Advanced glycation end products evoke inflammatory reactions in proximal tubular cells via autocrine production of dipeptidyl peptidase-4.

We have previously shown that albuminuria and renal levels of advanced glycation end products (AGEs), receptor for AGEs (RAGE), and oxidative stress are suppressed in dipeptidyl peptidase-4 (DPP-4)-deficient diabetic rats, thus suggesting the crosstalk between AGE-RAGE axis and DPP-4 in experimental diabetic nephropathy. Therefore, we examined here the role of DPP-4 in AGE-evoked inflammatory reactions in human proximal tubular cells. Proteins were extracted from proximal tubular cells, and conditioned medium was collected, both of which were subjected to western blot analysis using anti-DPP-4 antibody.

RAGE-aptamer attenuates deoxycorticosterone acetate/salt-induced renal injury in mice.

The mineralocorticoid receptor (MR) and its downstream signaling play an important role in hypertensive renal injury. The interaction of advanced glycation end products (AGE) with their receptor (RAGE) is involved in the progression of renal disease. However, the pathological crosstalk between AGE-RAGE axis and MR system in kidney derangement remains unclear.

Asymmetric Dimethylarginine Contributes to the Impaired Response to Erythropoietin in CKD-Anemia.

Erythropoietin-resistant anemia is associated with adverse cardiovascular events in patients with ESRD, but the underlying mechanism remains unclear. Here, we evaluated the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). In 54 patients with advanced CKD, erythrocyte but not plasma ADMA levels independently associated with low hemoglobin values, although levels of both types of ADMA were elevated compared with those in healthy volunteers.

Maternal exposure to high-fat and high-fructose diet evokes hypoadiponectinemia and kidney injury in rat offspring.

Background: Maternal exposure to overnutrition during fetal development contributes to metabolic and renal damage in offspring. Adiponectin plays a protective role against obesity-related renal injury. However, role of adiponectin in renal injury of offspring exposed to maternal overnutrition remains unknown.

The dipeptidyl peptidase inhibitor linagliptin and the angiotensin II receptor blocker telmisartan show renal benefit by different pathways in rats with 5/6 nephrectomy.

Dipeptidyl peptidase (DPP)-4 inhibitors delay chronic kidney disease (CKD) progression in experimental diabetic nephropathy in a glucose-independent manner. Here we compared the effects of the DPP-4 inhibitor linagliptin versus telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. Animals were allocated to 1 of 4 groups: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus linagliptin; and 5/6 nephrectomy plus telmisartan.

Carnitine deficiency is associated with late-onset hypogonadism and depression in uremic men with hemodialysis.

Late-onset hypogonadism (LOH) and depression contribute to cardiovascular disease (CVD) in male hemodialysis (HD) patients. Carnitine deficiency is frequently observed in HD patients, playing a role in CVD. We examined whether carnitine deficiency was independently associated with LOH and depression in these patients.

Asymmetric dimethylarginine accumulates in the kidney during ischemia/reperfusion injury.

Ischemia/reperfusion injury is the leading cause of acute tubular necrosis. Nitric oxide has a protective role against ischemia/reperfusion injury; however, the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in ischemia/reperfusion injury remains unclear. ADMA is produced by protein arginine methyltransferase (PRMT) and is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH).

Potential inhibitory effects of L-carnitine supplementation on tissue advanced glycation end products in patients with hemodialysis.

Background And Aims: Advanced glycation end products (AGEs) contribute to cardiovascular disease in patients with hemodialysis (HD). We have recently found that carnitine levels are inversely associated with skin AGE levels in HD patients. We examined whether L-carnitine supplementation reduced skin AGE levels in HD patients with carnitine deficiency.

Involvement of advanced glycation end product-induced asymmetric dimethylarginine generation in endothelial dysfunction.

Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, plays a role in endothelial dysfunction, an initial step of atherosclerosis. Advanced glycation end products (AGEs) also contribute to accelerated atherosclerosis. However, a pathophysiological crosstalk between ADMA and AGEs remains unclear.

DNA aptamer raised against AGEs blocks the progression of experimental diabetic nephropathy.

Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We screened DNA aptamer directed against AGEs (AGEs-aptamer) in vitro and examined its effects on renal injury in KKAy/Ta mice, an animal model of type 2 diabetes. Eight-week-old male KKAy/Ta or C57BL/6J mice received continuous intraperitoneal infusion of AGEs- or control-aptamer for 8 weeks.

Effects of switching from calcium carbonate to lanthanum carbonate on bone mineral metabolism in hemodialysis patients.

Phosphate binders are useful for the treatment of hyperphosphatemia in hemodialysis (HD) patients. This study was performed to examine the effects of switching from calcium carbonate (CC) to lanthanum carbonate (LC) on bone mineral metabolism and inflammatory markers in HD patients. We conducted 29 stable HD patients receiving CC, which was replaced by LC and followed-up for 12 weeks.

Evidence for a positive association between serum carnitine and free testosterone levels in uremic men with hemodialysis.

Background And Aims: Low free testosterone levels are associated with sexual dysfunction and an increased risk of cardiovascular disease in male hemodialysis patients. Carnitine deficiency is frequently observed in hemodialysis patients as well. However, the relationship between carnitine and testosterone levels remains unknown.

Experimental diabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice.

Background: Matrix metalloproteinase-2 (MMP-2) is responsible for the degradation of various types of extracellular matrix (ECM) proteins such as type IV collagen. Decreased MMP-2 expression and activity has been generally thought to contribute to increased accumulation of ECM at the advanced stage of diabetic nephropathy. However, the kinetics and role of MMP-2 in the early phase of diabetic nephropathy remain unclear.

Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients.

Aim: There is accumulating evidence that advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in patients with haemodialysis (HD). Carnitine deficiency is frequently observed in HD patients, which may also contribute to CVD. In this study, we examined whether carnitine deficiency was independently associated with increased tissue accumulation levels of AGE in HD patients.

Proteinuria elevates asymmetric dimethylarginine levels via protein arginine methyltransferase-1 overexpression in a rat model of nephrotic syndrome.

Aims: Proteinuria is an independent risk factor for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Asymmetric dimethylarginine (ADMA) is a mediator of endothelial dysfunction and is associated with proteinuria in CKD patients. Thus, ADMA can partially account for the increased risk of CVD in CKD patients presenting proteinuria.

Association of asymmetric dimethylarginine with severity of kidney injury and decline in kidney function in IgA nephropathy.

Background: Asymmetric dimethylarginine (ADMA) plays important roles in the pathogenesis of chronic kidney disease (CKD). We have recently found that ADMA is involved in glomerular sclerosis and tubulointerstitial fibrosis in an animal model of CKD. However, relationship between plasma ADMA levels and severity of renal damage in CKD patients remains unknown.

[Case of acute kidney injury related to intravenous zoledronic acid in a patient with multiple myeloma].

We report the first case of acute kidney injury related to intravenous zoledronic acid (ZA)in a patient with multiple myeloma in Japan. A 37-year-old male was diagnosed as having multiple myeloma (MM) of the Bence Jones lambda type. He showed a good response to two courses of vincristine, adriamycin and dexamethasone (VAD) therapy, and remarkable reduction was seen in plasma cells in bone marrow from 38.