Pulmonary hypertension concurrent with pericardial effusion and superior vena cava syndrome: who is the initiator?

The diagnosis of pulmonary hypertension(PH) should be made by combining clinical manifestations and echocardiographic probability.[1] Following the confirmation of PH, the classification should begin with the more common groups [group 2(PH due to left heart disease) and group 3(PH due to lung diseases and/or hypoxia)], then group 4(chronic thromboembolic PH and other pulmonary artery obstructions) and finally group 1(pulmonary arterial hypertension) and group 5(PH with unclear and/or multifactorial mechanisms).[1] In this case, we demonstrate a rare scenario of obstruction-caused group 4 PH.

Serum Myeloperoxidase Level in Systemic Lupus Erythematosus

SYSTEMIC lupus erythematosus （SLE） is a systemicautoimmune disease. Several mechanismshave been put forward as underlying the loss ofself-tolerance and development of organdysfunction, such as genetic, environmental, hormonal andimmunoregulatory factors.

Quantitative assessment of acute kidney injury by noninvasive arterial spin labeling perfusion MRI:a pilot study

The kidneys are essential for maintaining homeostasis,are responsible for the reabsorption of water,glucose and amino acids,and filter the blood by removing waste.Acute kidney injury(AKI) is a syndrome characterized by the rapid loss of renal excretory function and the accumulation of end metabolic products of urea and creatinine.AKI is associated with the later development of chronic kidney disease and end-stage kidney disease,and may eventually be fatal.Early diagnosis of AKI and assessments of the effects of treatment,however,are challenging.The pathophysiological mechanism of AKI is thought to be the imbalance between oxygen supply and demand in the kidneys.We have assessed the ability of arterial spin labeling(ASL) perfusion magnetic resonance imaging(MRI),without the administration of contrast media,to quantify renal blood flow(RBF) non-invasively.We found that RBF was significantly lower in AKI patients than in healthy volunteers.These results suggest that ASL perfusion MRI,a noninvasive measurement of RBF,may be useful in the early diagnosis of AKI.

Evaluation of renal artery stenosis using color Doppler sonography in young patients with multiple renal arteries

Background Some individuals have multiple renal arteries. Severe stenosis in one of the arteries may cause refractory hypertension. The detection of stenosis within one of the multiple renal arteries usually required invasive procedures, such as computed tomographic angiography （CTA） and magnetic resonance angiography （MRA）. This study reported the application of color Doppler sonography （CDS） in the detection of severe stenosis in one of the multiple arteries. Methods Patients with multiple renal arteries and one of the arteries with severe stenosis were retrospectively studied. Peak systolic velocities （PSV） of renal arteries and the intrarenal CDS patterns were collected and compared. The diagnosis was confirmed by digital subtraction angiography （DSA）. Results Four children with multiple renal arteries and one of the arteries with stenosis were investigated. They were admitted due to refractory hypertension. CDS screening identified two renal arteries in one kidney of each patient with one of the two renal arteries having stenosis 〉70%. The PSV of the stenosed arteries were much higher, and the intrarenal CDS patterns supplied by the stenosed arteries changed into T-P patterns. Conclusion Non-invasive CDS technology may be a useful method to identify severe stenosis in one of multiple renal arteries in younq patients.

Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure:A randomized,open-label,parallel-group,non-inferiority Phase III trail

Background:Erythropoietin is a glycoprotein that mainly regulates erythropoiesis.In patients with chronic renal failure with anemia,darbepoetin alfa can stimulate erythropoiesis,correct anemia,and maintain hemoglobin levels.This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections(Recombinant Human Erythropoietin injection,rHuEPO)when maintaining hemoglobin(Hb)levels within the target range(10.0-12.0 g/dL)for the treatment of renal anemia.Methods:Ninety-five patients were enrolled in this study from April 15,2013 to April 10,2014 at 25 sites.In this study,patients(n=95)aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group(n=56)and a twice or three times per week intravenous epoetin alfa group(n=39)for 28 weeks,who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease(CKD)and were undergoing hemodialysis or hemofiltration with ESA-naive(erythropoiesis stimulating agent-naive).The primary efficacy profile was the mean Hb level(the non-inferiority margin was-1.0 g/dL,week 21-28);the secondary efficacy profiles were the Hb increase rate(week 0-4),the target Hb achievement cumulative rate and time,the change trends of the Hb levels,and the target Hb maintenance ratio.Adverse events(AEs)were observed and compared,and the efficacy and safety were analyzed between the two treatment groups.Additionally,the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group,respectively;the difference of the lower limits of the 95%confidence intervals(CI)between the two groups was 0.1 g/dL(>-1.0 g/dL),and non-inferiority was proven;the Hb levels started to increase in the first four weeks at a similar increase rate;no obvious differences were observed between the groups in the target Hb achievement cumulative rates,and the Hb levels as well as the target Hb level maintenance rate changed over time.The incidence of AEs was 62.5%in the darbepoetin alfa group and 76.9%in the epoetin alfa group.All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion:Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well,which makes it not inferior to epoetin alfa intravenously twice or three times per week.Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients:A randomized,open-label,parallel-group,noninferiority phase III trial

Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method:This study was a multicenter,randomized,open-label,intergroup parallel control phase III noninferiority trial from April 19,2013 to September 9,2014 at 25 sites.In this study,the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks.The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week.All subjects underwent epoetin alfa administration during the 8-week baseline period.After that,subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group.The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period(noninferiority threshold:-1.0 g/dl)was tested between the two treatments.The time-dependent hemoglobin(Hb)concentration and the maintenance rate of the target Hb concentration(the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl)were also evaluated.Iron metabolism,including changes in the serum iron,total iron-binding capacity,ferritin,transferrin saturation,and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further.Adverse events(AEs)were also observed and compared,and the safety was analyzed between the two treatment groups.The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:Four hundred and sixty-six patients were enrolled in this study,and ultimately 384 cases were analyzed for safety,including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group.There were 211 cases in the per-protocol set,including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group.The changes in the average Hb concentrations from the baseline to the end of the evaluation period were-0.07 and-0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively.The difference between the two groups was 0.08 g/dl(95%confidence interval[CI]:-0.22 to 0.39),and the lower limit of the 95%CI was-0.22>-1.0 g/dl.The average Hb concentrations of the two groups were 10.88-11.43 g/dl(darbepoetin alfa)and 10.91-11.38 g/dl(epoetin alfa)during the study period of Weeks 0-28,with the maintenance rates of the target Hb concentration ranging within 71%-87%and 78%-95%in the darbepoetin alfa group and epoetin alfa group respectively.During the period of comparison between the two groups,the incidence of AEs in the darbepoetin alfa group was 61.42%,while in the epoetin alfa group it was 56.41%.All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion:The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

B cell-derived anti-beta 2 glycoprotein I antibody mediates hyperhomocysteinemia-aggravated hypertensive glomerular lesions by triggering ferroptosis

Hyperhomocysteinemia(HHcy)is a risk factor for chronic kidney diseases(CKDs)that affects about 85%CKD patients.HHcy stimulates B cells to secrete pathological antibodies,although it is unknown whether this pathway mediates kidney injury.In HHcytreated 2-kidney,1-clip(2K1C)hypertensive murine model,HHcy-activated B cells secreted anti-beta 2 glycoprotein I(β2GPI)antibodies that deposited in glomerular endothelial cells(GECs),exacerbating glomerulosclerosis and reducing renal function.Mechanistically,HHcy 2K1C mice increased phosphatidylethanolamine(PE)(18:0/20:4,18:0/22:6,16:0/20:4)in kidney tissue,as determined by lipidomics.GECs oxidative lipidomics validated the increase of oxidized phospholipids upon Hcy-activated B cells culture medium(Hcy-B CM)treatment,including PE(18:0/20:4+3[O],PE(18:0a/22:4+1[O],PE(18:0/22:4+2[O]and PE(18:0/22:4+3[O]).PE synthases ethanolamine kinase 2(etnk2)and ethanolamine-phosphate cytidylyltransferase 2(pcyt2)were increased in the kidney GECs of HHcy 2K1C mice and facilitated polyunsaturated PE synthesis to act as lipid peroxidation substrates.In HHcy 2K1C mice and Hcy-B CM-treated GECs,the oxidative environment induced by iron accumulation and the insufficient clearance of lipid peroxides caused by transferrin receptor(TFR)elevation and down-regulation of SLC7A11/glutathione peroxidase 4(GPX4)contributed to GECs ferroptosis of the kidneys.In vivo,pharmacological depletion of B cells or inhibition of ferroptosis mitigated the HHcy-aggravated hypertensive renal injury.Consequently,our findings uncovered a novel mechanism by which B cell-derived pathogenic anti-β2GPI IgG generated by HHcy exacerbated hypertensive kidney damage by inducing GECs ferroptosis.Targeting B cells or ferroptosis may be viable therapeutic strategies for ameliorating lipid peroxidative renal injury in HHcy patients with hypertensive nephropathy.