Cystatin C as a Predictor of Renal Function and Methotrexate-Associated Toxicities in Patients With Rheumatoid Arthritis.

OBJECTIVE: Methotrexate (MTX) is an anchor drug for most patients with rheumatoid arthritis (RA); however, its use may be limited depending on renal function. Therefore, this study aimed to examine the discrepancy in the estimated glomerular filtration rate (eGFR) using conventional serum creatinine (SCr)-, cystatin C-, and MTX-associated toxicities in patients with RA. METHODS: In total, 436 patients were enrolled, and eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on both cystatin C and SCr levels. The CKD and MTX dosing stages were classified according to eGFR. MTX-associated toxicities were also evaluated. RESULTS: The mean eGFR using CKD-EPI cystatin C (CKD-EPIcys) was 89.44 mL/min/1.73 m2, lower than the eGFR using CKD-EPI SCr (CKD-EPISCr) of 95.55 mL/min/1.73 m2. After converting eGFR to CKD-EPIcys by CKD-EPISCr, 29.8% of patients were reclassified to a higher stage according to the Kidney Disease: Improving Global Outcomes CKD stage. Also, according to the MTX guidelines, 6.4% of the group with an eGFR > 50 mL/min/1.73 m2 were reclassified to eGFR 10-50 mL/1.73 m2, requiring dose adjustment. The incidence of MTX-associated toxicities, such as anemia, leukopenia, and nephrotoxicity, was significantly higher in the CKD stage-changed group than in the nonstage-changed group. CONCLUSION: Our results showed that eGFR based on SCr was overestimated compared with eGFR based on cystatin C. In addition, we demonstrated that MTX-associated toxicities were significantly increased in the group with a changed stage when the eGFR was converted from CKD-EPISCr to CKD-EPIcys.

Agaricus bisporus Extract Exerts an Anti-Obesity Effect in High-Fat Diet-Induced Obese C57BL/6N Mice by Inhibiting Pancreatic Lipase-Mediated Fat Absorption.

Agaricus bisporus is well known as a source of polysaccharides that could improve human health. The objective of this study was to explore the anti-obesity effect of A. bisporus extract (ABE), abundant in polysaccharides, and its underlying mechanism. Pancreatic lipase inhibitory activity in vitro was determined after treatment with ABE and chitosan. Treatment with ABE and chitosan significantly decreased pancreatic lipase activity. Five-week-old male SD rats were randomly divided into three groups for acute feeding with vehicle, ABE at 80 mg/kg body weight (BW)/day, and ABE at 160 mg/kg BW/day. ABE dose-dependently increased plasma lipid clearance in an oral lipid tolerance test. Five-week-old male C57BL/6N mice were fed a control diet (CD), a high-fat diet (HFD), an HFD with ABE at 80 mg/kg BW/day, ABE at 160 mg/kg BW/day, or chitosan at 160 mg/kg BW/day for eight weeks. HFD-fed mice showed significant increases in body weight, fat mass, white adipose tissue, average lipid droplet size, and serum levels of glucose, triglyceride, ALT, and AST compared to those in the CD group. However, ABE or chitosan administration ameliorated these increases. ABE or chitosan significantly reduced dietary efficiency and increased fecal excretion levels of lipids, triglycerides, and total cholesterol. These in vitro and in vivo findings suggest that ABE might act as an anti-obesity agent by inhibiting pancreatic lipase-mediated lipid absorption, at least in part.

Immune-enhancing effect of hydrolyzed and fermented Platycodon grandiflorum extract in cyclophosphamide-induced immunosuppressed BALB/c mice.

BACKGROUND/OBJECTIVES: The immunomodulatory effect of Platycodon grandiflorum (PG) has been reported, but studies on its mechanism are still lacking. This study was undertaken to confirm whether the hydrolyzed and fermented PG extract (HFPGE) obtained by adding hydrolysis and fermentation to the extraction process has an immune-enhancing effect in the in vivo system. MATERIALS/METHODS: Five-week-old BALB/c mice were divided into 4 groups: normal control group (NOR), control group (CON), 150 mg/kg body weight (BW)/day HFPGE-treated group (T150), and 300 mg/kg BW/day HFPGE-treated group (T300). The mice were administered HFPGE for 4 weeks and intraperitoneally injected with cyclophosphamide (CPA, 80 mg/kg BW/day) on day 6, 7, and 8, respectively, to induce immunosuppression. The levels of immunoglobulins (Igs) and cytokines were measured in the serum. In splenocytes, proliferation and cytokine levels were measured. RESULTS: Serum IgA, IgG, and IgM levels were observed to decrease after CPA treatment, which was recovered by HFPGE administration. The levels of serum interleukin (IL)-12, tumor necrosis factor (TNF)-α, IL-8, and transforming growth factor (TGF)-ß were also decreased after exposure to CPA but increased after HFPGE administration. Decreased splenocyte proliferation was seen in CPA-treated mice, but was observed to increase in the T150 and T300 groups as compared to the NOR group. Compared to the CON group, splenocyte proliferation stimulated with concanavalin A (ConA) or lipopolysaccharide (LPS) in the HFPGE-treated groups was significantly increased. The cytokines secreted by ConA-stimulated splenocytes (IL-2, IL-12, interferon-γ, TNF-α) were increased in the T150 and T300 groups, and cytokines secreted by LPS-stimulated splenocytes (IL-4, IL-8, TGF-ß) were also increased by HFPGE administration. CONCLUSION: These results suggest that HFPGE stimulates the immunity in immunosuppressed conditions, thereby enhancing the immune response. Therefore, it is expected that HFPGE has the potential to be used as functional food and medicine for immune recovery in various immunocompromised situations.

Immunostimulatory activity of hydrolyzed and fermented Platycodon grandiflorum extract occurs via the MAPK and NF-κB signaling pathway in RAW 264.7 cells.

BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG) has long been known as a medicinal herb effective in various diseases, including bronchitis and asthma, but is still more widely used for food. Fermentation methods are being applied to increase the pharmacological composition of PG extracts and commercialize them with high added value. This study examines the hydrolyzed and fermented PG extract (HFPGE) fermented with Lactobacillus casei in RAW 264.7 cells, and investigates the effect of amplifying the immune and the probable molecular mechanism. MATERIALS/METHODS: HFPGE's total phenolic, flavonoid, saponin, and platycodin D contents were analyzed by colorimetric analysis or high-performance liquid chromatography. Cell viability was measured by the MTT assay. Phagocytic activity was analyzed by a phagocytosis assay kit, nitric oxide (NO) production by a Griess reagent system, and cytokines by enzyme-linked immunosorbent assay kits. The mRNA expressions of inducible nitric oxide synthase (iNOS) and cytokines were analyzed by reverse transcription-polymerase chain reaction, whereas MAPK and nuclear factor (NF)-κB activation were analyzed by Western blots. RESULTS: Compared to PGE, HFPGE was determined to contain 13.76 times and 6.69 times higher contents of crude saponin and platycodin D, respectively. HFPGE promoted cell proliferation and phagocytosis in RAW 264.7 cells and regulated the NO production and iNOS expression. Treatment with HFPGE also resulted in increased production of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, C-X-C motif chemokine ligand10, granulocyte-colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1, and the mRNA expressions of these cytokines. HFPGE also resulted in significantly increasing the phosphorylation of NF-κB p65, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. CONCLUSIONS: Taken together, our results imply that fermentation and hydrolysis result in the extraction of more active ingredients of PG. Furthermore, we determined that HFPGE exerts immunostimulatory activity via the MAPK and NF-κB signaling pathways.

Gynostemma pentaphyllum extract and its active component gypenoside L improve the exercise performance of treadmill-trained mice.

BACKGROUND/OBJECTIVES: The effectiveness of natural compounds in improving athletic ability has attracted attention in both sports and research. Gynostemma pentaphyllum (Thunb.) leaves are used to make traditional herbal medicines in Asia. The active components of G. pentaphyllum, dammarane saponins, or gypenosides, possess a range of biological activities. On the other hand, the anti-fatigue effects from G. pentaphyllum extract (GPE) and its effective compound, gypenoside L (GL), remain to be determined. MATERIALS/METHODS: This study examined the effects of GPE on fatigue and exercise performance in ICR mice. GPE was administered orally to mice for 6 weeks, with or without treadmill training. The biochemical analysis in serum, glycogen content, mRNA, and protein expressions of the liver and muscle were analyzed. RESULTS: The ExGPE (exercise with 300 mg/kg body weight/day of GPE) mice decreased the fat mass percentage significantly compared to the ExC mice, while the ExGPE showed the greatest lean mass percentage compared to the ExC group. The administration of GPE improved the exercise endurance and capacity in treadmill-trained mice, increased glucose and triglycerides, and decreased the serum creatine kinase and lactate levels after intensive exercise. The muscle glycogen levels were higher in the ExGPE group than the ExC group. GPE increased the level of mitochondrial biogenesis by enhancing the phosphorylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein and the mRNA expression of nuclear respiratory factor 1, mitochondrial DNA, peroxisome proliferator-activated receptor-δ, superoxide dismutase 2, and by decreasing the lactate dehydrogenase B level in the soleus muscle (SOL). GPE also improved PGC-1α activation in the SOL significantly through AMPK/p38 phosphorylation. CONCLUSIONS: These results showed that GPE supplementation enhances exercise performance and has anti-fatigue activity. In addition, the underlying molecular mechanism was elucidated. Therefore, GPE is a promising candidate for developing functional foods and enhancing the exercise capacity and anti-fatigue activity.

Gynostemma pentaphyllum extract and Gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1α pathway in C2C12 myotubes.

BACKGROUND/OBJECTIVES: Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism. Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells. MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry. Mitochondrial reactive oxygen species generation was measured using the 2'7'-dichlorofluorescein diacetate assay. RESULTS: GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolism-regulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domain-containing 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2. CONCLUSIONS: The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

Anti-inflammatory activity of palmitoylethanolamide ameliorates osteoarthritis induced by monosodium iodoacetate in Sprague-Dawley rats.

Novel treatment strategies are urgently required for osteoarthritis (OA). Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and elucidate the molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague-Dawley rats. The experimental animals were divided into normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). The changes in blood parameters, body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. Oral administration of PEA had no adverse effects on the BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and prostaglandin E2 considerably reduced in the PEA100 group compared with those in the CON group. In the synovia of knee joints, the mRNA expression of iNOS, 5-Lox, Cox-2, Il-1ß, Tnf-α, and Mmp-2, -3, -9, and -13 apparently increased with MIA administration. Meanwhile, Timp-1 mRNA expression apparently decreased in the CON group but increased to the normal level with PEA treatment. Thus, PEA can be an effective therapeutic agent for OA.

The clinical impact of gut microbiota in chronic kidney disease.

Gut microorganisms play critical roles in both maintaining host homeostasis and the development of diverse diseases. Gut dysbiosis, an alteration of the composition and function of gut microorganisms, is commonly seen in patients with chronic kidney disease (CKD). CKD itself contributes to a disruption of the symbiotic relationship between the gut microbiota and the host, while the resulting gut dysbiosis may play a part in stage progression of CKD. This bidirectional relationship supports the concept that the gut microbiota is considered a novel focus for the pathogenesis and management of CKD. This article examines the interaction between the gut microbiota and the kidney, the mutual effects of dysbiosis and CKD, and possible treatment options to restore gut eubiosis, and reduce CKD progression and its related complications.

Perception and attitudes of medical students on clinical clerkship in the era of the Coronavirus Disease 2019 pandemic.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) has been placing severe strain on global healthcare systems and medical education programs, leading to growing demands for medical students to assume the role of preliminary healthcare providers. OBJECTIVES: To assess the perception and attitudes of medical students about clinical clerkship training during the COVID-19 pandemic. DESIGN: A cross-sectional survey with web-based 3-fields/14-items questionnaire was conducted, from April 7 to 14, 2020, to evaluate their self-assessed perception and attitudes on clerkship training of hospital practice under the COVID-19 outbreak and spread among 161 (78 on pre-clerkship course, 83 on clinical clerkship course) medical students at Dankook University College of Medicine, Cheonan, Republic of Korea. RESULTS: Of the 151 medical students who completed the survey, 81 students (53.7%) considered themselves familiar with COVID-19. Although the students were concerned about the spread of the virus during clinical clerkship training, 118 (78.1%) students preferred the clerkship training in a hospital practice. The students in the clinical clerkship program preferred this over those in the pre-clerkship program (85.7% vs. 70.2%, P = 0.03), primarily because a clinical clerkship could not be replaced by an online class during the COVID-19 pandemic. In addition, their responses indicated, in order of significance, fear of not completing the clerkship course on time, willingness to participate as a preliminary healthcare provider in pandemic, the potential waste of tuition, and belief that a hospital is rather safe. The change in the academic calendar had not a positive impact on the lifestyles of many students. CONCLUSIONS: In circumstances such as the COVID-19 pandemic, educational strategies to clinical clerkship training for medical students should be developed to provide them with the opportunity to be actively involved in hospital practice under strict safety guidance focused on preventing virus infection and transmission.

Gynostemma Pentaphyllum Extract Ameliorates High-Fat Diet-Induced Obesity in C57BL/6N Mice by Upregulating SIRT1.

Gynostemma pentaphyllum is widely used in Asia as a herbal medicine to treat type 2 diabetes, dyslipidemia, and inflammation. Here, we investigated the anti-obesity effect and underlying mechanism of G. pentaphyllum extract (GPE) enriched in gypenoside L, gypenoside LI, and ginsenoside Rg3 and obtained using a novel extraction method. Five-week-old male C57BL/6N mice were fed a control diet (CD), high-fat diet (HFD), HFD + 100 mg/kg body weight (BW)/day GPE (GPE 100), HFD + 300 mg/kg BW/day GPE (GPE 300), or HFD + 30 mg/kg BW/day Orlistat (Orlistat 30) for 8 weeks. The HFD-fed mice showed significant increases in body weight, fat mass, white adipose tissue, and adipocyte hypertrophy compared to the CD group; but GPE inhibited those increases. GPE reduced serum levels of triglyceride, total cholesterol, and LDL-cholesterol, without affecting HDL-cholesterol. GPE significantly increased AMPK activation and suppressed adipogenesis by decreasing the mRNA expression of CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP1c), PPARγ coactivator-1α, fatty acid synthase (FAS), adipocyte protein 2 (AP2), and sirtuin 1 (SIRT1) and by increasing that of carnitine palmitoyltransferase (CPT1) and hormone- sensitive lipase (HSL). This study demonstrated the ameliorative effect of GPE on obesity and elucidated the underlying molecular mechanism.

Cyanidin-3-O-galactoside-enriched Aronia melanocarpa extract attenuates weight gain and adipogenic pathways in high-fat diet-induced obese C57BL/6 mice.

: Aronia melanocarpa are a rich source of anthocyanins that have received considerable interest for their relations to human health. In this study, the anti-adipogenic effect of cyanidin-3-O-galactoside-enriched Aronia melanocarpa extract (AM-Ex) and its underlying mechanisms were investigated in an in vivo system. Five-week-old male C57BL/6N mice were randomly divided into five groups for 8-week feeding with a control diet (CD), a high-fat diet (HFD), or a HFD with 50 (AM-Ex 50), 100 (AM-Ex 100), or 200 AM-Ex (AM-Ex 200) mg/kg body weight/day. HFD-fed mice showed a significant increase in body weight compared to the CD group, and AM-Ex dose-dependently inhibited this weight gain. AM-Ex significantly reduced the food intake and the weight of white fat tissue, including epididymal fat, retroperitoneal fat, mesenteric fat, and inguinal fat. Treatment with AM-Ex (50 to 200 mg/kg) reduced serum levels of leptin, insulin, triglyceride, total cholesterol, and low density lipoprotein (LDL)-cholesterol. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that AM-Ex suppressed adipogenesis by decreasing CCAAT/enhancer binding protein , peroxisome proliferator-activated receptor , sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor gamma coactivator-1, acetyl-CoA carboxylase 1, ATP-citrate lyase, fatty acid synthase, and adipocyte protein 2 messenger RNA (mRNA) expressions. These results suggest that AM-Ex is potentially beneficial for the suppression of HFD-induced obesity by modulating multiple pathways associated with adipogenesis and food intake.

A risk scoring model to predict renal progression associated with postcontrast acute kidney injury in chronic kidney disease patients.

Postcontrast acute kidney injury (AKI) occurs more frequently in patients with lower estimated glomerular filtration rate. We hypothesized that postcontrast AKI in chronic kidney disease (CKD) patients with distinct risk factors might be associated with accelerated renal progression.We undertook this retrospective cohort study to develop and validate a risk scoring model for predicting renal progression. In a development dataset, 18,278 contrast-enhanced CT scans were performed in 9097 patients with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m) who were not undergoing dialysis. Postcontrast AKI was observed in 5.8% (1051/18,278) of all contrast-enhanced CTs with 7.6% (689/9097) of the total CKD patients. We investigated the 1-year renal outcome in 224 eligible patients. A risk scoring model was developed with multivariate regression analysis and was assessed in external validation (independent 154 patients).Among 224 patients, 70 (31.3%) patients had progression of renal dysfunction at 1 year (defined as reduction in estimated GFR ≥25% at 1 year). A risk score of 4, 4, 6, 6, 7, or 6 was assigned to diabetes, baseline estimated GFR < 45 mL/min/1.73 m, hypertension, repeated contrast exposure, congestive heart failure, and persistent renal injury (defined as an elevation of serum creatinine ≥25% at 3 months), respectively. An increasing risk score was associated with renal progression. Of note, persistent renal injury was more prevalent in the progression group than in the non-progression group. The AUROC of the model in the development population was 0.765. In the validation dataset, however, the discriminative power decreased (AUROC = 0.653).Our suggested model provided the risk of renal progression, aiding in predicting prognosis, counseling, and improving outcomes in CKD patients complicated by postcontrast AKI.

Predictive Factors of Duration of Continuous Renal Replacement Therapy in Acute Kidney Injury Survivors.

The factors influencing continuous renal replacement therapy (CRRT) duration for critically ill patients with acute kidney injury (AKI) are unclear. Therefore, we investigated the clinical factors that could influence the duration of CRRT for AKI survivors. In this retrospective observational study, the medical records of all hospital survivors who required CRRT for AKI in intensive care units were analyzed. The CRRT duration (median, 6 days) was categorized as short-duration CRRT (≤ 6 days, n = 65) and long-duration CRRT (> 6 days, n = 59), according to the median CRRT duration. A urine output of less than 0.5 mL/kg/h (adjusted odds ratio [OR], 3.4; P = 0.010), mechanical ventilation use (adjusted OR, 7.9; P = 0.001), and extracorporeal membrane oxygenation (ECMO) use (adjusted OR, 6.5; P = 0.010) were independent predictors of long-duration CRRT, whereas serum creatinine and neutrophil gelatinase-associated lipocalin were not significant predictors. A clinical model demonstrated a good discriminatory ability to predict long-duration CRRT (area under the curve, 0.84; 95% confidence interval, 0.76-0.90). The urine output immediately before CRRT initiation and factors associated with disease severity significantly affected the duration of CRRT. Simultaneously considering the urine output, mechanical ventilation use, and ECMO use predicted CRRT duration in AKI survivors.

Efficacy of the HLA-B∗58:01 Screening Test in Preventing Allopurinol-Induced Severe Cutaneous Adverse Reactions in Patients with Chronic Renal Insufficiency-A Prospective Study.

BACKGROUND: Thus far, human leukocyte antigen (HLA)-B∗58:01 has been recognized as the most important risk factor for allopurinol induced severe cutaneous adverse reactions (SCARs). OBJECTIVE: To determine the usefulness of prospective screening for the HLA-B∗58:01 allele to identify Korean individuals at risk for SCARs induced by allopurinol treatment. METHODS: We prospectively enrolled 542 patients with chronic renal insufficiency (CRI) from 10 hospitals nationwide and performed DNA genotyping to determine whether they carried the HLA-B∗58:01 allele. Of these, 503 HLA-B∗58:01-negative patients (92.8% of total) were treated with allopurinol, and 39 HLA-B∗58:01-positive patients (7.2%) were treated with febuxostat, an alternative drug. The patients then were followed up biweekly for 90 days using a telephone survey to monitor symptoms of adverse drug reactions, including SCARs. As a control, we used the historical incidence rate of allopurinol-induced SCARs in 4002 patients with CRI from the same hospitals who were enrolled retrospectively. RESULTS: Nineteen patients in the prospective cohort developed mild and transient adverse reactions but none showed allopurinol-induced SCARs. By contrast, we identified 38 patients with allopurinol-induced SCARs (0.95%) in the historical control. The difference in the incidence of allopurinol-induced SCARs between the prospective cohort and historical control was statistically significant (0% vs 0.95%, respectively; P = .029). CONCLUSIONS: The present study demonstrated the clinical usefulness of the HLA-B∗58:01 screening test before allopurinol administration to prevent allopurinol-induced SCARs in patients with CRI.

Change in alkaline phosphatase activity associated with intensive care unit and hospital length of stay in patients with septic acute kidney injury on continuous renal replacement therapy.

BACKGROUND: Evidence suggests that alkaline phosphatase attenuates inflammatory response in sepsis by lipopolysaccharide detoxification and adenosine triphosphate dephosphorylation. We sought to determine changes in alkaline phosphatase (AP) activity during septic acute kidney injury (AKI) and clinical parameters associated with AP activity. METHODS: In this retrospective study, we investigated baseline (when initiating CRRT) and follow-up AP activity on day 3, and associated outcomes in patients who underwent continuous renal replacement therapy (CRRT) due to septic AKI. RESULTS: We analyzed the baseline AP activity of 155 patients and day 3 AP activity in 123 patients. Baseline AP activity was not associated with renal or inflammatory biomarkers, or outcomes. It did not significantly differ between the 75 survivors and 80 non-survivors (p = 0.155). AP activity was higher on day 3 than at baseline (105 U/L [interquartile range, 79-156] vs 90 U/L [interquartile range, 59-133]). In particular, liver and bone isoforms increased significantly (p < 0.05), but intestine isoforms did not reach statistical significance (p = 0.367). In addition, day 3 AP activity showed a weak correlation with length of ICU stay (r = 0.213, p = 0.018) and length of hospital stay (r = 0.216, p = 0.017), but not with survival (r = - 0.035, p = 0.698). CONCLUSION: Endogenous AP activity significantly increased in patients with septic AKI. However, neither baseline nor follow-up AP activity was associated with survival.

Effect of isoflavone-enriched whole soy milk powder supplementation on bone metabolism in ovariectomized mice.

BACKGROUND/OBJECTIVE: There is intense interest in soy isoflavone as a hormone replacement therapy for the prevention of postmenopausal osteoporosis. A new kind of isoflavone-enriched whole soy milk powder (I-WSM) containing more isoflavones than conventional whole soy milk powder was recently developed. The aim of this study was to investigate the effects of I-WSM on bone metabolism in ovariectomized mice. MATERIALS/METHODS: Sixty female ICR mice individually underwent ovariectomy (OVX) or a sham operation, and were randomized into six groups of 10 animals each as follows: Sham, OVX, OVX with 2% I-WSM diet, OVX with 10% I-WSM diet, OVX with 20% I-WSM diet, and OVX with 20% WSM diet. After an 8-week treatment period, bone mineral density (BMD), calcium, alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) 5b, osteocalcin (OC), procollagen 1 N-terminal propeptide (P1NP), and osteoprotegenin (OPG) were analyzed. RESULTS: BMD was significantly lower in the OVX group compared to the Sham group but was significantly higher in OVX + 10% I-WSM and OVX + 20% I-WSM groups compared to the OVX group (P < 0.05). Serum calcium concentration significantly increased in the OVX + 10% and 20% I-WSM groups. Serum ALP levels were significantly lower in the OVX + 10% and 20% I-WSM groups compared to the other experimental groups (P < 0.05). OC was significantly reduced in the OVX group compared to the Sham group (P < 0.05), but a dose-dependent increase was observed in the OVX groups supplemented with I-WSM. P1NP and OPG levels were significantly reduced, while TRAP 5b level was significantly elevated in the OVX group compared with the Sham group, which was not affected by I-WSM (P < 0.05). CONCLUSIONS: This study suggests that I-WSM supplementation in OVX mice has the effect of preventing BMD reduction and promoting bone formation. Therefore, I-WSM can be used as an effective alternative to postmenopausal osteoporosis prevention.

Hepatitis C virus infection in chronic kidney disease: paradigm shift in management.

Hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is associated with increased liver-related morbidity and mortality rates, accelerated progression to end-stage renal disease, and risk of cardiovascular events. CKD patients with HCV infection require antiviral therapy. Pegylated interferon (peg-IFN) plus ribavirin was the standard of care for HCV-infected CKD patients before the introduction of first-generation direct-acting antiviral (DAA) oral anti-HCV agents. Peg-IFN-based treatment has a low virologic response rate and poor compliance, resulting in a high dropout rate. Recently, several clinical trials of all-DAA combination regimens have reported excellent antiviral efficacy and few adverse drug reactions in HCV-infected patients with CKD. These positive results have revolutionized the treatment of chronic HCV infection in this population. In this review, we address the impact of chronic HCV infection in CKD patients, and discuss their management using next-generation DAAs.