Pterostilbene, a Bioactive Component of Blueberries, Alleviates Renal Interstitial Fibrosis by Inhibiting Macrophage-Myofibroblast Transition.

Pterostilbene (PTB) is a derivative of resveratrol present in grapes and blueberries. PTB is structurally similar to resveratrol, possessing properties such as being analgesic, anti-aging, antidiabetic, anti-inflammatory, anti-obesity, anti-oxidation, cholesterol-reductive, and neuroprotective. However, there have not been reports on the effect of PTB on macrophage-myofibroblast transition (MMT) induced fibrosis in kidney. In this study, we investigated the antifibrotic effects of PTB on the in vivo mouse unilateral ureteral obstruction (UUO) model and in vitro MMT cells. Kidneys subjected to UUO with PTB treatment were collected for the investigation of PTB mediating MMT derived renal interstitial fibrosis. We conducted kidney RNA-seq transcriptomes and TGF-[Formula: see text]1-induced bone marrow-derived macrophages assays to determine the mechanisms of PTB. We found that PTB treatment suppressed the interstitial fibrosis in UUO mice. PTB also attenuated the number of MMT cells in vivo and in vitro. The transcriptomic analysis showed that CXCL10 may play a central role in the process of PTB-treated renal fibrosis. The siRNA-mediated CXCL10 knockdown decreased the number of MMT cells in TGF-[Formula: see text]1-induced bone marrow-derived macrophages. Our results suggested that PTB attenuated renal interstitial fibrosis by mediating MMT by regulating transcriptional activity of CXCL10.

Inhibition of Fatty Acid-Binding Protein 4 Attenuated Kidney Fibrosis by Mediating Macrophage-to-Myofibroblast Transition.

The macrophage-to-myofibroblast transition (MMT) process is an important pathway that contributing to renal interstitial fibrosis (RIF). Fatty acid-binding protein 4 (FABP4) deteriorated RIF via promoting inflammation in obstructive nephropathy. However, the clinical significance of FABP4 in fibrotic kidney disease remains to be determined and little is known of the FABP4 signaling in MMT. Biopsy specimens of chronic kidney disease patients and kidneys subjected to unilateral ureteral obstruction (UUO) of FABP4-deficient mice or FABP4 inhibitor-treated mice were collected for the investigation of FABP4 mediating MMT of RIF. We conducted kidney RNA-seq transcriptomes and TGF-ß1-induced bone marrow-derived macrophage (BMDM) assays to determine the mechanisms of FABP4. We found that FABP4 expression correlated with RIF in biopsy specimens and the injured kidneys of UUO mice where FABP4 was co-expressed with MMT cells. In UUO mice, FABP4 deficiency and a highly selective FABP4 inhibitor BMS309403 treatment both suppressed RIF. FABP4 ablation also attenuated the UUO-induced number of MMT cells and serum amyloid A1 (Saa1) expression. The siRNA-mediated Saa1 knockdown decreased the number of MMT cells in vitro. In conclusion, FABP4 is an important factor contributing to RIF by mediating MMT, and genetic/pharmacological inhibition of FABP4 provides a novel approach for the treatment of kidney fibrosis.

Rhabdomyolysis-induced acute kidney injury in a patient with undifferentiated connective tissue disease: A case report and literature review rhabdomyolysis-induced AKI in a patient with UCTD.

RATIONALE: Acute kidney injury (AKI) accounts for 8% to 16% of hospital admissions and can quadruple hospital mortality, placing a serious burden on the health economy. Acute kidney injury (AKI) is mainly caused by dehydration, shock, infection, sepsis, heart disease, or as a side-effect of nephrotoxic drugs. About 10% to 60% of patients with rhabdomyolysis develop AKI, and 10% of AKI is attributable to rhabdomyolysis. However, rhabdomyolysis-induced AKI secondary to undifferentiated connective tissue disease (UCTD) has rarely been reported before. PATIENT CONCERNS: We report the case of a 50-year-old male of UCTD presented with dark brown urine, swelling and edema of the upper limbs, and decreased urine output. DIAGNOSIS: The patient was diagnosed with rhabdomyolysis-induced AKI secondary to UCTD. INTERVENTIONS: The patient was successfully treated with intravenous methylprednisolone with other supportive treatment. OUTCOMES: After 3 days of initiating treatment of medicinal charcoal tablets, sodium bicarbonate and intravenous fluids upon admission, the patient's serum creatinine changed mildly from 145.0 µmol/L to 156.0 µmol/L, but the urinary output increased from 1000 mL/24 h to 2400 mL/24 h, with his creatine kinase (CK) and myoglobin rose from 474 IU/L to 962 IU/L and from 641.5ng/mL to 1599 ng/mL, respectively. We then tried to empirically initiate UCTD therapy by giving corticosteroids. After the administration of the 40 mg of methylprednisolone daily, the serum creatinine level dropped to 97 µmol/L the second day, CK decreased to 85 IU/L within 1 week and myoglobin decreased to 65.05 ng/mL within 10 days. When maintenance dose of 4 mg daily was given, the patient showed no abnormalities in creatinine or CK levels. LESSONS: There have been few reports on the association between rhabdomyolysis-induced AKI and UCTD and its mechanism remains unclear. Clinicians should be aware of UCTD as a possible cause to rhabdomyolysis-induced AKI.

Citrate versus heparin lock for prevention of hemodialysis catheter-related complications: updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To provide updated evidence, we conducted a systematic review and meta-analysis to compare citrate lock with heparin in the prevention of hemodialysis catheter-related complications. METHODS: A systematic review and meta-analysis of randomized controlled trials were obtained by searching PubMed, EMBASE, Ovid, Cochrane library, and the Web of Science databases. Primary outcomes were catheter-related bloodstream infections (CRBI), exit-site infections, bleeding events, catheter removal for poor flow, and thrombolytic treatment. Secondary outcomes were thrombocytopenia, access-related admission, and all-cause mortality. RESULTS: The meta-analysis showed that the citrate lock containing antimicrobials can reduce the risk of CRBI when compared with heparin lock (RR: 0.34, 95% CI 0.24-0.49; I2 = 0%; P < 0.00001), and a tunneled cuffed catheter (TCC) was more beneficial for the prevention of CRBI (RR: 0.42, 95% CI 0.25-0.69; I2 = 40%; P = 0.0007) when compared with non-tunneled cuffed catheters (NTCC). The microbiological correlation analysis suggests that the occurrence of CRBI is closely related to S. aureus in catheters locked by citrate (P = 0.015) rather than by heparin (P = 0.868). In the analysis of exit-site infection, citrate lock with NTCC was more effective in preventing exit-site infection than heparin (RR: 0.48, 95% CI 0.31-0.75; I2 = 0%; P = 0.001). In addition, the risk of bleeding episodes was reduced in hemodialysis patients using citrate lock with TCC (RR: 0.53, 95% CI 0.32-0.86; I2 = 0%; P = 0.01) and patients with citrate alone (RR: 0.51, 95% CI 0.30-0.85; I2 = 12%; P = 0.010). The risk of catheter removal for poor flow (P = 0.91), thrombolytic treatment (P = 0.76), thrombocytopenia (P = 0.37), access-related admission (P = 0.10), and all-cause mortality (P = 0.62) was not significantly different. CONCLUSIONS: Antimicrobial-containing citrate lock solutions could reduce the risk of CRBI in hemodialysis patients. The occurrence of CRBI is closely related to S. aureus in catheters locked by citrate rather than by heparin. Citrate lock was effective in reducing exit-site infection in NTCC and bleeding events in TCC.

Long-segment central venous occlusion in a hemodialysis patient treated by segmented sharp recanalization strategy: A case report.

INTRODUCTION: Among hemodialysis population, central vein occlusion (CVO) is a common complication. Percutaneous transluminal angioplasty has become the mainstay treatment these days. But the treatment of long-segment central venous occlusion remains difficult. PATIENT CONCERNS: We presented a 73-year-old man on maintenance hemodialysis complaining of swelling of the right arm and face for 20 days. The patient underwent maintenance hemodialysis via a right internal jugular vein catheter for first 2 months of dialysis while the initial right radiocephalic wrist arteriovenous fistula (AVF) blood flow had been unsatisfactory (below 180 mL/min) for 1 month. DIAGNOSIS: Digital subtraction angiography revealed long-segment CVO extending from the right subclavian vein (SV) to the right innominate vein (IV), forming an obvious included angle at the right jugular angle. INTERVENTIONS: Since conventional guide wire transversal failed, segmented sharp recanalization was performed by separate transversal of the obstructive right SV and right IV, therefore crossing the whole lesion segment by segment, followed by balloon dilation and stent placement. OUTCOMES: No procedure-related complication was recorded during or after the operation. After a follow-up period of 5 months, the patient's AVF maintained satisfactory in blood flow, while the edema in his ipsilateral limb and face also notably ameliorated. CONCLUSION: The segmented sharp recanalization is a practical strategy in treating angled long-segment CVO which is refractory to traditional guide wire transversal in hemodialysis patients.

Improving the diagnostic accuracy of acute myocardial infarction with the use of high-sensitive cardiac troponin T in different chronic kidney disease stages.

High-sensitive cardiac troponin T (hs-TnT) is a critical biomarker in diagnosis of acute myocardial infarction (AMI). However, CKD individuals usually have elevated hs-TnT even in the absence of AMI. Our study aimed to explore the optimal cutoff-value of hs-TnT and further to improve diagnostic accuracy of AMI in CKD patients. Clinical data of 489 patients were collected from the maintained database between September 2010 and June 2014. CKD patients with AMI were assigned to CKD+AMI group and CKD patients without AMI were assigned to CKD group. Receiver operating characteristic curves were utilized to derive the optimal cutoff-value. In CKD+STEMI and CKD group, hs-TnT was increased with descending eGFR. In CKD+NSTEMI group, hs-TnT showed an upward trend with increasing SYNTAX Score. In patients with CKD+STEMI, hs-TnT was significantly correlated with SYNTAX Score in CKD stage 2, stage 4 and in total. In CKD patients, the optimal cutoff-value of hs-TnT for diagnosis of AMI was 129.45 ng/l with 75.2% sensitivity and 83.2% specificity. The cutoff-value appeared to be hs-TnT level of 99.55ng/l in CKD stage 3, 129.45 ng/l in CKD stage 4, 105.50 ng/l in CKD stage 5 and 149.35 ng/l in dialysis patients, respectively. In different stages of CKD, eGFR-range-specific optimal cutoff-values should be considered.