Ambulatory blood pressure is better associated with target organ damage than clinic blood pressure in patients with primary glomerular disease.

BACKGROUND: Blood pressure is an important and modifiable cardiovascular risk factor. Ambulatory blood pressure monitoring (ABPM) provides valuable prognostic information in patients with chronic kidney disease (CKD), yet little is known about the association of various types of BP measurements with target organ damage (TOD) in patients with primary glomerular disease. The goal of this study was to investigate whether ambulatory blood pressure is better associated with TOD than clinic blood pressure in patients with primary glomerular disease. METHODS: 1178 patients with primary glomerular disease were recruited in this cross-sectional study. TOD were assessed by the following 4 parameters: left ventricular mass index (LVMI or LVH, left ventricular hypertrophy), estimated glomerular filtration rate (eGFR< 60 ml/min/1.73m2), albumin-to-creatinine ratio (ACR ≥ 30 mg/g) and carotid intima-media thickness (cIMT) or plaque. Receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were used to evaluate the relationship between ambulatory or clinic systolic blood pressure (SBP) indexes and TOD. RESULTS: Among 1178 patients (mean age, 39 years,54% men), 116, 458, 1031 and 251 patients had LVH, eGFR < 60 ml/min/1.73m2, ACR ≥ 30 mg/g and cIMT≥0.9 mm or plaque respectively. Area under ROC curves for TOD in ambulatory SBP, especially nighttime SBP, was greater than that in clinic SBP (P < 0.05). Multivariate logistic regression analyses showed that 24 h SBP, daytime SBP and nighttime SBP were significantly associated with LVH, eGFR< 60 ml/min/1.73m2 and ACR ≥ 30 mg/g after adjustment for clinic SBP, while the association of clinic SBP was attenuated after further adjustment for nighttime SBP. CONCLUSIONS: Ambulatory blood pressure, especially nighttime blood pressure, is probably superior to clinic blood pressure and has a significant association with TOD in primary glomerular disease patients.

Activation of the Nrf2-ARE Pathway Ameliorates Hyperglycemia-Mediated Mitochondrial Dysfunction in Podocytes Partly Through Sirt1.

BACKGROUND/AIMS: Previously we have shown that activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-antioxidant response element (ARE) attenuated hyperglycemia-induced damage in podocytes, but the molecular mechanism remains unknown. METHODS: Tert-butylhydroquinone (t-BHQ) and small interfering RNAs (siRNAs) were used to regulate Nrf2 expression, while nicotinamide and siRNAs were used to regulate sirtuin 1 (Sirt1) activity and expression, respectively. Mitochondrial superoxide, membrane potential and ATP levels were measured to assess changes in mitochondrial function. Nephrin and synaptopodin expression were measured by western blot analysis. Human podocytes and db/db diabetic mice were used in this study. RESULTS: t-BHQ pretreatment of human podocytes exposed to high glucose (HG) alleviated mitochondrial dysfunction, enhanced the expression of Sirt1, nephrin and synaptopodin and lowered BSA permeability compared with podocytes exposed to HG without t-BHQ pretreatment (p< 0.05). Human podocytes exposed to HG had more severe mitochondrial dysfunction, lower expression of Sirt1, synaptopodin and nephrin and higher BSA permeability than podocytes exposed to HG when Nrf2 expression was downregulated by siRNAs (p< 0.05). The protection provided by activation of the Nrf-ARE pathway in podocytes exposed to HG was partially diminished when Sirt1 expression or activity was decreased by siRNAs or inhibitor compared with podocytes exposed to HG and pretreated with t-BHQ (p< 0.05). When nicotinamide and t-BHQ were both administered to db/db mice, we observed higher levels of urinary albumin/creatinine, lower nephrin and synaptopodin expression, more severe mesangial matrix deposition, collagen deposition on pathological slides and mitochondrial structural damage in podocytes compared to db/db mice treated only with t-BHQ. CONCLUSIONS: Our findings suggest that crosstalk between Sirt1 and the Nrf2-ARE anti-oxidative pathway forms a positive feedback loop and that protection provided by t-BHQ activation of the Nrf2-ARE pathway in db/db mice is partly dependent on Sirt1.