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Context: There are well-established interactions between the thyroid and the kidney. Thyroid hypofunction is associated with reduced renal plasma flow (RPF), and hypothyroidism is highly prevalent in chronic kidney disease; however, less is known about the thyroid-kidney axis in the euthyroid state., Objective: This work aimed to study the association of thyroid function with renovascular parameters in a well-phenotyped cohort of euthyroid normotensive and hypertensive individuals., Methods: This cross-sectional, multicenter study of the HyperPATH Consortium took place in 5 US and European academic institutions. A total of 789 individuals, aged 18 to 65 years, with serum thyrotropin (TSH) 0.4 to 5.5 mIU/L, participated; individuals with uncontrolled or secondary hypertension or on medication affecting the hypothalamus-pituitary-thyroid axis were excluded. Hemodynamic parameters including RPF, thyroid function testing, and the Thr92Ala deiodinase 2 (D2) polymorphism were assessed in the setting of a liberal and restricted salt diet. We searched for associations between thyroid function and renovascular parameters and accounted for confounding factors, such as older age, hypertension, and diabetes., Results: Serum TSH was inversely associated with RPF assessed in the setting both of liberal and restricted salt diets. This association remained significant and independent when accounting for confounding factors, whereas free thyroxine index (fTI) and the Thr92Ala polymorphism, associated with lower D2 catalytic activity and disrupted thyroid hormone tissue availability, were not independently associated with RPF. Serum TSH remained an independent predictor of RPF on a liberal salt diet when the analysis was restricted to healthy young individuals., Conclusion: Serum TSH levels, but not fTI nor the Thr92Ala D2 polymorphism, were independently inversely associated with RPF in individuals of the HyperPATH Consortium. These findings suggest a direct interconnection between TSH and renovascular dynamics even with TSH within reference range, warranting further investigation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To explore the cellular immune response of patients with resistant hypertension treated with renal denervation (RDN)., Methods and Results: Twenty-three patients were included and blood samples were obtained in six timings, pre and post procedure. Response was evaluated at six-months and one year and was observed in 69.6% and 82.6% of patients, respectively. Absolute values of HLA-DR+ double negative (DN) T cells were significantly lower in the group of 'responders' at one year, and interaction between the timings were found in three T cell subsets (T CD4, T CD8 and naïve T CD8 cells), with the 'responders' tending to present with lower absolute values and little inter-timing variation., Conclusions: 'Responders' significantly present with lower absolute values of activated DN T cells and have lower and more stable values of total T CD8+, CD4+, and naïve T CD8+ cells. These cell types may be able to predict response to RDN., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Chemerin and its receptor, chemokine-like receptor 1 (CmklR1), are associated with chemotaxis, inflammation, and endothelial function, especially in metabolic syndrome, coronary heart disease, and hypertension. In humans, circulating chemerin levels and renal function show an inverse relation. So far, little is known about the potential role of chemerin in hypertensive nephropathy and renal inflammation. Therefore, we determined systemic and renal chemerin levels in 2-kidney-1-clip (2k1c) hypertensive and Thy1.1 nephritic rats, respectively, to explore the correlation between chemerin and markers of renal inflammation and fibrosis. Immunohistochemistry revealed a model-specific induction of chemerin expression at the corresponding site of renal damage (tubular vs. glomerular). In both models, renal expression of chemerin (RT-PCR, Western blot) was increased and correlated positively with markers of inflammation and fibrosis. In contrast, circulating chemerin levels remained unchanged. Taken together, these findings demonstrate that renal chemerin expression is associated with processes of inflammation and fibrosis-related to renal damage. However, its use as circulating biomarker of renal inflammation seems to be limited in our rat models.

Background and Objectives: Diabetes mellitus (DM) and hypertension (HT) are characterized by cell damage caused by inflammatory and metabolic mechanisms induced by alteration in reduction-oxidative status. Serum advanced oxidation protein products (AOPP) are new markers of protein damage induced by oxidative stress. We evaluated serum levels of AOPP in a cohort of patients with DM and HT, with or without renal complications, compared with a control healthy population. Materials and Methods: The study group comprised of 62 patients with type 2 DM and 56 with HT. The 62 patients affected by DM were further distinguished in 24 subjects without renal impairment, 18 with diabetic nephropathy (DN), 20 with chronic kidney disease (CKD) stage 2-3 secondary to DN. The subgroup of 56 patients with primary HT comprised 26 subjects without renal complications and 30 with CKD (stage 2-3) secondary to HT. Thirty healthy controls, matched for age and sex, were recruited among blood donors. Results: Increased AOPP levels were found in DM patients compared with healthy subjects, although not significantly. This index was higher and more significant in patients with DN and CKD secondary to DN than in DM patients without nephropathy ( p < 0.05) or controls ( p < 0.0001). Patients with HT and with kidney impairment secondary to HT also had significantly higher AOPP serum levels than controls ( p < 0.01 and p < 0.0001, respectively). There were no significant differences in mean AOPP levels among DM and HT patients. Conclusion: Our study showed that oxidative stress was higher in diabetic or hypertensive subjects than in healthy controls and, in particular, it appeared to be more severe in patients with renal complications. We suggest that the assessment of AOPP in diabetic and hypertensive patients may be important to predict the onset of renal failure and to open a new perspective on the adoption of antioxidant molecules to prevent CKD in those settings.

BACKGROUND We assessed levels of circulating amino acids in different etiologies of chronic kidney disease (CKD) and the association of amino acids with risk factors of CKD progression. MATERIAL AND METHODS High-performance liquid chromatography-based analysis was used to determine amino acid profiles in patients with diabetic nephropathy (DN, n=20), hypertensive nephropathy (HN, n=26), and chronic nephritis (CN, n=33), and in healthy controls (HC, n=25). RESULTS All 3 types of CKD patients displayed decreased serum levels of serine, glycine, GABA, and tryptophan compared with healthy controls. Moreover, serine and tryptophan were positively correlated with glucose in DN cohorts. Total cholesterol was positively correlated with tryptophan levels in the DN cohort and negatively correlated with serine levels in the CN cohort. In the HN cohort, glycine was negatively correlated with triglyceride levels, and systolic blood pressure (SBP) was negatively correlated with GABA levels. CONCLUSIONS Patients with different etiologies of CKD have significantly different amino acids profiles, and this indicates specific supplementary nutritional needs in CKD patients.

Although angiotensin II (AngII) is known to cause renal injury and fibrosis, the underlying mechanisms remain poorly characterized. Here we show that hypertensive nephropathy (HN) patients and AngII-infused mice exhibit elevated levels of circulating miR103a-3p. We observe a positive correlation between miR-103a-3p levels and AngII-induced renal dysfunction. miR-103a-3p suppresses expression of the sucrose non-fermentable-related serine/threonine-protein kinase SNRK in glomerular endothelial cells, and glomeruli of HN patients and AngII-infused mice show reduced endothelial expression of SNRK. We find that SNRK exerts anti-inflammatory effects by interacting with activated nuclear factor-κB (NF-κB)/p65. Overall, we demonstrate that AngII increases circulating miR-103a-3p levels, which reduces SNRK levels in glomerular endothelial cells, resulting in the over-activation of NF-κB/p65 and, consequently, renal inflammation and fibrosis. Together, our work identifies miR-103a-3p/SNRK/NF-κB/p65 as a regulatory axis of AngII-induced renal inflammation and fibrosis.

Introduction: Hypertension is regarded as a condition of mild inflammation and endothelial imbalance. The aim of the study was to evaluate serum concentrations of biomarkers of inflammation and endothelial function: tumour necrosis factor alpha (TNF-α), endothelin-1 (ET-1), and N-terminal fragment of pro-atrial natriuretic peptide (NTpro-ANP) in hypertensive and normotensive children., Material and Methods: We studied 63 children aged 13.56 ± 3.73 years, divided into two groups: a group with primary hypertension (n = 50) and a group with renal hypertension (n = 13). The control group consisted of 34 normotensive children aged 12.76 ± 3.96 years. Biomarkers were measured with ELISA tests., Results: ET-1 levels were significantly higher in primary hypertension (9.93 ± 1.73 pg/ml) and renal hypertension (10.77 ± 1.50 pg/ml) in comparison to controls (4.03 ± 0.97 pg/ml), (p < 0.001, p < 0.001, respectively). NT-pro ANP concentrations in primary hypertension (71.03 ± 10.02 pg/ml), and renal hypertension (84.78 ± 6.44 pg/ml) were significantly higher than in the control group (29.62 ± 5.56 pg/ml) (p < 0.001, p < 0.001, respectively). TNF-α concentrations in primary hypertension (8.36 ± 1.60 pg/ml) and renal hypertension (7.35 ± 0.93 pg/ml) significantly exceeded concentrations in controls (4.49 ± 0.93 pg/ml), (p < 0.001, p < 0.001, respectively). ET-1 and NT-pro ANP concentrations in renal hypertension significantly exceeded those in primary hypertension (p = 0.049, p < 0.001, respectively) while TNF-α levels in renal hypertension were significantly lower than in primary hypertension (p = 0.046)., Conclusions: The results of our study show that ET-1, NT-pro ANP, and TNF-a concentrations are increased in hypertension in children. Our investigation indicates significant importance of inflammation and endothelial involvement in hypertension in youth.

Cirsium japonicum, a constituent of traditional Chinese medicine, has been shown to exert inflammatory effects as well as to improve the circulation and thus to counteract hematologic stasis. Studies have demonstrated that intermedin (IMD) has protective effects on hypertension in rats by regulating the Ang/NO metabolic pathway. In this study, we investigated whether by regulating the expression of IMD, Cirsium japonicum could improve cardiac function in rats with 2k1c-induced renal hypertension. Renal hypertension was induced in Sprague-Dawley rats by occluding the renal artery. The rats were maintained on a normal diet and randomly divided into four groups: sham, 2k1c, 2k1c with Cirsium japonicum (1.8 g/kg per day) and 2k1c with IMD (n = 10 in each group). Cardiac function, plasma angiotensin II (Ang II), IMD, serum nitric oxide (NO) and nitric oxide synthase (NOS), as well as the expression of IMD and adrenomedullin (ADM) in the aorta and left ventricle were analyzed. Administration of Cirsium japonicum or IMD significantly strengthened cardiac function in 2k1c-induced rats, increased serum NO and NOS levels, reduced plasma Ang II, and upregulated IMD expression in the aorta and left ventricle. These results demonstrate that Cirsium japonicum has cardioprotective effects on 2k1c-induced renal hypertension in rats via the IMD/NO pathway., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objectives: Identification of factors that contribute to urinary albumin losses in hypertensive nephropathy is crucial for prevention of renal deterioration. The aim of this study was to investigate the relationship of low-grade albuminuria with plasma aldosterone levels in treatment-naïve hypertensive patients free of additional comorbidities that might affect renal function., Methods: In 242 newly diagnosed patients with uncomplicated primary hypertension, we obtained duplicate 24-h urine collections for measurement of urinary albumin/creatinine ratio (UACR) and measured plasma aldosterone levels. Patients with diabetes, overt proteinuria (>300 mg/day), glomerular filtration rate less than 30 ml/min per 1.73 m, and previous renal diseases were excluded., Results: Increasing UACR was associated with significantly and progressively higher blood pressure (BP), HDL-cholesterol, and plasma aldosterone levels, and with lower glomerular filtration. Microalbuminuria (30-300 mg/day) was detected in 41 (17%) of 242 hypertensive patients, and these patients had significantly higher BP and plasma aldosterone levels (178 ± 113 vs. 128 ± 84 pg/ml; P = 0.001), and lower glomerular filtration than patients without microalbuminuria. UACR was directly and independently correlated with BP and plasma aldosterone levels. In a logistic regression model, presence of microalbuminuria was associated with plasma aldosterone levels independently of glomerular filtration and demographic, anthropometric, and metabolic variables., Conclusion: In nondiabetic, treatment-naïve patients with hypertension, low-grade albuminuria is independently associated with elevated plasma aldosterone. These findings suggest a contribution of aldosterone to the early glomerular changes occurring in hypertensive nephropathy.

Background/aims: Serum cortisol level is elevated in patients with essential hypertension. We aimed at investigating the association of serum cortisol levels with parameters of renal function in essential hypertension., Methods: One hundred and seventy-eight patients with essential hypertension participated in the study. Fasting serum samples were collected at 8:00 am. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine- cystatin C equation (eGFRcr-cys). Correlation analysis and stepwise regression analysis were used to detect the relationship between cortisol and eGFRcr-cys. The distributions of serum cortisol were split by the tertiles and subjects were stratified into those with low, median and high levels accordingly., Results: Serum cortisol levels were significantly higher in subjects whose eGFRcr-cys<90 ml/min/1.73 m2 than subjects whose eGFRcr-cys>90 ml/min/1.73 m2 (394.0±93.4 vs. 343.2±98.4 nmol/L, P=0.001). Age, systolic blood pressure, and serum total cholesterol, uric acid, cortisol levels were significantly associated with eGFRcr-cys, serum levels of creatinine and cystatin C. After adjusting for clinical factors, serum cortisol level had a statistically significant negative association with the eGFRcr-cys (β=-0.19, P=0.027), and positive associations with cystatin C (β=0.31, P=0.001) and creatinine (β=0.14, P=0.044). With the increment of cortisol tertile, the eGFRcr-cys significantly decreased (93.18±14.36 vs. 84.61±14.67 vs. 81.29±12.36 ml/min/1.73 m2 for low, median and high tertile, respecively, P=0.001)., Conclusion: Serum cortisol level was negatively correlated with eGFRcr-cys in subjects with essential hypertension. Further studies are needed to investigate whether cortisol plays a role in hypertensive nephropathy development., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

The aim of the present study was to investigate the protective effects of melatonin (MLT) on hypertension-induced renal injury and identify its mechanism of action. Twenty-four healthy male Wistar rats were divided into a sham control group (n=8), which was subjected to sham operation and received vehicle treatment (physiological saline intraperitoneally at 0.1 ml/100 g), a vehicle group (n=8), which was subjected to occlusion of the left renal artery and vehicle treatment, and the MLT group (n=8), which was subjected to occlusion of the left renal artery and treated with MLT (10 mg/kg/day). Pathological features of the renal tissues were determined using hematoxylin and eosin staining and Masson staining. Urine protein, serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Immunohistochemical analysis was performed to determine the expression of heme oxygenase‑1 (HO‑1), intercellular adhesion molecule‑1 (ICAM‑1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, reverse transcription polymerase chain reaction was conducted to determine the mRNA expression of HO‑1, ICAM‑1, eNOS and iNOS. A marked decrease in blood pressure was noticed in the MLT group at week 4 compared with that of the vehicle group (P<0.01). Furthermore, MLT treatment attenuated the infiltration of inflammatory cells and oedema/atrophy of renal tubules. MLT attenuated hypertension-induced increases in urine protein excretion, serum creatinine and MDA as well as decreases in SOD activity in renal tissues. Furthermore, MLT attenuated hypertension-induced increases in iNOS and ICAM‑1 as well as decreases in eNOS and HO‑1 expression at the mRNA and protein level. In conclusion, the results of the present study indicated that MLT had protective roles in hypertension‑induced renal injury. Its mechanism of action is, at least in part, associated with the inhibition of oxidative stress.

We investigated the involvement of cyclooxygenase-2 (COX-2) and the renin-angiotensin system in N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Male Wistar rats were treated with L-NAME (75.0 mg·(kg body mass)(-1)·day(-1), in their drinking water) for different durations (1-33 days). COX-2 and renin mRNA were measured using real-time PCR in the renal cortex, and prostanoids were assessed in the renal perfusate, whereas angiotensin II (Ang II) and Ang (1-7) were quantified in plasma. In some rats, nitric oxide synthase inhibition was carried out in conjunction with oral administration of captopril (30.0 mg·kg(-1)·day(-1)) or celecoxib (1.0 mg·kg(-1)·day(-1)) for 2 or 19 days. We found a parallel increase in renocortical COX-2 and renin mRNA starting at day 2 of treatment with L-NAME, and both peaked at 19-25 days. In addition, L-NAME increased renal 6-Keto-PGF(1α) (prostacyclin (PGI2) metabolite) and plasma Ang II from day 2, but reduced plasma Ang (1-7) at day 19. Captopril prevented the increase in blood pressure, which was associated with lower plasma Ang II and increased COX-2-derived 6-Keto-PGF(1α) at day 2 and plasma Ang (1-7) at day 19. Celecoxib partially prevented the increase in blood pressure; this effect was associated with a reduction in plasma Ang II. These findings indicate that renal COX-2 expression increased in parallel with renin expression, renal PGI2 synthesis, and plasma Ang II in L-NAME-induced hypertension.

Chronic kidney disease (CKD) is an important public health problem. Patients with end-stage renal disease have a significant renalase deficiency, which could be one of the mechanisms explaining high prevalence of hypertension in these patients. The aim of this study was to investigate the possible association of renalase gene (rs2296545) polymorphism with normotensive and hypertensive CKD in sampled Egyptian patients and to determine the effect of such polymorphism on epinephrine level. Renalase gene (rs2296545) polymorphism was genotyped in 178 patients with CKD (83 normotensive and 95 hypertensive nephrosclerosis) and 178 normal healthy adults using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Epinephrine level was measured by HPLC method. We found an association of renalase (rs2296545) CC genotype and C allele with CKD. Also, the epinephrine level was significantly increased in normotensive and hypertensive nephrosclerosis patients as compared to controls. CKD patients with CC genotype showed significant high epinephrine level as compared to CG and GG genotypes.

This study assessed the urinary albumin/creatinine ratio (ACR) and uric acid metabolism in 70 hypertensive patients with chronic kidney disease in whom urinary ACR had remained ≥30 mg/g under the treatment of the L-type calcium channel blocker amlodipine. Three months after switching to the N/L-type calcium channel blocker cilnidipine, blood pressure (BP) did not change; however, urinary ACR significantly decreased with cilnidipine. Serum uric acid levels showed no significant change. In cases where uric acid production had been high (urinary uric acid/creatinine ratio ≥0.5), the urinary uric acid/creatinine ratio decreased significantly after cilnidipine treatment, suggesting that cilnidipine can suppress excessive uric acid formation. These results suggest that switching from amlodipine to cilnidipine results in a significant reduction in urinary ACR as well as significant reduction in uric acid production. Thus, cilnidipine is more useful than amlodipine in improving albuminuria and uric acid metabolism in hypertensive patients with chronic kidney disease., (©2014 Wiley Periodicals, Inc.)

Background: Activated coagulation Factor XII (FXIIa) infusion increases peripheral resistance (TPR) and mean arterial pressure (MAP) of Brown Norway but not plasma kininogen deficient Brown Norway Katholiek (BNK) rats. FXIIa concentrations are elevated in hypertensive end-stage renal disease patients receiving conventional haemodialysis (CHD). Conversion to nocturnal haemodialysis (NHD) lowers peripheral resistance and MAP., Objective: To determine whether the plasma coagulation FXIIa-kallikrein-kinin axis contributes to the hypertension of chronic kidney disease (CKD)., Methods: Plasma FXIIa and haemodynamic data were acquired in 11 CHD patients before and after 2 months of NHD. Cardiac and systemic haemodynamics of Brown Norway and BNK rats rendered hypertensive and uremic by 5/6 nephrectomy (NX) were determined before and after acute FXIIa inhibition., Results: FXIIa was increased three-fold in CHD patients relative to control plasma (P < 0.05). After conversion to NHD, both ΔMAP and ΔTPR correlated with ΔFXIIa. In rats, plasma FXIIa was three-fold higher in both NX groups than respective SHAM controls (all P < 0.05), but MAP (147 ± 4 vs. 133 ± 2 mmHg; P < 0.05) and TPR (2.8 ± 0.2 vs. 2.3 ± 0.2 units; P < 0.05) were greater in Brown Norway NX (n = 16) than in BNK (n = 15) NX rats. FXIIa correlated with MAP only in Brown Norway NX, and plasma catecholamines were increased relative to SHAM only in Brown Norway NX (P < 0.05). In Brown Norway NX rats, FXIIa inhibitor infusion decreased MAP (-12 mmHg) and TPR (-0.5 Units) (both P < 0.05), and halved catecholamines (P < 0.05). No such changes occurred in BNK NX rats., Conclusion: FXIIa-kininogen mediated vasoconstriction contributes significantly to CKD hypertension in Brown Norway rats; this novel mechanism may be active in humans with CKD.

A soluble (pro)renin receptor (sPRR) circulates in plasma and is able to bind renin and prorenin. It is not known whether plasma sPRR concentrations vary with the activity of the renin-angiotensin system. We measured plasma sPRR, renin, prorenin, and aldosterone concentrations in 121 white and 9 black healthy subjects, 40 patients with diabetes mellitus, 41 hypertensive patients with or without renin-angiotensin system blockers, 9 patients with primary aldosteronism, and 10 patients with Gitelman syndrome. Median physiological plasma sPRR concentration was 23.5 ng/mL (interquartile range, 20.9-26.5) under usual uncontrolled sodium diet. sPRR concentration in healthy subjects, unlike renin and prorenin, did not display circadian variation or dependence on age, sex, posture, or hormonal status. sPRR concentrations were ≈25% lower in black than in white subjects, whereas renin concentrations were ≈40% lower. Patients with diabetes mellitus (average renin-high prorenin levels) and with hypertension only (average renin-average prorenin levels) had sPRR concentrations similar to healthy subjects. Renin-angiotensin system blockade was associated with increase of sPRR concentration by ≈12%. sPRR in patients with primary aldosteronism (low renin-low prorenin) and Gitelman syndrome (high renin-high prorenin) were similar and ≈10% higher than in healthy subjects. There was no correlation between sPRR and renin or prorenin. In conclusion, our results show that plasma sPRR concentrations are dependent on ethnicity and independent of renin, prorenin, and aldosterone concentrations in healthy subjects and in patients with contrasted degrees of renin-angiotensin system activity.

It is not known whether serum potassium levels affect blood pressure response to antihypertensive medication. The African American Study of Kidney Disease and Hypertension (AASK) Genomics Study (N=828) is a subset of the AASK trial that randomized 1094 African American men and women with hypertensive nephrosclerosis to ramipril, amlodipine or metoprolol. Participants were also randomized to a usual (102-107 mm Hg) or low (≤92 mm Hg) mean arterial pressure (MAP) treatment goal. Time-to-event analyses were used to determine the relationship between serum potassium at randomization and time (days) to reach an MAP of 107 mm Hg. Mean baseline serum potassium was 4.22 mmol l(-1) (s.d.±0.56 and range 2.8-6.0) and the median days to reach target MAP was 32 (interquartile range 8-95). The adjusted hazard ratio (HR) for each 1 mmol l(-1) increase in serum potassium was 1.31 (95% confidence interval (CI): 1.08-1.59) in the usual MAP group, and 1.21 (95% CI: 1.02-1.44) in the low MAP group. Secondary findings suggested that women in the usual MAP group on amlodipine were more likely to reach target MAP compared with women randomized to ramipril (HR: 2.05, 95% CI: 1.30-3.21). Older subjects in the low MAP group (≥55 years) were also more likely to reach target MAP on amlodipine compared with ramipril (HR: 1.57, 95% CI: 1.03-2.38). Serum potassium appears to be a significant predictor of time to blood pressure response, independent of drug class. The effect of serum potassium on blood pressure response to antihypertensive medications needs to be further studied in different patient populations.

Objectives: Ambulatory blood pressure monitoring is the standard for determining patients at risk of hypertension. Left ventricular hypertrophy is common in kidney transplant recipients. We evaluated the correlation between blood pressure measures achieved by ambulatory blood pressure monitoring and conventional (office) methods., Materials and Methods: This cross-sectional study was done from December 2009 to October 2010 at Alzahra Hospital in Isfahan, Iran. Sixty five participants, 35 kidney transplant recipients under 20 years old, and 30 control subjects of the same age were recruited. Five kidney recipients did not complete the study and were excluded. Blood pressure was measured by ambulatory blood pressure monitoring and conventional methods. Echocardiographic study was done for kidney transplant recipients. Serum brain natriuretic peptide and angiotensin II levels were determined in case and control groups., Results: Office-recorded systolic and/or diastolic hypertension was observed in 43.4% and 55.3% of patients. According to ambulatory blood pressure monitoring, 86% of kidney transplant recipients had systolic BP load. Left ventricular hypertrophy (defined according to the left ventricular mass index [left ventricular mass index/height]) was seen in 53.3% of the patients. The existence of left ventricular hypertrophy revealed a positive correlation with ambulatory blood pressure monitoring systolic and diastolic night blood pressure and systolic nondipper. Left ventricular mass index showed a positive correlation with brain natriuretic peptide level. Furthermore, the existence of left ventricular hypertrophy was positively correlated with angiotensin II level., Conclusions: Only ambulatory blood pressure monitoring systolic and diastolic blood pressures (nondippers) were positively correlated with left ventricular hypertrophy and higher left ventricular mass index. Serum levels of brain natriuretic peptide and angiotensin II had a positive relation with left ventricular hypertrophy. Measuring brain natriuretic peptide and angiotensin II in the clinical setting screens patients at risk of left ventricular hypertrophy.

Objective: Transforming growth factor-β (TGF-β) implicated in the pathogenesis of diabetic nephropathy. Hence, developing agents that antagonize fibrogenic signals is a critical issue facing researchers., Material and Methods: Fifty rats were allocated to five groups: 1=control rats, 2=diabetic hypertensive rats 3=diabetic hypertensive rats treated with spironolactone, 4=diabetic hypertensive rats treated with moexpril, 5=diabetic hypertensive rats treated with both spironolactone and moexpril. Measurement of TGF-β, aldosterone, creatinine and ACE. Degree of fibrosis was calculated., Results: Serum creatinine, mean arterial blood pressure (MAP), aldosterone, ACE, TGF-β and renal fibrosis increased significantly in untreated diabetic hypertensive rats compared with control rats. Administration of spironolactone, moexpril, or both decreased these changes., Conclusions: Addition of the spironolactone to moexpril was more effective in reducing fibrosis and improvement of renal function than monotherapy with either drug, possibly due to a dual inhibitory effect on the RAS, and thus suppression of TGF-β., (Copyright © 2009 Elsevier Masson SAS. All rights reserved.)

The study involved 53 patients with arterial hypertension in chronic kidney disease (chronic glomerulonephritis (CGN)). Lipid peroxidation was studied based on the content of diene conjugates and malondialdehyde. Protein peroxidation was studied based on the content of 2,4-dinitphenyl-aldogidrazons. The patients in all clinical variants of the CGN revealed increased activity of lipid peroxidation and the protein peroxidation, which is most pronounced in patients with nephrotic variant of CGN: increased levels of serum malondialdehyde medians occurred in 3.92 times and diene conjugates in 1.52 times (p<0.01). Increased activity of the oxidation of lipids and proteins has a negative impact on the organization of cell membranes of the renal structures and leads to loss of membrane barrier function.

Significance: The kidney helps to maintain low blood pressure in the human body, and impaired kidney function is a common attribute of aging that is often associated with high blood pressure (hypertension). Kidney-related pathologies are important contributors (either directly or indirectly) to overall human mortality. In comparison with other organs, kidney has an unusually wide range of oxidative status, ranging from the well-perfused cortex to near-anoxic medulla., Recent Advances: Oxidative stress has been implicated in many kidney pathologies, especially chronic kidney disease, and there is considerable research interest in oxidative stress biomarkers for earlier prediction of disease onset. Proteomics approaches have been taken to study of human kidney tissue, serum/plasma, urine, and animal models of hypertension., Critical Issues: Redox proteomics, in which oxidative post-translational modifications can be identified in protein targets of oxidative or nitrosative stress, has not been very extensively pursued in this set of pathologies., Future Directions: Proteomics studies of kidney and related tissues have relevance to chronic kidney disease, and redox proteomics, in particular, represents an under-exploited toolkit for identification of novel biomarkers in this commonly occurring pathology.

The study is to observe the effect of racemic TJ0711 on blood pressure and heart rate as well as protection of cardiovascular system of renal hypertensive rats after long-term administration. The renal hypertensive models were established by the two-kidney, one-clip (2K1C) method in Wistar rats. Four weeks later, assigned the rats whose SBP had increased at least 4 kPa randomly into 5 groups: racemic TJ0711 10, 20 and 40 mg x kg(-1) groups, carvedilol control group, model group and sham group (n=10), ig administration once daily. The changes of BP (blood press) and HR (heart rate) before and after administration were measured by tail-cuff method weekly. Plasma samples of all animals were taken in 6-8 weeks, and plasma MDA as well as renin, angiotensin II (Ang II) and endothelin-1 (ET-1) levels were measured. Left ventricle was cut off after 9 weeks, and left ventricular weight index (LVWI) and hydroxyproline were measured. The significant decrease of the BP of TJ0711 40 mg x kg(-1) group was observed after TJ0711 ig administration for 4 weeks, and this effect remained till the end of the study. In 8th week, the systolic blood pressure values were: TJ0711 40 mg x kg(-1) group 18.93 +/- 1.82 kPa (vs 21.30 +/- 2.30 kPa, P < 0.05); 20 mg x kg(-1) group 20.68 +/- 3.29 kPa (vs 22.19 +/- 2.88 kPa). The plasma MDA level of all treated groups was significantly lower than that of model group, so were the plasma renin, Ang II and ET-1 levels (P < 0.05). LVWI and hydroxyproline content of myocardial tissue decreased to some extent, but was not significant as compared with that of model group. The study showed that TJ0711 repeated dosing could reduce BP level beginning from drug administration; besides block adrenal alpha and beta receptors to play an antihypertensive role. The sustained antihypertensive effect also related to reduce plasma vasoconstrictor substances and oxidation product MDA. These effects benefited cardiovascular protection.

Objective: To study the effect of total glycosides of Ranunculus japoniucus (TGRJ) on blood pressure, nitric oxide (NO) calcium and angiotensin II (Ang II) in renal hypertensive rats (RHR)., Methods: 1) RHR were established by two kidney one clip (2K1C) and drugs were given by intragastric administration for 5 week, the blood pressure were measured at the end of 5 week,detected the concentration of NO in the serum and Ang II in the blood plasma,heart and kidney tissue. 2) Used a new generations of Ca2+ fluorescent probe (Fluo-3/AM) to mark calcium in vascular smooth muscle cells. Observed the fluorescence imaging by inverted fluorescence microscope and measured the fluorescence intensity of calcium by fluorescence spectrophotometer in vascular smooth muscle cells., Results: 1) The high, medium doses of TGRJ could decrease blood pressure of RHR (P<0.05), TGRJ could significantly increase the concentration of NO in the serum (P<0.01), but it showed no significant effect on the concentration of Ang II (P>0.05); 2) The Ang II could significantly promote the calcium ions in extracellular inner flow. The different doses of TGRJ could reduce the calcium ions in cells which were mediated by Ang II., Conclusion: TGRJ could decrease blood pressure in RHR. the mechanism might be related to increasing the rats' NO level and reducing the calcium ions level in cells which are increased by Ang II.

Salt-sensitive hypertension and chronic kidney disease (CKD) following recovery from acute kidney injury (AKI) may occur secondary to incomplete repair, or by activation of circulating factors stimulated by injury. We created two types of renal injury induced by unilateral ischemia-reperfusion (I/R); in a direct/ipsilateral AKI group, rats were subjected to unilateral I/R and the untouched contralateral kidney was removed by unilateral nephrectomy after 5 wk to isolate effects on the injured kidney. In the remote/contralateral AKI group, the injured kidney was removed after 5 wk to isolate effects on the untouched kidney. When these animals were subsequently challenged with elevated dietary sodium for an additional 4 wk (0.4 to 4%), both remote/contralateral and direct/ipsilateral AKI rats manifested a significant increase in blood pressure relative to sham-operated controls. Similarly, in acute studies, both ipsilateral and contralateral kidneys had impaired pressure natriuresis and hemodynamic responses. Reductions in vascular density were observed following direct/ipsilateral injury, but were not observed in the remote/contralateral kidney. However, both remote/contralateral and direct/ipsilateral kidneys contained interstitial cells, some of which were identified as activated (low CD62L/CD4+) T lymphocytes. In contrast, only the direct/ipsilateral AKI group demonstrated significant CKD following exposure to elevated salt. This was characterized by a significant reduction in creatinine clearance, an increase in albuminuria, and a dramatic expansion of interstitial inflammation. Taken together, these data suggest that the salt-sensitive features of AKI on hypertension and CKD are segregable such that effects on hemodynamics and hypertension occur independent of direct renal damage. However, prior direct injury to the kidney is required to elicit the full manifestation of CKD induced by elevated sodium intake.

Background/aims: The present study was performed to demonstrate the effect of electroacupuncture (EA) and acupuncture on renal failure (RF)-induced hypertension., Methods: We stimulated the Zusanli (ST36) and Taixi (KI3) acupoints in a rat model of RF-induced hypertension., Results: EA significantly reduced RF-induced hypertension (p < 0.05). In a histopathological study, increments in RF-induced glomerulosclerosis and tubulointerstitial fibrosis were attenuated by EA treatment (p < 0.05). The increase in albuminuria in the RF group was also reduced by EA treatment (p < 0.05). In blood analysis, the increment in RF-induced serum BUN and creatinine concentrations were decreased by EA (p < 0.05), and the decreases in RF-induced insulin-like growth factor-I (IGF-I) mRNA and protein levels were increased by EA in both the kidney and the serum (p < 0.05). The increases in RF-induced oxidative stress, e.g. inducible nitric oxide synthase, heme oxygenase and thiobarbituric acid-reactive substance expression, were significantly decreased in the RF-EA group (p < 0.01)., Conclusion: These findings suggest that the anti-hypertensive mechanism of EA could be related to the effects of oxidative stress on IGF-I in RF-induced hypertension., (Copyright © 2012 S. Karger AG, Basel.)

Background: Chronic kidney disease (CKD) is associated with increased risk for cardiovascular (CV) disease and is also associated with elevated uric acid, which is emerging as a nontraditional CV risk factor. We therefore evaluated uric acid as a risk factor for CV disease in subjects presenting to nephrologists with CKD who were not on medications known to alter endothelial function., Methods: 303 subjects with stage 3-5 CKD were followed for a mean of 39 months (range 6-46) and assessed for fatal and nonfatal CV events. Hyperuricemia was defined as uric acid >6.0 mg/dl for women and >7.0 mg/dl for men. In addition to other CV risk factors, endothelial function (flow-mediated dilatation), inflammatory markers (hsCRP), and insulin resistance (HOMA index and fasting insulin levels) were included in the analysis. We evaluated the association between uric acid and flow-mediated dilatation with linear regression. The impact of uric acid on composite CV events was assessed with Cox regression analysis., Results: Of a total of 303 patients, 89 had normouricemia and 214 had hyperuricemia. Both fatal (32 of 214 vs. 1 of 89 subjects) and combined fatal and nonfatal (100 of 214 vs. 13 of 89 subjects) CV events were more common in subjects with hyperuricemia compared with normal uric acid levels, and this was independent of estimated glomerular filtration rate, traditional CV risk factors including diabetes, hypertension and BMI, and nontraditional risk factors (hsCRP and endothelial function). The 46-month survival rate was 98.7% in the group with low uric acid compared to 85.8% in patients with high uric acid (p = 0.002)., Conclusions: Hyperuricemia is an independent risk factor for CV events in subjects presenting with CKD who are not on medications known to alter endothelial function., (Copyright © 2012 S. Karger AG, Basel.)

The aim of this study was to evaluate the relationship of local intrarenal renin angiotensin system (RAS) with hypertension and proteinuria in renal transplant recipients. Sixty-nine nondiabetic renal transplant recipients (39 male, mean age: 36.3 ± 11.5 years) were included in this study. All patients were in stable condition with GFR greater than 30 ml/min/1.73 m(2); (MDRD). Hypertension was defined to be present if there was a recorded diagnosis of hypertension, systolic blood pressure >130 mmHg and/or diastolic blood pressure >80 mmHg according to ambulatory blood pressure monitoring. None of the hypertensive patients were receiving RAS blockers. Spot urine samples were obtained to measure urinary angiotensinogen (AGT) using human AGT-ELISA, urinary creatinine and protein levels. The demographic properties and laboratory findings were similar between hypertensive and normotensive transplant recipients. Urinary AGT-creatinine ratio (UAGT/UCre) was significantly higher in hypertensive patients compared with the normotensives (8.98 ± 6.89 μg/g vs. 5.48 ± 3.33 μg/g; P = 0.037). Importantly, a significantly positive correlation was found between UAGT/Ucre levels and proteinuria in hypertensive patients (P = 0.01, r = 0.405). Local intrarenal RAS probably plays an important role in the development of hypertension and proteinuria in renal transplant recipients., (© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.)

Background: Advanced glycation end products (AGEs) are associated with comorbidity and death among patients on hemodialysis (HD). Angiotensin II type 1 receptor blockers (ARBs) can decrease the formation of AGEs in vitro. This study examines the ability of various ARBs to decrease plasma AGE levels in hypertensive patients on HD., Methods: This preliminary randomized prospective study included 24 hypertensive patients on HD who were treated with candesartan (8 mg/day). The patients were randomly assigned to an olmesartan (20 mg/day, n = 12) or a telmisartan (40 mg/day, n = 12) group and followed up 24 weeks. Blood pressure was monitored before each HD session, and plasma pentosidine, N-(epsilon)-carboxymethyl-lysine (CML), serum malondialdehyde-low-density lipoprotein (LDL), high-sensitive CRP, and serum total free radical (TFR) were measured at baseline, and at 4, 12, and 24 weeks., Results: Olmesartan was significantly associated with decreased systolic blood pressure compared with telmisartan. After 24 weeks of treatment, plasma pentosidine and CML levels were significantly decreased and serum TFR levels tended to be decreased in the olmesartan group, but remained unchanged in the telmisartan group., Conclusions: These results suggest that olmesartan can help to decrease plasma AGE levels in patients on HD.

Objective: To evaluate the relationship between metabolic syndrome (MetS) and the fasting serum leptin concentration in hemodialysis (HD) patients., Patients and Methods: Fasting blood samples were obtained from 101 HD patients. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation., Results: Forty-eight patients (47.5%) had MetS. Serum leptin concentrations were positively correlated with MetS (p<0.001). Serum leptin levels correlated with increasing numbers of MetS criteria in HD patients (p=0.001). Univariate linear regression analysis showed that the pre-HD body weight (p<0.001), waist circumference (p<0.001), body mass index (p=0.001), triglycerides (p=0.003), insulin level (p=0.043), and homeostasis model assessment of insulin resistance (p=0.003) positively correlated with serum leptin levels in HD patients and high-density lipoprotein-cholesterol (p=0.016) negatively correlated with serum leptin levels in HD patients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that pre-HD body weight (R(2)=0.175; p<0.001) was the independent predictor of the fasting serum leptin concentration., Conclusion: Fasting serum leptin levels positively correlated with MetS and the pre-HD body weight could influence serum leptin in HD patients., (Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

History: A 42-year-old man was found to have a four to six fold increase in the level of plasma ferritin since four years. In the age of 10 he had undergone unilateral resection of a dysplastic kidney associated with systemic hypertension. He had also developed recurrent venous thromboses caused by atresia of the inferior vena cava with azygos continuation, known since 23 years. Iron overload or hemochromatosis had been excluded, but despite numerous investigations the exact cause of the hyperferritinemia had not been elucidated. The patient, his grandfather, his mother and a brother had undergone cataract surgeries in both eyes. He presented at admission with prominent veins over the abdomen a postthrombotic syndrome., Investigation: Laboratory tests revealed a ferritin level 6 times above the upper limit of normal, but iron, transferrin saturation, and transferrin levels were normal. The patient was on oral anticoagulation (INR 2.2). Molecular genetic tests revealed heterozygous mutation IRE+ 32 G > T., Diagnosis, Treatment and Course: The findings indicated a hereditary hyperferritinemia cataract syndrome with an autosomal dominant trait. As functions of other organs are not affected, bilateral cataract surgery is "curative"., Conclusion: Early and correct diagnosis avoids unnecessary diagnostic and therapeutic interventions, such as extended and repeated laboratory tests, liver biopsies, phlebotomies and chelation therapy., (© Georg Thieme Verlag KG Stuttgart · New York.)

The renin-angiotensin-aldosterone system (RAAS) has pivotal roles in the pathogenesis of hypertension in hemodialysis-dependent chronic kidney disease (HDD-CKD) patients. Activated RAAS also increases inflammatory mediators by directly increasing proinflammatory gene expression and by putting oxidative stress on the vascular endothelium. Both hypertension and inflammation are major risk factors for cardiovascular disease (CVD) in HDD-CKD patients. In this study, we assessed the efficacy of a direct renin inhibitor, aliskiren, on blood pressure (BP) and CVD predictive biomarkers, such as brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hs-CRP) and diacron-reactive oxygen metabolite (d-ROM). A total of 30 hypertensive HDD-CKD patients were assigned to receive aliskiren (150 mg) orally once daily with their existing antihypertensives. After 8 weeks, aliskiren treatments reduced systolic blood pressure (SBP) from 169.0±20.1 to 153.7±19.6 mmHg (P<0.001) and diastolic blood pressure (DBP) from 78.1±12.0 to 73.0±13.6 mmHg (P=0.048). RAAS was suppressed by aliskiren treatment as follows: PRA (from 3.6±4.0 to 1.0±1.5 ngml(-1)h(-1) (P=0.004)), angiotensin I (from 1704.0±2580.9 to 233.7±181.0 pgml(-1) (P=0.009)), angiotensin II (from 70.2±121.5 to 12.4±11.5 pgml(-1) (P=0.022)) and aldosterone (from 107.9±148.0 to 73.1±34.6 pgml(-1) (NS)). The biomarkers for CVD were inhibited by aliskiren: BNP (from 362.5±262.1 to 300.0±232.0 pgml(-1) (P=0.043)), hS-CRP (from 6.2±8.1 to 3.5±3.7 mgl(-1) (P=0.022)) and d-ROM (from 367.0±89.8 to 328.3±70.9 U.CARR (P=0.022)). The inhibition levels of biomarkers for CVD by aliskiren did not correlate with the decreased levels of SBP and DBP. These results suggested that aliskiren was effective for BP control and may have cardiovascular protective effects in hypertensive HDD-CKD patients., (© 2011 The Japanese Society of Hypertension All rights reserved)

Objective: With the increasing longevity of heart transplant recipients, the long-term effects of cyclosporine on renal function have become more evident. Highly sensitive, early, and effective monitoring of posttransplant renal function is still being researched. This study aimed to evaluate the prognostic value of cystatin C for patients after heart transplantation., Methods: Seventy-three long-term recipients of a heart transplant more than 5 years before the study start were included in the analysis with a follow-up of 4 years. Serum creatinine, renal glomerular filtration rate calculated by the Modification of Diet in Renal Disease formula, and serum cystatin C levels were collected, and risk factors for renal dysfunction were assessed. Statistical analysis was performed for all patients., Results: Univariate analysis showed a prognostic impact of antihypertensive medication and onset of diabetes (P < .001) on renal failure after transplantation. Multivariate analysis yielded cystatin C measured at the study start as a superior prognostic parameter for all time points (area under the receiver operating characteristic 12 months: 0.963; 24 months: 0.910; 48 months: 0.949) compared with the conventionally used creatinine levels., Conclusions: Our results showed an enormous potential of serum cystatin C as an early prognostic and easy to obtain biomarker for renal dysfunction after heart transplantation., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

The ratio of aldosterone-to-renin activity is currently recommended as a screening test for primary aldosteronism (PA). There are many factors interfering the interpretation of aldosterone-renin ratio (ARR) and could hamper in-time diagnosis of PA. Here, we first report a patient with underlying Page phenomenon and an accidentally disclosed adrenal incidentaloma. High renin secretion from Page phenomenon had masked higher ARR into normal ARR obscuring the diagnosis of PA. However, adrenal venous sampling (AVS) confirmed the autonomous aldosterone secretion with left adrenal vein plasma aldosterone concentration (PAC) 124.1 ng/dl and a lateralization ratio 3.3. AVS may discriminate masked PA due to high renin secretion from Page kidney. It is suggested that clinicians should cautiously interpret aldosterone-renin ratio and consider diagnostic AVS if hyperaldosteronism is highly suspected especially in the background of other secondary hypertension.

Background: The relationship between kidney function and blood pressure (BP) components has been studied in chronic kidney disease patients. Whether cystatin C, a marker of kidney function, is associated in the normal range with systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) obtained using ambulatory blood pressure monitoring has not been previously studied., Methods: The sample subjects were 53 males and 34 females, mean age was 59.3+/-13.5 years. 76% were receiving antihypertensive drug treatment. Kidney function was evaluated by measuring serum cystatin C. Microalbuminuria was measured in a 24h urine collection. Glomerular filtration rate (GFR) was estimated using the abbreviated Modification of Diet in Renal Disease equations. The ambulatory BP was measured non-invasively for 24h by the Spacelab devices programmed to measure BP every 15 min during daytime and every 20 min during nighttime., Results: The highest quartile of cystatin C distribution showed an older age and worsel parameters of renal function (cystatin C, serum creatinine and GFR) than the other groups. No differences for gender or diabetes were found. 24h SBP and PP were higher in the fourth quartile compared to the fist one (p<0.01). 24h DBP was lower for the patients in the fourth quartile of cystatin C compared which any one of the other groups (p<0.001). The relationship between cystatin C, as well as GFR, with SBP and PP was statistically significant as renal function comes down. Contrariwise, as cystatin C increases DBP declines; but the correlation with GFR measured through MDRD 4 is not significant. In the same way, no correlation was found for GFR and microalbuminuria, but there was a statistically significant positive relationship between cystatin C and microalbuminuria severity (p<0.01). Multivariate regression analysis confirms these findings., Conclusions: Both SBP and pulse pressure were significantly associated with kidney function. DBP was negatively correlated with cystatin C concentrations but not with GFR. Cystatin C shows a positive relationship with microalbuminura severity. Cystatin C might have cardiovascular effects beyond its use as a marker of the renal function., (Copyright 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Patients with congenital solitary kidney have an increased risk of developing hypertension, proteinuria and renal insufficiency. However, the specific factors associated with the progression of renal function in adults with congenital solitary kidney remain still unclear. The purpose of this study was to identify factors that are independently associated with renal function progression in patients with congenital solitary kidney., Methods: Sixty-five Chinese adults with congenital solitary kidney (48 patients with unilateral renal agenesis and 17 with severe unilateral renal dysplasia) were recruited into our study retrospectively. Clinical data were analyzed., Results: Of sixty-five patients with congenital solitary kidney, the prevalence of hypertension, proteinuria and renal insufficiency was 36.9%, 35.4% and 38.5%, respectively. There was no significant difference in the glomerular filtration rate (GFR) between patients with and without hypertension, whereas GFR in patients with proteinuria was significantly lower than in those without proteinuria (p<0.05). While there was no statistically significant difference in prevalence of hypertension between patients with and without renal insufficiency, the prevalence of proteinuria in patients with renal insufficiency was significantly higher than in those without renal insufficiency (p<0.05). Logistic regression analysis revealed that kidney length and proteinuria were independently associated with the progression of renal function (OR=0.20, 95%CI 0.05-0.79, and OR=8.30, 95%CI 2.30-29.96, respectively)., Conclusion: Hypertension, proteinuria or renal insufficiency was present in approximately one-third of adults with congenital solitary kidney. Those with a kidney length of less than 120 mm or proteinuria had a much higher risk of renal insufficiency.

Background/aim: Serum gamma-glutamyltransferase (GGT), a biomarker of oxidative stress, is associated with an increased risk of diabetes and hypertension. However, it is not known whether higher serum GGT is independently associated with chronic kidney disease (CKD). Therefore, we examined the association between serum GGT levels and CKD in a representative sample of US adults., Methods: We conducted a cross-sectional study of 9,516 National Health and Nutrition Examination Survey 1999-2002 participants >or=18 years of age (52.40% women). Serum GGT was categorized into quartiles for the analysis. CKD (n = 622) was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m(2)., Results and Conclusion: Higher serum GGT levels were not associated with CKD after adjusting for age, sex, race/ethnicity, education levels, smoking, alcohol intake, body mass index (BMI), diabetes, hypertension and serum cholesterol. Compared to quartile 1 of GGT, the odds ratio (95% confidence interval) of CKD associated with quartile 4 was 1.02 (0.81-1.28); p trend = 0.377. Subgroup analyses that examined the relation between GGT and CKD by gender, alcohol intake, and BMI categories also showed a consistent null association. In summary, there was no association between increasing levels of serum GGT and CKD in a sample of US adults., (Copyright 2010 S. Karger AG, Basel.)

The contribution of inflammation to hypertension and target organ damage is under investigation. The matrix metalloproteinase (MMP) enzymes are inflammatory mediators that may contribute to hypertension and its target organ consequences. Here we probe MMPs as inflammatory mediators in hypertension, by studying all three MMP classes in uncomplicated hypertension as well hypertension with profound renal damage, such as hypertensive end-stage renal disease (ESRD). We assayed plasma levels of five MMPs: one collagenase (MMP-1), two gelatinases (MMP-2, MMP-9), and two stromelysins (MMP-3, MMP-10). In hypertension, MMP-9 was elevated versus normotensive controls. Systolic blood pressure (SBP) in all three subject groups positively correlated with MMP-9. In hypertensive-ESRD, MMP-2 and MMP-10 were elevated compared to both hypertensive and normotensive subjects. Several correlations occurred across MMPs, suggesting coordinate biosynthetic control. Our results suggest discrete patterns of MMP overexpression in hypertension, with MMP-9 elevated early, and MMP-2 and MMP-10 linked to target organ damage.

Transforming growth factor-beta1 (TGF-beta1) is known to induce progression of experimental renal disease. Here we determined whether there is an association between serum levels of TGF-beta1 and the risk factors for progression of clinically relevant renal disorders in 186 black and 147 white adults, none of whom had kidney disease or diabetes. Serum TGF-beta1 protein levels were positively and significantly associated with plasma renin activity along with the systolic and diastolic blood pressure in blacks but not whites after controlling for age, gender, and body mass index. These TGF-beta1 protein levels were also significantly associated with body mass index and metabolic syndrome and more predictive of microalbuminuria in blacks than in whites. The differential association between TGF-beta1 and renal disease risk factors in blacks and whites suggests an explanation for the excess burden of end-stage renal disease in the black population, but this requires validation in an independent cohort. Whether these findings show that it is the circulating levels of TGF-beta1 that contribute to renal disease progression or the findings reflect other unmeasured factors, further longitudinal studies are needed.

Background: The renin-angiotensin-aldosterone system plays a pivotal role in regulation of blood pressure and electrolyte homeostasis and is a target in the treatment of hypertension and renal diseases. However, the factors correlated with plasma renin activity (PRA) are unclarified in general Japanese population. To examine this point, we conducted a community-based cross-sectional study., Methods: Subjects of this study were 2,056 individuals (mean age, 61 years; 934 men; 1,122 women) over 40-year-old without antihypertensive medication in Takahata town, Japan. PRA was measured by radioimmunoassay. Estimated 24-h urine sodium (e24hUNa) and potassium excretion were calculated from morning spot urine., Results: The median value of PRA was higher in men compared to women (1.1 ng/ml/h vs. 0.7 ng/ml/h, P < 0.001). The increased PRA (>2.0 ng/ml/h) were detected in 248 men (26.3%) and 142 women (12.7%). One-factor analysis of variance showed that PRA was correlated with blood pressure, uric acid, hemoglobin, total protein, total cholesterol, low-density lipoprotein cholesterol, serum adiponectin and e24hUNa in men. In women, PRA was correlated with age, blood pressure, total protein, high-density lipoprotein cholesterol (HDL-C), serum insulin, e24hUNa and obesity. Multivariate logistic regression analysis showed that high PRA (>2.0 ng/ml/h) was independently associated with low blood pressures, low e24UNa and high serum total protein both in men and women, smoking only in men and high HDL-C only in women, respectively., Conclusions: This study revealed that PRA was higher in men than women and was associated negatively with blood pressures and urine sodium excretion, and positively with total protein, smoking and HDL-C in Japanese population.

Background/aims: The N-amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and elevated levels are indicative of heart failure. Few correlates of NT-proBNP levels have been identified in persons with moderate chronic kidney disease (CKD), and data from those without heart failure and from African Americans are especially limited., Methods: The African American Study of Kidney Disease and Hypertension (AASK) enrolled nondiabetic African Americans with hypertensive kidney disease (glomerular filtration rate [GFR] = 20-65 ml/min/1.73 m(2)) and no evidence of clinical heart failure. NT-proBNP was measured in 982 AASK participants., Results: In unadjusted analyses, GFR (r = -0.39; p < 0.001), hematocrit (r = -0.21; p < 0.001) and body mass index (BMI; r = -0.07; p = 0.04) were inversely correlated, and systolic blood pressure (r = 0.30; p < 0.001) and log UPCR (r = 0.32; p < 0.001) were positively correlated with log NT-proBNP levels. After adjustment for potential confounders, lower GFR and hematocrit and higher systolic blood pressure and protein:creatinine ratio remained significantly associated with higher NT-proBNP., Conclusion: Lower GFR and hematocrit, and higher urinary protein excretion may be associated with volume expansion in CKD. These results suggest that these processes are associated with increased NT-proBNP in CKD and may play a role in the development of heart failure.

Background: Adiponectin is secreted by adipose tissue and may play a role in cardiovascular disease. We examined adiponectin levels in patients with type 2 diabetes who participated in the Telmisartan vs. Ramipril in Renal Endothelial Dysfunction (TRENDY) study., Methods: A total of 87 patients were assessed at baseline and following 9 weeks treatment with the angiotensin-receptor blocker telmisartan (final dose, 80 mg; n = 45) or the angiotensin-converting enzyme inhibitor ramipril (final dose, 10 mg; n = 42). Adiponectin levels were measured in plasma by radioimmunoassay., Results: Adiponectin levels were inversely correlated with systolic (SBP; r = -0.240, P < 0.05) and diastolic (DBP; r = -0.227, P < 0.05) blood pressure at baseline and following treatment with telmisartan or ramipril (SBP: r = -0.228, P < 0.05; DBP: r = -0.286, P < 0.05). Changes in adiponectin levels were related to changes in SBP (r = -0.357, P < 0.01) and DBP (r = -0.286, P < 0.01). There was a significant increase in adiponectin levels in the telmisartan (0.68 (95% confidence interval (CI), 0.27 to 1.10) microg/ml, P < 0.01) but not in the ramipril group (0.17 (95% CI, -0.56 to 0.90) microg/ml, P = 0.67). Blood pressure reduction in the telmisartan group (DeltaSBP: -13.5 (95% CI, -17.0 to -10.0) mm Hg; DeltaDBP: -7.6 (95% CI, -9.8 to -5.3) mm Hg, each P < 0.001) was significantly (P < or = 0.01 for SBP and P < 0.01 for DBP) greater than in the ramipril group (DeltaSBP: -6.1 (95% CI, -6.2 to -2.0) mm Hg; DeltaDBP: -2.7 (95% CI, -5.0 to -0.5) mm Hg; P < 0.01 and P < 0.05, respectively)., Conclusion: Adiponectin is correlated with blood pressure in patients with type 2 diabetes. Whether increased adiponectin contributes to the blood pressure-lowering effect of telmisartan needs further study.

Background: Experimentally-induced hyperuricaemia [due to inhibition of uricase with oxonic acid (OA)] in rats causes hypertension and renal alterations which can be prevented by lowering uric acid (UA) with allopurinol. Febuxostat (Fx), an investigational, nonpurine and selective xanthine oxidase inhibitor, is a more effective UA-lowering agent than allopurinol. We therefore tested the hypothesis that Fx might be useful in treating hyperuricemia-induced hypertension and renal damage., Methods: Four groups of male rats were studied: OA (750 mg/kg by daily gavage) was given for 8 weeks and Fx (5-6 mg/kg/day in drinking water; OA+Fx: n = 10) or placebo (OA+P: n = 11) were administered for 4 weeks beginning at 4 weeks after initiation of the study. Two groups of normal (N) rats were studied as controls (N+P and N+Fx: n = 10/group). Systolic blood pressure (SBP) and fasting plasma UA were measured in all animals at baseline and at 4 and 8 weeks. Glomerular haemodynamics by micropuncture techniques were determined at 8 weeks followed by histological evaluation of glomerular and afferent arteriole morphologies., Results: In OA-induced hyperuricaemic rats, Fx lowered UA and ameliorated systemic and glomerular hypertension as well as mesangial matrix expansion and the development of preglomerular arteriolar disease as indicated by a reduction of the arteriolar area and media-to-lumen ratio. In normal rats, Fx tended to lower UA and had no effect on blood pressure, renal hemodynamics and afferent arteriole morphology., Conclusion: These results suggest that Fx merits further evaluation for the treatment of hypertension and renal alterations induced by hyperuricaemia.

Hypertension in subjects on long term dialysis is frequent. Its origins are found in extracellular volume overload, which is complicated by increased peripheral arterial resistance. The latter is affected by many systems, including that of renin-angiotensin, endothelin, nitric oxide, the sympathetic nervous system, and others. The interaction between these factors may explain why the control of hypertension in dialysis patients requires ongoing attention to the many aspects of good dialysis.

Plasma renin levels can be used to classify hypertension. A significant proportion of hypertensive individuals display a low-renin profile and thus low-renin hypertension (LRH) requires appropriate diagnosis and treatment. LRH includes essential, secondary and genetic forms, the most common of which are low-renin essential hypertension and primary aldosteronism. Several studies have investigated the relationship between PRA status and clinical response to different antihypertensive therapies. The present review will discuss the differential diagnosis of LRH subtypes and the most appropriate treatment options based on the pathophysiological background of this condition.

Background: Whether benign hypertensive nephrosclerosis (BHN) causes end-stage renal failure (ESRF) is controversial. One reason for this is the lack of biopsy evidence confirming the clinical diagnosis in most cases., Aim: To investigate whether biopsy-proven BHN leads to ESRF., Design: Retrospective analysis., Methods: We analysed all cases of biopsy-proven BHN from a single centre over a period of 20 years (n = 60), followed-up for a mean +/- SD 6.7 +/- 5.5 years., Results: Patients were divided into those with stable renal function (n = 17) and those with declining function (n = 43). Mean eGFR at the time of biopsy was lower in the declining function group (29 +/- 3 vs. 44 +/- 4 ml/min/1.73 m(2), serum creatinine 280 +/- 165 vs. 161 +/- 89 mumol/l, p < 0.001), of whom 72% progressed to ESRF. Median renal survival for the whole group was 6.8 years, with 5- and 10-year survivals of 56% and 35%, respectively. Renal survival was significantly affected by initial serum creatinine, and mean systolic and diastolic blood pressures during follow-up period. Mean protein excretion was higher in the declining group, but not significantly so. On multivariate analysis, only diastolic blood pressure during follow-up predicted renal survival (p = 0.017). Median patient survival for the whole group was 9.95 years post renal biopsy, with 5- and 10-year survivals of 70% and 49% respectively. Survival was affected by initial serum creatinine, initial serum albumin and mean systolic blood pressure during follow-up. On multivariate analysis, only initial serum creatinine was significantly correlated with survival (p = 0.017)., Discussion: Biopsy-proven BHN led to ESRF in a high percentage of our patients, and was associated with significant mortality.

Background/aim: Adiponectin is an adipose tissue-specific protein with antiatherogenic and insulin-sensitizing properties. In patients with essential hypertension, plasma adiponectin concentrations are lower than in healthy subjects. Antihypertensive drugs do not uniformly influence components of the metabolic syndrome. Therefore, the aim of this study was to evaluate the influence of 6 months' monotherapy with different antihypertensive drugs on plasma adiponectin concentration in essential hypertension patients., Methods: Forty essential hypertension patients were randomized to receive enalapril, metoprolol, amlodipine or indapamide. Plasma concentrations of adiponectin, insulin, glucose and body fat content were estimated twice: before and after 6 months of antihypertensive monotherapy., Results: Plasma adiponectin concentration did not change significantly after enalapril (11.5 +/- 4.8 vs. 11.1 +/- 4.1 mg/l), metoprolol (10.2 +/- 4.2 vs. 9.8 +/- 4.5 mg/l), and amlodipine (9.0 +/- 6.0 vs. 8.5 +/- 5.4 mg/l) treatment. However, a significant decrease of plasma adiponectin concentration (from 11.6 +/- 4.6 to 10.2 +/- 4.2 mg/l, p = 0.047) was observed in patients treated with indapamide. Additionally in these patients, a significant increase of the HOMA-IR index was found (p = 0.021)., Conclusion: Treatment with indapamide was followed by a significant decrease of plasma adiponectin concentration. This may participate in the pathogenesis of carbohydrate metabolism disturbances often found in patients treated with thiazide-type diuretics., (Copyright 2007 S. Karger AG, Basel.)