Protective Effect of Phosphate Restriction on Renal Function

Alfrey, Allen C.; Karlinsky, Malcolm L.; Haut, Lewis

doi:10.1007/978-1-4615-9167-2_26

Cited by 12 publications

(12 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, in weaning animals, the achievement of a positive external balance is dependent on intestinal absorption and the ability of the kidneys to reclaim filtered P i . Little P i is lost in the feces, reflecting its extensive absorption, a process stimulated by dietary P i deprivation and 1,25(OH) 2 (9,34,38,41).…”

Section: Discussionmentioning

confidence: 99%

“…Npt2b ϩ/Ϫ mice had lower plasma P i and creatinine levels, suggesting that reduced intestinal Npt2b prevents hyperphosphatemia and the progression of renal failure in this mouse model. Indeed, reductions in P i intake have been linked to regression of proteinuria, stabilization of glomerular filtration rate, and, in some reports, improved survival in animal models of severe renal failure (1,2,7,12,15,18,19,22).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b^+/−mice

Ohi

Hanabusa

Ueda

et al. 2011

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

An inorganic phosphate (Pi)-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent Pi (Na/Pi) transport system is involved in intestinal Pi absorption and is regulated by several factors. The type II sodium-dependent Pi transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports Pi. In the present study, we analyzed the phenotype of Npt2b−/− and hetero+/− mice. Npt2b−/− mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b+/− mice showed hypophosphatemia and low urinary Pi excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)2D3 levels were significantly increased in Npt2b+/− mice compared with Npt2b+/+ mice. Npt2b mRNA levels were reduced to 50% that in Npt2b+/+ mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b+/− mice. At 20 wk of age, Npt2b+/− mice showed hypophosphaturia and reduced Na/Pi cotransport activity in the distal intestine. Npt2b+/+ mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b+/− mice treated with adenine had significantly reduced plasma Pi levels compared with Npt2b+/+ mice. Intestinal Npt2b protein and Na+/Pi transport activity levels were significantly lower in Npt2b+/− mice than in the Npt2b+/+ mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b^+/−mice

Ohi

Hanabusa

Ueda

et al. 2011

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…Genetic aKlotho deficiency and high dietary phosphate accelerated CKD progression post-AKI. Phosphate toxicity is not only a consequence of declined renal function 49 but also, a risk factor for promotion of CKD progression, [72][73][74] ectopic calcification, 15,58,59,75,76 and cardiovascular events 48,50,60,77 in humans. We showed that phosphate reduced aKlotho in the kidney even in normal mice and further downregulated the already low aKlotho in the kidney of CKD mice.…”

Section: Discussionmentioning

confidence: 99%

αKlotho Mitigates Progression of AKI to CKD through Activation of Autophagy

Shi¹,

Flores²,

Gillings³

et al. 2015

JASN

148

209

View full text Add to dashboard Cite

AKI confers increased risk of progression to CKD. aKlotho is a cytoprotective protein, the expression of which is reduced in AKI, but the relationship of aKlotho expression level to AKI progression to CKD has not been studied. We altered systemic aKlotho levels by genetic manipulation, phosphate loading, or aging and examined the effect on long-term outcome after AKI in two models: bilateral ischemia-reperfusion injury and unilateral nephrectomy plus contralateral ischemia-reperfusion injury. Despite apparent initial complete recovery of renal function, both types of AKI eventually progressed to CKD, with decreased creatinine clearance, hyperphosphatemia, and renal fibrosis. Compared with wild-type mice, heterozygous aKlotho-hypomorphic mice (aKlotho haploinsufficiency) progressed to CKD much faster, whereas aKlotho-overexpressing mice had better preserved renal function after AKI. High phosphate diet exacerbated aKlotho deficiency after AKI, dramatically increased renal fibrosis, and accelerated CKD progression. Recombinant aKlotho administration after AKI accelerated renal recovery and reduced renal fibrosis. Compared with wild-type conditions, aKlotho deficiency and overexpression are associated with lower and higher autophagic flux in the kidney, respectively. Upregulation of autophagy protected kidney cells in culture from oxidative stress and reduced collagen 1 accumulation. We propose that aKlotho upregulates autophagy, attenuates ischemic injury, mitigates renal fibrosis, and retards AKI progression to CKD.

show abstract

“…The role of P in the progression of renal failure (11) and the protective effects of P restriction on renal function (12) have been known for more than 20 yr. Chronic renal failure causes a reduction in nephron mass and in P excretion.…”

mentioning

confidence: 99%

The Effects of Sevelamer Hydrochloride and Calcium Carbonate on Kidney Calcification in Uremic Rats

Cozzolino

Dusso²,

Liapis

et al. 2002

Journal of the American Society of Nephrology

102

View full text Add to dashboard Cite

Abstract. The control of serum phosphorus (P) and calciumphosphate (Ca ϫ P) product is critical to the prevention of ectopic calcification in chronic renal failure (CRF). Whereas calcium (Ca) salts, the most commonly used phosphate binders, markedly increase serum Ca and positive Ca balance, the new calcium-and aluminum-free phosphate binder, sevelamer hydrochloride (RenaGel), reduces serum P without altering serum Ca in hemodialysis patients. Using an experimental model of CRF, these studies compare sevelamer and calcium carbonate (CaCO 3 ) in the control of serum P, secondary hyperparathyroidism (SH), and ectopic calcifications. 5/6 nephrectomized rats underwent one of the following treatments for 3 mo: uremic ϩ high-P diet (U-HP); UHP ϩ 3% CaCO 3 (U-HPϩC); UHP ϩ 3% sevelamer (U-HPϩS). Sevelamer treatment controlled serum P independent of increases in serum Ca, thus reducing serum Ca ϫ P product and further deterioration of renal function, as indicated by the highest creatinine clearances. Sevelamer was as effective as CaCO 3 in the control of high-P-induced SH, as shown by similar serum PTH levels, parathyroid (PT) gland weight, and markers of PT hyperplasia.Also, both P binders elicited similar efficacy in reducing the myocardial and hepatic calcifications induced by uremia. However, sevelamer caused a dramatic reduction of renal Ca deposition (29.8 Ϯ 8.6 g/g wet tissue) compared with both U-HP (175.5 Ϯ 45.7 g/g wet tissue, P Ͻ 0.01) and the U-HPϩC (58.9 Ϯ 13.7 g/g wet tissue, P Ͻ 0.04). Histochemical analyses using Von Kossa and Alizarin red S staining of kidney sections confirmed these findings. The high number of foci of calcification in the kidney of uremic controls (108 Ϯ 25) was reduced to 33.0 Ϯ 11.3 by CaCO 3 and decreased even further with sevelamer (16.4 Ϯ 8.9, P Ͻ 0.02 versus CaCO 3 ). Importantly, the degree of tubulointerstitial fibrosis was also markedly lower in U-HPϩS (5%) compared with either U-HPϩC (30%) or U-HP (50%). It is concluded that in experimental CRF in rats, despite a similar control of serum P and SH, sevelamer is more effective than CaCO 3 in preventing renal Ca deposition and tubulointerstitial fibrosis, including better preservation of renal function. These findings cannot be extrapolated to human disease, and further studies in patients are necessary to determine the benefits of either P binder.In end-stage renal disease, hyperphosphatemia and elevated calcium-phosphate (Ca ϫ P) product associate with ectopic calcifications and increased risk of calciphylaxis, resulting in higher prevalence of morbidity and mortality from cardiovascular events (1-6). High serum phosphorus (P) levels worsen uremia-induced secondary hyperparathyroidism by enhancing parathyroid hyperplasia and parathyroid hormone (PTH) synthesis and secretion (7-8). Elevated PTH levels cause ectopic calcification not only by enhancing serum P and Ca ϫ P product through inducing high bone turnover, but also by increasing both serum and intracellular calcium (Ca) (9 -10). The control of serum P in patients with ch...

show abstract

Protective Effect of Phosphate Restriction on Renal Function

Cited by 12 publications

References 18 publications

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b^+/−mice

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b^+/−mice

αKlotho Mitigates Progression of AKI to CKD through Activation of Autophagy

The Effects of Sevelamer Hydrochloride and Calcium Carbonate on Kidney Calcification in Uremic Rats

Contact Info

Product

Resources

About

Protective Effect of Phosphate Restriction on Renal Function

Cited by 12 publications

References 18 publications

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b+/−mice

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b+/−mice

αKlotho Mitigates Progression of AKI to CKD through Activation of Autophagy

The Effects of Sevelamer Hydrochloride and Calcium Carbonate on Kidney Calcification in Uremic Rats

Contact Info

Product

Resources

About

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b^+/−mice

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b^+/−mice