Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults.

BACKGROUND: Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study. METHODS: In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5-7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation. RESULTS: Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3-8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences. CONCLUSIONS: Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

Omega-3 fatty acid and menaquinone-7 combination are helpful for aortic calcification prevention, reducing osteoclast area of bone and Fox0 expression of muscle in uremic rats.

BACKGROUND: Osteopenia, sarcopenia, and vascular calcification (VC) are prevalent in patients with chronic kidney disease and often coexist. In the absence of proven therapies, it is necessary to develop therapeutic or preventive nutrients supplementation for osteopenia, sarcopenia, and VC. The present study investigated the effect of omega-3 fatty acid (FA) and menaquinone-7 (MK-7) on osteopenia, sarcopenia, and VC in adenine and low-protein diet-induced uremic rats. METHODS: Thirty-two male Sprague-Dawley rats were fed diets containing 0.75% adenine and 2.5% protein for three weeks. Rats were randomly divided into four groups that were fed diets containing 2.5% protein for four weeks: adenine control (0.9% saline), omega-3 FA (300 mg/kg/day), MK-7 (50 µg/kg/day), and omega-3 FA/MK-7. Von Kossa staining for aortic calcification assessment was performed. Osteoclast surface/bone surface ratio (OcS/BS) of bone and muscle fiber were analyzed using hematoxylin and eosin staining. Osteoprotegerin (OPG) immunohistochemical staining was done in the aorta and bone. Molecules related with sarcopenia were analyzed using western blotting. RESULTS: Compared to the normal control, OcS/BS and aortic calcification, and OPG staining in the aorta and bone were significantly increased in the adenine controls. OPG staining and aortic calcification progressed the least in the group supplemented with both omega-3 FA/MK-7. In the adenine controls, the regular arrangement of muscle fiber was severely disrupted, and inflammatory cell infiltration was more prominent. These findings were reduced after combined supplementation with omega-3 FA/MK-7. Furthermore, decreased mammalian target of rapamycin and increased Forkhead box protein 1 expression was significantly restored by combined supplementation. CONCLUSIONS: Combined nutrients supplementation with omega-3 FA and MK-7 may be helpful for aortic VC prevention, reducing osteoclast activation and improving sarcopenia-related molecules in adenine and low-protein diet induced uremic rats.

Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model.

Mitochondrial dysfunction contributes to the pathogenesis of kidney injury related with cardiovascular disease. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) protects renal tubular cells by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2). AMP-activated protein kinase (pAMPK)-mediated phosphorylation and sirtuin 1/3 (SIRT1/3)-mediated deacetylation are required for PGC-1α activation. In the present study, we aimed to investigate whether omega-3 fatty acids (FAs) regulate the expression of mediators of mitochondrial biogenesis in 5/6 nephrectomy (Nx) rats. Male Sprague-Dawley rats were assigned to the following groups: sham control, Nx, and Nx treated with omega-3 FA. The expression of PGC-1α, phosphorylated PGC-1α (pPGC-1α), acetylated PGC-1α, and factors related to mitochondrial biogenesis was examined through Western blot analysis. Compared to the control group, the expression of PGC-1α, pAMPK, SIRT1/3, Nrf1, mTOR, and Nrf2 was significantly downregulated, and that of Keap 1, acetylated PGC-1α, and FoxO1/3, was significantly upregulated in the Nx group. These changes in protein expression were rescued in the omega-3 FA group. However, the expression of pPGC-1α was similar among the three groups. Omega-3 FAs may involve mitochondrial biogenesis by upregulating Nrf1 and Nrf2. This protective mechanism might be attributed to the increased expression and deacetylation of PGC-1α, which was triggered by SIRT1/3.

Comparison of clinical outcome between incremental peritoneal dialysis and conventional peritoneal dialysis: a propensity score matching study.

BACKGROUND: Incremental peritoneal dialysis (iPD) can be useful in patients with residual renal function (RRF). RRF was well preserved and similar survival was shown in iPD compared to conventional PD (cPD) in previous study. However, the long-term survival of iPD remains unclear compared to cPD in diabetic patients. This study evaluated whether patient survival, hospitalization and peritonitis, and PD survival in iPD were lower than cPD or not. METHODS: We conducted a 12-year retrospective observational study of 303 PD patients (232 cPD and 71 iPD) using propensity score matching by age, gender, and diabetes mellitus (DM). Finally, 78 cPD patients and 39 iPD patients were included and 44 patients had DM. Incremental PD was defined as starting PD with two or three manual exchanges per day. RESULTS: The median duration of iPD was 24.1 months and iPD had higher RRF than cPD. Compared to cPD, the patient survival, PD survival and hospitalization benefits were not found in iPD but diabetic iPD patients had significantly longer survival and less hospitalization. Cumulative risk for peritonitis was lower iPD and PD duration of iPD was longer than those of cPD. The iPD was an independent factor associated with survival in patients with DM. CONCLUSIONS: Incremental PD may be a safe PD modality to initiate and maintain PD in less uremic patients with tolerable RRF. Incremental PD would be a benefit for survival in diabetic patients. Further prospective studies are necessary to confirm the effectiveness of iPD in PD patients with similar RRF.

Omega-3 fatty acid decreases oleic acid by decreasing SCD-1 expression in the liver and kidney of a cyclosporine-induced nephropathy rat model.

AIM: Stearoyl-CoA desaturase (SCD)-1 and elongase-6 (Elovl-6) are associated with fatty acid (FA) synthesis. We evaluated the effect of omega-3 FA on erythrocyte membrane FA contents through SCD-1 and Elovl-6 expression in the liver and kidney of a cyclosporine (CsA)-induced rat model. METHODS: Male Sprague Dawley rats were divided into control, CsA, and CsA treated with omega-3 FA groups. We measured SCD-1 and Elovl-6 expression levels via western blot and immunohistochemistry analysis. RESULTS: Erythrocyte membrane oleic acid content was lower in the CsA with omega-3 FA group compared to the CsA group. Compared to the control group, CsA-induced rats showed elevated SCD-1 expression in the kidney and liver, which omega-3 FA treatment reversed. Elovl-6 expression was increased in the liver, but decreased in the kidney in CsA group compared to control, which omega-3 FA treatment also reversed. CONCLUSIONS: Omega-3 FA supplementation decreased erythrocyte membrane oleic acid content by modulating SCD-1 and Elovl-6 expression in the kidney and liver of CsA-induced rats.

Effect of Omega-3 Fatty Acid on STAMP2 Expression in the Heart and Kidney of 5/6 Nephrectomy Rat Model.

Six transmembrane protein of prostate 2 (STAMP2) is a critical modulator of inflammation and metabolism in adipose tissue. There are no data on the expression of STAMP2 in chronic kidney disease, which is an inflammatory disease related to metabolic disorders. This study aimed to investigate STAMP2 expression in the kidney and heart in 5/6 nephrectomy (Nx) rats, and the effect of omega-3 fatty acid (FA) on STAMP2 expression. Male Sprague Dawley rats were divided into three groups: sham control (0.9% saline), 5/6 Nx (0.9% saline), and 5/6 Nx treated with omega-3 FA (300 mg per kg per day by gastric gavage). The expression of STAMP2 in the kidney and heart were examined by western blotting. Serum creatinine levels were higher in 5/6 Nx rats than in controls. Compared with sham controls, the expression of IκB, NF-κB, NOX4, SREBP-1, and LXR were upregulated and STAMP2 and phosphorylated-AMPK expression were downregulated in the kidney and heart of 5/6 Nx rats. Omega-3 FA supplementation prevented these changes in biomarkers related to inflammation and metabolic lipid disorders. Omega 3-FA supplementation induced the upregulation of STAMP2 protein in 5/6 Nx rats, which was associated with an attenuation of inflammation- and metabolic disease-related markers.

The Effect of Mycophenolate Mofetil versus Cyclosporine as Combination Therapy with Low Dose Corticosteroids in High-risk Patients with Idiopathic Membranous Nephropathy: a Multicenter Randomized Trial.

BACKGROUND: Appropriate immunosuppressive therapy for patients with idiopathic membranous nephropathy (MN) remains controversial. The effect of mycophenolate mofetil (MMF) versus cyclosporine (CsA) combined with low-dose corticosteroids was evaluated in patients with idiopathic MN in a multi-center randomized trial (www.ClinicalTrials.gov NCT01282073). METHODS: A total of 39 biopsy-proven idiopathic MN patients with severe proteinuria were randomly assigned to receive MMF combined with low-dose corticosteroids (MMF group) versus CsA combined with low-dose corticosteroids (CsA group), respectively, and followed up for 48 weeks. Complete or partial remission rate of proteinuria and estimated glomerular filtration rate (eGFR) at 48 weeks were compared. RESULTS: The level of proteinuria at baseline and at 48 weeks was 8.9 ± 5.9 and 2.1 ± 3.1 g/day, respectively, in the MMF group compared to 8.4 ± 3.5 and 3.2 ± 5.7 g/day, respectively, in the CsA group. In total, 76.1% of the MMF group and 66.7% of the CsA group achieved remission at 48 weeks (95% confidence interval, -0.18 to 0.38). There was no difference in eGFR between the two groups. Anti-phospholipase A2 receptor Ab levels at baseline decreased at 48 weeks in the complete or partial remission group (P = 0.001), but were unchanged in the no-response group. There were no significant differences between the two groups in changes in the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index scores from baseline to 48 weeks. CONCLUSION: In combination with low-dose corticosteroids, the effect of MMF may not be inferior to that of CsA in patients with idiopathic MN, with similar adverse effects including gastrointestinal symptoms. Trial registry at ClinicalTrials.gov (NCT01282073).

Abdominal aortic calcification score among several vascular calcification scores of plain radiograph is the most reliable predictor of severe coronary artery calcification in dialysis patients.

AIM: Coronary artery calcification (CAC) score on computed tomography (CT) or vascular calcification (VC) scores on plain radiographs are associated with cardiovascular events and fracture. We investigated which VC score among several VC scores on plain radiographs is predictor of CAC, and whether VC scores are related with bone mineral density (BMD) in dialysis patients. METHODS: We checked several plain radiographs (hands and pelvis [HP], feet and lateral lumbar spine), BMD and multidetector CT scans of 55 patients maintaining dialysis in this cross-sectional study. We analyzed data to find predictors for severe CAC which was defined as CAC scores >400 on CT. RESULTS: Patients with severe CAC on CT had a higher proportion of abdominal aortic calcification (AAC) score ≥5, HP score ≥3 and feet ≥1 than those without severe CAC. The CAC score on CT was positively correlated with all VC scores on plain radiographs. The AAC and CAC scores were negatively correlated with T-scores for the BMD at the forearm and positively correlated with osteoprotegerin levels. Among several VC scores on plain radiographs, the AAC ≥5 were independently associated with severe CAC on CT. CONCLUSIONS: Several plain radiographs evaluating VC scores, including a lateral lumbar spine view at the very least, can replace CT checking CAC score in dialysis patients. The AAC score ≥5 may not only reveal severe CAC but also give a hint of low bone mass at the forearm.

The effects of omega-3 fatty acid on vitamin D activation in hemodialysis patients: a pilot study.

The high incidence of cardiovascular disease and vitamin D deficiency in chronic kidney disease patients is well known. Vitamin D activation by omega-3 fatty acid (FA) supplementation may explain the cardioprotective effects exerted by omega-3 FA. We hypothesized that omega-3 FA and 25-hydroxyvitamin D (25(OH)D) supplementation may increase 1,25-dihydroxyvitamin D (1,25(OH)2D) levels compared to 25(OH)D supplementation alone in hemodialysis (HD) patients that have insufficient or deficient 25(OH)D levels. We enrolled patients that were treated for at least six months with 25(OH)D < 30 ng/mL (NCT01596842). Patients were randomized to treatment for 12 weeks with cholecalciferol supplemented with omega-3 FA or a placebo. Levels of 25(OH)D and 1,25(OH)2D were measured after 12 weeks. The erythrocyte membrane FA contents were also measured. Levels of 25(OH)D were increased in both groups at 12 weeks compared to baseline. The 1,25(OH)2D levels at 12 weeks compared to baseline showed a tendency to increase in the omega-3 FA group. The oleic acid and monounsaturated FA content decreased, while the omega-3 index increased in the omega-3 FA group. Omega-3 FA supplementation may be partly associated with vitamin D activation, although increased 25(OH)D levels caused by short-term cholecalciferol supplementation were not associated with vitamin D activation in HD patients.

Vascular calcification on plain radiographs is related with the severity of lesions detected by coronary angiography in dialysis patients.

Coronary artery disease (CAD) is a primary cause of mortality and morbidity in dialysis patients. However, it is difficult to select the proper point for coronary angiographic procedure, because dialysis patients frequently do not display typical symptoms. Vascular calcification (VC) scores of artery or aorta on plain radiographs are associated with CAD events and may be predictive of CAD in dialysis patients. Therefore, we evaluated whether high or meaningful VC scores on plain radiographs are related with the severity of lesions detected by coronary angiography (CAG) in dialysis patients. We retrospectively enrolled dialysis patients who underwent CAG and checked several plain radiographs within one year before or after CAG. Significant VC is defined as high or meaningful VC scores, such as long abdominal aortic calcification and medial artery calcification on feet. Of all 55 patients, 41 patients (74.5%) exhibited significant VC on plain radiographs and 23 patients (41.8%) underwent stent insertion. Among the 23 patients, longer stents were used in 18 patients with significant VC (34.1 ± 19.5 mm vs. 16.6 ± 15.2 mm, P = 0.029). Patients with significant VC showed higher prevalence rate of severe coronary artery calcification (P = 0.007) and diffuse/tubular stenosis (P = 0.012), detected by CAG, than those without significant VC. Thus, high or meaningful VC scores on plain radiographs were associated with the degree of calcification or stenosis detected by CAG. In conclusion, VC scores on plain radiographs may be predictive of calcification or stenosis of coronary artery before CAG in dialysis patients.

Effect of pitavastatin on erythrocyte membrane fatty acid content in patients with chronic kidney disease: two-arm parallel randomized controlled trial.

Background: Statins reduce the risk of cardiovascular events in patients with chronic kidney disease (CKD). Although diabetes mellitus (DM) is a reported side effect of statin treatment, some studies have indicated that pitavastatin does not cause DM. The present study investigated the effect of pitavastatin on the fatty acid (FA) content of erythrocyte membranes, which affects the occurrence of DM and cardiovascular diseases. In addition, changes in adiponectin and glycated hemoglobin (HbA1c) levels were evaluated after pitavastatin treatment. Methods: A total of 45 patients were enrolled, 28 of whom completed the study. Over 24 weeks, 16 patients received 2 mg pitavastatin and 12 patients received 10 mg atorvastatin. Dosages were adjusted after 12 weeks if additional lipid control was required. There were 10 and nine patients with DM in the pitavastatin and atorvastatin groups, respectively. Erythrocyte membrane FAs and adiponectin levels were measured using gas chromatography and enzyme-linked immunosorbent assay, respectively. Results: In both groups, saturated FAs, palmitic acid, trans-oleic acid, total cholesterol, and low-density lipoprotein cholesterol levels were significantly lower than those at baseline. The arachidonic acid (AA) content in the erythrocyte membrane increased significantly in the pitavastatin group, but adiponectin levels were unaffected. HbA1c levels decreased in patients treated with pitavastatin. No adverse effects were associated with statin treatment. Conclusion: Pitavastatin treatment in patients with CKD may improve glucose metabolism by altering erythrocyte membrane AA levels. In addition, pitavastatin did not adversely affect glucose control in patients with CKD and DM.

Dynamics of serum anion gaps with in-hospital mortality: Analysis of the multi-open databases.

BACKGROUND: Few studies have investigated the relationship between the anion gap, including the corrected anion gap, and patient mortality in intensive care units (ICUs) without restricting the analysis to specific diseases or medical specialties. Our primary objective was to investigate the association between the anion gap and ICU mortality using multiple open-access databases. METHODS: We identified 4229 subjects from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, whose entries were from between 2008 and 2019. For each patient, the anion gap and corrected anion gap were calculated, and the study sample was divided into tertile groups (T) according to these levels. The association between the anion gap and in-hospital mortality was assessed using hazard ratios (HRs) and 95% confidence intervals (CIs) derived from a multivariable-adjusted Cox proportional hazards model. Besides MIMIC-IV, we also incorporated study samples from two other databases (MIMIC-III and electronic ICU) to calculate summary HRs using a random-effects meta-analysis. RESULTS: Within MIMIC-IV, 1015 patients (24%) died during an average follow-up period of 15.5 days. The fully adjusted HRs and 95% CIs for T2 and T3, relative to T1, were 1.31 (95% CI 1.08-1.58) and 1.54 (95% CI 1.24-1.90), respectively. When grouped by corrected anion gap, the results remained statistically significant. In the meta-analysis, the summary HRs and 95% CIs for T2 and T3 were 1.24 (95% CI 1.08-1.43) and 1.55 (95% CI 1.33-1.82), respectively. CONCLUSIONS: Both the anion gap and corrected anion gap were associated with in-hospital mortality regardless of specific diseases or medical specialties.

Rosuvastatin attenuates inflammation, apoptosis and fibrosis in a rat model of cyclosporine-induced nephropathy.

BACKGROUND/AIM: Cyclosporine (CsA)-induced kidney injury is characterized by renal dysfunction with inflammatory cell infiltrations, apoptosis and fibrosis. Pleiotropic effects of statins may exert anti-inflammatory, antiapoptotic and antifibrotic actions beyond lipid control. The aim of this study is to investigate whether rosuvastatin (RUS) has anti-inflammatory, antiapoptotic and antifibrotic effects on chronic CsA-induced nephropathy in a rat model. METHODS: Male Sprague-Dawley rats fed a low-sodium diet were divided into three treatment groups: control (0.9% saline injection), CsA (15 mg/kg/day by subcutaneous injection), CsA + RUS (10 mg/kg/day by gastric gavage). Renal function, CsA level and lipid levels were measured at the end of 4 weeks. The expression of ED-1, transforming growth factor-ß(1) (TGF-ß(1)) and α-smooth muscle actin (α-SMA) for inflammation and fibrosis were examined by Western blot analysis. The expression levels of apoptosis-associated factors were examined by Western blot analysis. Apoptosis was evaluated using the terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling (TUNEL) method. RESULTS: Kidney function was decreased in CsA-treated rats compared with controls, which was attenuated by RUS. RUS did not affect the lipid level or the blood CsA level. TUNEL staining showed that RUS inhibited CsA-induced tubular apoptosis. RUS decreased CsA-induced increased expression of Bax/Bcl-2 ratio. The expressions of ED-1, α-SMA, TGF-ß(1), Smad2/3, Smad4 and p-JNK were increased in CsA-treated rats, which were attenuated by RUS. Tubular atrophy and interstitial fibrosis in CsA-treated rats were attenuated by RUS supplementation. CONCLUSION: RUS supplementation attenuates proinflammatory and apoptosis-related factors and inhibits the fibrotic pathways including the smad-dependent and smad-independent pathways in a rat model of CsA-induced nephropathy.

Erythrocyte n-3 polyunsaturated fatty acids and the risk of type 2 diabetes in Koreans: a case-control study.

BACKGROUND: There is inconsistent epidemiologic evidence for an association between tissue levels of n-3 polyunsaturated fatty acids (PUFAs) and the risk of type 2 diabetes. The purpose of the present study was to investigate whether erythrocyte levels of n-3 PUFAs are negatively associated with the risk of type 2 diabetes and correlated with levels of glucose and HbA1c in Koreans. METHODS: A total of 130 patients with type 2 diabetes and 260 age- and sex-matched controls participated in this study. RESULTS: The risk of type 2 diabetes was negatively associated with erythrocyte levels of 22:5n3 and 22:6n3, which were negatively correlated with HbA1c levels after adjusting for age, sex and body mass index. Additionally, the risk of type 2 diabetes was negatively associated with erythrocyte levels of 18:0 and 20:4n6, but positively associated with erythrocyte levels of 16:0, 18:1n9, 18:3n3, 18:2n6, 18:3n6, n-6/n-3 PUFA ratio, 18:1t and 18:2n6t, and Δ-6 desaturase (18:3n6/18:2n6) and Δ-9 desaturase (18:1n9/18:0) activities. CONCLUSIONS: The risk of type 2 diabetes was negatively associated with erythrocyte levels of n-3 PUFA, which were negatively correlated with HbA1c levels in Koreans, suggesting that n-3 PUFAs might reduce the risk of type 2 diabetes in Asians.

Vascular calcification on plain radiographs is associated with carotid intima media thickness, malnutrition and cardiovascular events in dialysis patients: a prospective observational study.

BACKGROUND: Vascular calcification (VC) and carotid intima media thickness (CIMT) are strongly associated with cardiovascular (CV) disease. We hypothesized that significant VC on plain radiographs is associated with CIMT and CV events in dialysis patients. In addition, we evaluated risk factors for VC progression on plain radiographs in dialysis patients. METHODS: In this 2-year observational, prospective study, 67 dialysis patients were included. We checked plain radiographs at baseline and after 2 years. Laboratory tests and malnutrition score were obtained at baseline, after 12 months, and after 24 months. RESULTS: The mean age of patients was 56.3 ± 10.3 years and duration of dialysis was 41.3 ± 34.5 months. The prevalence of significant VC was 61.2% and the prevalence of carotid artery atheromatous plaques was 55.6%. Mean CIMT, malnutrition scores, CRP level and prevalence of carotid atheromatous plaques were significantly higher in patients with significant VC. Serum albumin and total iron binding capacity were significantly lower in patients with significant VC compared to patients without significant VC. During a mean observational period of 22 months, patients without significant VC showed lower CV events by the Kaplan-Meyer method (p = 0.010). Progression of VC was found in 35.7% among 56 patients followed up. Hemoglobin after 24 months was an independent factor for progression of VC (Exp(B) = 0.344, 95% Confidence Interval = 0.13 - 0.96, p = 0.034). CONCLUSIONS: Significant VC on plain radiograph was associated with CIMT, malnutrition, inflammation, and CV events in dialysis patients. Conditions which increase hemoglobin level may retard progression of VC in dialysis patients.

Role of B-type natriuretic peptide as a marker of mortality in acute kidney injury patients treated with continuous renal replacement therapy.

OBJECTIVES: Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) is associated with poor outcome. Plasma B-type natriuretic peptide (BNP) is a biomarker related to fluid volume overload, and is elevated in AKI patients. The purpose of the study was to assess whether BNP levels at the time of starting CRRT could be used as a predictor of mortality in patients with AKI receiving CRRT. METHODS: We conducted a prospective observational cohort study enrolling 149 patients with AKI receiving CRRT. The primary outcome was mortality during CRRT. RESULTS: The median BNP level of 84 (56.3%) patients who expired was significantly higher than that of those who survived (1812.5 vs. 475.0 pg/mL; p = 0.01). Receiver operating characteristic curves demonstrated BNP levels as a predictor of mortality during CRRT with an area under the curve of 0.77 (p = 0.000), and the optimal threshold for BNP was 1054 pg/mL. Patients with BNP levels above 1054 pg/mL had a significantly higher mortality (76.6 vs. 34.7%; p = 0.01). CONCLUSION: Elevated BNP level is associated with mortality in patients with AKI receiving CRRT.

Factors associated with gait speed: results from the RolE of AST120 (Renamezin) in sarCOpenia preVEntion in pRe-dialYsis chronic kidney disease patients (RECOVERY) study.

Background: Gait speed is an important measure of functional ability. This study aimed to investigate the factors associated with gait speed in patients with chronic kidney disease. The study focused on sarcopenic components, plasma uremic or inflammatory marker levels, and quality of life effects. Methods: The RolE of AST120 (Renamezin) in sarCOpenia preVEntion in pRe-dialYsis chronic kidney disease patients is a 48-week, randomized controlled, parallel-group, open-label, multicenter trial to determine the role of Renamezin (Daewon Pharmaceutical Co., Ltd.) in patients with chronic kidney disease. The participants were classified into four groups according to gait speed: ≤0.8, 0.8-1.0, ≤1.0-1.3, and ≥1.3 m/sec. Linear regression analysis was performed to identify the factors associated with gait speed. Results: The group with a gait speed of ≤0.8 m/sec was the oldest and had the highest proportion of participants with low education level and medical aid. Participants with a gait speed of ≤0.8 m/sec showed the lowest physical and mental component scale scores. The interleukin-6 (IL-6) level tended to be the higher trend in the lowest gait speed group. In the multivariate linear regression analysis adjusted for age, sex, diabetes mellitus, and estimated glomerular filtration rate, insurance status, handgrip strength, IL-6 level, hemoglobin level, mental component scale score, and physical component scale score were significantly associated with gait speed. Conclusion: In conclusion, gait speed is associated with handgrip strength, IL-6 level, and various components of quality of life in predialysis chronic kidney disease patients.

Association between diastolic dysfunction by color tissue Doppler imaging and vascular calcification on plain radiographs in dialysis patients.

BACKGROUND/AIM: Diastolic dysfunction is frequently associated with left ventricular hypertrophy, which is indicative of future cardiovascular events. Vascular calcification (VC) is known to be associated with coronary artery disease in dialysis patients. The present study was to determine the interrelationship between LV diastolic dysfunction by tissue Doppler imaging and VC on plain radiographs in dialysis patients. METHODS: Fifty-six dialysis patients were recruited and VC scores were evaluated by plain radiographic film. The ratio of early diastolic transmitral inflow velocity (E) to early diastolic mitral annular velocity (E') was measured by tissue Doppler imaging. We defined diastolic dysfunction as an E/E' ratio >15 on tissue Doppler imaging. RESULTS: Patients with diastolic dysfunction showed a higher percentage of coronary artery disease history, abdominal aortic calcification (AAC) scores ≥5, high LV mass index, and high left atrium volume compared to patients without diastolic dysfunction. The E/E' ratio was significantly higher in patients with significant VC, VC scores of the pelvis and hands ≥3, and AAC scores ≥5 on plain radiographs. AAC scores ≥5 were considered an independent predictor of diastolic dysfunction. CONCLUSION: VC on plain radiographs is associated with the E/E' ratio and AAC scores ≥5 are important clues for LV diastolic dysfunction in dialysis patients.

Factors influencing survival according to elapsed time in peritoneal dialysis patients.

The survival of patients undergoing peritoneal dialysis (PD) has improved over the past decade, but their mortality rate remains high. The aim of the current study was to identify correctable and uncorrectable factors influencing survival according to the elapsed time in patients undergoing PD. We retrospectively analyzed data from medical records of 118 patients who had undergone PD for >6 months. We analyzed laboratory findings at three time points (point of PD initiation, 6-month point of PD and 3-month point prior to death or last follow-up) during PD treatment and prescribed medications taken for >50% of the follow-up period. Three-year survival group was younger, had lower prevalence rates of ischemic heart disease (p = 0.024) and heart failure (HF) (8.5% vs. 34.6%, p = 0.003), higher serum albumin levels (albumin 2) at the 6-month point of PD, and higher serum albumin (albumin3) and creatinine (creatinine3) levels at the 3-month point prior to death or last follow-up than nonsurvival group. Patients without underlying HF, patients treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers during the last 6 months (p = 0.0042), and those having creatinine 3 >9.5 mg/dL (p = 0.0029), and albumin 2 (p = 0.0209) and albumin 3 >3.5 g/dL (p = 0.0003) showed significantly higher survival curves. HF and albumin 3 were found to be independent factors for 3-year survival and long-term survival, respectively, by the multivariate Cox regression model. In conclusion, HF was useful information for predicting 3-year survival, and low serum albumin levels according to elapsed time should be corrected for survival of PD patients.

Phase angle as a marker for muscle health and quality of life in patients with chronic kidney disease.

BACKGROUND & AIMS: Sarcopenia is associated with adverse health outcomes in individuals with chronic kidney disease (CKD); hence, a convenient and reliable method for monitoring muscle health is required. This study investigated the utility of the phase angle (PhA) to estimate muscle health and health-related quality of life (HRQoL) in patients with CKD. METHODS: Data were obtained from a multicenter randomized trial that examined the effect of AST-120 on sarcopenia and HRQoL. The PhA and skeletal muscle mass index (SMI) were derived from bioelectrical impedance analyses at baseline, 24-week, and 48-week. In addition, handgrip strength (HGS), 6 m gait speed (GS), and HRQoL were obtained simultaneously. RESULTS: In total, 149 participants were included. PhA was linearly related to SMI, HGS, and GS (r = 0.616, 0.619, and 0.290, respectively; all P < 0.001). Moreover, PhA was associated with the criteria for low muscle mass and low muscle strength (both P < 0.001), and it predicted the presence of sarcopenia (P = 0.001). Substantial agreement was observed in the diagnosis of sarcopenia (κ = 0.510; P < 0.001). In addition, PhA was related to various aspects of HRQoL, including physical functioning, general health, mental health, physical component scale, mental component scale, work status, quality of social interaction, sexual function, and social support. In the longitudinal analysis, SMI increased in the increasing PhA group (a PhA slope ≥ 0.2° per year), and HGS was reduced in the decreasing PhA group (a PhA slope of < -0.2° per year) as compared to the constant PhA group (a PhA slope of -0.2 to 0.2° per year; both P = 0.054). The GS pattern did not differ among the three groups. In addition, the prevalence of sarcopenia was comparable at baseline (P = 0.220); however, its proportion rose in the decreasing PhA group and reduced in the increasing PhA group (P at 48-week = 0.058). With regards to aspects of HRQoL, role limitations due to physical health problems worsened in the decreasing PhA group. CONCLUSIONS: PhA appears to be a reliable marker for estimating muscle health and HRQoL in patients with CKD. In addition, monitoring PhA may help estimate the longitudinal patterns of muscle health and HRQoL.