Past, Present, and Future of Phosphate Management

Doshi, Simit; Wish, Jay B.

doi:10.1016/j.ekir.2022.01.1055

Cited by 26 publications

(21 citation statements)

References 89 publications

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“…Hypocalcemia increases PTH levels (secondary hyperparathyroidism), resulting in increased bone resorption of calcium, thereby causing soft tissue mineralization and bone de-mineralization. Aluminum- and calcium-based phosphate binders, sevelamer carbonate, and lanthanum carbonate are most frequently used for treating hyperphosphatemia [ 14 , 23 , 24 ]. In this clinical study, researchers aimed to compare the therapeutic and other vital parameter effects of aluminum- and calcium-free phosphate binder for six months in CKD patients.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of Lanthanum Carbonate and Sevelamer Carbonate as Phosphate Binders in Chronic Kidney Disease—A Comparative Clinical Study

et al. 2023

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(1) Background: Hyperphosphatemia is correlated with an increased rate of mortality and morbidity due to cardiovascular diseases in chronic kidney disease (CKD) patients. It can be improved by restricting dietary intake of phosphate and oral phosphate binders, such as lanthanum carbonate and sevelamer carbonate. (2) Objective: To evaluate the clinical efficacy of sevelamer carbonate in comparison to lanthanum carbonate as phosphate binders for the treatment of hyperphosphatemia in CKD patients. (3) Methods: A randomized control comparative clinical study was conducted for one year on 150 CKD patients associated with hyperphosphatemia, divided into two groups, i.e., Group 1 (n = 75) treated with sevelamer carbonate 800 mg thrice daily and Group 2 (n = 75) treated with lanthanum carbonate 500 mg thrice daily. The patients were assessed at the time of enrollment in the study, after three months and after six months from baseline for different parameters, i.e., complete blood count, liver function tests, renal function tests, electrolytes, and serum phosphate level. (4) Results: 150 CKD patients aged 51–60 participated in the study. The mean age of patients was 54 ± 4.6 years, and males (55.71%) were more common than females (44.29%). Hypertension was the common comorbidity in both groups with chronic kidney disease. After six months of treatment, the mean serum phosphate level was significantly decreased from 8.31 ± 0.09 mg/dL to 5.11 ± 0.18 (38%) in Group 1 and from 8.79 ± 0.28 mg/dl to 4.02 ± 0.12 (54%; p < 0.05) in Group 2, respectively. In both groups, no significant difference was found in other parameters such as parathyroid hormone, calcium, uric acid, LFT, RFT, CBC, etc. (5) Conclusion: Lanthanum carbonate is more efficacious in lowering serum phosphate concentrations and effectively managing hyperphosphatemia as compared to sevelamer carbonate.

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Section: Discussionmentioning

confidence: 99%

“…Particularly aluminum- and calcium-free phosphate binders such as sevelamer carbonate and lanthanum carbonate are available on the market as treatment options for hyperphosphatemia. Both decrease serum phosphate levels and low-density lipoprotein (LDL) cholesterol and increase high-density lipoprotein (HDL) [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Lanthanum Carbonate and Sevelamer Carbonate as Phosphate Binders in Chronic Kidney Disease—A Comparative Clinical Study

et al. 2023

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“…SLC34 transporters are also inhibited by EOS789 but at slightly higher concentrations. The properties of EOS789 indicate that it has therapeutic potential for hyperphosphatemia associated with chronic kidney disease ( Tsuboi et al, 2020 ; Hill Gallant et al, 2021 ; Doshi and Wish, 2022 ; Tsuboi et al, 2022 ). For a recent review of Na + -Pi cotransporter pharmacology, see Wagner, 2023 .…”

Section: Pi Influx: Mammalian Na + -Pi Cotransportersmentioning

confidence: 99%

Role of transporters in regulating mammalian intracellular inorganic phosphate

Jennings

2023

Front. Pharmacol.

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This review summarizes the current understanding of the role of plasma membrane transporters in regulating intracellular inorganic phosphate ([Pi]In) in mammals. Pi influx is mediated by SLC34 and SLC20 Na+-Pi cotransporters. In non-epithelial cells other than erythrocytes, Pi influx via SLC20 transporters PiT1 and/or PiT2 is balanced by efflux through XPR1 (xenotropic and polytropic retrovirus receptor 1). Two new pathways for mammalian Pi transport regulation have been described recently: 1) in the presence of adequate Pi, cells continuously internalize and degrade PiT1. Pi starvation causes recycling of PiT1 from early endosomes to the plasma membrane and thereby increases the capacity for Pi influx; and 2) binding of inositol pyrophosphate InsP8 to the SPX domain of XPR1 increases Pi efflux. InsP8 is degraded by a phosphatase that is strongly inhibited by Pi. Therefore, an increase in [Pi]In decreases InsP8 degradation, increases InsP8 binding to SPX, and increases Pi efflux, completing a feedback loop for [Pi]In homeostasis. Published data on [Pi]In by magnetic resonance spectroscopy indicate that the steady state [Pi]In of skeletal muscle, heart, and brain is normally in the range of 1–5 mM, but it is not yet known whether PiT1 recycling or XPR1 activation by InsP8 contributes to Pi homeostasis in these organs. Data on [Pi]In in cultured cells are variable and suggest that some cells can regulate [Pi] better than others, following a change in [Pi]Ex. More measurements of [Pi]In, influx, and efflux are needed to determine how closely, and how rapidly, mammalian [Pi]In is regulated during either hyper- or hypophosphatemia.

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“…Thus, it may directly contribute to vascular damage by pro-inflammatory actions on the vascular smooth muscle cell leading to endothelial dysfunction and promoting vascular calcification [ 23 , 24 ]. Furthermore, a high dietary phosphate content may contribute to atherogenesis [ 25 ] and has also been linked to a more rapid progression of CKD to ESKD [ 19 , 26 , 27 ]. Using data from the US Renal Data System, Block et al [ 4 ] found an increased risk of death (relative risk, 1.27) associated with serum phosphate levels > 6.5 mg/dL.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Medical Nutrition Intervention on the Management of Hyperphosphatemia in Hemodialysis Patients with Stage 5 Chronic Kidney Disease: A Case Series

Moroșan

Popovici

Elian

et al. 2023

IJERPH

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The treatment and interdisciplinary management of patients with chronic kidney disease (CKD) continue to improve long-term outcomes. The medical nutrition intervention’s role is to establish a healthy diet plan for kidney protection, reach blood pressure and blood glucose goals, and prevent or delay health problems caused by kidney disease. Our study aims to report the effects of medical nutrition therapy—substituting foods rich in phosphorus-containing additives with ones low in phosphates content on phosphatemia and phosphate binders drug prescription in stage 5 CKD patients with hemodialysis. Thus, 18 adults with high phosphatemia levels (over 5.5 mg/dL) were monitored at a single center. Everyone received standard personalized diets to replace processed foods with phosphorus additives according to their comorbidities and treatment with prosphate binder drugs. Clinical laboratory data, including dialysis protocol, calcemia, and phosphatemia, were evaluated at the beginning of the study, after 30 and 60 days. A food survey was assessed at baseline and after 60 days. The results did not show significant differences between serum phosphate levels between the first and second measurements; thus, the phosphate binders’ initial doses did not change. After 2 months, phosphate levels decreased considerably (from 7.322 mg/dL to 5.368 mg/dL); therefore, phosphate binder doses were diminished. In conclusion, medical nutrition intervention in patients with hemodialysis significantly reduced serum phosphate concentrations after 60 days. Restricting the intake of processed foods containing phosphorus additives—in particularized diets adapted to each patient’s comorbidities—and receiving phosphate binders represented substantial steps to decrease phosphatemia levels. The best results were significantly associated with life expectancy; at the same time, they showed a negative correlation with the dialysis period and participants’ age.

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Past, Present, and Future of Phosphate Management

Cited by 26 publications

References 89 publications

Efficacy of Lanthanum Carbonate and Sevelamer Carbonate as Phosphate Binders in Chronic Kidney Disease—A Comparative Clinical Study

Efficacy of Lanthanum Carbonate and Sevelamer Carbonate as Phosphate Binders in Chronic Kidney Disease—A Comparative Clinical Study

Role of transporters in regulating mammalian intracellular inorganic phosphate

The Impact of Medical Nutrition Intervention on the Management of Hyperphosphatemia in Hemodialysis Patients with Stage 5 Chronic Kidney Disease: A Case Series

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