Calcimimetic restores diabetic peripheral neuropathy by ameliorating apoptosis and improving autophagy.

Decreased AMPK-eNOS bioavailability mediates the development of diabetic peripheral neuropathy (DPN) through increased apoptosis and decreased autophagy activity in relation to oxidative stress. Schwann cells are responsible for maintaining structural and functional integrity of neurons and for repairing damaged nerves. We evaluated the neuro-protective effect of cinacalcet on DPN by activating the AMPK-eNOS pathway using db/db mice and human Schwann cells (HSCs).

Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney.

The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis, which counteracts the effects of Ang II, is protective for end-organ damage. To evaluate the ability of resveratrol (RSV) to modulate the RAS in aging kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or chow containing resveratrol, for six months.

Correction: Treatment combining aliskiren with paricalcitol is effective against progressive renal tubulointerstitial fibrosis via dual blockade of intrarenal renin.

[This corrects the article DOI: 10.1371/journal.pone.

Cinacalcet-mediated activation of the CaMKKβ-LKB1-AMPK pathway attenuates diabetic nephropathy in db/db mice by modulation of apoptosis and autophagy.

Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice.

The protective effect of resveratrol on vascular aging by modulation of the renin-angiotensin system.

Background And Aims: This study evaluated the effects of resveratrol on arterial aging and the renin-angiotensin system (RAS) in mice and vascular smooth muscle cells (VSMCs).

Methods: Aging mice were divided into control and resveratrol groups. Histological changes, inflammation, oxidative stress, RAS components, and the expression of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α), and anti-oxidative enzymes was measured in thoracic aortas of 24-month-old mice.

D‑Pinitol alleviates cyclosporine A‑induced renal tubulointerstitial fibrosis via activating Sirt1 and Nrf2 antioxidant pathways.

Although the mechanism of cyclosporine A (CsA)‑induced renal injury remains to be fully elucidated, accumulating evidence suggests that oxidative stress is critical in producing CsA‑induced structural and functional renal impairment. The present study investigated the effect of D‑pinitol, a cyclitol present in soybean, on chronic CsA nephropathy. Male ICR mice were treated with vehicle, CsA (30 mg/kg/day), D‑pinitol (50 mg/kg/day) or a combination of CsA and D‑pinitol for 28 days.

The Adiponectin Receptor Agonist AdipoRon Ameliorates Diabetic Nephropathy in a Model of Type 2 Diabetes.

Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor- (PPAR) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J mice, glomerular endothelial cells (GECs), and podocytes.

Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury.

Background: Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling.

Serum 1,25-dihydroxyvitamin D Better Reflects Renal Parameters Than 25-hydoxyvitamin D in Patients with Glomerular Diseases.

Impaired vitamin D metabolism may contribute to the development and progression of chronic kidney disease. The purpose of this study was to determine associations of circulating vitamin D with the degree of proteinuria and estimated glomerular filtration rate (eGFR) in patients with biopsy-proven glomerular diseases. Clinical and biochemical data including blood samples for 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)D) levels were collected from patients at the time of kidney biopsy.

Altered Metabolism of Blood Manganese Is Associated with Low Levels of Hemoglobin in Patients with Chronic Kidney Disease.

Blood manganese (Mn) level has been reported to be higher in patients with anemia or iron deficiency. The purpose of this study was to analyze the relationship between blood Mn level and anemia in patients with chronic kidney disease (CKD). A total of 334 patients with CKD who were not treated with dialysis were included in this study.

Extracellular Superoxide Dismutase Attenuates Renal Oxidative Stress Through the Activation of Adenosine Monophosphate-Activated Protein Kinase in Diabetic Nephropathy.

Aims: Oxidative stress plays a crucial role in the pathogenesis of diabetic nephropathy (DN). We evaluated whether extracellular superoxide dismutase (EC-SOD) has a renoprotective effect through activation of adenosine monophosphate-activated protein kinase (AMPK) in diabetic kidneys.

Results: Human recombinant EC-SOD (hEC-SOD) was administered to 8-week-old male C57BLKS/J db/db mice through intraperitoneal injection once a week for 8 weeks.

Treatment combining aliskiren with paricalcitol is effective against progressive renal tubulointerstitial fibrosis via dual blockade of intrarenal renin.

The aim of this study was to assess any potential additive effects of a treatment combining aliskiren with paricalcitol on reducing renal fibrosis. C57BL/6J mice were treated individually with aliskiren and/or paricalcitol until 7 days after initiation of unilateral ureteral obstruction (UUO).In obstructed kidneys of UUO mice, monotherapy with aliskiren or paricalcitol significantly attenuated interstitial fibrosis, collagen IV accumulation, and α-smooth muscle actin- and terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling-positive cells.

T-type calcium channel blocker attenuates unilateral ureteral obstruction-induced renal interstitial fibrosis by activating the Nrf2 antioxidant pathway.

Besides its effect on high blood pressure, T-type calcium channel blocker is renoprotective in experimental models of renal fibrosis. However, the exact mechanism of T-type calcium channel blocker on tubulointerstitial fibrosis is unclear. We investigated whether the renoprotective effect of T-type calcium channel blocker is associated with modulation of the signaling of oxidative stress-induced renal fibrosis.

Resveratrol increases AdipoR1 and AdipoR2 expression in type 2 diabetic nephropathy.

Background: Adiponectin has multiple functions including insulin sensitization, anti-inflammation and antiatherogenesis in various organs. Adiponectin activates 5'-adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)α via the adiponectin receptor (AdipoR) 1 and 2, which are critical for regulating lipids and glucose homeostasis and for controlling oxidative stress. We investigated whether resveratrol can inhibit renal damage in type 2 diabetic db/db mice and the underlying mechanisms of its effects.

PPARα agonist, fenofibrate, ameliorates age-related renal injury.

The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress.

Anthocyanin-rich Seoritae extract ameliorates renal lipotoxicity via activation of AMP-activated protein kinase in diabetic mice.

Background: Anthocyanins are major constituents of food colours and have been reported to possess anti-diabetic activities for potential medicinal use. The precise role of anthocyanins in diabetic nephropathy is poorly understood. We investigated whether anthocyanin-rich Seoritae extract (SE) can potentially prevent oxidative stress and lipotoxicity, which are the main causes of renal damage in diabetic nephropathy, via activation of AMP-activated protein kinase (AMPK) and the consequent effects on its target molecules.

Safety and tissue yield for percutaneous native kidney biopsy according to practitioner and ultrasound technique.

Background: Although percutaneous renal biopsy remains an essential tool in the diagnosis and treatment of renal diseases, in recent times the traditional procedure of nephrologists has been performed by non-nephrologists rather than nephrologists at many institutions. The present study assessed the safety and adequacy of tissue yield during percutaneous renal biopsy according to practitioners and techniques based on ultrasound.

Methods: This study included 658 native renal biopsies performed from 2005 to 2010 at a single centre.

Fenofibrate improves renal lipotoxicity through activation of AMPK-PGC-1α in db/db mice.

Peroxisome proliferator-activated receptor (PPAR)-α, a lipid-sensing transcriptional factor, serves an important role in lipotoxicity. We evaluated whether fenofibrate has a renoprotective effect by ameliorating lipotoxicity in the kidney. Eight-week-old male C57BLKS/J db/m control and db/db mice, divided into four groups, received fenofibrate for 12 weeks.

Vascular endothelial growth factor-receptor 1 inhibition aggravates diabetic nephropathy through eNOS signaling pathway in db/db mice.

The manipulation of vascular endothelial growth factor (VEGF)-receptors (VEGFRs) in diabetic nephropathy is as controversial as issue as ever. It is known to be VEGF-A and VEGFR2 that regulate most of the cellular actions of VEGF in experimental diabetic nephropathy. On the other hand, such factors as VEGF-A, -B and placenta growth factor bind to VEGFR1 with high affinity.

Assessment of tubular reabsorption of phosphate as a surrogate marker for phosphate regulation in chronic kidney disease.

Background/aims: Fibroblast growth factor 23 (FGF23) and soluble α-Klotho are emerging potential biomarkers of phosphorus and vitamin D metabolism which change in concentration in early chronic kidney disease (CKD) in order to maintain normal phosphorus levels. Tubular reabsorption of phosphate (TRP) has been commonly used to assess renal tubular phosphate transport. The aim of this study was to evaluate the usefulness of TRP as a surrogate marker of parameters of CKD-mineral bone disease (CKD-MBD) in CKD.

Association of blood manganese level with diabetes and renal dysfunction: a cross-sectional study of the Korean general population.

Background: The purpose of this study was to evaluate the association between blood manganese levels and the prevalence of chronic diseases in the Korean population.

Methods: This was a cross-sectional study based on the Korean National Health and Nutrition Examination Survey (KNAHNES). The study included 3996 participants 20 years of age or older whose blood manganese levels had been measured.

Delayed treatment with oleanolic acid attenuates tubulointerstitial fibrosis in chronic cyclosporine nephropathy through Nrf2/HO-1 signaling.

Background: Nuclear factor erythroid-2-related factor-2 (Nrf2) is known to protect against tissue injury by orchestrating antioxidant and detoxification responses to oxidative stress. This study investigated whether upregulation of Nrf2-dependent signaling by oleanolic acid (OA), which is known to activate Nrf2, could attenuate renal inflammation and fibrosis in cyclosporine (CsA)-induced kidney injury.

Methods: Male ICR mice were divided into four treatment groups: Vehicle (VH, n = 6), VH + OA (n = 6), CsA (n = 8), and CsA + OA (n = 8).