Mediating function of heart failure in the causal relationship between diastolic blood pressure and hypertensive renal disease with renal failure:a mediated Mendelian randomization study

Objective:To study the causality relationship between diastolic blood pressure(DBP)and hypertensive renal disease with renal failure(HRDRF)and the mediating role of hear t failure(HF)in the causality relationship by network Mendelian randomization(MR).Methods:Genome-wide analysis of DBP,HRDRF,and HF was downloaded from the public database(Genome-Wide Analysis Study[GWAS])and was used to analyze the results and to conduct mediated MR analysis.Results:Analysis showed that DBP was positively correlated with HRDRF(OR=1.0002,95%CI:1.0001–1.0003,P=1.8076e-05)and DBP was positively correlated with HF(OR=1.0295,95%CI:1.0221–1.0370,P=2.5292e-15).HF and HRDRF had a positive causal effect(OR=1.0001,95%CI:1.0000–1.0001,P=0.0152).Mediation analysis showed that the contribution ratio of HF to the combined effect of DBP and HRDRF was 24.69%.Conclusions:DBP can increase the risk of renal disease with renal failure,and HF may play an impor tant role in mediating this causal relationship.

Renal Protective Effects of Eucommia Glycosides on Renal Hypertension Rats

Objective:To investigate the antihypertensive,antioxidant and renal protective effects of Eulcommia glycosides on renal hypertensive rats with two-kidney and one-clip type.Materials and Methods:A total of 50 healthy male SD rats were fed adaptive for one week,and after 2 weeks of 2 K1 C operation,they were divided into 5 groups:sham operation group,model control group,benazepri group,ulcommin high-dose group and low-dose group,with 8 rats in each group.Rats in each group were given continuously intragastric administration for 4 weeks,and systolic blood pressure of caudal artery was measured before modeling,2 weeks after modeling,and after treatment.Urinary microalbumin(MALB)was measured at 24 hours.Serum AngⅡand ROS were measured by taking blood from abdominal aorta.The right kidney of rats was taken to measure the expression level of NOX4 m RNA and pathological observation by HE staining.Results:Compared with sham operation group,blood pressure,serum AngⅡ,ROS content,NOX4 m RNA expression level and MALB in kidney tissue of model group were significantly increased(P<0.05).Compared with model control group,the above indexes in treatment groups were significantly decreased(P<0.05).There was no statistical significance among all treatment groups(P<0.05).Under light microscope,normal glomeruli and renal tubules were observed in rats of sham operation group.Slight glomerular atrophy and fibrous hyperplasia were observed in the renal tissue of model control rats,and inflammatory cells were observed in renal interstitium.The above symptoms were slightly relieved in the treatment group compared with the model control group.Conclusion:Eucommia glycosides can reduce blood pressure and protect the kidney,and the mechanism may be related to the inhibition of renal oxidation.

HYPERTENSION IN RENAL ALLOGRAFT RECIPIENTS

Objective To further evaluate the effect of hypertension on renal graft function, and the relationship between hypertension, hyperlipoidemia and ischemic heart disease. Methods 102 renal transplant recipients with a functioning renal graft for more than 1 year were enrolled in this study. Renal function was followed for the further 24 months. Results The overall prevalence of hypertension was 89.2%(91/102) and 36.2%(33/91) hypertensive patients had uncontrolled blood pressure. After 24 months those with high blood pressure had significantly higher Scr levels than normotensive patients (P<0.05). The number of different antihypertensive classes required was related to Scr (P<0.05). Plasma cholesterol levels in hypertension patients especially in blood pressure uncontrolled group were significantly elevated (P<0.01). Ischemic heart disease was more common in hypertensive patients (P<0.05). Cyclosporine A was associated with hypertension more frequently than azathioprine and FK506, whereas low-dose prednisolone did not appear to influence blood pressure. Conclusion The data further confirmed that hypertension was associated with hyperlipidemia and ischemic heart disease, and emerged as a predictor of renal graft dysfunction. Whether cyclosporine A should be converted to new immunosuppressive agents and which class of antihypertensive medication is more effective in this population remain open questions.

Proximal Iliac Artery Stenosis in Allograft Renal Transplant, a Diagnostic beyond Echo-Doppler, Treatment Approach

Background: Transplant Renal Artery Stenosis (TRAS) is a well-known vascular complication after a kidney transplant. It is associated with premature renal failure, uncontrolled hypertension, and allograft loss. However, Proximal Iliac Artery Stenosis to a Kidney Transplant (Prox-TRAS) is an uncommon cause of vascular graft complication leading to acute renal failure and refractory hypertension with a less incidence around and only a few cases reports have been described in the medical literature. Methods: We reviewed the medical record of kidney transplant recipients of the General Hospital of Ciudad Real, Spain, from March 2008 to March 2019. We identified all cases (260) with the diagnosis of renal vascular hypertension by imaging studies. Of those 260 renal vascular stenoses, five (5) were diagnosed with proximal iliac artery stenosis through Angio-CT and arteriography. We performed an analysis of clinical parameters and evolution. Results: Prox-TRAS was diagnosed in 5 of the 260 patients who presented acute or progressive allograft dysfunction with refractory hypertension, with an incidence rate of 1.4%. In 4 of them (1.1%), we had to resort to another imaging test, angio-CT, arteriography, as the echo-doppler was unable to identify the abnormalities. Hypertension was a constant finding along with impaired renal function (100%);with respect to Prox-TRAS, its onset was later (12 - 60 months) after transplantation. An increase in TA (140 ± 10 and 80.7 ± 7 to 160 ± 18 and 85 ± 7 mmHg, p-0.009) was observed. There was an increase in the use of hypotensive drugs (2.1 ± 1.1 and 4.3 ± 1, p-0.003). Similarly, in all cases, a worsening of basal creatinine from 0.9 to 0.1 ± to 1.2 ± (P × 0.004) was also observed. Prox-TRAS was a cause of the increase in both creatinine and TA (140 ± 10 and 80.7 ± 7 to 160 ± 18 and 85 ± 7 mmHg, P 0.009). All cases were treated by Percutaneous transluminal angioplasty with stent placement, N= 5. In the follow-up, improvement was obtained from the claudication clinic as well as renal function and blood pressure, CRB (from 2.7 ± 1.4 to 1.8 ± 0.4 mg/dL, P-0.02) and TA (160 ± 18/85 ± 7mmHg at 138 ± 7/82 ± 9, p 0.018). Kidney function, blood pressure remained unchanged during follow-up (130 ± 36 months). Conclusion: Through these cases review, we propose highlighting the importance of extending imaging studies to the iliac artery of the kidney graft in case of high suspected renal vascular hypertension;showing the role and safety of angioplasty as a reasonable and effective treatment in the identified cases. We assessed the possibility of the limited role of Duplex Sonography (DS) regarding clinical and angiographic. PTA is the appropriate initial treatment of Prox-TRAS, with low morbidity and mortality rates, achieving improvement of graft function and amelioration of hypertension.

Relationship between Serum Uric Acid Levels and Kidney Arteriole Resistance in Patients with Type 2 Diabetes Associated with Hypertension

Objectives To investigate the relationship between serum uric acid levels and arteriole resistance detected with the color Doppler energy imaging (CDEI) and to explore the risks of impaired regulation of vascular tone by uric acid in kidneys of hypertension patients. Methods In 12 healthy control cases, 28 non-diabetic hypertension (nNIDDM +H) cases and 25 type 2 diabetic hypertension (NIDDM+H) cases, uric acid (UA) levels were measured with uricase-peroxidase method. Arteriole resistance index (RI) and pulsate index (PI) in separate sections of renal artery included MAR, SRA, IRA were detected using CDEI with 2.1~4.2 Hz Doppler transducer in kidneys. Results In comparison, UA was significantly higher in non-diabetic hyper- tension group and diabetic hypertension group than in control group (P<0.01, separately). UA levels was also significantly higher in NIDDM+H group than in nNIDDM+H, P < 0.029. RI in separate sections of renal artery was significantly higher in nNIDDM+H, or NIDDM+H group than in control group ( all P < 0.01) , and it was significantly higher in NIDDM +H than nNIDDM+H groups (P < 0.05 and P < 0.01). In nNIDDM +H and NIDDM +H groups UA levels and IRA-RI could be elevated significantly following with the impaired heart function being aggravated (χ2 = 13.028, P=0.005, χ2=13.29, P=0.004); the dosage of HCT being increased (χ2 =14.216, P=0.001, χ2 = 14.661, P=0.001); the levels of GHbA1 being excessed unnormally (P=0.000). The correlation between UA and IRA-RI in both hypertension groups were directly related, in nNIDDM+H group r=0.842, P=0.000, in NIDDM+H group, r=0.797, P=0.000. Conclusions Uric acid levels and IRA-RI in hyper-tension patients were directly related. Uric acid levels and IRA-RI could be partly dependent on the severity of heart dysfunction, diuretic dose, and serum glucose status of diabete patients in long-term. Uric acid and the xanthine oxidase metabolic pathway may contribute to impaired regulation of arteriole tone in hypertension patients.

Advance on Chinese Medicine for Hypertensive Renal Damage:Focus on the Complex Molecular Mechanisms

Hypertensive renal damage(HRD)is a major cause of end-stage renal disease.Among the causes of end-stage renal disease,HRD accounts for nearly 34%of the total number of cases.Antihypertensive treatment is primarily drug-based,but therapeutic efficacy is less effective and can have serious side effects.Chinese medicine(CM)has significant advantages in the treatment of HRD.CM is rich in various active ingredients and has the property of targeting multiple targets and channels.Therefore,the regulatory network of CM on disease is complex.A large number of CM have been employed to treat HRD,either as single applications or as part of compound formulations.The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system,antioxidation,anti-inflammation,rescue of endothelial function,regulation of vasoactive substance secretion and obesity-related factors,etc.This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects.

Nutcracker syndrome

The nutcracker phenomenon [left renal vein(LRV) entrapment syndrome] refers to compression of the LRV most commonly between abdominal aorta and superior mesenteric artery.Term of nutcracker syndrome(NCS) is used for patients with clinical symptoms associated with nutcracker anatomy.LRV entrapment divided into 2 types:anterior and posterior.Posterior and right-sided NCSs are rare conditions.The symptoms vary from asymptomatic hematuria to severe pelvic congestion.Symptoms include hematuria,orthostatic proteinuria,flank pain,abdominal pain,varicocele,dyspareunia,dysmenorrhea,fatigue and orthostatic intolerance.Existence of the clinical features constitutes a basis for the diagnosis.Several imaging methods such as Doppler ultrasonography,computed tomography angiography,magnetic resonance angiography and retrograde venography are used to diagnose NCS.The management of NCS depends upon the clinical presentation and the severity of the LRV hypertension.The treatment options are ranged from surveillance to nephrectomy.Treatment decision should be based on the severity of symptoms and their expected reversibility with regard to patient's age and the stage of the syndrome.

Explore the direct and/or the synergistic antihypertensive effects of wind-dispelling herbs involving Fangfeng and Baizhi on hypertensive rats with liver-yang hyperactivity based on vasoactive substances

Objective： To explore the direct and/or the enhancing antihypertensive effects of wind-dispelling herbs involvingFangfeng （Saposhnikoviae Radix） and Baizhi （Angelicae dahuricae Radix） using liver-yang hyperactivity renalhypertension rat. Methods： Model rats with hyperactivity of liver-yang hyperactivity were prepared using male SD rats.Once successful, the rats were randomly divided into groups and given medicine by gavage for 4 weeks. Blood wascollected from the abdominal aorta to prepare serum. Serum nitric oxide （NO） concentration was determined bychemical colorimetry. The contents of ET, TXB2 and 6-K-PGF1a were determined by enzyme linked immunosorbentassay （ELISA）. Results： Compared with the control model group, the blood pressure, serum ET and TXB2 of rats in thewind dispelling medicine group was not significantly reduced, while those of rats in captopril group, Tianma GoutengDecoction I group （TGD group） decreased significantly （P 〈0.05 for both）. Interestingly, the blood pressure, serum ETand TXB2 of rats in the combination group （wind dispelling medicine ＆ TGD） decreased significantly compared withboth wind dispelling medicine group and TGD group. Meanwhile, the levels of serum NO and 6- K-PGF1a in thecombination group was much higher than those in the wind dispelling medicine group or TGD group （P 〈0.05 for both）.However, the levels of serum NO and 6- K-PGF1a in the wind dispelling medicine group was not significantly increasedcompared with the model group. Conclusion： There is no direct pressure lowering effects of wind dispelling medicinealone, while wind dispelling medicine could potentiates the antihypertensive effects of Tianma Gouteng Decoction I.Besides, the synergistic effects may be related to decreased ET and TXB2 levels and the increased NO and 6- K-PGF1alevels.

Protective Effects of Combination of Radix Astragali and Radix Salviae Miltiorrhizae on Kidney of Spontaneously Hypertensive Rats and Renal Intrinsic Cells

Objective: To evaluate the effects of combination of Radix Astragali(RA) and Radix Salviae Miltiorrhizae(RS) on kidney of spontaneously hypertensive rats(SHRs) and renal intrinsic cells. Methods: SHRs were intragastrically administrated with RA(5.09 g/kg) and RS(2.55 g/kg) either alone or with combination for 4 weeks;valsartan(13.35 mg/kg) was used as a positive control. Blood pressure and renal ultrasonography were monitored periodically. The biomarkers [microalbumin(m ALB), cystatin C, angiotensin Ⅱ(Ang Ⅱ), interleukin-1 beta(IL-1β), and β2-microglobulin(β2-Mg), etc.] in serum and urine were measured by enzyme-linked immunosorbent assay(ELISA). The protein expressions [phosphorylated adenosine 5’-monophosphate-activated protein kinase-α1(p-AMPKα1), sestrin-β, calcium/calmodulin-dependent protein kinase kinase-β(Ca MKK-β), phosphoinositide 3-kinases(PI3 K), serine-threonine protein kinase 1(AKT1), and vascular endothelial growth factor receptor 2(VEGFR2)] in renal cortex were determined by Western blot. In vitro, the hypertensive cellular model was established by applying 2×10^-6 mol/L Ang Ⅱ. The primary human podocytes, human glomerular endothelial cells(HRGECs), and human proximal tubular epithelial cells(HK-2 s) were pre-incubated with sulfotanshinone sodium(Tan, 10 μg/m L) and/or calycosin-7-O-β-D-glucoside(Cal, 5 μg/m L). The cellular viability and apoptosis were assayed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) and Annexin V/PI staining, respectively. The level of endothelial nitric oxide synthase(eNOS) in culture supernatant was determined by ELISA. Results: RA+RS significantly decreased the diastolic blood pressure, renal vascular resistance index, and parenchymal thickness, increased 24 h urinary volume as well as lowered the levels of urine m ALB and serum cystatin C, IL-1β and β2-Mg of SHRs(P<0.05 vs. SHRs). The decreased protein levels of p-AMPKα1, sestrinβ and Ca MKK-β and the increased protein levels of PI3 K, AKT1 and VEGFR2 in renal cortex of SHRs were normalized after RA+RS treatment(P<0.05). In vitro, Tan and Cal attenuated the Ang Ⅱ-induced abnormal proliferation and increased the apoptosis of HRGECs and HK-2 s and improved the level of e NOS in culture supernatant. Whereas, neither of them showed powerful effect on podocyte. Conclusion: The combination of RA and RS had potential effects on alleviating the renal damages of SHRs and the renoprotection was independent of blood pressure level.