A Comparison of the Long-Term Effects of Lanthanum Carbonate and Calcium Carbonate on the Course of Chronic Renal Failure in Rats with Adriamycin-Induced Nephropathy

Takashima, Tsuyoshi; Sanai, Toru; Miyazono, Motoaki; Fukuda, Makoto; Kishi, Tomoya; Nonaka, Yasunori; Yoshizaki, Mai; S, Sato; Ikeda, Yûji

doi:10.1371/journal.pone.0097859

Cited by 3 publications

(4 citation statements)

References 31 publications

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“…Given that activated charcoal, calcium carbonate, and chitosan (all of which were components in the SC) have previously been reported to improve BUN 9,10,[12][13][14] , and, that the SC was associated with improved BUN in the 4/6 INx SC(+) group in this study, it is possible that continuous intake of the SC may not only affect renal tissue repair, but may also affect protein absorption or metabolic processes outside the kidney, thereby reducing the decline in renal function. Additionally, although the amount of each component contained in the SC was smaller than the quantities used in previous reports [10][11][12]14,15,17,36 , the 4/6 INx model's mimicry of moderate CKD may have allowed the effect of the SC to be apparent. This study has several limitations.…”

Section: Discussionmentioning

confidence: 99%

“…Most recently, therapeutic approaches to CKD have focused on use of a low-protein diet combined with effective supplements. Supplementary compounds that have demonstrated isolated beneficial effects include activated charcoal to reduce renal failure by absorbing toxins in the body 9 , 10 , Quercus salicina (a broadleaf evergreen tree in the Fagaceae family) to prevent formation of uroliths in rats 11 , calcium carbonate to reduce blood phosphate levels in rats with CKD 12 , chitosan (a component of crustacean shells) to alleviate CKD in dogs by absorbing toxins in the intestinal tract 9 , 13 , 14 , sodium alginate to improve renal failure and diabetes when used in combination with chitosan 15 , and folic acid to ameliorate renal anemia and to delay the progression of CKD 16 , 17 . However, the effects of supplements in CKD remain unclear, and further basic research is needed.…”

Section: Introductionmentioning

confidence: 99%

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Establishment and application of a new 4/6 infarct nephrectomy rat model for moderate chronic kidney disease

Sugai,

Hirano,

Oda

et al. 2024

Acta Cir. Bras.

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Purpose: To develop a new 4/6 infarct nephrectomy (INx) model rat mimicking moderate chronic kidney disease (CKD) and to evaluate its application. Methods: We modified the conventional 5/6 INx rat model to create the 4/6 INx model by ligating the renal artery branch to induce infarction of one-third of the left kidney after right kidney removal and compared biochemically and histologically both models. To demonstrate the application of the 4/6 INx model, the effects of a supplementary compound containing calcium carbonate, chitosan, palm shell activated charcoal etc., that is effective for both CKD and its complications, were compared between both models. Results: Impairment of renal function in the 4/6 INx group was significantly more moderate than in the 5/6 INx group ( P < 0.05). The 4/6 INx group showed less histological damage in kidney than in the 5/6 INx group. The supplementary compound did not improve CKD in the 5/6 INx group, but ameliorated elevation of blood urea nitrogen in the 4/6 INx group. Conclusions: We developed the 4/6 INx model, which is more moderate than the conventional 5/6 INx model. This model could potentially demonstrate the effectiveness of drugs and supplements intended to prevent CKD and its progression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Establishment and application of a new 4/6 infarct nephrectomy rat model for moderate chronic kidney disease

Sugai,

Hirano,

Oda

et al. 2024

Acta Cir. Bras.

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“…Phosphate binders are able to absorb phosphate in the intestine, forming insoluble products that are eliminated with the faeces, thus decreasing serum phosphate levels [27].…”

Section: Discussionmentioning

confidence: 99%

“…The use of calcium-based phosphorus binders has the recognised side effect of increasing the risk of hypercalcemia in human medicine [27], although little data is available in veterinary medicine [7], especially in cats.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of a Feed Supplement in Advanced Stages of Feline Chronic Kidney Disease

Vergnano

Valle

Bruni³

et al. 2016

Acta Scientiae. Vet.

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Background: Chronic kidney disease (CKD) is a very common pathology in cats, especially in the geriatric age. A proper renal diet is considered the current standard of care to enhance patients’ long-term survival and quality of life. However, when diet alone is not sufficient, it is necessary to supplement it with specific substances: these are phosphate binders and alkalinizing agents. The aim of this study was to evaluate the effectiveness of a feed supplement containing calcium carbonate, calcium lactate gluconate, chitosan and sodium bicarbonate in controlling hyperphosphatemia and metabolic acidosis in cats with severe CKD (IRIS, International Renal Interest Society, stage 3 and 4).Materials, Methods & Results: 10 cats (median BW 4.00 (3.20; 5.70) Kg, BCS 3/5 (2.25; 3.75), 11 (8.25;12.00) years) fed with a balanced renal diet were included in the study. To be enrolled in the study cats had to be affected by CKD in stages 3 or 4 and show hyperphosphatemia. Treatment consisted in oral administration of the product (Renal, Candioli Pharma) at 0.2 g/kg/day mixed with the food for 60 days. The animals were evaluated at the beginning of the study and at 15, 30, 60 days (T0, T15, T30, T60) for: clinical condition, BW, BCS, blood pressure and for routinely hematochemical, biochemical and urinary parameters. Owners were asked to assess appetite of the cat, palatability of the supplement, presence of vomit and/or diarrhoea, general health and vitality. All statistical analyses were performed using SAS software. After checking normality data were analyzed using Kruskal-Wallis and Wilcoxon tests. Results are expressed as median (interquartile range). For the parameters P (P < 0.0001), iCa (P = 0.0008) and HCO3 (P = 0.0002) there were statistically significant differences among times of supplementation (T0, T15, T30, T60). Statistically significant reduction of serum phosphorus concentration was obtained through the study (reduction of 59% at T60 vs T0). Also a statistically significant increase of bicarbonate was seen (7% from T0 to T60). At T60 was also recorded an increase of ionized calcium level, which however was in normal range. For the other laboratory parameters, no statistical difference was recorded. All the owners reported a good palatability of the product. The decrease of vomit and diarrhea episodes and the increase of the appetite reported were statistically significant (P < 0.05).Discussion: The restriction of available dietary phosphorus is now recognised as one of the major contributors in slowing the disease progression and improving survival rates. Phosphate binders are able to absorb phosphate (P) in the intestine, forming insoluble products that are eliminated with the faeces, thus decreasing serum phosphate levels. The phosphate binders contained in the product tested in the present trial were chitosan, calcium lactate gluconate and calcium carbonate. During the study P decreased significantly from T0 to T60, reaching the target post-treatment plasma P concentration for IRIS stage 3 after 30 days. Another important recommendation for CKD treatment is to use alkalinisation therapy if metabolic acidosis is present. The feed supplement tested in this study also contained sodium bicarbonate. In our study, 90% of the patients at the inclusion examination had metabolic acidosis. At the end of the study, the median blood bicarbonate concentration was in the normal range, thus reaching the IRIS treatment target. The feed supplement tested was therefore effective in reducing blood phosphate levels and in increasing blood bicarbonate levels, thus improving the cats’ clinical conditions for the duration of the study without any adverse effect.

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Phosphate Binders Prevent Phosphate-Induced Cellular Senescence of Vascular Smooth Muscle Cells and Vascular Calcification in a Modified, Adenine-Based Uremic Rat Model

et al. 2014

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Clinical and experimental studies have reported that phosphate overload plays a central role in the pathogenesis of vascular calcification in chronic kidney disease. However, it remains undetermined whether phosphate induces cellular senescence during vascular calcification. We established a modified uremic rat model induced by a diet containing 0.3% adenine that showed more slowly progressive kidney failure, more robust vascular calcification, and longer survival than the conventional model (0.75% adenine). To determine the effect of phosphate on senescence of vascular smooth muscle cells (VSMCs) and the protective effect of phosphate binders, rats were divided into four groups: (1) normal control rats; (2) rats fed with the modified adenine-based diet (CKD); (3) CKD rats treated with 6% lanthanum carbonate (CKD-LaC); and (4) CKD rats treated with 6% calcium carbonate (CKD-CaC). After 8 weeks, CKD rats showed circumferential arterial medial calcification, which was inhibited in CKD-LaC and CKD-CaC rats. CKD rats showed increased protein expression of senescence-associated β-galactosidase, bone-related proteins, p16 and p21, and increased oxidative stress levels in the calcified area, which were inhibited by both phosphate binders. However, serum levels of oxidative stress and inflammatory markers, serum fibroblast growth factor 23, and aortic calcium content in CKD-CaC rats were higher than those in CKD-LaC rats. In conclusion, phosphate induces cellular senescence of VSMCs in the modified uremic rat model, and phosphate binders can prevent both cellular senescence and calcification of VSMCs via phosphate unloading. Our modified adenine-based uremic rat model is useful for evaluating uremia-related complications, including vascular calcification.

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A Comparison of the Long-Term Effects of Lanthanum Carbonate and Calcium Carbonate on the Course of Chronic Renal Failure in Rats with Adriamycin-Induced Nephropathy

Cited by 3 publications

References 31 publications

Establishment and application of a new 4/6 infarct nephrectomy rat model for moderate chronic kidney disease

Establishment and application of a new 4/6 infarct nephrectomy rat model for moderate chronic kidney disease

Effectiveness of a Feed Supplement in Advanced Stages of Feline Chronic Kidney Disease

Phosphate Binders Prevent Phosphate-Induced Cellular Senescence of Vascular Smooth Muscle Cells and Vascular Calcification in a Modified, Adenine-Based Uremic Rat Model

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