Fatal Hypermagnesemia in Patients Taking Magnesium Hydroxide.

Hypermagnesemia is a rare but potentially fatal electrolyte disorder often overlooked because of its unfamiliarity. Magnesium is regulated through a balance of bone, intestinal absorption, and renal excretion. Hypermagnesemia typically arises from excessive magnesium intake or reduced renal excretion; however, it also occurs in patients with normal kidney function. Herein, we report two cases of hypermagnesemia in patients taking magnesium hydroxide for constipation. The first case involved an 82-year-old woman with end-stage renal disease who developed metabolic encephalopathy due to hypermagnesemia, after taking 3,000 mg of magnesium hydroxide daily for constipation. Her magnesium level was 9.9 mg/dL. Her treatment involved discontinuing magnesium hydroxide and continuing hemodialysis, which led to her recovery. In the second case, a 50-year-old woman with a history of cerebral hemorrhage and mental retardation developed hypermagnesemia despite having normal renal function. She was also taking magnesium hydroxide for constipation, and her magnesium level was 11.0 mg/dL. She experienced cardiac arrest while preparing for continuous renal replacement therapy (CRRT). After achieving return of spontaneous circulation, CRRT was initiated, and her magnesium level showed a decreasing trend. However, vital signs and lactate levels did not recover, leading to death. These cases highlight the importance of prompt diagnosis and intervention for hypermagnesemia and the need to regularly monitor magnesium levels in individuals receiving magnesium-containing preparations, especially those with impaired kidney function.

Insulin resistance is associated with incident chronic kidney disease in population with normal renal function.

Background: Insulin resistance is prevalent in chronic kidney disease and may accelerate the progression of chronic kidney disease. This study aimed to investigate whether insulin resistance is associated with the development of incident chronic kidney disease in a population with normal renal function. Methods: A total of 3,331 participants from a community-based cohort with normal renal function were prospectively analyzed. We determined the relationship of insulin resistance indices with the incident chronic kidney disease using the Cox proportional hazard model and Kaplan-Meier survival analysis. Results: During a mean follow-up of 11.03 ± 4.22 years, incident chronic kidney disease occurred in 414 participants (12.4%). The high homeostasis model assessment-insulin resistance level group had an increased risk of incident chronic kidney disease (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.13-1.74; p = 0.002) compared to the normal group after adjustment for age, sex, history of hypertension, body mass index, total cholesterol, alcohol drinking status, smoking status, and baseline estimated glomerular filtration rate. The risk of incident chronic kidney disease also increased with the lower quantitative insulin sensitivity check index level (HR, 0.62; 95% CI, 0.41-0.92; p = 0.02) and higher leptin-adiponectin ratio level (HR, 1.23; 95% CI, 1.06-1.42; p = 0.006). Conclusion: Higher insulin resistance indices are associated with the incidence of chronic kidney disease. Our data suggest that increased insulin resistance may be involved in the development of incident chronic kidney disease in a population with normal renal function.

Prognostic role of the neutrophil-to-lymphocyte ratio in patients with chronic kidney disease.

BACKGROUND/AIMS: The neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in cardiovascular disease, infection, inflammatory disease, and several malignancies. Therefore, the NLR has a possible predictive value in patients with chronic kidney disease (CKD), but this predictive value has not been validated. Here, we aimed to investigate the possibility of NLR as a predictor of CKD progression. METHODS: This retrospective observational study included 141 patients with non-dialysis CKD. The participants were divided into terciles (T1, T2, and T3) according to NLR. The primary outcome was defined as a composite kidney event, which included a decline in the estimated glomerular filtration rate (eGFR) of at least 50% or initiation of renal replacement therapy during the follow-up period. RESULTS: The mean follow-up duration was 5.45 ± 2.11 years. The mean NLRs were 1.35 ± 0.05 in T1 (n = 47), 2.16 ± 0.04 in T2 (n = 47), and 4.29 ± 0.73 in T3 (n = 47). The group with the highest NLR (T3) had higher baseline CKD and serum creatinine and lower eGFR levels than the group with the lowest NLR (T1). The cumulative incidence rate of composite kidney events was significantly higher in T3 compared with T1 (p < 0.001, log-rank test). Cox regression analysis revealed that high NLR was associated with the risk of composite kidney events (adjusted hazard ratio, 3.33; 95% confidence interval, 1.43-7.76). CONCLUSION: A higher NLR reflects the more advanced stage of CKD and suggests a role for NLR as a biomarker for predicting CKD progression.

Effects of Blood Pressure According to Age on End-Stage Renal Disease Development in Patients With Diabetes: A Nationwide Population-Based Cohort Study.

BACKGROUND: Recent hypertension guidelines have recommended lower blood pressure (BP) targets in high-risk patients. However, there are no specific guidelines based on age or systolic and diastolic blood pressure (SBP and DBP, respectively). We aimed to assess the effects of age-related BP on development of end-stage renal disease (ESRD) in patients with diabetes. METHODS: A total of 2 563 870 patients with diabetes aged >20 years were selected from the Korean National Health Screening Program from 2009 to 2012 and followed up until the end of 2019. Participants were categorized into age and BP groups, and the hazard ratios for ESRD were calculated. RESULTS: During a median follow-up of 7.15 years, the incidence rates of ESRD increased with increasing SBP and DBP. The hazard ratio for ESRD was the highest in patients younger than 40 years of age with DBP≥100 mm Hg. The effect of SBP and DBP on ESRD development was attenuated with age (interaction P was <0.0001 for age and SBP, and 0.0022 for age and DBP). The subgroup analysis for sex, antihypertension medication, and history of chronic kidney disease showed higher hazard ratios for ESRD among males, younger than 40 years, not taking antihypertension medications and chronic kidney disease compared to those among females, older than 40 years, antihypertension medication, and nonchronic kidney disease groups. CONCLUSIONS: Higher SBP and DBP increase the risk of developing ESRD in patients with diabetes, and in particular, younger individuals face greater risk. Therefore, intensive BP management is warranted in younger patients to prevent ESRD.

Association between serum osteoprotegerin level and renal prognosis in nondialysis patients with chronic kidney disease in the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (the KNOW-CKD Study).

BACKGROUND: Osteoprotegerin is an important regulator of bone metabolism and vascular calcification. The association between serum osteoprotegerin level and chronic kidney disease (CKD) progression has not been elucidated. We investigated the prognostic value of serum osteoprotegerin levels in nondialysis CKD patients. METHODS: We analyzed 2,082 patients enrolled in the Korean Cohort Study for Outcomes in Patients with CKD between 2011 and 2016. Patients were divided into quartiles by their serum osteoprotegerin levels. The primary outcome was the occurrence of ≥1 of the following: dialysis initiation, kidney transplantation, a two-fold increase in serum creatinine level from baseline, or a 50% decrease in the estimated glomerular filtration rate (eGFR). Cox proportional hazard regression models were used to investigate the prognostic value of the serum osteoprotegerin level to CKD progression. RESULTS: The median follow-up period was 48.9 months, and 641 patients (30.8%) experienced the primary outcome. The hazard ratio of serum osteoprotegerin for renal progression in the full extended Cox proportional hazard model was 1.064 (95% confidence interval, 1.041-1.088). Subgroup analyses by age, presence of diabetes, and eGFR showed significant results consistent with the overall analysis results. CONCLUSION: Serum osteoprotegerin level is independently associated with renal prognosis and could have prognostic importance in CKD progression.

Retroperitoneal emphysema caused by a renal abscess: a case report.

We report a case of retroperitoneal emphysema caused by a renal abscess. A 45-year-old man with underlying type 2 diabetes mellitus visited the emergency department with right flank pain and a fever. On physical examination, right costovertebral tenderness in the ipsilateral flank was noted. Leukocytosis and high inflammatory marker levels were observed. Urinalysis showed pyuria and glucosuria. Urine culture was positive for Streptococcus agalactiae. A computed tomography scan of the abdomen showed a focal, low-attenuation lesion in the right kidney with a 3 cm, exophytic, high-attenuation lesion in the right kidney upper pole and gas-containing fluid collection within the retroperitoneal space. The diagnosis was retroperitoneal emphysema caused by a renal abscess. As the vital signs were stable and the patient refused puncture, we decided on a course of antibiotics alone with follow-up without percutaneous drainage or surgery. The patient improved without any complications. This is a rare case of a renal abscess penetrating the renal fascia and progressing to a posterior paranephric emphysema. The patient was treated with antibiotics alone and cured successfully. Early diagnosis and proper treatment are needed, and percutaneous drainage or urgent surgery would be beneficial for such cases depending on the patient's condition.

Venous thromboembolism and severe hypernatremia in a patient with lithium-induced nephrogenic diabetes insipidus and acute kidney injury: a case report.

We report a case of thromboembolism in a patient with hypernatremia resulting from lithium-induced nephrogenic diabetes insipidus (NDI). A 49-year-old female patient on chronic lithium therapy due to bipolar disorder was transferred to the emergency department with signs of dehydration, altered mental status, and increased oxygen demand. She was admitted to a local psychiatric clinic first because of an exacerbation of a manic episode. When she was transferred to our clinic, her blood pressure was 130/80 mmHg, she was tachycardic (110 beats/min), had tachypnea (24 breaths/min), normal body temperature (36.5 ℃), and an oxygen saturation of 94% via a face mask (10 L/min). Laboratory results showed hypertonic hypernatremia (osmolality, 363 mOsm/kg; sodium, 171 mEq/L), low urine osmolality (osmolality, 231 mOsm/kg), and normal urine sodium (Na, 63 mEq/L). Her serum lithium concentration was above the therapeutic range (1.52 mmol/L). An increase in cardiac markers and changes in electrocardiogram were detected; therefore, echocardiography was performed, which showed right ventricular dysfunction and small left ventricular chamber size. Computed tomography of the chest and lower extremities showed pulmonary thromboembolism (PTE) and deep venous thrombosis (DVT). She was treated with hypotonic fluid to correct hypernatremia and intravenous heparin for thromboembolism. The size of the thromboembolism decreased, and hypernatremia was corrected. She was discharged with a direct oral anticoagulant (DOAC). Here, we report a case of severe hypernatremia and venous thromboembolism in lithium-induced NDI.

Predictive Model for High Coronary Artery Calcium Score in Young Patients with Non-Dialysis Chronic Kidney Disease.

Cardiovascular disease is a major complication of chronic kidney disease. The coronary artery calcium (CAC) score is a surrogate marker for the risk of coronary artery disease. The purpose of this study is to predict outcomes for non-dialysis chronic kidney disease patients under the age of 60 with high CAC scores using machine learning techniques. We developed the predictive models with a chronic kidney disease representative cohort, the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD). We divided the cohort into a training dataset (70%) and a validation dataset (30%). The test dataset incorporated an external dataset of patients that were not included in the KNOW-CKD cohort. Support vector machine, random forest, XGboost, logistic regression, and multi-perceptron neural network models were used in the predictive models. We evaluated the model's performance using the area under the receiver operating characteristic (AUROC) curve. Shapley additive explanation values were applied to select the important features. The random forest model showed the best predictive performance (AUROC 0.87) and there was a statistically significant difference between the traditional logistic regression model and the test dataset. This study will help identify patients at high risk of cardiovascular complications in young chronic kidney disease and establish individualized treatment strategies.

Association of Urinary Potassium Excretion with Blood Pressure Variability and Cardiovascular Outcomes in Patients with Pre-Dialysis Chronic Kidney Disease.

Dietary potassium intake is a dilemma in patients with chronic kidney disease (CKD). We investigated the association of urine potassium excretion, a surrogate for dietary potassium intake, with blood pressure variability (BPV) and cardiovascular (CV) outcomes in patients with pre-dialysis CKD. A total of 1860 participants from a cohort of pre-dialysis CKD (KNOW-CKD) patients were divided into the quartiles by spot urine potassium-to-creatinine ratio. The first quartile (26.423 ± 5.731 mmol/gCr) was defined as low urine potassium excretion. Multivariate linear regression analyses revealed an independent association of low urine potassium excretion with high BPV (adjusted ß coefficient 1.163, 95% confidence interval 0.424 to 1.901). Cox regression analyses demonstrated that, compared to high urine potassium excretion, low urine potassium excretion is associated with increased risk of CV events (adjusted hazard ratio 2.502, 95% confidence interval 1.162 to 5.387) but not with all-cause mortality. In conclusion, low urine potassium excretion is associated with high BPV and increased risk of CV events in patients with pre-dialysis CKD. The restriction of dietary potassium intake should be individualized in patients with pre-dialysis CKD.

Persistent Resistant Hypertension Has Worse Renal Outcomes in Chronic Kidney Disease than that Resolved in Two Years: Results from the KNOW-CKD Study.

Apparent treatment-resistant hypertension (ATRH) is closely related to chronic kidney disease (CKD); however, the long-term outcomes and the effects of improvement in ATRH in patients with CKD are not well understood. We evaluated the relationship between the persistence of ATRH and the progression of CKD. This cohort study enrolled 1921 patients with CKD. ATRH was defined as blood pressure above 140/90 mmHg and intake of three different types of antihypertensive agents, including diuretics, or intake of four or more different types of antihypertensive agents, regardless of blood pressure. We defined ATRH subgroups according to the ATRH status at the index year and two years later. The prevalence of ATRH at baseline was 14.0%. The presence of ATRH at both time points was an independent risk factor for end-point renal outcome (HR, 1.41; 95% CI, 1.04-1.92; p = 0.027). On the other hand, the presence of ATRH at any one of the time points was not statistically significant. In conclusion, persistent ATRH is more important for the prognosis of renal disease than the initial ATRH status. Continuous follow-up and appropriate treatment are important to improve the renal outcomes.

Hyperuricemia is a risk factor for the progression to end-stage renal disease in minimal change disease.

BACKGROUND: Minimal change disease (MCD) is one of the most common causes of nephrotic syndrome worldwide. Hyperuricemia increases the end-stage renal disease (ESRD) risk in glomerulonephritis. In this study, we aimed to determine the effect of high serum uric acid levels on the progression to ESRD in MCD. METHODS: A total of 800 patients diagnosed with MCD by kidney biopsy were retrospectively analyzed. We determined the relationship of hyperuricemia with the progression to ESRD in MCD using the Cox proportional hazard model and Kaplan-Meier survival analysis. The primary outcome was defined as the initiation of dialysis or kidney transplantation. RESULTS: A total of 42 patients (5.3%) progressed to ESRD during the follow-up period. In the restricted cubic spline curve, serum uric acid levels exhibited a positive correlation with ESRD progression in patients with MCD. In the fully adjusted model, the risk of MCD progression increased by 29% for every 1 mg/dL increase in the baseline serum uric acid level (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09-1.54; p = 0.004). Falling into the high uric acid group (serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women) was also a risk factor for progression of MCD to ESRD (HR, 3.40; 95% CI, 1.59-7.31; p < 0.001). CONCLUSION: Our study shows that hyperuricemia is an independent risk factor for the progression to ESRD in patients with MCD.

Proteinuria and Psoriasis Risk: A Nationwide Population-Based Study.

Psoriasis, a chronic inflammatory dermatosis, has been associated with chronic kidney disease or end-stage renal disease. However, the association of the changes or amount of proteinuria with psoriasis development has not been evaluated. Using the Korean National Health Screening database, we assessed psoriasis development until 2018 in 6,576,851 Koreans who underwent health examinations in 2009 and 2011. Psoriasis was defined using the International Classification of Diseases, 10th revision (ICD-10) code L40. The risk of psoriasis was evaluated according to change in proteinuria (never [Neg (no proteinuria)/Neg], new [Neg/Pos (proteinuria present)], past [Pos/Neg] and persistent [Pos/Pos] proteinuria) and the proteinuria amount. During a median 7.23-year follow-up, 162,468 (2.47%) individuals developed psoriasis. After adjustments, the hazard ratio (HR) for psoriasis was higher in the persistent proteinuria group (1.32 [1.24-1.40]) than in the never proteinuria group. The past proteinuria group showed better renal outcome (1.03 [1.00-1.07]) than the new (1.05 [1.01-1.07]) and never proteinuria (reference, 1.00) groups did. The amount of random urine proteinuria was associated with increased HR for psoriasis. Subgroup analyses for age, sex, estimated glomerular filtration rate (eGFR), hypertension and diabetes showed that the persistent proteinuria group had a higher risk of psoriasis than the never proteinuria group, especially at eGFR < 60 mL/min/1.73 m2. Persistent proteinuria is associated with psoriasis risk, and the proteinuria amount significantly affects psoriasis development.

Parental educational status independently predicts the risk of prevalent hypertension in young adults.

Identification of individuals at risk of hypertension development based on socio-economic status have been inconclusive, due to variable definitions of low socio-economic status. We investigated whether educational status of individuals or their parents predicts prevalent hypertension in young adult population, by analyzing data of more than 37,000 non-institutionalized subjects from Korea National Health and Nutrition Examination Survey 2008 to 2017. Although low educational status of individual subjects was robustly associated with elevation of systolic blood pressure and increased prevalence of hypertension in general population, its impact on prevalent hypertension differed across age subgroups, and was remarkably attenuated in young adults. Parental educational status was significantly associated with prevalent hypertension in young adults, but not or only marginally in elderly population. Low parental educational status was also associated with high sodium intake in young adults, irrespective of subject's own educational status. These collectively indicate that parental educational status, rather than individual's own educational status, better and independently predicts prevalent hypertension in young adults, and that young adults with low parental educational status are prone to intake more sodium, possibly contributing to the increased risk of hypertension development. We expect that our findings could help define young individuals at risk of high sodium intake and hypertension.

The Association between Serum Hemoglobin and Renal Prognosis of IgA Nephropathy.

Immunoglobin A (IgA) nephropathy causes chronic kidney disease worldwide. Therefore, identifying risk factors associated with the progression of IgA nephropathy is crucial. Anemia is a common complication of chronic kidney disease; however, few studies have investigated the effect of serum hemoglobin on the renal prognosis of IgA nephropathy. This study aimed to determine the effect of serum hemoglobin on the progression of IgA nephropathy. We retrospectively analyzed 4326 patients with biopsy-proven IgA nephropathy. We evaluated the effect of serum hemoglobin on IgA nephropathy progression using Kaplan-Meier survival analyses, the log-rank test, and the Cox proportional hazards model. The primary end-point was progression of IgA nephropathy, defined as dialysis initiation or kidney transplantation. Serum hemoglobin showed a nonlinear relationship with the progression of IgA nephropathy. The Cox proportional hazards model showed that the risk of progression of IgA nephropathy decreased 0.87 times for every 1.0 g/dL increase in serum hemoglobin. In subgroup analyses, reduced serum hemoglobin was an independent risk factor for IgA nephropathy progression only in women. There was no statistically significant interaction of serum hemoglobin between men and women (P interaction = 0.177). Results of Sensitivity analysis were robust and consistent. Serum hemoglobin at diagnosis was an independent predictor for IgA nephropathy progression.

A Case Report of Very Severe Hyperphosphatemia (19.3 mg/dL) in a Uremic Patient Taking Honey and Persimmon Vinegar.

We report a case of severe hyperphosphatemia in advanced CKD with poor compliance. A 55-year-old male patient with underlying type 2 diabetes mellitus, hypertension, and chronic kidney disease presented emergently with general weakness and altered mental status. The creatinine level was 14 mg/dL (normal range: 0.5-1.3 mg/dL) 2 months prior to consultation, and he was advised initiation of hemodialysis, which he refused. Subsequently, the patient stopped taking all prescribed medications and self-medicated with honey and persimmon vinegar with the false belief it was detoxifying. At the time of admission, he was delirious, and his laboratory results showed blood urea nitrogen level of 183.4 mg/dL (8-23 mg/dL), serum creatinine level of 26.61 mg/dL (0.5-1.3 mg/dL), serum phosphate level of 19.3 mg/dL (2.5-5.5 mg/dL), total calcium level of 4.3 mg/dL (8.4-10.2 mg/dL), vitamin D (25(OH)D) level of 5.71 ng/mL (30-100 ng/mL) and parathyroid hormone level of 401 pg/ml (9-55 pg/mL). Brain computed tomography revealed non-traumatic spontaneous subdural hemorrhage, presumably due to uremic bleeding. Emergent hemodialysis was initiated, and hyperphosphatemia and hypocalcemia were rectified; calcium acetate and cholecalciferol were administered. The patient's general condition and laboratory results improved following dialysis. Strict dietary restrictions with patient education were implemented. Multifaceted interventions, including dietary counseling, administration of phosphate-lowering drugs, and lifestyle modifications, should be implemented when encountering patients with CKD, considering the extent of the patient's adherence.

High serum adiponectin as a biomarker of renal dysfunction: Results from the KNOW-CKD study.

High serum adiponectin is noted in several conditions of chronic kidney disease (CKD) and is a predictor for end stage renal disease. However, the relationship between adiponectin level and renal disease progression is not well established. This study aimed to determine the relationship between serum adiponectin levels and CKD progression. This prospective longitudinal study included 2238 patients from the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease. Patients were divided into quartiles according to their serum adiponectin level. Composite renal outcome was defined as one or more of the following: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate (eGFR) during the follow-up period. A cox proportional hazard ratio model was applied to analyze the relationship between composite renal outcome and serum adiponectin levels. Serum adiponectin level was inversely associated with eGFR (p < 0.001) and positively correlated with urine albumin-creatinine ratio. The highest quartile of serum adiponectin was associated with an increased risk of adverse renal outomes (HR, 1.39; 95%CI, 1.05-1.84; p=0.021). On time-dependent receiver operating characteristic curve analysis, predictive ability of adiponectin for renal outcomes disappeared after adjusting for eGFR. Therefore, serum adiponectin may be a biomarker of renal dysfunction rather than a true risk factor in CKD progression.

Micrococcus aloeverae - A Rare Cause of Peritoneal Dialysis-Related Peritonitis Confirmed by 16S rRNA Gene Sequencing.

The number of patients receiving peritoneal dialysis has increased worldwide. Herein, we report the first case to our knowledge of continuous ambulatory peritoneal dialysis (CAPD) peritonitis caused by Micrococcus aloeverae, which was initially reported to be caused by Micrococcus luteus in the dialysate culture report but later identified by 16S ribosomal ribonucleic acid (rRNA) gene sequencing as M. aloeverae. A 59-year-old woman visited the emergency room due to abdominal pain. She was hospitalized with CAPD peritonitis. The patient initially responded to empirical antibiotic treatment comprising intraperitoneal cefazolin (15 mg/kg/day) and ceftazidime (1 g/day); however, the leukocyte count of dialysate effluent increased again. M. luteus was isolated four times from peritoneal dialysate cultures. We treated the patient with intraperitoneal administration of vancomycin (2 g loading, followed by 1 g every 7 days) but needed to switch from CAPD to temporary hemodialysis. We analyzed the 16S rRNA sequence to confirm the exact causative organism, and the results revealed that the organism was M. aloeverae. Because M. aloeverae and M. luteus have sequence similarity, 16S rRNA sequencing is a useful method to distingush them.

Inhibition of lipopolysaccharide-induced nitric oxide production by antofine and its analogues in RAW 264.7 macrophage cells.

Based on the anti-inflammatory activity of phenanthroindolizidine alkaloids, the inhibitory effect of antofine and its analogues on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was examined, and structure-activity relationships are discussed. Antofine and several analogues suppressed NO production in LPS-stimulated RAW 264.7 cells. The MeO group at C(2), and the bulkiness of the substituents at C(3) and C(6) in the phenanthrene ring might be critical for this effect. Besides, regulation of iNOS expression might be involved in the inhibitory effect of antofine on LPS-induced NO production in macrophage cells.

Suppression of inducible nitric oxide synthase by (-)-isoeleutherin from the bulbs of Eleutherine americana through the regulation of NF-kappaB activity.

Eleutherine americana Merr. et Heyne (Iridaceae) has been used as a folk medicine for the treatment of coronary disorders and wound-healing. In our previous phytochemical study, several pyranonaphthoquinoids, including (-)-isoeleutherin, were isolated from the bulbs of E. americana. Because inhibitors of inducible nitric oxide synthase (iNOS) might be useful as anti-inflammatory agents, we investigated the potential of pyranonaphthoquinoids to inhibit iNOS activity. We found that (-)-isoeleutherin inhibits lipopolysaccharide (LPS)-stimulated induction of nitric oxide (NO) in a dose-dependent manner (IC(50)=7.4 microM). Using western blots and reverse transcription-polymerase chain reaction, we showed that (-)-isoeleutherin suppresses the expression of iNOS protein and mRNA. In addition, (-)-isoeleutherin inhibited the expression of various cytokines such as interleukin-1beta and interferon-beta. Activation of the transcriptional activity of NF-kappaB by LPS was also inhibited by treatment with (-)-isoeleutherin, suggesting that (-)-isoeleutherin-mediated suppression of iNOS expression is associated with the regulation of transcription factor NF-kappaB. These findings suggest that (-)-isoeleutherin might be a novel anti-inflammatory agent, and that it may work by inhibiting NFkB activation in macrophages.