Nicotinamide prevents the development of hyperphosphataemia by suppressing intestinal sodium-dependent phosphate transporter in rats with adenine-induced renal failure

Eto, Nobuaki; Miyata, Yoko; Ohno, Hiroaki; Yamashita, Takefumi

doi:10.1093/ndt/gfh781

Cited by 126 publications

(120 citation statements)

References 19 publications

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“…In addition, the Na/Pi IIb co-transporter mediates the intestinal phosphate reabsorption. In animal models of renal failure, the nicotinic acid metabolite nicotinamide downregulated the Na/Pi IIb expression in the jejunum brush border and thereby prevented hyperphosphatemia (21,22). The findings of our study indicate that in addition to nicotinamide, nicotinic acid administration to dialysis patients leads to a significant serum phosphate decrease, presumably by a similar mechanism.…”

Section: Discussionmentioning

confidence: 52%

Niacin Lowers Serum Phosphate and Increases HDL Cholesterol in Dialysis Patients

Müller

Mehling

Otto

et al. 2007

Clinical Journal of the American Society of Nephrology

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Background and objectives: Adverse effects complicate the use of drugs that are prescribed for phosphate control in dialysis patients. Alternative treatment options are needed.Design, setting, participants, & measurements: Nicotinic acid inhibits intestinal phosphate reabsorption and increases HDL cholesterol. This study tested the phosphate-lowering and HDL-increasing effect of Niaspan (prolonged-release nicotinic acid) in patients who were undergoing dialysis. Efficacy, safety, and tolerability of Niaspan were prospectively studied. Twenty dialysis patients, who were receiving a stable dosage of a calcium salt-containing drug for phosphate control, received after a 2-wk washout period Niaspan for 12 wk. Patients were started on 375 mg/d, and the dosage was increased every 2 wk to achieve 500, 1000, 1500, and 2000 mg/d, respectively. Clinical and laboratory parameters were prospectively recorded in patients who tolerated a target dosage of >1000 mg/d.Results: Seventeen patients tolerated >1000 mg/d Niaspan (mean dosage 1470 ؎ 110 mg/d). Niaspan treatment for 12 wk decreased serum phosphate values from 7.2 ؎ 0.5 to 5.9 ؎ 0.6 mg/dl (P < 0.015). In contrast, Niaspan did not affect serum calcium levels. A significant increase in HDL cholesterol from 40 ؎ 3.2 to 59 ؎ 5.5 mg/dl (34%) was also observed with Niaspan (P ‫؍‬ 0.0005).Conclusions: Niaspan effectively lowered serum phosphate levels and significantly increased HDL cholesterol. Niaspan may provide an alternative or adjunctive treatment option in dialysis patients.

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Section: Discussionmentioning

confidence: 52%

Niacin Lowers Serum Phosphate and Increases HDL Cholesterol in Dialysis Patients

Müller

Mehling

Otto

et al. 2007

Clinical Journal of the American Society of Nephrology

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“…[7][8][9][10] Nicotinamide has been shown to inhibit sodium-dependent phosphate transport activity in rat small intestine, reduce Npt2b mRNA expression, and attenuate hyperphosphatemia in an adenine-induced renal failure model. 11,12 Reduction in serum phosphate with corresponding modulation of Npt2a and 2b mRNA expression has also been observed in rats treated with liver X receptor agonists. 13 These data cumulatively support the possibility that inhibition of this transporter may be a viable therapeutic alternative.…”

mentioning

confidence: 88%

“…Nonetheless, these agents are also known to have pleiotropic actions, which may also contribute to changes in mineral homeostasis. 12,14 A recent study in uremic Npt2b +/2 mice provides initial evidence that Npt2b reduction specifically decreases hyperphosphatemia. 15 However, because this study was performed using developmental heterozygous mice with ARF, it is unknown whether the effects of Npt2b deletion can be sustained over the course of CKD progression due to upregulation of Npt2a.…”

mentioning

confidence: 99%

Npt2b Deletion Attenuates Hyperphosphatemia Associated with CKD

Schiavi

Tang

Bracken

et al. 2012

Journal of the American Society of Nephrology

106

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The incidence of cardiovascular events and mortality strongly correlates with serum phosphate in individuals with CKD. The Npt2b transporter contributes to maintaining phosphate homeostasis in the setting of normal renal function, but its role in CKD-associated hyperphosphatemia is not well understood. Here, we used adenine to induce uremia in both Npt2b-deficient and wild-type mice. Compared with wild-type uremic mice, Npt2b-deficient uremic mice had significantly lower levels of serum phosphate and attenuation of FGF23. Treating Npt2b-deficient mice with the phosphate binder sevelamer carbonate further reduced serum phosphate levels. Uremic mice exhibited high turnover renal osteodystrophy; treatment with sevelamer significantly decreased the number of osteoclasts and the rate of mineral apposition in Npt2b-deficient mice, but sevelamer did not affect bone formation and rate of mineral apposition in wild-type mice. Taken together, these data suggest that targeting Npt2b in addition to using dietary phosphorus binders may be a therapeutic approach to modulate serum phosphate in CKD.

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“…Potentially relevant to diabetic patients with renal failure, nicotinamide also has been shown to reduce intestinal absorption of phosphate and prevent the development of hyperphosphatemia and progressive renal dysfunction [81]. In animal and cell culture studies, nicotinamide also can maintain normal fasting blood glucose in animals with streptozotocin-induced diabetes [82,83], reduce peripheral nerve injury during elevated glucose [84], lead to the remission of type 1 DM in mice with acetyl-l-carnitine [85], and can inhibit oxidative stress pathways that lead to apoptosis [63, [86][87][88][89].…”

Section: Innovative Strategies For Neurovascular Protection During Dmmentioning

confidence: 99%

Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus

Maiese

2008

Biomedicine & Pharmacotherapy

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SummaryOxidative stress is a principal pathway for the dysfunction and ultimate destruction of cells in the neuronal and vascular systems for several disease entities, non promoting the ravages of oxidative stress to any less of a degree than diabetes mellitus. Diabetes mellitus is increasing in incidence as a result of changes in human behavior that relate to diet and daily exercise and is predicted to affect almost 400 million individuals worldwide in another two decades. Furthermore, both type 1 and type 2 diabetes mellitus can lead to significant disability in the nervous and cardiovascular systems, such as cognitive loss and cardiac insufficiency. As a result, innovative strategies that directly target oxidative stress to preserve neuronal and vascular longevity could offer viable therapeutic options to diabetic patients in addition to more conventional treatments that are designed to control serum glucose levels. Here we discuss the novel application of nicotinamide, Wnt signaling, and erythropoietin that modulate cellular oxidative stress and offer significant promise for the prevention of diabetic complications in the nervous and vascular systems. Essential to this process is the precise focus upon diverse as well as common cellular pathways governed by nicotinamide, Wnt signaling, and erythropoietin to outline not only the potential benefits, but also the challenges and possible detriments of these therapies. In this way, new avenues of investigation can hopefully bypass toxic complications, or at the very least, avoid contraindications that may limit care and offer both safe and robust clinical treatment for patients.

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Nicotinamide prevents the development of hyperphosphataemia by suppressing intestinal sodium-dependent phosphate transporter in rats with adenine-induced renal failure

Abstract: Nicotinamide inhibited intestinal Pi absorption in a rat model of CRF, at least in part by inhibiting the expression of NaPi-2b, and appeared to protect against the deterioration of renal function.

Cited by 126 publications

References 19 publications

Niacin Lowers Serum Phosphate and Increases HDL Cholesterol in Dialysis Patients

Niacin Lowers Serum Phosphate and Increases HDL Cholesterol in Dialysis Patients

Npt2b Deletion Attenuates Hyperphosphatemia Associated with CKD

Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus

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