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.

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.

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.