Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program.

BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.

Anesthetic and surgical considerations for staged bilateral nephrectomies in a pediatric patient: A case report / Consideraciones anestésicas y quirúrgicas en nefrectomía bilateral en dos tiempos en un paciente pediátrico: Reporte de caso

Abstract We present a 9-year-old patient with end-stage renal disease, on peritoneal dialysis, who underwent a staged prone retroperitoneoscopic bilateral nephrectomy. Bilateral nephrectomy was indicated in preparation for renal transplant in the context of genetic predisposition malignancy when immunosuppressed. The two mirror-image surgeries enable the comparison of the anesthetic management and outcomes in a single patient. Features of interest to anesthesiologists include approach to a child with chronic kidney disease, different requirements for intraoperative antihypertensives; pain management strategies, including a comparison of erector spinae plane block with and without adjunct dexmedetomidine; anesthetic management of retroperitoneoscopic pediatric surgery and the first description of using a Foley bag attached to a peritoneal dialysis catheter to aid in diagnosis and repair of posterior peritoneal cavity entry.

Resumen Se presenta un paciente de 9 años de edad con enfermedad renal terminal, en diálisis peritoneal, quien se sometió a nefrectomía bilateral retroperitoneoscópica estadificada en posición prona. Se indicó la nefrectomía bilateral en preparación para trasplante renal en el contexto de predisposición genética hacia desarrollar una patología maligna al estar inmunosuprimido. Las dos cirugías en espejo permiten hacer una comparación del manejo anestésico y de los desenlaces en un mismo paciente. Las características de interés para los anestesiólogos incluyen el abordaje de un niño con enfermedad renal crónica, con requisitos diferentes de antihipertensivos intraoperatorios; estrategias para el manejo del dolor, incluyendo una comparación de bloqueo del plano del erector espinal con y sin dexmedetomidina adyuvante; manejo anestésico de cirugía pediátrica retroperitoneoscópica y la primera descripción del uso de una bolsa Foley conectada a un catéter de diálisis peritoneal para ayudar en el diagnóstico y la reparación de la entrada de la cavidad peritoneal posterior.

Captopril renal scintigraphy in diagnosis of renovascular hypertension and the impact of plasma renin activity / 中国医学影像技术

Objective: To observe the diagnostic efficiency of Captopril renal scintigraphy (CRS) for renovascular hypertension (RVH) and the impact of plasma renin activity (PRA). Methods: Plasma levels of PRA, angiotensin Ⅱ (AngⅡ) and aldosterone (ALD) in peripheral blood in orthostatic position and supine position of 35 RVH patients who underwent basic renal scintigraphy and CRS examination were retrospectively analyzed. According to CRS, the patients were divided into positive group and negative group. The levels of PRA, AngⅡ and ALD were analyzed. ROC curve was used to analyze PRA and obtain the minimum threshold. Results: There were 24 cases in positive group and 11 cases in negative group. The orthostatic position PRA in positive group was significantly higher than that in negative group (Z=3.11,P0.05). ROC curve analysis showed that the area under the curve was 0.84. When the threshold point of PRA was 2.47 ng/(ml·h), the sensitivity and specificity were 83.33% and 81.82%, respectively. Conclusion: Orthostatic position PRA is an important impact factor of diagnostic sensitivity of CRS for RVH. Combining with orthostatic position plasma PRA can improve the value of CRS for diagnosis and treatment of RVH.

Six-Month Results of Treatment-Blinded Medication Titration for Hypertension Control After Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial.

BACKGROUND: The multicenter, international, randomized, blinded, sham-controlled RADIANCE-HTN SOLO trial (A Study of the ReCor Medical Paradise System in Clinical Hypertension) demonstrated a 6.3 mm Hg greater reduction in daytime ambulatory systolic blood pressure (BP) at 2 months by endovascular ultrasound renal denervation (RDN) compared with a sham procedure among patients not treated with antihypertensive medications. We report 6-month results after the addition of a recommended standardized stepped-care antihypertensive treatment to the randomized endovascular procedure under continued blinding to initial treatment. METHODS: Patients with a daytime ambulatory BP ≥135/85 mm Hg and <170/105 mm Hg after a 4-week discontinuation of up to 2 antihypertensive medications, and a suitable renal artery anatomy, were randomized to RDN (n=74) or sham (n=72). Patients were to remain off antihypertensive medications throughout the first 2 months of follow-up unless safety BP criteria were exceeded. Between 2 and 5 months, if monthly measured home BP was ≥135/85 mm Hg, a standardized stepped-care antihypertensive treatment was recommended consisting of the sequential addition of amlodipine (5 mg/d), a standard dose of an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and hydrochlorothiazide (12.5 mg/d), followed by the sequential uptitration of hydrochlorothiazide (25 mg/d) and amlodipine (10 mg/d). Outcomes included the 6-month (1) change in daytime ambulatory systolic BP adjusted for medications and baseline systolic BP, (2) medication burden, and (3) safety. RESULTS: A total of 69/74 RDN patients and 71/72 sham patients completed the 6-month ambulatory BP measurement. At 6 months, 65.2% of patients in the RDN group were treated with the standardized stepped-care antihypertensive treatment versus 84.5% in the sham group (P=0.008), and the average number of antihypertensive medications and defined daily dose were less in the RDN group than in the sham group (0.9±0.9 versus 1.3±0.9, P=0.010 and 1.4±1.5 versus 2.0±1.8, P=0.018; respectively). Despite less intensive standardized stepped-care antihypertensive treatment, RDN reduced daytime ambulatory systolic BP to a greater extent than sham (-18.1±12.2 versus -15.6±13.2 mm Hg, respectively; difference adjusted for baseline BP and number of medications: -4.3 mm Hg, 95% confidence interval, -7.9 to -0.6, P=0.024). There were no major adverse events in either group through 6 months. CONCLUSIONS: The BP-lowering effect of endovascular ultrasound RDN was maintained at 6 months with less prescribed antihypertensive medications compared with a sham control. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02649426.

Therapeutic effect of valsartan combined beraprost sodium on hypertension complicated early renal in‐jury／ / 心血管康复医学杂志

To observe and analyze therapeutic effect of valsartan combined beraprost sodium on patients with hypertension (EH) complicated early renal injury (ERI).Methods : A total of 480 EH + ERI patients treated in our hospital in near two years were randomly and equally divided into valsartan group and combined treatment group (received valsartan combined beraprost sodium) , both groups were treated for three months .Levels of blood pressure , renal function related indexes were compared between two groups before and after treatment .Results :Compared with before treatment , after three months , there were significant reductions in levels of blood pressure , serum creatinine , urine β2 microglobulin and D‐dimer , and significant rise in creatinine clearance rate (Ccr) in two groups , P＝0.001 all.Compared with valsartan group after treatment , there were significant reductions in levels of blood pressure [ (130. 92 ± 5.92)／(80.18 ± 6.69) mmHg vs.(120. 93 ± 6. 53)／(69.98 ± 6.32) mmHg] , serum creatinine [ (93.92 ± 10. 49) μmol／L vs.(83. 14 ± 11. 03) μmol／L] , urine β2 microglobulin [ (385.41 ± 35.54) μg／L vs.(362.65 ± 26.59) μg／L] and D‐dimer [ (1. 75 ± 0.44) mg／L vs.(1. 01 ± 0.11) mg／L] , and significant rise in Ccr [ (63.22 ± 7. 66) ml／min vs.(79.13 ± 8.83) ml／min] in combined treatment group , P＝0.001 all.Conclusion :Compared with valsartan monotherapy , valsartan combined beraprost sodium can more significantly reduce blood pressure and protect renal function in hypertensive patients with early renal injury .

Lessons from CKD-Related Genetic Association Studies-Moving Forward.

Over the past decade, genetic association studies have uncovered numerous determinants of kidney function in the general, diabetic, hypertensive, CKD, ESRD, and GN-based study populations (e.g., IgA nephropathy, membranous nephropathy, FSGS). These studies have led to numerous novel and unanticipated findings, which are helping improve our understanding of factors and pathways affecting both normal and pathologic kidney function. In this review, we report on major discoveries and advances resulting from this rapidly progressing research domain. We also predict some of the next steps the nephrology community should embrace to accelerate the identification of genetic and molecular processes leading to kidney dysfunction, pathophysiologically based disease subgroups, and specific therapeutic targets, as we attempt to transition toward a more precision-based medicine approach.

Mechanisms of Naoshuantong capsule in the prevention of cold wave-induced stroke in hypertensive rats: a differential proteomics study / 国际脑血管病杂志

Objective To investigate the preventive effect and mechanisms of Naoshuantong capsule in stroke induced by artificial cold wave in hypertensive rats.Methods A total of 130 SD rats were randomly divided into a sham operation group (n =30),a model control group (n =50) and a Naoshuantong treatment group (n=50;intragastric administration of Naoshuantong,0.5 g/kg,2/d for 7 days).Renovascular hypertensive rats model were established by two-kidney,two clip method.At 13th week after operation,rats were exposed to artificial cold wave for 3 days (12 h light of 22 ℃ and 12 h dark of 4 ℃,3 cycles).The brain tissue samples were extracted at the end of the experiment.Differential protein proteomic techniques were used for the identification,functional classification and preliminary analysis of the differentially expressed protein spots,and Western blot was used for the validation of some key proteins.Results There was no occurrence of stroke in the sham operation group,and the incidence of stroke in the model control group (36.00％,18/50) was significantly higher than that in the Naoshuantong treatment group (18.00％,9 / 50;x2 =4.110,P =0.043).With the two-dimensional gel electrophoresis analysis,6 different proteins were identified from 14 protein spots.Among them,the up-regulated superoxide dismutase 2 (SOD2) and the down-regulated B-cell lymphoma 10 (Bcl-10) were found to be at the central location of protein interactions,which has been verified by Western blot.Conclusion Naoshuantong can reduce the occurrence of stroke induced by artificial cold wave in renovascular hypertensive rats.SOD2 up-regulating and Bcl-10 downregulating may be involved in the mechanisms of of Naoshuantong in the prevention of cold wave-induced stroke in hypertensive rats.

Ruthenium Complex Improves the Endothelial Function in Aortic Rings From Hypertensive Rats / Complexo de Rutênio Melhora a Função Endotelial em Anéis de Aorta de Ratos Hipertensos Renais

Abstract Background: The endothelium is a monolayer of cells that extends on the vascular inner surface, responsible for the modulation of vascular tone. By means of the release of nitric oxide (NO), the endothelium has an important protective function against cardiovascular diseases. Objective: Verify if cis- [Ru(bpy)2(NO2)(NO)](PF6)2 (BPY) improves endothelial function and the sensibility of conductance (aorta) and resistance (coronary) to vascular relaxation induced by BPY. Methods: Normotensive (2K) and hypertensive (2K-1C) Wistar rats were used. For vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: BPY(0.01 to10 µM) and concentration effect curves to acetylcholine were performed. In addition, cumulative concentration curves were performed to BPY (1.0 nM to 0.1 µM) in aortic and coronary rings, with intact and denuded endothelium. Results: In aorta from 2K-1C animals, the treatment with BPY 0.1µM increased the potency of acetylcholine-induced relaxation and it was able to revert the endothelial dysfunction. The presence of the endothelium did not modify the effect of BPY in inducing the relaxation in aortas from 2K and 2K-1C rats. In coronary, the endothelium potentiated the vasodilator effect of BPY in vessels from 2K and 2K-1C rats. Conclusion: Our results suggest that 0.1 µM of BPY is able to normalize the relaxation endothelium dependent in hypertensive rats, and the compound BPY induces relaxation in aortic from normotensive and hypertensive rats with the same potency. The endothelium potentiate the relaxation effect induced by BPY in coronary from normotensive and hypertensive rats, with lower effect on coronary from hypertensive rats.

Resumo Fundamento: O endotélio é uma monocamada de células que se estende sobre a superfície interna vascular, responsável pela modulação do tônus vascular. Por meio da liberação de óxido nítrico (NO), o endotélio tem uma função protetora importante contra doenças cardiovasculares. Objetivo: Verificar se o cis- [Ru (BPY)2 (NO2) (NO)] (PF6) 2 (BPY) melhora a função endotelial e a sensibilidade da condutância (aorta) e da resistência (coronária) ao relaxamento vascular induzido por BPY. Métodos: Foram utilizados ratos Wistar normotensos (2K) e hipertensos (2K-1C). Para o estudo de reatividade vascular, as aortas torácicas foram isoladas, os anéis com endotélio intacto foram incubados com: BPY (0,01 a 10 µM) e se realizaram curvas de efeito de concentração para acetilcolina. Adicionalmente, foram feitas curvas de concentração cumulativas para BPY (1,0 nM a 0,1 µM) nos anéis aórticos e coronários, com endotélio intacto e nu. Resultados: Na aorta de animais 2K-1C, o tratamento com BPY 0,1 µM aumentou a potência do relaxamento induzido pela acetilcolina e foi capaz de reverter a disfunção endotelial. A presença do endotélio não modificou o efeito da BPY na indução do relaxamento em aortas de ratos 2K e 2K-1C. Na coronária, o endotélio potencializou o efeito vasodilatador do BPY em vasos de ratos 2K e 2K-1C. Conclusão: Nossos resultados sugerem que 0,1 µM de BPY é capaz de normalizar o relaxamento dependente do endotélio em ratos hipertensos, e o composto BPY induz relaxamento na aorta de ratos normotensos e hipertensos com a mesma potência. O endotélio potencializa o efeito de relaxamento induzido pela BPY em coronárias de ratos normotensos e hipertensos, com menor efeito em coronárias de ratos hipertensos.

Emerging concepts for patients with treatment-resistant hypertension.

Treatment-resistant hypertension (TRH) is defined as elevated blood pressure despite treatment with three properly dosed antihypertensive drugs, and is associated with adverse cardiovascular and renal outcomes and increased mortality. Treatment of patients with TRH focuses on maximizing the doses of antihypertensive drugs and adding drugs with complementary mechanisms of action, including a combination of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, calcium channel blockers, and thiazide-like diuretics. Randomized clinical trials have demonstrated the efficacy of the mineralocorticoid receptor antagonist spironolactone as a fourth-line therapy for patients with TRH. Other pharmacologic considerations include adding α-blockers, combined α-ß-blockers, centrally acting α-agonists, or direct vasodilators. However, a small, but important subset of patients remain hypertensive despite combination regimens with multiple antihypertensive drugs, underscoring the need for novel blood pressure-lowering therapies. Over recent years, alternative approaches for treating TRH have emerged, including agonists of natriuretic peptides, endothelin-receptor antagonists, and additional vasoactive drugs. Lastly, device-based interventions, such as renal denervation or carotid baroreflex activation, may supplement drug therapy for these patients. This review summarizes current knowledge on the management of TRH, with focus on novel therapeutic strategies designed to achieve optimal blood pressure control.

Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population.

BACKGROUND AND OBJECTIVES: Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. RESULTS: In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m(2). CONCLUSION: Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.

The clinical study ofXuebijing injection combined with routine western medicine therapy on the treatment of hypertensive renal damage / 国际中医中药杂志

Objective To evaluate the curative effect ofXuebijing injection combined with routine western medicine therapy in the treatment of hypertensive renal damage.Methods A total of 114 patients with hypertension were randomly divided into 2 groups according to the random number table method, 57 patients in each group. The control group was given conventional treatment (maleic acid enalapril and amlodipine and atorvastatin cutting atorvastatin calcium), and the treatment group were givenXuebijing injection based on the conventional treatment. The two groups were treated for 6 months. The changes of blood pressure, renal function and serum inflammatory cytokine levels were evaluated.Results After treatment, the mean value of 24 h systolic blood pressure, mean value of 24 h diastolic blood pressure, systolic blood pressure variability and diastolic blood pressure variability in the treatment group were significantly lower than those in the control group (2 months after treatment:t values were 5.256, 5.595, 5.265, 2.564,P<0.05; 6 months after treatment:t values were 6.251, 5.267, 4.466, 5.264,P<0.05); the urinary mAlb, beta 2-MG, and urine albumin to creatinine ratio in the treatment group were significantly lower than those in the control group (2 months after treatment:t value were 5.566, 5.282, 2.862,P<0.05; 6 months after treatment:t value were 5.263, 6.565, 3.642,P<0.05);two plasma D-dimer, IL-6, TNF-α and fibrinogen levels in the treatment group were significantly lower than those in the control group (2 months after treatment:t value were 3.565, 5.652, 3.985, 5.251,P<0.05; 6 months after treatment:t value were 5.268, 4.836, 3.622, 4.265,P<0.05).ConclusionsXuebijing injection combined with routine western medicine therapy on hypertensive renal damage may have protective effect, and its curative effect was superior to simple maleic acid enalapril and amlodipine and atorvastatin cutting atorvastatin calcium therapy.

Tianma-Gouteng decoction combined with valsartan for renal hypertension / 国际中医中药杂志

Objective To observe and explore clinical efficacy ofTianma-Gouteng decoction combined valsartan in the treatment of patients with renal hypertension and its effects on renal function. Methods A total of 130 patients with renal hypertension were enrolled and randomly divided into a study group (68 patients) and a control group (62 patients). Both groups were given prescription of lower sodium diet, exercising and enalaprilscheme. On this basis, the control group plus valsartan, and the study group was further added withTianma-Gouteng decoction. After 2 courses treatment, renal function, and blood pressure of both groups were compared, and clinical efficacy on blood pressure were evaluated.Results After treatment, the SBP (126.8 ± 9.1 mmHg vs. 134.1 ± 8.8 mmHg,t=4.648), DBP (82.4± 5.0 mmHgvs. 85.3 ± 5.4 mmHg, t=3.167), Scr (148.5 ± 46.3μmol/Lvs. 172.1 ± 52.0μmol/L, t=2.723), BUN (8.3 ± 2.7 mmol/Lvs. 9.7 ± 3.1 mmol/L,t=2.734) and 24hAlb (1.7 ± 0.6 gvs. 1.9 ± 0.7 g,t=2.209) in the study group were significantly lower than control group (P<0.05 orP<0.01). The total effective rate in the study group was significantly increased than that in the control group (91.2%vs. 79.0%;χ2=0.383,P=0.050).Conclusion Valsartan combined with Tianma-Gouteng decocntion can reduce blood pressure, and alleviate the kidney damage effectively.

The therapeutic effect of elderly dialysis patients with refractory hypertension / 中国医师进修杂志

Objective To investigate the treatment of elderly dialysis patients with refractory hypertension.Methods Sixty-six patients were randomly divided into two groups of A group and B group,with 33 cases in each group.Patients in A group were treated by routine hemodialysis 3 times per week and hemoperfusion 1 time every 2 weeks.Patients in B group were treated by routine hemodialysis 2 times per week and hemodiafiltration 1 time per week plus hemoperfusion 1 time every 2 weeks.The levels of blood pressure,plasma endothelin (ET),angiotensin-Ⅱ (AT Ⅱ),renin (RA),parathyroid hormone (PTH) in two groups before and after treatment were compared.Results Before and after treatment,the levels of blood pressure,ET,AT Ⅱ,RA and PTH in A group were (183.42 ± 16.20)/(109.15 ± 7.69) and (151.45 ± 3.31)/(88.71 ±4.95) mmHg(1 mmHg =0.133 kPa),(173.45 ±41.25) and (160.38 ±25.31) ng/L,(69.21 ± 18.47)and(57.25 ± 23.34) ng/L,(1.21 ± 0.15) and (0.87 ± 0.14) μ g/L,(530.27 ± 43.28) and (272.43 ± 34.19) ng/Lrespectively.Before and after treatment,the levels of blood pressure,ET,AT Ⅱ,RA and PTH in B group were (185.34 ± 12.26)/ (112.38 ± 6.24) and (141.59 ± 4.15)/ (80.39 ± 2.73) mmHg,(178.21 ± 34.35) and (149.12 ±21.34) ng/L,(68.38 ±23.57) and (47.17 ± 15.61) ng/L,(1.19 ±0.29) and (0.69 ±0.41) μg/L,(528.62 ± 42.53) and (253.15 ± 31.62) ng/L respectively.The levels of blood pressure,ET,AT Ⅱ,RA and PTH in two groups after treatment were significantly decreased compared with those before treatment (P ＜0.05),and there were significant differences between two groups (P ＜ 0.05).Conclusion Combined with hemoperfusion in the treatment of elderly hemodialysis patients with refractory hypertension,the effect of combined hemodiafiltration is significant,and it is worthy of promotion.

WNK-SPAK-NCC cascade revisited: WNK1 stimulates the activity of the Na-Cl cotransporter via SPAK, an effect antagonized by WNK4.

The with-no-lysine (K) kinases, WNK1 and WNK4, are key regulators of blood pressure. Their mutations lead to familial hyperkalemic hypertension (FHHt), associated with an activation of the Na-Cl cotransporter (NCC). Although it is clear that WNK4 mutants activate NCC via Ste20 proline-alanine-rich kinase, the mechanisms responsible for WNK1-related FHHt and alterations in NCC activity are not as clear. We tested whether WNK1 modulates NCC through WNK4, as predicted by some models, by crossing our recently developed WNK1-FHHt mice (WNK1(+/FHHt)) with WNK4(-/-) mice. Surprisingly, the activated NCC, hypertension, and hyperkalemia of WNK1(+/FHHt) mice remain in the absence of WNK4. We demonstrate that WNK1 powerfully stimulates NCC in a WNK4-independent and Ste20 proline-alanine-rich kinase-dependent manner. Moreover, WNK4 decreases the WNK1 and WNK3-mediated activation of NCC. Finally, the formation of oligomers of WNK kinases through their C-terminal coiled-coil domain is essential for their activity toward NCC. In conclusion, WNK kinases form a network in which WNK4 associates with WNK1 and WNK3 to regulate NCC.

Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus.

BACKGROUND: The primary objective of this mechanistic open-label, stratified clinical trial was to determine the effect of 8 weeks' sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus (T1D). METHODS AND RESULTS: Inulin (glomerular filtration rate; GFR) and paraaminohippurate (effective renal plasma flow) clearances were measured in individuals stratified based on having hyperfiltration (T1D-H, GFR ≥ 135 mL/min/1.73m(2), n=27) or normal GFR (T1D-N, GFR 90-134 mL/min/1.73m(2), n=13) at baseline. Renal function and circulating levels of renin-angiotensin-aldosterone system mediators and NO were measured under clamped euglycemic (4-6 mmol/L) and hyperglycemic (9-11 mmol/L) conditions at baseline and end of treatment. During clamped euglycemia, hyperfiltration was attenuated by -33 mL/min/1.73m(2) with empagliflozin in T1D-H, (GFR 172±23-139±25 mL/min/1.73 m(2), P<0.01). This effect was accompanied by declines in plasma NO and effective renal plasma flow and an increase in renal vascular resistance (all P<0.01). Similar significant effects on GFR and renal function parameters were observed during clamped hyperglycemia. In T1D-N, GFR, other renal function parameters, and plasma NO were not altered by empagliflozin. Empagliflozin reduced hemoglobin A1c significantly in both groups, despite lower insulin doses in each group (P≤0.04). CONCLUSIONS: In conclusion, short-term treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin attenuated renal hyperfiltration in subjects with T1D, likely by affecting tubular-glomerular feedback mechanisms. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01392560.

Clinical application of prostaglandin E1 in the treatment of hypertensive renal damage of early stage / 中国医师进修杂志

Objective To observe the effect ofprostaglandin E1 intravenously in the improvement of the function of renal glomeruli and renal tubules in hypertensive patients complicated with microalbuminuria.Methods Totally 60 hypertensive patients complicated with microalbuminuria and nocturia who had received losartan for above 12 weeks,according to random number table method were divided into treatment group and control group,with 30 cases in each group.Original antihypertensive drugs were used continuously in treatment group and control group,and patients in treatment group received prostaglandin E1 intravenously for 3 courses of treatment,with losartan and other antihypertensive drugs routinely.Using self-contrast before and after treatment and contrast with control group,the change of urinary level of microalbumin (mALB),osmotic pressure,β2-microglodulin (β 2-MG) and N-acetyl-β-D-glucosaminidase (NAG) were compared.Results The blood pressure after treatment in both groups were decreased,but there was no statistically significant difference compared with that before treatment (P ＞ 0.05).After treatment of 12 weeks,urinary levels of mALB,β 2-MG and NAG in treatment group were lower than those in control group [(88.6 ± 14.2)μg/min vs.(123.9 ± 14.8) μg/min,(0.84 ±0.41) mg/L vs.(1.61 ±0.49) mg/L,(30.2 ± 10.5) U/L vs.(75.7 ± 12.8) U/L],and osmotic pressure was higher than that in control group [(591 ± 71) mmol/L vs.(454 ± 67) mmol/L],the difference had statistical significance (P ＜ 0.01).Conclusion Prostaglandin E1can reduce the renal ischemic state in early stage of hypertensive renal damage and can improve renal function.

A Comparison Study of Combined Medication of Telmisartan with Amlodipine on the Reversal Left Ventricular Remodeling in Renal Hypertensive Rats / 天津医药

Objective To compare the effects of telmisartan and (or) amlodipine on the reversal left ventricular re-modeling in two-kidney one clip hypertensive rats. Methods A total of 50 healthy male SD rats were randomly divided into 5 groups (n=10):two-kidney one clip renal hypertensive (2KIC) model group, sham group, telmisartan (10 mg/kg) group, am-lodipine (2.5 mg/kg) group and telmisartan (10 mg/kg)+amlodipine(2.5 mg/kg) group. The model of two-kidney one clip re-nal hypertensive rats was established. The tail arterial blood pressure was detected once a week. After 20 weeks, rats were sacrificed and specimens were collected. The left ventricular mass index (LVMI) was assessed. The myocardial ultrastructur-al changes were observed by electron microscope. Values of plasma renin activity (PRA), angiotensionⅡ(AngⅡ) and atrial natriuretic peptide (ANP) were measured by enzyme linked immunosorbent assay (ELISA).Results Compared with sham group, the levels of systolic blood pressure (SBP), LVMI, PRA, AngⅡand ANP were significantly higher in 2KIC group (P＜0.01). Compared with 2KIC group, values of SBP, LVMI, PRA and ANP were significantly lower in telmisartan group and am-lodipine group (P＜0.01), but the value of AngⅡwas significantly higher (P＜0.01). The levels of SBP, LVMI, AngⅡand ANP were significantly lower in combined medication group than those of single drug medication group (P＜0.01). There was no significant difference in the plasma PRA level between those groups (P>0.05). Results of myocardial electron microsco-py showed that the left ventricular remodeling was significantly improved in combined treatment group. Conclusion Telmisartan and amlodipine can effectively improve the left ventricular remodeling induced by hypertension. There was more effective therapy using both medications together.

Mid-aortic syndrome in a 3-year-old girl successfully treated by aorto-aortic grafting and renal artery implantation into the graft.

Mid-aortic syndrome, an uncommon acquired or congenital condition characterized by segmental narrowing of the abdominal or distal descending thoracic aorta, is frequently accompanied by ostial stenosis of the aorta's branches. If left untreated, it can result in life-threatening complications secondary to severe hypertension.We report the case of a 3-year-old girl with congenital mid-aortic syndrome, who was diagnosed by chance in the course of a viral illness, and whose high blood pressure values were first dismissed as inaccurate. Attempts to achieve medical or endovascular control of her hypertension were unsuccessful. She was thereafter successfully treated by aorto-aortic bypass grafting, resection of the stenotic segments of both renal arteries, and implantation of the patent arterial segments into the graft.