Xiangbao Yu

Effects of coupled plasma filtration adsorption on immune function of patients with multiple organ dysfunction syndrome.

Objective To investigate the effects of coupled plasma filtration adsorption (CPFA) on the immune function of patients with multiple organ dysfunction syndrome (MODS). Methods This study was a prospective, pilot, before-and-after self-crossover, clinical trial. Seven patients diagnosed with MODS and severe infection were randomly allocated to both 10 hours of CPFA and 10 hours of high-volume hemofiltration (HVHF) with a 12-hour interval and in random order. Serum concentrations of 7 cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1Ra), and soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) were measured during each treatment. The HLA-DR expression by the blood monocytes and the TNF-α production by the patients’ blood (both spontaneous and lipopolysaccharide stimulated) were tested before and after the treatment. TNF-α production of normal human monocytes (THP-1 cells) incubated in vitro with the patient plasma was also measured. Results During CPFA, the fall in serum TNF-α and rise in serum IL-1Ra coincided with the rise in ratios of sTNFR2/TNF-α and IL-1Ra/IL-1β (p<0.05), which were different from those seen within HVHF (p<0.05). HLA-DR expression increased after CPFA (84.32% ± 4.63% vs. 73.65% ± 11.52%, p=0.037), but there was no change after HVHF (p>0.05). Spontaneous and lipopolysaccharide-induced TNF-α production increased over time with CPFA (p=0.038, p=0.034, respectively), but did not change with HVHF (p>0.05). Patient plasma suppressed the production of TNF-α by cultured normal monocytes. This effect decreased over time with CPFA (p=0.041), but there was no effect with HVHF (p>0.05). Conclusions CPFA was superior to HVHF in increasing the ratios of antiinflammatory to proinflammatory mediators, improving antigen presentation ability, and restoring leukocyte responsiveness. These findings suggest a potential role for CPFA in the treatment of MODS.

Radial artery calcification in end‐stage renal disease patients is associated with deposition of osteopontin and diminished expression of α‐smooth muscle actin

Aim:  Vascular access is the lifeline of haemodialysis patients and radial‐cephalic fistula is the preferred type of access. We investigated vascular calcification in uraemia radial arteries and compared it with clinical parameters.

Plasma FGF23 levels and heart rate variability in patients with stage 5 CKD

SummaryFibroblast growth factor 23(FGF23) is a bone-derived hormone which regulates mineral homeostasis but may also have a role in cardiovascular disease. Here, we found that higher plasma FGF23 was independently associated with decreased heart rate variability in stage 5 CKD patients and parathyroidectomy may reverse these abnormal indicators.IntroductionLower heart rate variability (HRV) in patients with chronic kidney disease (CKD) compared with healthy controls is associated with increased risk of cardiovascular disease (CVD). Higher levels of plasma FGF23 also predict higher risk of CVD. Here, we aimed to evaluate the relationship between plasma FGF23 levels and HRV in patients with stage 5 CKD and to investigate longitudinal changes of them together with the correlation between their changes in two severe secondary hyperparathyroidism (SHPT) subgroups with successful parathyroidectomy (PTX) and persistent SHPT.MethodsThis cross-sectional study included 100 stage 5 CKD patients, 78 controls, and a prospective study in two PTX subgroups classified as successful PTX (n = 24) and persistent SHPT (n = 4) follow-up. Blood examination and 24-h Holter monitoring for HRV were measured.ResultsMost HRV indices were lower in stage 5 CKD patients than in healthy controls, and plasma FGF23 levels were higher. In multivariate stepwise regression models, levels of plasma FGF23 and serum parathyroid hormone (PTH) were correlated with HRV. The successful PTX subgroup had significant improvements over baseline in HRV indices. Persistent SHPT subgroup had numerically similar changes in HRV indices. However, plasma FGF23 levels decreased in both subgroups.ConclusionsPlasma FGF23 levels were higher in CKD patients than in controls, much higher in patients with severe SHPT. FGF23 was independently associated with decreased HRV in stage 5 CKD. Successful PTX may reverse these abnormal indicators and contribute to decreases in the risk of cardiovascular disease.

Role of TGF-β1 in Bone Matrix Production in Vascular Smooth Muscle Cells Induced by a High-Phosphate Environment

Aims: We demonstrated a relationship between transforming growth factor-β1 (TGF-β1) and production of bone matrix in vascular smooth muscle cells (VSMCs) induced by a high-phosphate environment. Methods: Rat VSMCs were incubated in a high-phosphate (2.5 or 3.5 mM) or TGF-β1 (2 or 5 ng/ml) environment. TGF-β1 monoclonal neutralization antibody (50 µg/ml) was added to inhibit the TGF-β1 signal in high-phosphate medium. Production of TGF-β1 was analyzed by Western blot and real-time PCR. Core binding factor a1 (Cbfa1), osteopontin (OP), collagen type I (Col I) and osteocalcin (OC) was investigated by Western blot and immunofluorescence staining. Mineral deposition was assessed by von Kossa staining and o-cresolphthalein complexone method. Results: VSMCs transformation induced by high phosphate occurs via an autocrine loop of TGF-β1. First, high phosphate stimulated the production of TGF-β1 in VSMCs. Second, TGF-β1 could induce increased expression of osteoblast-specific transcription factor Cbfa1 and osteogenic molecule in VSMCs. Third, the TGF-β1 neutralization antibody largely attenuated the upregulation of Cbfa1 and bone matrix in high-phosphate-stimulated cells. However, neutralization of TGF-β1 could not inhibit high-phosphate-induced VSMCs calcification, indicating that TGF-β1 was not necessary for the deposition of calcium. Conclusion: TGF-β1 plays a crucial role in bone matrix production but not calcium deposition in VSMCs induced by a high-phosphate environment, and the blockade of TGF-β1 signaling may thus be a therapeutic strategy for use with vascular disease in a high-phosphate environment.

Diagnostic Accuracy Study of Intraoperative and Perioperative Serum Intact PTH Level for Successful Parathyroidectomy in 501 Secondary Hyperparathyroidism Patients

Parathyroidectomy (PTX) is an effective treatment for severe secondary hyperparathyroidism (SHPT); however, persistent SHPT may occur because of supernumerary and ectopic parathyroids. Here a diagnostic accuracy study of intraoperative and perioperative serum intact parathyroid hormone (iPTH) was performed to predict successful surgery in 501 patients, who received total PTX + autotransplantation without thymectomy. Serum iPTH values before incision (io-iPTH0), 10 and 20 min after removing the last parathyroid (io-iPTH10, io-iPTH20), and the first and fourth day after PTX (D1-iPTH, D4-iPTH) were recoded. Patients whose serum iPTH was >50 pg/mL at the first postoperative week were followed up within six months. Successful PTX was defined if iPTH was <300 pg/mL, on the contrary, persistent SHPT was regarded. There were 86.4% patients underwent successful PTX, 9.8% remained as persistent SHPT and 3.8% were undetermined. Intraoperative serum iPTH demonstrated no significant differences in two subgroups with or without chronic hepatitis. Receiver operating characteristic (ROC) curves showed that >88.9% of io-iPTH20% could predict successful PTX (area under the curve [AUC] 0.909, sensitivity 78.6%, specificity 88.5%), thereby avoiding unnecessary exploration to reduce operative complications. D4-iPTH >147.4 pg/mL could predict persistent SHPT (AUC 0.998, sensitivity 100%, specificity 99.5%), so that medical intervention or reoperation start timely.

Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy

Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m2. Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD.

Different effect of cyclosporine and tacrolimus on renal expression of P-glycoprotein in human kidney transplantation.

OBJECTIVE To investigate the differential effects of cyclosporine (CsA) and tacrolimus (TAC) on renal expression of P-glycoprotein (P-gp) in a cohort of kidney transplant recipients. METHODS We enrolled 78 cadaveric kidney transplant recipients recurring basal immunosuppressive protocol with prednisone + mycophenolate mofetil + calcineurin inhibitor (CsA or TAC). RESULTS We performed a 3-year analysis of 60 patients. There was no difference in age, gender, or cold ischemic time between two groups, Serum creatinine, urine protein, and blood fat levels of the CsA group were significantly higher than the TAC group (P < .05), while the creatinine clearance was remarkably lower than the TAC group (P < .05). The incidence of tubular atrophy, arteriohyalinosis, and interstitial fibrosis and nephrotoxic lesions among the CsA group were higher than the TAC group, as well as the chronic allograft nephropathy (CAN) Banff score (P < .05). P-gp was predominantly present in the a tubular apical membrane, basal membrane, and cytoplasm. The intensity and extent of tubular staining score in the CsA group were lower compared with the TAC group (P < .01 and P < .05, respectively). CONCLUSION Less P-gp expression in the CsA group than the TAC group may be the molecular action pathway of the high incidence of CsA nephrotoxicity and CsA-induced CAN. This study perhaps unraveled a novel interpretation that the differences of CsA and TAC on long-term allograft survival were due to increases dynamic effects of CsA at the exposures employed in this study.

Parathyroidectomy Increases Heart Rate Variability and Leptin Levels in Patients with Stage 5 Chronic Kidney Disease.

Background: In chronic kidney disease (CKD) patients, decreased heart rate variability (HRV) reflects impaired cardiac automatic nervous function and high risk of cardiovascular disease (CVD). Lower HRV in patients with severe secondary hyperparathyroidism (SHPT), a clinical manifestation of CKD-mineral and bone disorder (CKD-MBD), could be reversed by parathyroidectomy (PTX). It has been proved that leptin interacts with the autonomic nervous function. However, the associations between leptin and HRV in CKD patients and their longitudinal changes in SHPT patients after PTX are still unknown. Methods: This was a cross-sectional study including 141 stage 5 CKD patients, and a prospective study in 36 severe SHPT patients with PTX. HRV was measured by Holter and serum leptin was measured by ELISA. Serum leptin levels were adjusted for body mass index (BMI) and transformed using natural logarithm (lnleptin/BMI). Results: With a gradient of lnleptin/BMI across quartiles from Q1 to Q4 in CKD patients, HRV indices showed no differences among quartiles. Patients in Q1 group had higher mean 24 h heart rates, and lower ln(very low frequency) (lnVLF) than other quartiles, although there were no statistically significant difference. In multivariate stepwise regression, serum leptin/BMI was an independent predictor for low frequency/high frequency. HRV indices and lnleptin/BMI levels were increased in severe SHPT patients after PTX. Compared to other quartiles, SHPT patients in Q1 group had larger improvement of lnVLF after PTX. Conclusion: Circulating leptin levels may be a novel treatment target to reduce CVD risk in advanced CKD-MBD patients.

Low-Site Peritoneal Catheter Implantation Decreases Tip Migration and Omental Wrapping

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Effect of coupled plasma filtration adsorption on endothelial cell function in patients with multiple organ dysfunction syndrome

Objective The purpose of our study was to investigate the effect of coupled plasma filtration adsorption (CPFA) on endothelial cell (EC) function in patients with multiple organ dysfunction syndrome (MODS). Methods Besides routine therapy, the 24 MODS patients underwent both CPFA and high volume hemofiltration (HVHF), scheduled randomly at intervals of 12 hours. Patient serum from 0, 5, and 10 hours of therapy was collected to measure soluble E-selectin (sE-selectin) and soluble thrombomodulin (sTM) by the ELISA method. Human umbilical vein endothelial cells (HUVEC) were incubated for 24 hours with the patient serum and the supernatant liquid was gathered to detect sTM and sE-selectin. The proliferation function of the ECs was detected by methyl thiazolyl tetrazolium (MTT) method. Results 1. The serum levels of sE-selectin and sTM were significantly higher in MODS patients than in controls; serum sE-selectin and sTM decreased remarkably after a single circulation in CPFA (p<0. 05) but not in HVHF (p>0. 05); the level of sE-selectin and sTM in systemic circulation had no change during CPFA or HVHF (p>0.05); 2. sTM in supernatant liquid incubated with serum from 5 hours of CPFA and 10 hours of HVHF decreased remarkably (p<0.05), while sE-selectin decreased significantly (p<0. 05) from 10 hours of CPFA, but there was no change from 5 hours and 10 hours of HVHF (p>0. 05); 3. when incubated with serum taken from the device pre- or post-CPFA, the optical density (OD) value of the latter was higher. The OD value increased gradually when incubated with serum from 0, 5, and 10 hours of CPFA (p<0.05), but changed little from HVHF. Conclusions CPFA can eliminate sE-selectin and sTM and improve the secretion function of ECs. CPFA was somewhat better and earlier than HVHF, while to a certain degree it can weaken the inhibitory effect of serum on the proliferation function of ECs.