than those in normal BT. A significant positive correlation was noted between BTs and NO levels (r = 0.152, p = 0.009) but not with TNF-α levels. The prevalence of abnormal BTs was higher as eGFR declined. Old age, renal insufficiency, anemia, and thrombocytopenia were independent associations for abnormal BT.

The present study investigated the changes that occurred in the mammalian target of rapamycin (mTOR) signaling pathway in the kidney as a result of deoxycorticosterone acetate (DOCA)-salt hypertension. Rats were implanted with DOCA strips (200 mg/kg) 1 week after unilateral nephrectomy and were then supplied with 0.9% saline to drink. Four weeks after DOCA implantation, systolic blood pressure (SBP) was measured by use of the tail-cuff method. The expression levels of phosphorylated phosphatidylinositol-3-kinase (PI3K), Akt, and mTOR, as well as the protein expression levels of ED-1 and cyclooxygenase-2 (COX-2), transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (SMA), caspase-3, Bax, and Bcl-2, were then examined in the kidney by semiquantitative immunoblotting. DOCA-salt hypertensive rats were found to have significantly increased SBP as well as an increased kidney weight-to-body weight ratio. Moreover, the phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of DOCA-salt hypertensive rats compared with the control, as was the protein expression of ED-1, COX-2, TGF-β1, and α-SMA. The expression levels of caspase-3 and Bax were increased significantly, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the kidney of DOCA-salt hypertensive rats.

Background: Sjögren's syndrome is a systemic autoimmune disease in which lymphatic cells destroy the salivary and lacrimal glands. Glomerulonephritis is thought to be a rare occurrence in primary Sjögren's syndrome. Furthermore, concurrent glomerular involvement and lymphoma in patients with Sjögren's syndrome has seldom been reported., Case Presentation: A 52-year-old woman with primary Sjögren's syndrome developed membranous glomerulonephritis and Epstein-Barr virus-positive diffuse large B-cell lymphoma (DLBCL). She was diagnosed with Sjögren's syndrome based on the dry eyes, dry mouth, positive anti-nuclear antibody test, anti-Ro (SS-A) antibody, salivary gland biopsy, and salivary scintigraphy. Moreover, renal biopsy confirmed the diagnosis of membranous glomerulonephritis. Three months later, her small bowel was perforated with pneumoperitoneum, and the biopsy revealed Epstein-Barr virus-positive DLBCL., Conclusions: We observed the first case of primary Sjögren's syndrome associated with Epstein-Barr Virus-positive DLBCL and membranous glomerulonephritis. Because of the possibility of malignancy-associated membranous glomerulonephritis in patients with primary Sjögren's syndrome, we should be careful and examine such patients for hidden malignancy.

Aim: Renal dysfunction has been associated with many types of neuropathy and the incidence of myocardial infarction (MI) presenting without chest pain can be expected to be higher in patients with renal dysfunction. We evaluated clinical outcomes of painless MI patients and relationship between renal dysfunction and painless MI., Methods and Results: Study population consisted of 9,735 patients (63 ± 13 years, men 70.7 %), whose discharge diagnosis by cardiac enzyme and electrocardiogram was MI. The study subjects were divided into two groups according to presence of chest pain (painful MI group, n = 8,249; painless MI group, n = 1486). Rates of in-hospital death, 1-month and 12-month composite MACE, cardiac death, and non-cardiac death were significantly higher in painless MI patients. In a multivariate logistic analysis, compared with glomerular filtration rate (GFR) > 90 mL/min/1.73 m(2), odds ratio of painless MI was increased proportionally in patients with GFR of 30-59, 15-29 and <15 mL/min/1.73 m(2) (odds ratio [OR] 1.25, 95 % confidence interval [CI] 1.05-1.49; OR 1.88, CI 1.39-2.53; OR 2.32, CI 1.65-3.26) In addition, the concomitant presence of renal dysfunction and diabetes mellitus significantly affected the prevalence of painless MI., Conclusion: Poorer outcomes of painless MI patients and the increased probability of painless MI proportional to declining GFR indicate that the possibility of painless MI should be considered in patients with renal dysfunction, particularly concomitant with diabetes mellitus.

Background: The presence of chronic kidney disease is an independent prognostic factor in patients with myocardial infarction (MI). We compared the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation and the Modification of Diet in Renal Disease (MDRD) study equation with regard to prognostic value in patients with MI., Methods: This study analyzed a retrospective cohort of 11 050 consecutive patients who had MI and were enrolled in the Korea Acute Myocardial Infarction Registry from November 2005 to August 2008. We applied the CKD-EPI equation and the MDRD study equation to determine the estimated glomerular filtration rate (eGFR) in a cohort of patients with MI., Results: The mean eGFR(CKD-EPI) was slightly higher than that of eGFR(MDRD) (73.16 versus 72.23 mL/min/1.73 m(2); P < 0.001). The prevalence of eGFR(CKD-EPI) <60 mL/min/1.73 m(2) was 26.9%, whereas that of eGFR(MDRD) was 28.5%. The area under the receiver operating characteristic curve was significantly larger for predicting the 1-year major adverse cardiovascular event (MACE) and 1-year all-cause mortality with CKD-EPI equation (0.648 versus 0.641, 0.768 versus 0.753, respectively; P < 0.001). The net reclassification index for improvement in risk of 1-year MACE and 1-year all-cause mortality were 4.09% (P< 0.001) and 9.25% (P< 0.001), respectively., Conclusions: The application of the eGFR(CKD-EPI) demonstrated better predictive values for clinical outcomes than eGFR(MDRD) in a cohort of patients with MI.

Background: The clinical outcomes of ST-segment elevation myocardial infarction (STEMI) are poor in patients with renal insufficiency. This study investigated changes in the likelihood that patients received optimal medical care throughout the entire process of myocardial infarction management, on the basis of their glomerular filtration rate (GFR)., Methods: This study analyzed 7,679 patients (age, 63 ± 13 years; men 73.6%) who had STEMI and were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) from November 2005 to August 2008. The study subjects were divided into 5 groups corresponding to strata used to define chronic kidney disease stages., Results: Patients with lower GFR were less likely to present with typical chest pain. The average symptom-to-door time, door-to-balloon time, and symptom-to-balloon time were longer with lower GFR than higher GFR. Primary reperfusion therapy was performed less frequently and the results of reperfusion therapy were poorer in patients with renal insufficiency; these patients were less likely to receive adjunctive medical treatment, such as treatment with aspirin, clopidogrel, β-blocker, angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB), or statin, during hospitalization and at discharge. Patients who received less intense medical therapy had worse clinical outcomes than those who received more intense medical therapy., Conclusions: Patients with STEMI and renal insufficiency had less chance of receiving optimal medical care throughout the entire process of MI management, which may contribute to worse outcomes in these patients.

Background: Despite strong evidence linking decreased glomerular filtration rate (GFR) to worse outcomes, the impact of GFR on mortality and morbidity in patients with acute myocardial infarction (AMI) is not well defined., Study Design: Retrospective cohort study., Setting & Participants: 12,636 patients with AMI in the Korea AMI Registry database from November 2005 to July 2008. 93% of patients in this registry had coronary angiography, and 91% of patients with coronary angiography had percutaneous coronary intervention (PCI)., Predictor: GFR was estimated (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and patients were grouped into 5 eGFR categories: >90, 60-89, 30-59, 15-29, and <15 mL/min/1.73 m(2)., Outcomes: Primary end points were death and in-hospital complications. Secondary end points were major adverse cardiac events (MACEs) during a 1-month (short-term) and 1-year (long-term) follow-up after AMI., Results: Mean eGFR was 72.8 ± 24.6 mL/min/1.73 m(2), mean age was 64 ± 13 years, and 70.4% were men. A graded association was observed between eGFR and clinical outcomes. In adjusted analyses, compared with eGFR >90 mL/min/1.73 m(2), patients with eGFR of 30-59, 15-29, and <15 mL/min/1.73 m(2) experienced increased risks of short- (respective HRs of 2.30 [95% CI, 1.70-3.11], 3.10 [95% CI, 2.14-4.14], and 3.64 [95% CI, 2.44-5.43]; P < 0.001) and long-term MACEs (HRs of 1.58 [95% CI, 1.32-1.90], 2.12 [95% CI, 1.63-2.75], and 2.50 [95% CI, 1.89-3.29]; P < 0.001). Older age, Killip class higher than I, PCI, and high-sensitivity C-reactive protein level also were associated with higher short- and long-term MACEs. Use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and statins was associated with decreased risk of MACEs., Limitations: Single assessment of serum creatinine., Conclusion: eGFR was associated independently with mortality and complications after AMI. PCI, β-blocker, ACE inhibitor or ARB, and statin use were associated with decreased risks of short- and long-term MACEs., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

A 52-year-old man undergoing continuous ambulatory peritoneal dialysis presented with two consecutive episodes of peritonitis caused by unusual organisms, namely, Brevibacterium and Pantoea agglomerans. The patient was successfully treated with a 2-week course of cefazolin and ceftazidime for the Brevibacterium-associated peritonitis, and a 3-week course of gentamicin for the P. agglomerans-associated peritonitis. Although these environmental organisms are rarely responsible for human infection, the number of reported cases of human infection by these unusual organisms has increased. This report emphasizes the potential for infection by environmental organisms in patients undergoing peritoneal dialysis.

The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduce major adverse cardiac events (MACE) and mortality in patients with acute coronary syndrome. We investigated the effectiveness of statin therapy in reducing MACE in patients with acute myocardial infarction (AMI) and renal dysfunction (RD). In the present retrospective study of 12,853 patients with AMI, the patients were categorized into 4 groups: group I, statin therapy and no RD (estimated glomerular filtration rate ≥60 ml/min/1.73 m(2)); group II, neither statin therapy nor RD; group III, statin therapy and RD; group IV, no statin therapy but RD. The primary end points were death and complications during the hospital course. The secondary end points were MACE during 1 year of follow-up after AMI. Significant differences in the composite MACE during 12 months of follow-up were observed among the 4 groups (group I, 11.7%; group II, 19.0%; group III, 26.7%; and group IV, 45.5%; p <0.001). In a Cox proportional hazards model, mortality at 12 months increased stepwise from group II to IV compared to group I. Moreover, MACE-free survival in the severe RD group (estimated glomerular filtration rate <30 mL/min/1.73 m(2)) was also greater in the statin-treated group. In conclusion, statin therapy reduced MACE at 1 year of follow-up in patients with AMI regardless of RD., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The present study was performed to examine whether paricalcitol may prevent the cisplatin-induced kidney injury. Furthermore, potential molecular mechanisms underlying the protective effect of paricalcitol were explored. Male Sprague-Dawley rats were treated with vehicle (n=12), cisplatin (n=12, 6 mg/kg/day, i.p.), or cisplatin+paricalcitol (n=12, 0.2 μg/kg/day, s.c.) for 4 days. In another series of experiment, HK-2 cells were treated with cisplatin (50 μM), with or without paricalcitol (0.2 ng/ml). Paricalcitol counteracted the cisplatin-induced decline in renal function. Paricalcitol also suppressed the expression of TGF-β1, Smad signaling, and the subsequent epithelial-to-mesenchymal process in cisplatin-treated rats. The expression of P-p53 and p21 was increased in cisplatin-induced nephropathy. These changes were completely prevented or significantly attenuated with paricalcitol co-treatment. The expression of p27(kip1) was increased in cisplatin-treated rats, which was, however, further augmented by the paricalcitol co-treatment. In HK-2 cells, cisplatin increased the expression of p-ERK1/2 and P-p38. Cisplatin also increased the expression of fibronectin and CTGF. Cisplatin increased the expression of pro-apoptotic markers. The expression of CDK2 and Cyclin E as well as that of PCNA was increased. These changes were completely prevented or significantly attenuated by the paricalcitol pretreatment. In contrast, cisplatin increased the expression of p27(kip1), which was further augmented by the paricalcitol-pretreatment. These results suggest that paricalcitol may ameliorate cisplatin-induced renal injury by suppressing the fibrotic, apoptotic and proliferative factors. Its underlying mechanisms may include inhibition of TGF-β1, mitogen-activated protein kinase signaling, p53-induced apoptosis, and augmentation of p27(kip1)., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The role of the kidney in combating metabolic acidosis has been a subject of considerable interest for many years. The present study was aimed to determine whether there is an altered regulation of renal acid base transporters in acute and chronic acid loading. Male Sprague-Dawley rats were used. Metabolic acidosis was induced by administration of NH(4)Cl for 2 days (acute) and for 7days (chronic). The serum and urinary pH and bicarbonate were measured. The protein expression of renal acid base transporters [type 3 Na(+)/H(+) exchanger (NHE3), type 1 Na(+)/HCO(3) (-) cotransporter (NBC1), Na-K(+) ATPase, H(+)-ATPase, anion exchanger-1 (AE-1)] was measured by semiquantitative immunoblotting. Serum bicarbonate and pH were decreased in acute acid loading rats compared with controls. Accordingly, urinary pH decreased. The protein expression of NHE3, H(+)-ATPase, AE-1 and NBC1 was not changed. In chronic acid loading rats, serum bicarbonate and pH were not changed, while urinary pH was decreased compared with controls. The protein expression of NHE3, H(+)-ATPase was increased in the renal cortex of chronic acid loading rats. These results suggest that unaltered expression of acid transporters combined with acute acid loading may contribute to the development of acidosis. The subsequent increased expression of NHE3, H(+)-ATPase in the kidney may play a role in promoting acid excretion in the later stage of acid loading, which counteract the development of metabolic acidosis.

We report an unusual case of probable Creutzfeldt-Jakob disease (CJD) in hemodialysis patient. A woman 59 years of age with a past history of hypertension and end-stage renal disease presented with a stuporous state preceded by rapidly progressive cognitive dysfunction, myoclonus, and akinetic mutism. At first, the cause of the altered mental status was assumed to be uremic or hypertensive encephalopathy combined with fever. Proper managements, however, did not improve the neurologic symptoms. Diffusion-weighted magnetic resonance imaging revealed bilaterally asymmetric high signal intensity in both basal ganglia and cerebral cortices. Electroencephalography showed diffuse generalized theta-to-delta range slow wave and intermittent medium-to-high voltage complexes with a characteristic triphasic pattern on both hemispheres. Cerebrospinal fluid assay for the 14-3-3 protein was positive and diagnostic of CJD.

Cisplatin is a chemotherapeutic agent used for treating solid tumors. However, nephrotoxicity is the dose-limiting factor in its clinical use. The present study was aimed to determine whether altered regulation of the local nitric oxide (NO) and natriuretic peptide (NP) systems is involved in the pathogenesis of cisplatin-induced nephropathy. Cisplatin (6 mg/kg) was injected intraperitoneally into male Sprague-Dawley rats. The control group was not treated with cisplatin. Expression levels of nitric oxide synthase (NOS), nitrotyrosine, soluble guanylyl cyclase and neutral endopeptidase (NEP) in the kidneys were determined 4 days after treatment by semiquantitative immunoblotting. mRNA expression of NPs and natriuretic peptide receptors (NPRs) was determined by real-time polymerase chain reaction. The activities of soluble and particulate guanylyl cyclase were determined by measuring the amount of cyclic 3',5'-guanosine monophosphate (cGMP) generated in responses to sodium nitroprusside and atrial natriuretic peptide (ANP), respectively. In the test rats, creatinine clearance was decreased, while sodium and water excretion were increased. The expression of inducible NOS (iNOS) and nitrotyrosine was increased in the cortex/outer stripe of outer medullar and inner medullar, while that of endothelial and neuronal NOS was decreased in the inner medullar. Excretion of NO metabolites was increased in these rats. The catalytic activity of soluble guanyly cyclase was blunted in the papilla after cisplatin was administered. The mRNA expression of ANP, brain natriuretic peptide, and C-type natriuretic peptide was increased, while that of NPR-A and NPR-C were decreased in the test rats. The catalytic activity of soluble and particulate guanylyl cyclase in the papilla was blunted after cisplatin was administered. In conclusion, increased production of NO by iNOS may contribute to cytotoxic injury, resulting in cisplatin-induced nephropathy, while the up-regulation of renal natriuretic peptide synthesis together with the down-regulation of NEP and NPR-C may contribute to the natriuresis and diuresis seen in cisplatin-induced nephropathy., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background:  The question as to whether triple antiplatelet therapy is superior to dual antiplatelet therapy for patients with acute myocardial infarction (AMI) and renal dysfunction, who undergo percutaneous coronary intervention (PCI), is unresolved., Methods and Results:  As part of the Korea Acute Myocardial Infarction Registry (KAMIR), 2,288 AMI patients with renal dysfunction (glomerular filtration rate <60ml/min·1.73m(2)) received either dual (aspirin plus clopidogrel; n=1,587) or triple (aspirin plus clopidogrel and cilostazol; n=701) antiplatelet therapy. Major adverse cardiac events (MACE) at 1 month and 1 year were compared between these 2 groups. On comparison with the dual therapy group, the triple therapy group had a similar incidence of major bleeding events but a significantly lower incidence of in-hospital mortality. The MACE rate at 1 month was significantly higher for the dual therapy group than for the triple therapy group (16.3% vs. 11.1%, P<0.05), and this difference was mainly attributed to death rather than repeat PCI (12.9% vs. 9.1%, P<0.05). The MACE rate at 1 year and the MACE-free survival time, however, did not differ between the groups., Conclusions:  In AMI patients with renal dysfunction, triple antiplatelet therapy has a favorable in-hospital and short-term MACE impact, but it does not have an impact on the 1-year MACE-free survival.

Background/aims: Sildenafil, the first selective phosphodiesterase-5 (PDE5) inhibitor to be widely used for treating erectile dysfunction, has been investigated with regard to its cardioand renoprotective effects in animal models. This study further investigated the renoprotective effects of sildenafil and their molecular mechanisms in deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rats., Methods: DOCA strips (200 mg/kg) were implanted in rats 1 week after unilateral nephrectomy. These rats were fed on a control diet, with or without sildenafil (50 mg·kg(-1)day(-1)), for 2 weeks. Systolic blood pressure (SBP) was measured by the tail cuff method, and the urinary albumin-to-creatinine ratio (ACR) was calculated. The extent of glomerulosclerosis and tubulointerstitial fibrosis was determined by Masson's trichrome stain. Renal expression of ED-1, transforming growth factor-β1 (TGF-β1), Bax, and Bcl-2 were determined by semiquantitative immunoblotting, polymerase chain reaction (PCR), and immunohistochemistry. TUNEL staining was used for detecting apoptotic cells., Results: The increased SBP in DSH rats was not attenuated by sildenafil treatment. The decreased creatinine clearance and increased ACR in DSH rats, compared with control animals, were attenuated by sildenafil treatment. Further, sildenafil treatment attenuated glomerulosclerosis and tubulointerstitial fibrosis in DSH rats and counteracted the increased expression of ED-1, TGF-β1, and Bax and the decreased expression of Bcl-2 in the kidneys of these rats. The increase in the number of apoptotic cells in DSH rats was attenuated by sildenafil treatment., Conclusion: Sildenafil effectively prevented the progression of renal injury in DSH rats via its anti-inflammatory, antifibrotic, and antiapoptotic effects., (Copyright © 2012 S. Karger AG, Basel.)

Fabry disease is a rare X-linked recessive glycosphingolipid storage disease that is caused by a deficiency of the lysosomal α-galactosidase A (GLA) enzyme, encoded by the GLA gene. This deficiency leads to the accumulation of glycosphingolipids throughout the body, which, in turn, causes multisystem diseases associated with renal, cardiovascular, and cerebrovascular complications. Recent molecular studies of GLA have demonstrated the existence of atypical variants in Fabry disease, suggesting significant genotype-phenotype correlations. In this study, we describe a renal variant of Fabry disease caused by a novel small insertion mutation in the GLA gene.

Background: Diabetes mellitus and renal dysfunction are prognostic factors after acute myocardial infarction (AMI). However, few studies have assessed the effects of renal insufficiency in association with diabetes in the context of AMI. Here, we investigated the clinical outcomes according to the concomitance of renal dysfunction and diabetes mellitus in patients with AMI., Methods: From November 2005 to August 2008, 9905 patients (63 ± 13 years; 70% men) with AMI were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR) and were categorized into 4 groups: Group I (n = 5700) had neither diabetes nor renal insufficiency (glomerular filtration rate [GFR] ≥ 60 ml/min/1.73 m2), Group II (n = 1730) had diabetes but no renal insufficiency, Group III (n = 1431) had no diabetes but renal insufficiency, and Group IV (n = 1044) had both diabetes and renal insufficiency. The primary endpoints were major adverse cardiac events (MACE), including a composite of all cause-of-death, myocardial infarction, target lesion revascularization, and coronary artery bypass graft after 1-year clinical follow-up., Results: Primary endpoints occurred in 1804 (18.2%) patients. There were significant differences in composite MACE among the 4 groups (Group I, 12.5%; Group II, 15.7%; Group III, 30.5%; Group IV, 36.5%; p < 0.001). In a Cox proportional hazards model, after adjusting for multiple covariates, the 1-year mortality increased stepwise from Group III to IV as compared with Group I (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.34-2.86; p = 0.001; and HR, 2.42; 95% CI, 1.62-3.62; p < 0.001, respectively). However, Kaplan-Meier analysis showed no significant difference in probability of death at 1 year between Group III and IV (p = 0.288)., Conclusions: Renal insufficiency, especially in association with diabetes, is associated with the occurrence of composite MACE and indicates poor prognosis in patients with AMI. Categorization of patients with diabetes and/or renal insufficiency provides valuable information for early-risk stratification of AMI patients., (© 2011 Kim et al; licensee BioMed Central Ltd.)

Purpose: This study aimed to compare the incidence and clinical significance of transient versus persistent acute kidney injury (AKI) on acute ST elevation myocardial infarction (STEMI)., Materials and Methods: The study was a retrospective cohort of 855 patients with STEMI. AKI was defined as an increase of ≥0.3 mg/dL in creatinine level at any point during hospital stay. The study population was classified into 5 groups: 1) patients without AKI; 2) patients with mild AKI that was resolved by discharge (creatinine change less than 0.5mg/dL compared with admission creatinine during hospital stay, transient mild AKI); 3) patients with mild AKI that did not resolve by discharge (persistent mild AKI); 4) patients with moderate/severe AKI that was resolved by discharge (creatinine change more than 0.5 mg/dL compared with admission creatinine, transient moderate/severe AKI); 5) patients with moderate/ severe AKI that did not resolve by discharge (persistent moderate/severe AKI). We investigated 1-year all-cause mortality after hospital discharge for the primary outcome of the study. The relation between AKI and 1-year mortality after STEMI was analyzed., Results: AKI occurred in 74 (8.7%) patients during hospital stay. Adjusted hazard ratio for mortality was 3.139 (95% CI 0.764 to 12.897, p=0.113) in patients with transient, mild AKI, and 8.885 (95% CI 2.710 to 29.128, p<0.001) in patients with transient, moderate/severe AKI compared to patients without AKI. Persistent moderate/severe AKI was also independent predictor of 1 year mortality (hazard ratio, 5.885; 95% CI 1.079 to 32.101, p=0.041)., Conclusion: Transient and persistent moderate/severe AKI during acute myocardial infarction is strongly related to 1-year all cause mortality after STEMI.

Background: Patients with chronic kidney disease have had conflicting results between drug-eluting stents (DES) and bare-metal stents (BMS). The aim of the present study was to determine whether DES is preferable for the treatment of acute myocardial infarction (AMI) with renal insufficiency, and to elucidate the impact of diabetes mellitus (DM) on outcomes of each stent., Methods and Results: As a part of the Korea Acute Myocardial Infarction Registry (KAMIR), 2,175 AMI patients with renal insufficiency (glomerular filtration rate <60ml/min) comprising 208 patients with BMS and 1,967 DES implantation were selected. Primary outcome was major adverse cardiac event (MACE), defined as a composite of mortality, nonfatal myocardial infarction, and target lesion revascularization. In the overall population, the MACE rate at 1 year was significantly higher in the BMS group than that of DES (44% vs. 26%, P<0.05), which was mainly due to death rather than repeat intervention (44% vs. 26%, P<0.05). In the diabetic group with DES implantation, the MACE rate was higher compared with the DES group without DM, mainly due to repeat intervention (5% vs. 8%, P<0.05)., Conclusions: In AMI patients with renal insufficiency, DES implantation exhibits a favorable 1-year clinical outcome than BMS implantation, and subgroup analysis for diabetic subjects showed worse outcomes in the DM group with implanted DES.

Background/aims: Many patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin., Methods: The clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus., Results: Forty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders (1.46 ± 0.02) than in the oral responders (1.36 ± 0.03, p < 0.01) and in non-responders (n = 141, 1.37 ± 0.01, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR., Conclusions: A considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine-AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.