scholarly journals Chronic Kidney Disease-Induced Arterial Media Calcification in Rats Prevented by Tissue Non-Specific Alkaline Phosphatase Substrate Supplementation Rather Than Inhibition of the Enzyme

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1138
Author(s):  
Britt Opdebeeck ◽  
Ellen Neven ◽  
José Luis Millán ◽  
Anthony B. Pinkerton ◽  
Patrick C. D’Haese ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Alkaline Phosphatase ◽  
Kidney Disease ◽  
Inorganic Phosphate ◽  
Bone Mineralization ◽  
Control Diet ◽  
High Serum ◽  
Specific Alkaline Phosphatase ◽  
Metabolic Defects ◽  
Alkaline Phosphatase Substrate

Patients with chronic kidney disease (CKD) suffer from arterial media calcification and a disturbed bone metabolism. Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes the calcification inhibitor pyrophosphate (PPi) into inorganic phosphate (Pi) and thereby stimulates arterial media calcification as well as physiological bone mineralization. This study investigates whether the TNAP inhibitor SBI-425, PPi or the combination of both inhibit arterial media calcification in an 0.75% adenine rat model of CKD. Treatments started with the induction of CKD, including (i) rats with normal renal function (control diet) treated with vehicle and CKD rats treated with either (ii) vehicle, (iii) 10 mg/kg/day SBI-425, (iv) 120 µmol/kg/day PPi and (v) 120 µmol/kg/day PPi and 10 mg/kg/day SBI-425. All CKD groups developed a stable chronic renal failure reflected by hyperphosphatemia, hypocalcemia and high serum creatinine levels. CKD induced arterial media calcification and bone metabolic defects. All treatments, except for SBI-425 alone, blocked CKD-related arterial media calcification. More important, SBI-425 alone and in combination with PPi increased osteoid area pointing to a less efficient bone mineralization. Clearly, potential side effects on bone mineralization will need to be assessed in any clinical trial aimed at modifying the Pi/PPi ratio in CKD patients who already suffer from a compromised bone status.

scholarly journals A phosphate and calcium-enriched diet promotes progression of 5/6-nephrectomy-induced chronic kidney disease in C57BL/6 mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
J. Radloff ◽  
N. Latic ◽  
U. Pfeiffenberger ◽  
C. Schüler ◽  
S. Tangermann ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Calcium Phosphate ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Time Course ◽  
Bone Mineralization ◽  
Fibroblast Growth Factor 23 ◽  
Functional Decline ◽  
Left Ventricular ◽  
Normal Diet

AbstractC57BL/6 mice are known to be rather resistant to the induction of experimental chronic kidney disease (CKD) by 5/6-nephrectomy (5/6-Nx). Here, we sought to characterize the development of CKD and its cardiac and skeletal sequelae during the first three months after 5/6-Nx in C57BL/6 mice fed a calcium- and phosphate enriched diet (CPD) with a balanced calcium/phosphate ratio. 5/6-NX mice on CPD showed increased renal fibrosis and a more pronounced decrease in glomerular filtration rate when compared to 5/6-Nx mice on normal diet (ND). Interestingly, despite comparable levels of serum calcium, phosphate, and parathyroid hormone (PTH), circulating intact fibroblast growth factor-23 (FGF23) was 5 times higher in 5/6-Nx mice on CPD, relative to 5/6-Nx mice on ND. A time course experiment revealed that 5/6-Nx mice on CPD developed progressive renal functional decline, renal fibrosis, cortical bone loss, impaired bone mineralization as well as hypertension, but not left ventricular hypertrophy. Collectively, our data show that the resistance of C57BL/6 mice to 5/6-Nx can be partially overcome by feeding the CPD, and that the CPD induces a profound, PTH-independent increase in FGF23 in 5/6-Nx mice, making it an interesting tool to assess the pathophysiological significance of FGF23 in CKD.

MO566THE BONE EXPRESSION OF WNT INHIBITORS IN THE EXPERIMENTAL MODEL OF EARLY CHRONIC KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Evdokia Bogdanova ◽  
Natalia Semenova ◽  
Olga Galkina ◽  
Irina Zubina ◽  
Olga Beresneva ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Experimental Model ◽  
Inorganic Phosphate ◽  
Molecular Mechanisms ◽  
Fibroblast Growth Factor 23 ◽  
Bone Matrix ◽  
Serum Levels ◽  
Chow Diet ◽  
Dickkopf 1

Abstract Background and Aims Molecular mechanisms implicated in the initial stages of inorganic phosphate (Pi) imbalance in chronic kidney disease (CKD) remain poorly understood.The aim of the study was to evaluate whether canonical Wnt pathway inhibitors (iWnt) involved in early response to Pi retention in CKD. Methods Mild CKD was induced by 3/4 nephrectomy (NE) in spontaneously hypertensive rats (SHR) fed rat chow diet containing 0.6 % phosphate. Controls were sham operated SHR (SO). Duration of experimental exposure (NE or SO) was 2 and 6 months. Serum levels of creatinine (Cr), inorganic phosphate (Pi), fractional Pi excretion (FEPi), intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), alfa-Klotho (KL), sclerostin (SOST) and Dickkopf-1 (DKK1) were measured. The following morphological characteristics by light microscopy of bone metaphysis and kidney tissues: the area of renal interstitial fibrosis (RF) (Masson's trichrome), bone matrix volume (MV), the active osteoblasts to trabecular cells number ratio (aOB/cells), eroded surface to bone surface ratio (ES/BS) (hematoxylin & eosin), and bone SOST and DKK1 proteins expression (by IHC) were analyzed and calculated quantitatively. Statistical comparisons among groups were performed using Mann–Whitney U-test and Kruskal-Wallis H-test. Results Serum Cr, RF and indices of Pi exchange in the experimental model corresponded to early CKD (Table). Pi elevated in NE6 suggestive for its renal retention. KL level decreased (Table) in all experimental groups vs control. No differences were observed in serum levels FGF23 (p=0.62) and PTH (p=0.63). Serum SOST and DKK1 levels were significantly higher in NE6 group compared to SO6 (Table). The bone SOST and DKK1 expression increased in NE6 compared to SO6 (Figure). aOB/cells were lower in NE2, SO6 and NE6 vs SO2 (all p-values<=0.041). ES/BS increased in NE2 (vs SO2) while being lowest in NE6 and SO6 animals (Table). SOST and DKK1 metaphyseal expression increased in NE6 compared to SO2, SO6, NE2 (Figure). Osteocyte SOST expression increased in SO6 compared to SO2 and NE2 without differences in later groups. Osteoblast SOST expression was also higher in SO6 vs SO2 (Figure). Conclusion Increased serum levels of sclerostin and Dickkopf-1 and their bone expression are apparent in early stages of experimental CKD associating with hyperphosphatemia. Alterations of bone resorption and osteoblast depopulation occurred before the increase of serum Pi likely reflecting incipient stages of renal Pi retention. These molecular and cellular events seem to be independent of systemic FGF23 and PTH response.

scholarly journals A Pilot Randomized Crossover Trial Assessing the Safety and Short-Term Effects of Walnut Consumption by Patients with Chronic Kidney Disease

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 63 ◽  
Author(s):  
Pilar Sanchis ◽  
Marilisa Molina ◽  
Francisco Berga ◽  
Elena Muñoz ◽  
Regina Fortuny ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Inositol Phosphates ◽  
Control Diet ◽  
Fibroblast Growth Factor 23 ◽  
Serum Levels ◽  
Short Term ◽  
Daily Consumption ◽  
Randomized Crossover Trial

The aim of this study of patients with chronic kidney disease (CKD) is to assess the safety of daily consumption of walnuts on the physiological levels of phosphorous, potassium, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), and to assess the short-term benefits of this intervention on risk factors associated with cardiovascular events. This led us to perform a prospective, randomized, crossover, pilot clinical trial examined 13 patients with CKD. Subjects were randomly assigned to a diet of 30 g of walnuts per day or the control diet. After 30 days, each group was given a 30-day washout period, and then switched to the alternate diet for 30 days. Urinary and serum levels of phosphorous and potassium, multiple vascular risk factors, and urinary inositol phosphates (InsPs) were measured at baseline and at the end of the intervention period. Our results showed that the walnut dietary supplement led to reduced blood pressure, LDL cholesterol, and albumin excretion, but had no effect on the physiological levels of phosphorous, potassium, PTH, and FGF23. This is the first report to show that daily consumption of walnuts by patients with CKD does not alter their physiological levels of phosphorous, potassium, PTH, and FGF23 when included in a sodium-, protein-, phosphate-, and potassium-controlled diet, and it could be an effective strategy for reducing cardiovascular risk in patients with CKD.

scholarly journals Pharmacologic epigenetic modulators of alkaline phosphatase in chronic kidney disease

2020 ◽  
Vol 29 (1) ◽  
pp. 4-15 ◽  
Author(s):  
Mathias Haarhaus ◽  
Dean Gilham ◽  
Ewelina Kulikowski ◽  
Per Magnusson ◽  
Kamyar Kalantar-Zadeh
Keyword(s):  
Chronic Kidney Disease ◽  
Alkaline Phosphatase ◽  
Kidney Disease

scholarly journals Admission characteristics of pediatric chronic kidney disease

2011 ◽  
Vol 51 (4) ◽  
pp. 192 ◽  
Author(s):  
Eka Laksmi Hidayati ◽  
Partini Pudjiati Trihono
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
High Serum ◽  
Glomerular Disease ◽  
Recurrent Fever ◽  
Cross Sectional ◽  
Disease Etiology ◽  
Urea Level ◽  
Ckd Stage ◽  
End Stage

Background Chronic kidney disease (CKD) in children is a potentially fatal disease if left untreated. Early detection and treatment are important to slow progression to end-stage renal disease requiring dialysis.Objective We aimed to find characteristics of CKD patients at admission and evaluate factors associated with end-stage CKD (stage 5).Methods Our cross-sectional study was based on medical records of CKD patients aged less than 18 years in Cipto Mangunkusumo Hospital, Jakarta, from January 2007 to December 2009. Diagnosis and stages of CKD were based on the Kidney Disease Outcomes Quality Initiative (K/DOQI) criteria. Data on disease etiology, symptoms, nutritional status and laboratory tests were collected. Bivariate and multivariate analyses were performed to examine the association between end-stage CKD and its possible risk factors.Results Of the 142 cases eligible for analysis, 55% were boys. Subjects’ median age was 73.5 months (interquartile range of 23.5-122.5 months). Edema and recurrent fever were the two most frequent symptoms of CKD if diagnosed at stages 2-4, while breathlessness was the most frequent symptom of CKD if diagnosed at stage 5. The most common etiologies were glomerulonephritis (49.3%) and anomalies of the kidney and urinary tract (32.4%). Of our CKD subjects, 21.8% were in stage 5. Independent predictors of stage 5 CKD at presentation were hypertension (OR 3.88; 95% CI 1.17 to 12.87; P=0.026), urea level > 60 mg/dL (OR 39.11; 95%CI 4.86 to 314.74; P<0.001) and non-glomerulonephritis as the etiology (OR 6.51; 95%CI 2.12 to 19.92; P<0.001).Conclusion Glomerular disease was the most common cause of CKD in our study. Stage 5 CKD was present in 21.8% of subjects at admission and could be predicted by the presence of hypertension, high serum urea level, and non-glomerular disease as the etiology.

Dietary Changes Involving Bifidobacterium longum and Other Nutrients Delays Chronic Kidney Disease Progression

2018 ◽  
Vol 47 (5) ◽  
pp. 325-332 ◽  
Author(s):  
Yuko Iwashita ◽  
Masaki Ohya ◽  
Mitsuru Yashiro ◽  
Tomohiro Sonou ◽  
Kazuki Kawakami ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Kidney Function ◽  
Sham Group ◽  
Control Diet ◽  
Bifidobacterium Longum ◽  
Inorganic Phosphorus ◽  
Mineral And Bone Disorder ◽  
Serious Adverse Events

Background: Recent studies suggest that prebiotic and/or probiotic treatments ameliorate kidney function in humans and animals by improving the gut environment. However, the gut microbiota and kidney disease interactions remain to be determined. This study investigated whether synbiotics modulate the gut microbiota and ameliorate kidney function using a rat model of chronic kidney disease (CKD). As uremic toxins are associated with CKD-related mineral and bone disorder, the secondary aim was to evaluate the relationship between synbiotics and secondary hyperparathyroidism (SHPT). Methods: 5/6 nephrectomy (Nx) rats were developed as the CKD model. Sham-operated (sham) rats were used as the control. To investigate the effectiveness of prebiotics (glutamine, dietary fiber, and oligosaccharide) and probiotics (Bifidobacterium longum strain; GFOB diet), rats were randomly assigned to 4 groups: Nx group fed the GFOB diet (n = 10); Nx group fed the control (CON) diet (n = 10); sham group fed the GFOB diet (n = 5); and sham group fed the control diet (n = 5). Blood, feces, and kidney samples were collected and analyzed. Results: Serum creatinine (Cre) and blood urea nitrogen in the Nx GFOB group were significantly lower than those in the Nx CON group. Serum indoxyl sulfate in the Nx GFOB group was lower than that in the Nx CON group, and significantly correlated with serum Cre. Inorganic phosphorus and intact parathyroid hormone in the Nx GFOB group were significantly lower than those in the Nx CON group. Conclusion: Improving the gut environment using synbiotics ameliorated kidney function and might be a pharmacological treatment for SHPT without any serious adverse events.

Serum Markers of Low-Turnover Bone Disease in Mexican Children with Chronic Kidney Disease Undergoing Dialysis

2006 ◽  
Vol 26 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Marcela Ávila-Díaz ◽  
Mario Matos ◽  
Elvia García-López ◽  
María-del-Carmen Prado ◽  
Florencia Castro-Vázquez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Alkaline Phosphatase ◽  
Kidney Disease ◽  
Diastolic Blood Pressure ◽  
Serum Calcium ◽  
Bone Disease ◽  
Linear Growth ◽  
Serum Markers ◽  
Z Score

Background The frequency of low-turnover bone disease (LTBD) in patients with chronic kidney disease (CKD) has increased in past years. This change is important because LTBD is associated with bone pain, growth delay, and higher risk for bone fractures and extraosseous calcifications. LTBD is a histological diagnosis. However, serum markers such as parathyroid hormone (PTH) and calcium levels offer a noninvasive alternative for diagnosing these patients. Objective To describe the prevalence of LTBD in pediatric patients with renal failure undergoing some form of renal replacement therapy, using serum calcium and intact PTH levels as serum markers. Methods In this cross-sectional study, 41 children with CKD undergoing dialysis treatment (31 on continuous ambulatory peritoneal dialysis and 10 on hemodialysis) were included. There were no inclusion restrictions with respect to gender, cause of CKD, or dialysis modality. The children were studied as outpatients. The demographic data, CKD course, time on dialysis, phosphate-binding agents, and calcitriol prescription were registered, as well as weight, height, Z-score for height, linear growth rate, and Z-score for body mass index. Serum calcium, phosphorus, aluminum, PTH, alkaline phosphatase, osteocalcin, glucose, creatinine, urea, cholesterol, and triglycerides were measured. Results There were 20 (48.8%) children with both PTH <150 pg/mL and corrected total calcium >10 mg/dL who were classified as having LTBD[(+)]; the remaining 21 (51.2%) children were classified as having no LTBD[(–)]. The LTBD(+) patients were younger (11.2 ± 2.7 vs 13.2 ± 2.4 years, p < 0.01) but they had no differences regarding Z-scores for height. Linear growth in 6 months was less than expected in both groups (-0.15 ± 0.23 cm/month), but the difference between expected and observed growth was higher in the LTBD(+) group (-0.24 ± 0.14 vs –0.07 ± 0.28 cm/mo, p < 0.03). LTBD(+) patients also had lower serum creatinine (8.69± 2.75 vs 11.19 ± 3.17 mg/dL, p < 0.01), higher serum aluminum levels [median (range) 38.4 (9 – 106) vs 28.1 (9 – 62) μg/L, p < 0.05], and lower systolic blood pressure (112.0 ± 10.3 vs 125.0 ±12.9 mmHg, p < 0.015) and diastolic blood pressure (76.0 ± 9.7 vs 84.5 ± 8.2 mmHg, p < 0.017). A significant correlation was found between PTH and alkaline phosphatase ( r = 0.68, p < 0.001), but not between PTH and aluminum. Conclusion The LTBD(+) biochemical profile was found in 48.8% of the children and was associated with impaired linear growth. Aluminum contamination, evidenced by higher serum aluminum levels, may have had a pathogenic role in these disorders. Higher systolic and diastolic blood pressure levels may be related to higher serum PTH levels.

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