Impact of needle type on substitution volume during online hemodiafiltration: plastic cannulae versus metal needles

Plastic cannulae have attracted increasing interest as an alternative to traditional metal needles with the aim of reducing cannulation-related complications. We investigated whether the substitution volumes during hemodiafiltration differ using these two types of needles in dialysis patients. Methods: An intervention study involving 26 hemodialysis patients was conducted in Korea between March and September in 2021. Patients first received online hemodiafiltration using traditional metal needles, and thereafter plastic cannulae were used in a stepwise protocol. Repeated-measures design and linear mixed-effect models were used to compare substitution volumes between the two needle types with the same inner diameter. Results: The mean patient age was 62.7 years, and their mean dialysis vintage was 95.2 months. Most patients (92.3%) had an arteriovenous fistula as the vascular access. The substitution volume increased as blood flow and needle size increased for both plastic cannulae and metal needles. The substitution volume was significantly higher with 17-gauge (G) plastic cannulae than with 16-G metal needles at blood flow rates of 280, 300, and 330 mL/min. Similar results were obtained for 15-G metal needles and 16-G plastic cannulae at a blood flow rate of 330 mL/min. However, the patient ratings of pain on a visual analogue scale were higher for plastic cannulae. Conclusion: Higher substitution volumes were obtained at the same prescribed blood flow rate with plastic cannulae than with metal needles during online hemodiafiltration. Plastic cannulae are an option for achieving high-volume hemodiafiltration for patients with low blood flow rates.

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.

When and why to start continuous renal replacement therapy in critically ill patients with acute kidney injury

Acute kidney injury (AKI) is a common condition in critically ill patients, and may contribute to significant medical, social, and economic consequences, including death. Although there have been advances in medical technology, including continuous renal replacement therapy (CRRT), the mortality rate of AKI is high, and there is no fundamental treatment that can reverse disease progression. The decision to implement CRRT is often subjective and based primarily on the clinician’s judgment without consistent and concrete guidelines or protocols regarding when to initiate and discontinue CRRT and how to manage complications. Recently, several randomized controlled trials addressing the initiation of renal replacement therapy in critically ill patients with AKI have been completed, but clinical application of the findings is limited by the heterogeneity of the objectives and research designs. In this review, the advantages and disadvantages of CRRT initiation, clinical guideline recommendations, and the results of currently published clinical trials and meta-analyses are summarized to guide patient care and identify future research priorities.

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.

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.

Association of Blood Pressure at Specific Time-Points with 1-Year Renal Outcomes in Patients with Diabetic Chronic Kidney Disease

BACKGROUND@#The 24-hour mean blood pressure (mBP) is the best predictor of organ damage; however, it is not easily applicable in clinical practice. The APrODiTe study suggested that systolic blood pressure (SBP) values at 7:00 AM and 9:30 PM were associated with the 24-hour mSBP in patients with chronic kidney disease (CKD). We investigated the association of the SBP values at these time-points with the renal outcomes in patients with diabetic CKD during 1-year follow-up.@*METHODS@#Ninety-six patients with diabetic CKD were included at 1-year follow-up. The renal outcomes were an increase in the random urine protein/creatinine ratio or estimated glomerular filtration rate (eGFR) deterioration, which means a decrease in eGFR ≥5 mL/min/1.73 m² compared to the baseline values.@*RESULTS@#The baseline SBP values at 7:00 AM, and 9:30 PM, and the 24-hour mSBP were 135.6±24.9 mmHg, 141.7±25.6 mmHg, and 136.4±20.7 mmHg, respectively. The SBP values measured at the same time-points after 1 year were similar to those at baseline. The SBP at 7:00 AM was significantly associated with eGFR deterioration in the univariate and multivariate analyses (odds ratio [OR]: 1.032; 95% confidence interval [CI]: 1.006–1.059; p=0.016). The SBP at 7:00AM and 24-hour mSBP did not show a concordant association with sustained proteinuria in the linear and logistic analyses. In the subgroup analysis, the association between the SBP at 7:00 AM and eGFR deterioration persisted in patients with CKD stage 3–5 (OR: 1.041; 95% CI: 1.010–1.073; p=0.010).@*CONCLUSION@#The SBP at 7:00 AM, in addition to the 24-hour mSBP, is also associated with eGFR deterioration in patients with diabetic CKD, particularly in those with CKD stage 3–5.

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.

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.

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.

Physician perceptions of blood pressure control in patients with chronic kidney disease and target blood pressure achievement rate

BACKGROUND: Blood pressure (BP) control is the most-established method for the prevention of chronic kidney disease (CKD) progression. However, the ideal BP target for CKD patients is still under debate. METHODS: We performed a survey of regular registered members of the Korean Society of Nephrology to determine physician perceptions of BP control in patients with CKD. In addition, we evaluated the target BP achievement rate using data from the APrODiTe-2 study. RESULTS: Two-thirds of physicians considered the target BP for CKD to be 300 mg/day (33.7%); GFR ≥ 60 (76.4%); GFR < 30 (47.8%); no evidence of ASO (67.8%); and the presence of ASO (42.9%). CONCLUSION: The target BP was lower in patients with higher cerebro-cardiovascular risks. These patient groups also showed lower target BP achievement rates. We also found a relatively lower application and clinical reflection rate of home or ambulatory BP monitoring.

Idiopathic hypereosinophilic syndrome presenting with urinary frequency, abdominal pain, and diarrhea

Idiopathic hypereosinophilic syndrome (IHES) is a rare disorder defined by persistent blood eosinophilia, evidence of eosinophil-associated organ dysfunction and absence of secondary causes. Eosinophilic infiltration and its mediator release can cause damage to multiple organs. Although IHES can involve every organ system, bladder involvement is rarely evidenced. We recently reported a case of IHES with both bladder and gastrointestinal tract involvement. A 43-year-old woman visited Hallym University Sacred Heart Hospital complaining of urinary frequency, abdominal pain, and diarrhea for several months. Abdominal pelvic computed tomographic scan showed diffuse wall thickenings in her bladder and colon with small pelvic ascites. Laboratory investigation showed a marked peripheral eosinophilia and tissue biopsies confirmed eosinophilic infiltration in the bladder wall, esophagus, and duodenum. The patient was treated with prednisolone and her eosinophilia and symptoms have gradually improved.

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.

Characteristics of Acute Pyelonephritis in the Elderly / 대한내과학회지

BACKGROUND/AIMS: Acute pyelonephritis is relatively common in women. It has been well studied in young adults, but rarely in geriatric patients. Given that the population of Korea is aging rapidly, this study examined the clinical characteristics of acute pyelonephritis in Korean geriatric patients. METHODS: We retrospectively studied 499 patients diagnosed with acute community-acquired pyelonephritis from March 2002 to February 2005. All patients admitted to Hallym University Kangnam Sacred Heart Hospital from the emergency room or out-patient department were recruited. Pregnant women and hospital-acquired cases were excluded. RESULTS: Ninety-nine subjects (19.8%) were aged 65 years or over (mean age 73.1 +/- 6.3 years, range 65-93). Elderly patients had a greater male predominance, longer hospital stay, and higher rate of positive urine cultures than patients younger than 65 years. The presence of diabetes mellitus, complicated acute pyelonephritis, and a higher serum creatinine level were associated with geriatric patients. The distribution of infectious microorganisms was similar between the two groups. Old age (> 65 years) was an important risk factor for a long hospital stay, along with male gender, renal dysfunction, white blood count (WBC) and high serum alkaline phosphatase levels. CONCLUSIONS: Geriatric patients with acute pyelonephritis tended to be male, and have diabetes mellitus, renal dysfunction, complicated infections, and a longer duration of hospitalization.

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.

Over-expression of Liver X Receptor-alpha(LXR alpha by TO901317 Exaggerated the Production of Mesangial Matrix / 대한신장학회지

PURPOSE: To provide the insight into the role of LXR alpha on the progression of diabetic nephropathy, we measured the production of extracellular matrix in the cultured mesangial cells treated with the LXR agonist. METHODS: With the mesangial cells extracted from C57BL6 mice, we cultured them in the presence of 25 mM glucose with or without TO901317, an agonist of LXRalpha We transfected siRNAs of SREBP1 and LXR alpha into the mesangial cell to suppress the activity of the two genes. RESULTS: TO901317 increased expressions of LXR alpha, SREBP-1, TGF beta-1, and collagen IV and triglyceride amount in mesangial cells cultured in 25mM glucose. These effects of TO901317 were attenuated by inhibiting transcription of LXR alpha or SREBP-1 with transfection of siRNAs. In mesangial cells transfected with siRNA of SREBP-1, changes by TO901317 were attenuated regardless of increased expression of LXR alpha. That suggested the activation of SREBP-1, an downstream gene of LXR alpha, would be more important to induce changes in mesangial cells by TO901317. CONCLUSION: The TO901317, an agonist of LXR alpha, increases extracellular matrix, collagen IV, and TGF beta-1 production in cultured mesangial cells. The SREBP-1 as well as dyslipidemia in mesangial cells enhanced by LXR agonist would be the important mechanism to induce those changes.

The Mildly Elevated Serum Bilirubin Level is Negatively Associated with the Incidence of End Stage Renal Disease in Patients with IgA Nephropathy

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: 0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m2 or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy.

The Bilirubin Level is Negatively Correlated with the Incidence of Hypertension in Normotensive Korean Population

Reactive oxygen species have been known to be an important factor in the pathogenesis of hypertension. Bilirubin, one of the metabolites of heme degraded by heme oxygenase, is a potent anti-oxidant. We verified the effect of serum bilirubin level on the incidence of hypertension in normotensive subjects. We grouped 1,208 normotensive subjects by the criterion of the highest quintile value of serum bilirubin, 1.1 mg/dL. The incidence of hypertension was higher in group 1 with bilirubin less than 1.1 mg/ dL than in group 2 with bilirubin 1.1 mg/dL or more (186/908 vs. 43/300, p=0.018). The relative risk for hypertension was 0.71 (95% confidence interval, 0.51-0.99), p=0.048 in group 2 compared to group 1 by Cox's proportional hazard model. Among the groups stratified by gender, smoking, and liver function status, the group 2 showed a lower risk of hypertension in females and in non-smokers. In conclusion, a mild increase within the physiological range of serum bilirubin concentration was negatively correlated with the incidence of hypertension. The effect of bilirubin on the development of hypertension was more evident in females and in non-smokers.