Retention of fetuin-A in renal tubular lumen protects the kidney from nephrocalcinosis in rats

Matsui, Isao; Hamano, Takayuki; Mikami, Satoshi; Inoue, Kazunori; Shimomura, Atsushi; Nagasawa, Yasuyuki; Michigami, Toshimi; Ohnishi, Tomokazu; Fujii, Naohiko; Nakano, Chikako; Kusunoki, Yasuo; Kitamura, Harumi; Iwatani, Hirotsugu; Takabatake, Yoshitsugu; Kaimori, Jun‐Ya; Matsuba, Go; Okoshi, Kento; Kimura-Suda, Hiromi; Tsubakihara, Yoshiharu; Rakugi, Hiromi; Isaka, Yoshitaka

doi:10.1152/ajprenal.00329.2012

Cited by 40 publications

(39 citation statements)

References 24 publications

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“…Higher excretion of fetuin-A into urine has been reported to reflect the insulin resistance and inflammatory responses in obesity and type 2 diabetes [43] and it may reflect the increase in the serum levels of fetuin-A and alterations in the changes in the permeability of glomerular capillaries. Fetuin-A is reported to pass through the slit diaphragm and re-introduced to proximal tubular cells by megalin-mediated endocytosis [44]. Zhou et al also reported that urinary exosomal fetuin-A was increased in the rats treated with cisplatin injection and in the ICU patients with acute kidney injury [45].…”

Section: Discussionmentioning

confidence: 99%

Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray

et al. 2013

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We analyzed the urine samples of patients with type 2 diabetes at various stages of diabetic nephropathy by lectin microarray to identify a biomarker to predict the progression of diabetic nephropathy. Japanese patients with type 2 diabetes at various stages of nephropathy were enrolled and we performed lectin microarray analyses (n = 17) and measured urinary excretion of fetuin-A (n = 85). The increased signals of urine samples were observed in Siaα2-6Gal/GalNAc-binding lectins (SNA, SSA, TJA-I) during the progression of diabetic nephropathy. We next isolated sialylated glycoproteins by using SSA-lectin affinity chromatography and identified fetuin-A by liquid chromatography–tandem mass spectrometer. Urinary excretion of fetuin-A significantly increased during the progression of albuminuria (A1, 0.40±0.43; A2, 0.60±0.53; A3 1.57±1.13 ng/gCr; p = 7.29×10−8) and of GFR stages (G1, 0.39±0.39; G2, 0.49±0.45; G3, 1.25±1.18; G4, 1.34±0.80 ng/gCr; p = 3.89×10−4). Multivariate logistic regression analysis was employed to assess fetuin-A as a risk for diabetic nephropathy with microalbuminuria or GFR<60 mL/min. Fetuin-A is demonstrated as a risk factor for both microalbuminuria and reduction of GFR in diabetic nephropathy with the odds ratio of 4.721 (1.881–11.844) and 3.739 (1.785–7.841), respectively. Collectively, the glycan profiling analysis is useful method to identify the urine biomarkers and fetuin-A is a candidate to predict the progression of diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray

et al. 2013

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“…Elevated PTH levels can also stimulate cytosolic free calcium concentrations, whereas metabolic acidosis results in decreased lumenal citrate, an important inhibitor of calcium phosphate precipitation (73, 99). Inflammation and deficiencies of inhibitors of calcification (i.e., fetuin-A) in combination with these imbalances in phosphorus homeostasis create a perfect storm for ectopic calcification, which can manifest in the vasculature and in the renal parenchyma (113, 116, 117, 138, 149). …”

Section: Dysregulation Of Phosphorus Homeostasismentioning

confidence: 99%

Dietary Phosphorus Intake and the Kidney

Chang

Anderson

2017

Annu. Rev. Nutr.

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Although phosphorus is an essential nutrient required for multiple physiological functions, recent research raises concerns that high phosphorus intake could have detrimental effects on health. Phosphorus is abundant in the food supply of developed countries, occurring naturally in protein-rich foods and as an additive in processed foods. High phosphorus intake can cause vascular and renal calcification, renal tubular injury, and premature death in multiple animal models. Small studies in human suggest that high phosphorus intake may result in positive phosphorus balance and correlate with renal calcification and albuminuria. Although serum phosphorus is strongly associated with cardiovascular disease, progression of kidney disease, and death, limited data exist linking high phosphorus intake directly to adverse clinical outcomes. Further prospective studies are needed to determine whether phosphorus intake is a modifiable risk factor for kidney disease.

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“…Nephrocalcinosis in 6-week-old male Wistar rats was induced by continuous injection of rat PTH 1-34 (Bachem, Bubendorf, Switzerland) at a dosage of 40 mg/kg per day via an osmotic mini-pump (Alzet, Cupertino, CA) for 50 hours. 50 L-LyszHCl or glycine at a dose of 20 mmol/kg was administered via a gastric tube at 2 hours, 14 hours, 26 hours, and 38 hours after the implantation of the osmotic pump.…”

Section: Animalsmentioning

confidence: 99%

“…5,50,51 All rats were handled in a humane manner in accordance with the guidelines of the Animal Committee of Osaka University. Figure 6.…”

Section: Animalsmentioning

confidence: 99%

Dietary L-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

Shimomura¹,

Matsui²,

Hamano

et al. 2014

Journal of the American Society of Nephrology

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Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary L-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+L-lysinezHCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. L-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary L-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of L-lysine. Dietary L-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/ phosphate solution. In conclusion, dietary supplementation of L-lysine ameliorated VC by modifying key pathways that exacerbate VC.

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Retention of fetuin-A in renal tubular lumen protects the kidney from nephrocalcinosis in rats

Cited by 40 publications

References 24 publications

Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray

Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray

Dietary Phosphorus Intake and the Kidney

Dietary L-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

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