Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients

Background@#Anti-heparin/platelet factor 4 (PF4) antibodies may trigger severe thrombotic complications in hemodialysis (HD) patients. Tetrameric PF4 has a high affinity for extracellular DNA, which is a key component of neutrophil extracellular traps (NETs); therefore, the interactions between anti-heparin/PF4 antibodies and NETs can contribute to prothrombotic events. This prospective observational study included both incident and maintenance HD (MHD) patients. @*Methods@#Anti-heparin/PF4 antibody levels were measured by enzyme-linked immunosorbent assay; an optical density > 1.8 was regarded as clinically significant. In incident HD patients, we additionally measured serum nucleosome levels as representative markers of NETs, and the contributions of anti-heparin/PF4 and increased serum nucleosome levels to the primary functional patency loss of vascular access was assessed. @*Results@#The frequency of anti-heparin/PF4 antibodies was significantly higher in incident HD patients compared to MHD patients (23.6% vs. 7.7%). Serum nucleosome levels, as well as the white blood cell counts, neutrophil counts, and high-sensitivity C-reactive protein levels, were significantly higher in anti-heparin/PF4 antibody-positive patients compared to the control. Platelet counts tended to be lower in the patients with anti-heparin/PF4 of >1.8 than in the controls. Relative risk calculations showed that the presence of anti-heparin/PF4 antibodies increased the risk of primary functional patency failure by 4.28-fold, and this risk increased further with higher nucleosome levels. Furthermore, in the anti-heparin/PF4 antibody-positive group, the time to first vascular intervention was much shorter, and the risk of repeated intervention was higher, compared to the controls. @*Conclusion@#In incident HD patients, the presence of anti-heparin/PF4 antibodies was associated with increased NET formation; this could be a strong predictor of vascular access complications.

Outcomes of vascular access in hemodialysis patients: Analysis based on the Korean National Health Insurance Database from 2008 to 2016

BACKGROUND: Controversies exist whether arteriovenous fistula (AVF) placement is preferred over arteriovenous graft (AVG) for elderly patients. Current guidelines did not offer specific recommendations. Thus, this study was conducted to analyze the all-cause mortality and primary patency associated with various vascular access (VA) types according to age group. METHODS: This retrospective observational study investigated the Korean insurance claims data of chronic kidney disease patients who began hemodialysis between January 2008 and December 2016. We investigated all-cause mortality associated with initial VA in incident hemodialysis patients and primary patency between AVF and AVG according to age group. RESULTS: The proportion of patients with a tunneled dialysis catheter (TDC) that was first placed for VA increased from 18.4% in 2008 to 52.3% in 2016. Incident hemodialysis patients with a TDC or AVG for the initial VA had significantly higher mortality risk than patients with an AVF, except for patients over 85 years, who showed no significant difference in all-cause mortality regardless of VA type. In the patency analysis on initial AV access, AVG had significantly poorer primary patency than AVF in all age groups. CONCLUSION: AVF had better patency than AVG in all age groups; however, the benefit of AVF attenuated in the older age groups. The mortality rate between AVF and AVG was not significantly different in patients over 85 years. Therefore, a “patient-first” approach should be emphasized over a “fistula-first” approach in AV access creation for incident hemodialysis patients older than 85 years.

Serum alkaline phosphatase and γ-glutamyl transferase in acute pyelonephritis

BACKGROUND: Elevated serum alkaline phosphatase (AP) and γ-glutamyl transferase (γ-GT) are commonly observed in patients with acute pyelonephritis. The goal of this study was to examine the clinical significance of elevated serum AP and γ-GT levels and to explore the mechanisms underlying these changes. METHODS: We examined serum AP and γ-GT levels in 438 patients with acute pyelonephritis. Urine AP/creatinine (Cr), urine γ-GT/Cr, fractional excretion of AP, and fractional excretion of γ-GT (FE(γ-GT)) were evaluated in patients with elevated and normal serum levels. AP isoenzymes were also examined. RESULTS: We identified 77 patients (17.6%) with elevated serum AP and 134 patients (30.6%) with elevated serum γ-GT. Among them, both enzymes were elevated in 64 patients (14.6%). Older age, longer hospital stay, elevated baseline serum Cr, and complicated pyelonephritis were associated with increases in serum AP and γ-GT. Multivariate analysis showed that high serum AP levels were significantly correlated with renal impairment (odds ratio, 2.13; 95% confidence interval, 1.08–4.19; P = 0.029). FE(γ-GT) was significantly lower in patients with elevated serum enzyme levels. The liver fraction for AP isoenzyme profile did not increase in patients with elevated serum AP. CONCLUSION: Our results demonstrated that elevated serum AP and γ-GT levels are associated with complicated pyelonephritis and renal impairment. Lower FE(γ-GT) levels in patients with elevated serum enzymes may be the result of decreased urinary excretion of these enzymes.

Impact of sarcopenia on long-term mortality and cardiovascular events in patients undergoing hemodialysis

BACKGROUND/AIMS@#A high body mass index (BMI) is known to correlate with better survival in patients on hemodialysis (HD). However, the impacts of body composition and sarcopenia on survival have not been well studied in this population.@*METHODS@#One hundred and forty-two prevalent HD patients were recruited and followed prospectively for up to 4.5 years. Low muscle mass (measured using a portable, whole-body, bioimpedance spectroscopic device) was defined as a lean tissue index (LTI) two standard deviations (SD) or more below the normal gender-specific mean for young people. Low muscle strength was a handgrip strength (HGS) of less than 30 kg in males and less than 20 kg in females. Sarcopenia was considered present when both LTI and HGS were reduced.@*RESULTS@#The mean age was 59.8 ± 13.1 years; 57.0% were male and 47.2% had diabetes. Forty-seven patients (33.1%) had sarcopenia. During follow-up, 28 patients (19.7%) died, and low LTI (adjusted hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.10 to 6.97) and low HGS (HR 5.65; 95% CI, 1.99 to 16.04) were independently associated with mortality. Sarcopenia was a significant predictor for death (HR, 6.99; 95% CI, 1.84 to 26.58; p = 0.004) and cardiovascular events (HR, 4.33; 95% CI, 1.51 to 12.43; p = 0.006).@*CONCLUSIONS@#Sarcopenia was strongly associated with long-term mortality and cardiovascular events in HD patients. Assessment of muscle strength and muscle mass may provide additional prognostic information to survival in patients with end-stage renal disease.

Current treatment status and medical costs for hemodialysis vascular access based on analysis of the Korean Health Insurance Database

BACKGROUND/AIMS: The Republic of Korea is a country where the hemodialysis population is growing rapidly. It is believed that the numbers of treatments related to vascular access-related complications are also increasing. This study investigated the current status of treatment and medical expenses for vascular access in Korean patients on hemodialysis. METHODS: This was a descriptive observational study. We inspected the insurance claims of patients with chronic kidney disease who underwent hemodialysis between January 2008 and December 2016. We calculated descriptive statistics of the frequencies and medical expenses of procedures for vascular access. RESULTS: The national medical expenses for access-related treatment were 7.12 billion KRW (equivalent to 6.36 million USD) in 2008, and these expenses increased to 42.12 billion KRW (equivalent to 37.67 million USD) in 2016. The population of hemodialysis patients, the annual frequency of access-related procedures, and the total medical cost for access-related procedures increased by 1.6-, 2.6-, and 5.9-fold, respectively, over the past 9 years. The frequency and costs of access care increased as the number of patients on hemodialysis increased. The increase in vascular access-related costs has largely been driven by increased numbers of percutaneous angioplasty. CONCLUSIONS: The increasing proportion of medical costs for percutaneous angioplasty represents a challenge in the management of end-stage renal disease in Korea. It is essential to identify the clinical and physiological aspects as well as anatomical abnormalities before planning angioplasty. A timely surgical correction could be a viable option to control the rapid growth of access-related medical expenses.

Long-term prognosis of end-stage renal disease patients with normal myocardial perfusion as determined by single photon emission computed tomography

BACKGROUND/AIMS@#Normal myocardial perfusion is closely associated with very low rates of cardiac events and better long-term outcomes; however, little is known about its prognostic value in patients with end-stage renal disease (ESRD).@*METHODS@#A total of 286 incident patients underwent baseline cardiac evaluations using echocardiography and stress-rest single-photon emission computed tomography. Perfusion scans for 177 patients (61.9%) who had a summed stress score (SSS) < 4 were normal.@*RESULTS@#During the 4-year follow-up period, 79 cardiac events occurred. Patients with a SSS < 4 had significantly lower annual rates of cardiac events than did those with a SSS ≥ 4 (6.4% vs. 13.2%; hazard ratio, 0.54; 95% confidence interval, 0.31 to 0.94). Among patients with a SSS < 4, however, cardiac event rates significantly differed according to the presence of comorbid conditions such as old age, diabetes, history of coronary artery disease, and elevated C-reactive protein levels. In addition, the presence of left ventricular (LV) systolic dysfunction and LV hypertrophy at the start of hemodialysis strongly influenced future cardiac events.@*CONCLUSIONS@#In patients with ESRD, normal perfusion scans usually indicate a significantly low risk of adverse cardiac events. However, even in patients with normal perfusion scans, the cardiovascular prognosis is largely dependent on baseline inflammation levels and comorbidities.

Comparison of tolvaptan treatment between patients with the SIADH and congestive heart failure: a single-center experience

BACKGROUND/AIMS: Tolvaptan is a very effective treatment for hypervolemic or euvolemic hyponatremia. We compared the clinical efficacy of and response to tolvaptan in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and congestive heart failure (CHF). METHODS: We retrospectively reviewed the medical records of 50 patients (SIADH, n = 30; CHF, n = 20) who were prescribed tolvaptan between July 2013 and October 2015. Tolvaptan was prescribed when the serum sodium level was 135 mmol/L. RESULTS: After the initiation of tolvaptan therapy, there was an immediate response in the urine volume and serum sodium level in all patients. The improvements in the urine volume and serum sodium concentration were highest within the first 24 hours of treatment. In addition, the mean change in the serum sodium level during the first 24 hours was significantly higher in patients with SIADH than in those with CHF (∆Na, 9.9 ± 4.5 mmol/L vs. 6.9 ± 4.4 mmol/L, respectively; p = 0.025). Also, the mean maintenance dose was lower, and the total duration of tolvaptan use was slightly shorter in the SIADH group than CHF group (21.5 ± 14.9 days vs. 28.0 ± 20.1 days, p = 0.070). CONCLUSIONS: The early response to tolvaptan treatment was better in patients with SIADH than in those with CHF. Thus, the tolvaptan treatment strategy should be differed between patients with SIADH and those with CHF.

A Low Baseline Glomerular Filtration Rate Predicts Poor Clinical Outcome at 3 Months after Acute Ischemic Stroke

BACKGROUND AND PURPOSE: Chronic kidney disease (CKD) is an established risk factor for numerous cardiovascular diseases including stroke. The relationship between the baseline estimated glomerular filtration rate (eGFR) and clinical 3-month outcomes in patients with acute ischemic stroke were evaluated in this study. METHODS: This was a prospective cohort study involving a hospital-based stroke registry; 1373 patients with acute ischemic stroke were enrolled. Patients were divided into the following four groups according their eGFR (calculated using the CKD Epidemiology Collaboration equations): > or =60, 45-59, 30-44, and or =3); secondary endpoints were neurological deterioration (increase in National Institutes of Health Stroke Severity score of > or =4 at discharge compared to baseline) during hospitalization and in-hospital mortality. RESULTS: The overall eGFR was 84.5+/-20.8 mL/min/1.73 m2 (mean+/-SD). The distribution of baseline renal impairment was as follows: 1,218, 82, 40, and 33 patients had eGFRs of > or =60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. At 3 months after the stroke, 476 (34.7%) patients exhibited poor functional outcome. Furthermore, a poor functional outcome occurred more frequently with increasingly advanced stages of CKD (rates of 31.9%, 53.7%, 55.0%, and 63.6% for CKD stages 1/2, 3a, 3b, and 4/5, respectively; p<0.001). Multivariate analysis revealed that a baseline eGFR of <30 mL/min/1.73m2 increased the risk of a poor functional outcome by 2.37-fold (p=0.047). In addition, baseline renal dysfunction was closely associated with neurological deterioration during hospitalization and with in-hospital mortality. CONCLUSIONS: A low baseline eGFR was strongly predictive of both poor functional outcome at 3 months after ischemic stroke and neurological deterioration/mortality during hospitalization.

The association between an abnormal post-voiding urine volume and a lower estimated glomerular filtration rate in patients with type 2 diabetes with no voiding symptoms

BACKGROUND/AIMS: Diabetic cystopathy is a frequent complication of diabetes mellitus. This study assessed the association between the post-voiding residual (PVR) urine volume and diabetic nephropathy in type 2 diabetics with no voiding symptoms. METHODS: This study investigated 42 patients with type 2 diabetes who were followed regularly at our outpatient clinic between July 1, 2008 and June 30, 2009. No patient had voiding problems or International Prostate Symptom Scores (IPSSs) > or = 12. An urologist performed the urological evaluations and the PVR was measured using a bladder scan. A PVR > 50 mL on two consecutive voids was considered abnormal, which was the primary study outcome. RESULTS: The mean patient age was 60 +/- 10 years; the IPSS score was 3.7 +/- 3.3; and the diabetes duration was 11.9 +/- 7.8 years. Seven of the 42 patients (16.7%) had a PVR > 50 mL. The presence of overt proteinuria or microalbuminuria was associated with an increased risk of a PVR > 50 mL (p 50 mL had a significantly lower estimated glomerular filtration rate (eGFR) compared with those with a PVR 50 mL. CONCLUSIONS: Patients with diabetic nephropathy had a significantly higher PVR and a lower eGFR was associated with an abnormal PVR.

Therapeutic Plasma Exchange Using the Spectra Optia Cell Separator Compared With the COBE Spectra

BACKGROUND: The Spectra Optia (SPO) is a novel continuous-flow centrifugal apheresis system based on the COBE Spectra (CSP) platform. There have been few attempts to validate the advantages of the SPO. We performed a retrospective study comparing the two cell separators for therapeutic plasma exchange (TPE) procedures in kidney transplant (KT) patients and seeing efficacy and safety. METHODS: We analyzed 720 TPE procedures performed between August 2012 and July 2014. Procedures included desensitization TPE before KT and TPE for the management of acute and chronic antibody-mediated graft rejection. Demographic characteristics, operational TPE variables, and laboratory data were analyzed. RESULTS: Demographic characteristics for the SPO (n=389) and CSP (n=331) groups did not differ significantly. The procedure time to exchange one plasma volume was 94.2+/-10.3 min in the SPO group and 100.4+/-11.2 min in the CSP group (P<0.001). The plasma removal efficiency (PRE) was 92.5+/-4.9% in the SPO group and 83.2+/-3.7% in the CSP group (P<0.001). There were no significant differences across the two apheresis systems for changes in hematologic parameters. CONCLUSIONS: Compared with the CSP, the SPO was associated with an improved PRE and a shorter procedure time to exchange one plasma volume. Our results in KT patients show that the SPO is superior to the CSP in TPE procedures.

Identification of Pancreatic Cancer-Associated Tumor Antigen from HSP-Enriched Tumor Lysate-Pulsed Human Dendritic Cells

PURPOSE: Vaccine strategies utilizing dendritic cells (DCs) to elicit anti-tumor immunity are the subject of intense research. Although we have shown that DCs pulsed with heat-treated tumor lysate (HTL) induced more potent anti-tumor immunity than DCs pulsed with conventional tumor lysate (TL), the underlying molecular mechanism is unclear. In order to explore the molecular basis of this approach and to identify potential antigenic peptides from pancreatic cancer, we analyzed and compared the major histocompatibility complex (MHC) ligands derived from TL- and HTL-pulsed dendritic cells by mass spectrophotometry. MATERIALS AND METHODS: Human monocyte-derived dendritic cells were pulsed with TL or HTL prior to maturation induction. To delineate differences of MHC-bound peptide repertoire eluted from DCs pulsed with TL or HTL, nanoflow liquid chromatography-electrospray ionization-tandem mass spectrometry (nLC-ESI-MS-MS) was employed. RESULTS: HTL, but not TL, significantly induced DC function, assessed by phenotypic maturation, allostimulation capacity and IFN-gamma secretion by stimulated allogeneic T cells. DCs pulsed with TL or HTL displayed pancreas or pancreatic cancer-related peptides in context of MHC class I and II molecules. Some of the identified peptides had not been previously reported as expressed in pancreatic cancer or cancer of other tissue types. CONCLUSION: Our partial lists of MHC-associated peptides revealed the differences between peptide profiles eluted from HTL-and TL-loaded DCs, implying that induced heat shock proteins in HTL chaperone tumor-derived peptides enhanced their delivery to DCs and promoted cross-presentation by DC. These findings may aid in identifying novel tumor antigens or biomarkers and in designing future vaccination strategies.

Clostridium difficile-associated diarrhea in dialysis patients

BACKGROUND: Dialysis patients have impaired host defense mechanisms and frequently require antibiotics for various infective complications. In this study, we investigated whether dialysis patients have greater risk for Clostridium difficile-associated diarrhea (CDAD). METHODS: During the 4-year study period (2004-2008), 85 patients with CDAD were identified based on a retrospective review of C difficile toxin assay or histology records. Nosocomial diarrheal patients without CDAD were considered as controls (n=403). We assessed the association between renal function and the prevalence and clinical outcomes of CDAD. RESULTS: There was a significant difference in the prevalence rate of chronic kidney disease (CKD) between CDAD and non-CDAD patients (P<0.001). Sixteen patients (18.8%) of the CDAD group were treated with dialysis, whereas 21 patients (5.2%) of the non-CDAD group were treated with dialysis. There was a significant association between renal function and CDAD in patients on dialysis [odds ratio (OR)=4.44, 95% confidence interval (CI) 2.19-8.99, P<0.001], but not in patients with CKD stage 3-5 (OR=1.10, 95% CI 0.63-1.92, P=0.73). In multivariate analysis, CKD stage 5D was an independent risk factor for the development of CDAD (OR=13.36, 95% CI 2.94-60.67, P=0.001). CONCLUSION: Our data indicate that dialysis patients might be at a greater risk of developing CDAD, which suggests that particular attention should be provided to CDAD when antibiotic treatment is administered to dialysis patients.

Clostridium difficile-associated diarrhea in dialysis patients

BACKGROUND: Dialysis patients have impaired host defense mechanisms and frequently require antibiotics for various infective complications. In this study, we investigated whether dialysis patients have greater risk for Clostridium difficile-associated diarrhea (CDAD). METHODS: During the 4-year study period (2004-2008), 85 patients with CDAD were identified based on a retrospective review of C difficile toxin assay or histology records. Nosocomial diarrheal patients without CDAD were considered as controls (n=403). We assessed the association between renal function and the prevalence and clinical outcomes of CDAD. RESULTS: There was a significant difference in the prevalence rate of chronic kidney disease (CKD) between CDAD and non-CDAD patients (P<0.001). Sixteen patients (18.8%) of the CDAD group were treated with dialysis, whereas 21 patients (5.2%) of the non-CDAD group were treated with dialysis. There was a significant association between renal function and CDAD in patients on dialysis [odds ratio (OR)=4.44, 95% confidence interval (CI) 2.19-8.99, P<0.001], but not in patients with CKD stage 3-5 (OR=1.10, 95% CI 0.63-1.92, P=0.73). In multivariate analysis, CKD stage 5D was an independent risk factor for the development of CDAD (OR=13.36, 95% CI 2.94-60.67, P=0.001). CONCLUSION: Our data indicate that dialysis patients might be at a greater risk of developing CDAD, which suggests that particular attention should be provided to CDAD when antibiotic treatment is administered to dialysis patients.

A Case of Hemocholecystitis in a Patient with Microscopic Polyangiitis / 대한내과학회지

Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis, primarily associated with rapidly progressive glomerulonephritis and alveolar hemorrhage. Approximately 50% of MPA cases are associated with gastrointestinal involvement, but rarely do cases involve the gall bladder. We report an unusual case of MPA complicated by hemocholecystitis. A 62-year-old woman was admitted to our hospital with rapidly progressive renal dysfunction and pneumonia unresponsive to antibiotics. A chest CT scan showed bilateral diffuse alveolar consolidation, and perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) staining was positive. During the course of hospitalization, the patient complained of severe abdominal pain, and an abdominal CT scan revealed acalculous cholecystitis with hemorrhage. Cholecystectomy was performed, and a gall bladder biopsy revealed fibrinoid necrosis of small arteries without granuloma. Cholecystitis should be considered in patients with unexplained upper abdominal pain and MPA.

Pulmonary Hypertension in End-Stage Renal Disease Patients with Maintenance Hemodialysis / 대한신장학회지

PURPOSE: Pulmonary hypertension can occur from diverse etiologies. It was reported that pulmonary hypertension also complicated dialysis patents, but the exact mechanisms were not determined. The aim of this study was to evaluate the prevalence and risk factors of pulmonary hypertension in maintenance hemodialysis patients. In addition, we studied the relationship between pulmonary hypertension and arteriovenous access. METHODS: Fifty-nine chronic hemodialysis patients underwent clinical evaluation. Pulmonary artery pressure (PAP) was estimated by Doppler echocardiography. Pulmonary hypertension was defined as PAP > or =35 mmHg. RESULTS: Mean PAP value of subjects was 39.3+/-13.2 mmHg. Pulmonary hypertension was found in 31 (53%) of patients receiving hemodialysis (49.0+/-10.6 mmHg; range 37 to 84 mmHg). Clinical and biochemical parameters did not differ significantly between patients with pulmonary hypertension and without pulmonary hypertension. In 19 patients, PAP was elevated from 27.8+/-10.2 mmHg to 41.8+/-11.9 mmHg (p<0.001) after onset of hemodialysis via arteriovenous fistula. And pulmonary hypertension developed in 12 of 15 patients with normal PAP after onset of hemodialysis treatment. CONCLUSION: The prevalence of pulmonary hypertension was high, and hemodialysis via arteriovenous access may be involved in the development of pulmonary hypertension.

Low-Dose Nafamostat Mesilate in Hemodialysis Patients at High Bleeding Risk / 대한신장학회지

PURPOSE: Systemic anticoagulation, usually with heparin, is required to prevent thrombosis in the blood circuit of hemodialysis. In patients at high bleeding risk, strategies to minimize the bleeding risk include heparin-free or regional anticoagulation methods. Nafamostat mesilate with conventional dose (35 mg/hr) has been used for this purpose. But it is an expensive anticoagulant to use conveniently for the dialysis therapy. Application of low-dose nafamostat mesilate has almost never been tried yet on hemodiaysis management. In this study, we examined the effect of low-dose nafamostat mesilate compared to heparin-free in hemodialysis patients with high risk of bleeding. METHODS: The current study was conducted on 35 hemodialysis patients with high bleeding risk (on-going bleeding, hemorrhage, surgery or severe thrombocytopenia). In the low-dose nafamostat group (n=17, mean age: 59+/-15 years), 238 sessions were performed with continuous infusion of nafamostat mesilate (12.5 mg/hr). In the control group with saline-flushing no heparin methods (n=18, mean age: 57+/-17 years), 247 sessions were analyzed. RESULTS: No significant differences were found in baseline characteristics between the low-dose nafamostat group and the saline group. In the progress of bleeding complications, there were no significant differences between the two groups (11.8% vs. 11.1%). In saline group, however, massive clotting occurred in 44.5 per 1000 sessions, while it occurred in 4.2 per 1000 sessions in the low-dose nafamostat group (p=0.006). CONCLUSION: In patients at high bleeding risk, low-dose nafamostat mesilat can be used as an inexpensive, effective, and safe anticoagulant for hemodialysis.

The Usefulness of Urinary Angiotensinogen as a Biomarker of Renal Progression in Autosomal Dominant Polycystic Kidney Disease / 대한신장학회지

PURPOSE: The renin-angiotensin-aldosterone system activation has been suggested as a potential risk factor for renal progression in autosomal dominant polycystic kidney disease (ADPKD). This study was performed to evaluate urinary angiotensinogen as a biomarker of renal progression in ADPKD. METHODS: Patients with estimated glomerular filtration rate (eGFR) > or =30 mL/min/1.73m2 were enrolled in the study. Specimens (blood and urine) and computed tomography (CT) were taken from each subject. The eGFR was calculated by 4-variable MDRD equation and total kidney volume (TKV) was measured from CT images by modified ellipsoid method. Urinary angiotensinogen (AGT) and neutrophil gelatinaseassociated lipocalin (NGAL) were measured by ELISA. The concentration of AGT was adjusted with random urine creatinine (Cr). The association between urinary biomarkers, TKV and eGFR were evaluated. RESULTS: A total of 59 (M:F=31:28) subjects were enrolled in the study and their mean age was 46 years. The eGFR and TKV at the enrollment were 77.3+/-15.6 mL/min/1.73m2 and 1389.8+/-925.1 mL, respectively. Log AGT/Cr was associated with TKV (r2=0.117, p=0.01) in the earlier stage of disease (TKV<3,000 mL). However, it did not show significant correlation with eGFR. Log NGAL was not associated with either TKV or eGFR. Urinary AGT/Cr was closely related to the number of anti-hypertensive medication, TKV, and the presence of albuminuria, although there was no correlation with plasma renin activity or aldosterone level. CONCLUSION: Urinary angiotensinogen may be a useful biomarker of disease progression in ADPKD patients.

Effects of Keto Acids on Serum Albumin Level in Hemodialysis Patients with Hypoalbuminemia / 대한신장학회지

PURPOSE: Malnutrition is a strong predictor of increased morbidity and mortality in patients on maintenance dialysis. Although a number of studies were performed to determine effective treatment, there is no proven medication for malnutrition. This study aimed to evaluate the effect of keto acids (ketosteril(R)) on serum albumin levels in hemodialysis patients with hypoalbuminemia. METHODS: Hemodialysis patients with hypoalbumineia (serum albumin < or = 3.8 g/dL) were enrolled. Exclusion criteria were previous supplementation of keto acids before the initiation of dialysis, acute infection, liver cirrhosis, malignancy and persistent hypercalcemia. Patients were treated with ketosteril for 6 months and serum albumin levels were compared to age- and gender-matched hemodialysis patients. RESULTS: There were no significant differences in the baseline serum albumin levels between ketosteril group (n=19) and the control group (n=19). After 6 months, the mean (+/-SD) serum albumin level in the ketosteril group rose from 3.46+/-0.40 g/dL to 3.66+/-0.37 g/dL (p=0.01), but not the control group. However, the difference between the two groups was not significant (p=0.06). Multivariate analysis showed that the ketosteril supplementation (p=0.03) and the baseline serum albumin level (< or = 3.4 g/dL, p=0.04) were predictors of increased serum albumin. There was no severe hypercalcemia during the study period. CONCLUSION: There was an improvement of serum albumin levels in hemodialysis patients with hypoalbuminemia after the supplementation of keto acids.

Saline Versus Nafamostat Mesilate Anticoagulation for Continuous Veno-venous Hemofiltration (CVVH) in Patients at High Risk of Bleeding: A Prospective Study / 대한신장학회지

PURPOSE:In patients with a higherrisk of bleeding, performing CVVH with heparin or saline anticoagulation is associated with increased bleeding or thrombotic risk. Nafamostat mesilate (NM), a serine proteinase inhibitor, while inhibiting various clotting factors in filter circuit, is characterized by short half life resulting in little systemic anticoagulation effect. Accordingly, we prospectively evaluated the anticoagulant effect and safety of NM in patients with a higher risk of bleeding who underwent CVVH. METHODS:Among 43 patients with high risk of bleeding [defined by (1) INR>2, aPTT>20 sec, platelet2, aPTT>20 sec, platelet<50,000/mm3), the positive effect of NM on circuit lifespan persisted irrespective of the coagulation status. CONCLUSION:As compared with saline bolus, nafamostat mesilate infusion was associated with higher CVVH filter life. In patients with high risk of bleeding, nafamostat mesilate can be used as a safe and effective anticoagulant for CVVH with acceptable filter life

Sulodexide-induced Hyperkalemia: A Case Report / 대한신장학회지

Sulodexide is composed of two glycosaminoglycans (fast-moving heparin 80%, dermatan sulfate 20%) that are capable of preventing diabetic nephropathy by correcting abnormal glycosaminoglycan metabolism. Considering heparin-like propertyof sulodexide, side effect profiles of sulodexide are expected to be similar with those of heparin. Among those side effects, we remarked on heparin-induced hyperkalemia and hereby report a case of severe hyperkalemia during the use of sulodexide. A 52-year-old man with diabetic nephroapthy and hypertension was admitted to our hospital because of severe hyperkalemia up to 7.5 meq/L. His clinical condition was stable and medications including losartan and furosemide had not been changed for last 6 months except the addition of sulodexide, which was started 30 days prior to admission. Despite intensive use of Kayexalate and immediate discontinuation of losartan, hyperkalemia aggravated up to 8.0 meq/L. After recognition of possible sulodexide-induced hyperkalemia, sulodexide was discontinued, which resulted in rapid correction of hyperkalemia. In view of the above discussed clinical consideration, we suspect sulodexide as a major cause of hyperkalmia and report this case with a review of literature.