Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats

2021 ◽  
pp. 153537022110572
Author(s):  
Wander Barros do Carmo ◽  
Bárbara Bruna Abreu Castro ◽  
Luísa Cardoso Manso ◽  
Priscylla Aparecida Vieira do Carmo ◽  
Clóvis Antônio Rodrigues ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Parathyroid Hormone ◽  
Calcium Carbonate ◽  
Kidney Disease ◽  
Therapeutic Option ◽  
Fractional Excretion ◽  
Control Group ◽  
Clinical Settings ◽  
Iron Based

Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO3) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO3 groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 ± 18.6 vs. 41.5 ± 22.1 µmol/L; P = 0.001), phosphate (3.5 ± 0.8 vs. 2.2 ± 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 ± 0.2 vs. 0.2 ± 0.17; P = 0.0001), and FGF23 (81.36 ± 37.16 pg/mL vs. 7.42 ± 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 ± 0.20; CKD/CH-FeCl: 0.40 ± 0.16; CKD/CaCO3 0.34 ± 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.

scholarly journals Serum intact parathyroid hormone levels in cats with chronic kidney disease

2013 ◽  
Vol 33 (2) ◽  
pp. 229-235 ◽  
Author(s):  
Luciano H. Giovaninni ◽  
Marcia M. Kogika ◽  
Marcio D. Lustoza ◽  
Archivaldo Reche Junior ◽  
Vera A.B.F. Wirthl ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Stage Iv ◽  
Control Group ◽  
Intact Parathyroid Hormone ◽  
Acid Base ◽  
Acid Base Status ◽  
Serum Ionized Calcium ◽  
Progression Of Renal Disease

Chronic kidney disease (CKD) is frequently observed in cats and it is characterized as a multisystemic illness, caused by several underlying metabolic changes, and secondary renal hyperparathyroidism (SRHPT) is relatively common; usually it is associated with the progression of renal disease and poor prognosis. This study aimed at determining the frequency of SRHPT, and discussing possible mechanisms that could contribute to the development of SRHPT in cats at different stages of CKD through the evaluation of calcium and phosphorus metabolism, as well as acid-base status. Forty owned cats with CKD were included and divided into three groups, according to the stages of the disease, classified according to the International Renal Interest Society (IRIS) as Stage II (n=12), Stage III (n=22) and Stage IV (n=6). Control group was composed of 21 clinically healthy cats. Increased serum intact parathyroid hormone (iPTH) concentrations were observed in most CKD cats in all stages, and mainly in Stage IV, which hyperphosphatemia and ionized hypocalcemia were detected and associated to the cause for the development of SRHPT. In Stages II and III, however, ionized hypercalcemia was noticed suggesting that the development of SRHPT might be associated with other factors, and metabolic acidosis could be involved to the increase of serum ionized calcium. Therefore, causes for the development of SRHPT seem to be multifactorial and they must be further investigated, mainly in the early stages of CKD in cats, as hyperphosphatemia and ionized hypocalcemia could not be the only factors involved.

scholarly journals Study of serum homocysteine level in patients with chronic kidney disease and its association with renal function and serum albumin

2020 ◽  
Vol 8 (6) ◽  
pp. 2195
Author(s):  
Vandana Yadav ◽  
Vivek Prakash ◽  
Bushra Fiza ◽  
Maheep Sinha
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Serum Albumin ◽  
Control Group ◽  
Serum Homocysteine ◽  
The Mean ◽  
Gandhi Medical College ◽  
And Control

 Background: Chronic kidney disease (CKD) includes irreversible destruction of nephrons leading to progressive decline in glomerular filtration rate. A preferential defect in Homocysteine disposal could hypothetically occur in CKD and subsequently lead to hyperhomocysteinemia. Understanding the status of Homocysteine and other parameters in CKD is useful in the management of the disease. Objective of the study is to estimate serum Homocysteine in CKD patients and its association with renal function and serum albumin in patients with CKD.Methods: The study design involves hospital based observational comparative study. The study was conducted in Department of Biochemistry in association with Department of Nephrology of Mahatma Gandhi Medical College and Hospital, Jaipur between May 2017 to June 2018. 100 diagnosed patients of CKD, visiting the Outpatient Department of Nephrology were enrolled as cases for the study. Patients having cardiovascular disease, Chronic liver disease, Age more than 60 years and pregnant females were excluded from study. The control group consists of 100 age and sex matched healthy individuals.Results: The mean serum creatinine levels of case and control group were 7.50±3.74 mg% and 0.83±0.22 mg% respectively. The mean of serum homocysteine levels of subject group was 27.35±12.52 µmol/L while the mean serum homocysteine levels of control group was 11.06±3.52 µmol/L. The serum homocysteine levels were significantly higher in the CKD patient group. The serum level of albumin in CKD patients and control group were 2.86±0.86 g/dl and 4.10±0.58 g/dl respectively. A positive correlation was found between serum creatinine and serum homocysteine levels. A negative correlation between serum homocysteine and serum albumin was found.Conclusions: Findings of the present study exhibit that serum homocysteine levels are elevated in CKD in comparison to healthy controls and it is positively correlated with serum creatinine level.

P0739PANEL OF SENSITIVE BIOMARKERS OF THE PRIMARY RESPONSE TO RENAL INJURY FOR AN EARLY DIAGNOSIS OF CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria João Valente ◽  
Susana Rocha ◽  
Irina Lousa ◽  
Flávio Reis ◽  
Sara Nunes ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Injury ◽  
Primary Response ◽  
Control Group ◽  
Tubulointerstitial Injury ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Ckd Stage

Abstract Background and Aims The identification of early kidney injury biomarkers is of utmost importance, since most widely used markers of kidney function vary only after several biological changes. Biomarkers allowing an earlier diagnosis of chronic kidney disease (CKD) would avoid delays in the treatment of patients. It is unlikely that a single marker is sufficient to detect the onset of CKD considering the multiple pathophysiological changes underlying primary renal response to renal injury. Several markers of inflammation, endothelial (dys)function, glomerular and tubulointerstitial injuries have been proposed and could be used combined as a panel of markers with different specificities, allowing an early detection of renal injury. Our aim was to study a panel of biomarkers proposed as early markers of renal injury, with different specificities, to evaluate and compare their sensitivities at different CKD stages. Method In this preliminary study, we enrolled 22 healthy individuals and 27 CKD patients separated into 3 groups, according to the CKD stage: 9 in stages 1 and 2; 9 in stage 3, and 9 in stages 4 and 5. None of the patients presented inflammatory, infectious or neoplastic diseases. Diagnosis and CKD stage assignment were performed according to KDIGO guidelines. We evaluated circulating levels of cystatin C (CystC), creatinine (Cr), beta trace protein (BTP) as markers of renal function; tissue inhibitor metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL) and transforming growth factor-β (TGF-β) as markers of interstitial tubulointerstitial injury; asymmetric dimethylarginine (ADMA) and tissue plasminogen activator (t-PA), as markers of endothelial (dys)function; pentraxin 3 (PTX3), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as markers of inflammation; and, pro B-type natriuretic peptides (proBNP), as a marker of cardiac (dys)function. Results In early stages of CKD (1 and 2), we found significant changes in markers of renal function (BTP, but not Cr and CystC), of tubular interstitial injury (TIMP-1 and TGF-β), of inflammation (TNF-α), of endothelial (ADMA) and cardiac (proBNP) dysfunction (vs. controls). In stage 3, we found significant changes (vs. stages 1-2) in markers of renal function (Cr and CystC), inflammation (TNF-α, IL-6), endothelial dysfunction (t-PA) and tubulointerstitial injury (TIMP-1); in stages 4-5 (vs. stage 3), we found significant changes only in the classic marker, Cr, and a trend towards increased CystC. Moreover, we found that at stages 1-2 all patients showed higher levels of BTP and proBNP when compared to the median value in the control group; TIMP-1 and ADMA were increased in 7/9 patients; TNF-α was increased in 7/9 patients; and 7/9 patients had lower values of TGF-β compared to the median value of controls. For the classical markers, Cr and CystC, we found that 5/9 and 4/9 patients, respectively, had lower values than the median value of controls; however, only 2/9 patients showed abnormal creatinine values (vs. reference values). Conclusion Our data suggest that a panel including classic (Cr and CystC) and more sensitive blood markers of the primary response to renal injury (BTP, TIMP-1 or TGF-β, ADMA, TNF-α and proBNP) would allow an earlier diagnosis of CKD, avoiding a delay in diagnosis and management of CKD patients.

Efeitos do Tratamento Crônico com Sinvastatina na Função Renal de Ratos Submetidos a um Modelo Experimental de Doença Renal Crônica/ Effects of Chronic Treatment with Sinvastatin on Renal Function in Rats Subjected to an Experimental Model of Chronic Ki

1970 ◽  
Vol 4 (2) ◽  
pp. 64-73
Author(s):  
André Luiz Rios Dos Santos ◽  
Nilo César do Vale Baracho
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Experimental Model ◽  
Chronic Treatment ◽  
Chronic Renal Disease ◽  
Male Rats ◽  
Control Group ◽  
Group 2 ◽  
Moderate Chronic Kidney Disease

Objetivos: Avaliar os efeitos do tratamento crônico com sinvastatina na função renal de ratos submetidos a um modelo experimental de doença renal crônica. Metodologia: Foram utilizados 30 ratos, machos, adultos jovens, da linhagem Wistar, com peso entre 200 e 250 g e idade entre 60 e 90 dias. Os animais foram divididos aleatoriamente em 3 grupos com 10 ratos cada. Foi realizada a cirurgia seguindo o modelo experimental de doença renal crônica moderada (DRC-M) baseado na metodologia descrita por Ormrod & Miller, 1980. Após os procedimentos cirúrgicos, os animais receberam os referidos tratamentos, por um período de duas semanas: Grupo 1 - Animais com DRC-M tratados com água destilada VO (Gavagem) (n=10). Grupo 2 - Animais com DRC-M tratados com 5mg/Kg de sinvastatina VO (n=10). Grupo 3 - Animais com DRC-M tratados com 10mg/Kg de sinvastatina VO (n=10). Resultados: A indução de DRC-M não produziu alterações significativas sobre o débito urinário, ingesta hídrica, ingesta alimentar e parâmetros da função renal estudados, quando comparados o grupo controle com sinvastatina 5mg/Kg ou com sinvastatina 10mg/Kg ou quando comparados os grupos sinvastatinas entre si. Conclusão: Esses dados demonstram que o tratamento com sinvastatina, independente da dosagem do trabalho, não produziu melhora da função renal de ratos submetidos a um modelo experimental de Doença Renal Crônica Moderada (DRC-M).  Palavras-chave: doença renal crônica, sinvastatina, experimentos com ratos ABSTRACT Objectives: To evaluate the effects of chronic treatment with sinvastatin on renal function in rats subjected to an experimental model of chronic renal disease. Methods: 30 male rats were young adults, the Wistar strain, weighing between 200 and 250 g and aged between 60 and 90 days were used. The animals were randomly divided into 3 groups with 10 rats in each. Surgery was performed following the experimental moderate chronic (CKD-M) model of kidney disease based on the methodology described by Miller & Ormrod, 1980. After the surgical procedures, animals receive these treatments for a period of two weeks: Group 1 - animals with CKD-M with distilled water and treated orally (gavage) (n = 10). Group 2 - animals with CKD-M and treated with sinvastatin 5mg/kg orally (n = 10). Group 3- animals with CKD-M and sinvastatin treated with 10mg/kg orally (n = 10). Results: Induction of CKD-M produced no significant change on urine output, fluid intake, food intake and renal function parameters studied when comparing the control group with sinvastatin or sinvastatin 5mg/kg or 10mg/kg when comparing groups sinvastatin to each other. Conclusion: These data demonstrate that treatment with sinvastatin dosage independent from the work produced no improvement in renal function in rats subjected to an experimental model of Moderate Chronic Kidney Disease (CKD-M). Keywords: Chronic Kidney Disease, sinvastatin, experiments with rats. 

scholarly journals Association between Allelic Variations of -174G/C Polymorphism of Interleukin-6 Gene and Chronic Kidney Disease-Mineral and Bone Disorder in Iraqi Patients

2020 ◽  
Vol 17 (4) ◽  
pp. 1145
Author(s):  
Mohanad Radeef
Keyword(s):  
Chronic Kidney Disease ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Vitamin D3 ◽  
Interleukin 6 ◽  
Maintenance Hemodialysis ◽  
Control Group ◽  
Significant Elevation ◽  
Mineral And Bone Disorder ◽  
Hormone Levels

This study designed to examine association between-174G/C polymorphism of interleukin-6 gene and phosphate, calcium, vitamin D3, and parathyroid hormone levels in Iraqi patient with chronic kidney disease on maintenance hemodialysis. Seventy chronic renal failure patients (patients group) and 20 healthy subjects (control group) were genotyped for interleukin-6 polymorphism and genotyping was performed by conventional polymerase chain reaction-restriction fragment length polymorphism. No significant differences in phosphate levels were observed in patients and control with different interleukin-6 genotypes. Control had non-significant differences in calcium levels, while patients with GG and CG genotypes displayed significant elevation with time. Conversely, control and patients with GG and CC genotypes had significant elevation in vitamin D3 levels with time. Regarding parathyroid hormone, control had non-significant differences, while patients with GG and CC genotypes displayed significant elevation with time. Patients with GG genotype displayed significant changes in calcium, vitamin D3 and parathyroid hormone levels with time.

scholarly journals Recombinant Erythropoietin Provides Protection against Renal Fibrosis in Adenine-Induced Chronic Kidney Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Estefanía Vázquez-Méndez ◽  
Yanet Gutiérrez-Mercado ◽  
Edgar Mendieta-Condado ◽  
Francisco Javier Gálvez-Gastélum ◽  
Hugo Esquivel-Solís ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Inflammatory Cells ◽  
Erythropoietin Receptor ◽  
Control Group ◽  
Recombinant Erythropoietin ◽  
Tubular Atrophy ◽  
Human Recombinant Erythropoietin

Chronic kidney disease (CKD) causes anemia by renal damage. In CKD, the kidney is submitted to hypoxia, persistent inflammation, leading to fibrosis and permanent loss of renal function. Human recombinant erythropoietin (rEPO) has been widely used to treat CKD-associated anemia and is known to possess organ-protective properties that are independent from its well-established hematopoietic effects. Nonhematopoietic effects of EPO are mediated by an alternative receptor that is proposed to consist of a heterocomplex between the erythropoietin receptor (EPOR) and the beta common receptor (βcR). The present study explored the effects of rEPO to prevent renal fibrosis in adenine-induced chronic kidney disease (Ad-CKD) and their association with the expression of the heterodimer EPOR/βcR. Male Wistar rats were randomized to control group (CTL), adenine-fed rats (Ad-CKD), and Ad-CKD with treatment of rEPO (1050 IU/kg, once weekly for 4 weeks). Ad-CKD rats exhibited anemia, uremia, decreased renal function, increased infiltration of inflammatory cells, tubular atrophy, and fibrosis. rEPO treatment not only corrected anemia but reduced uremia and partially improved renal function as well. In addition, we observed that rEPO diminishes tubular injury, prevents fibrosis deposition, and induces the EPOR/βcR heteroreceptor. The findings may explain the extrahematopoietic effects of rEPO in CKD and provide new strategies for the treatment of renal fibrosis in CKD.

scholarly journals P0271SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR-D LEVEL CORRELATES WITH RENAL FUNCTION AND ALBUMINURIA IN PATIENT WITH DIABETIC CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hyeongwan Kim ◽  
Jong Hwan Chong ◽  
Woong Park ◽  
Sung Kwang Park ◽  
Won Kim
Keyword(s):  
Chronic Kidney Disease ◽  
Vascular Endothelial Growth Factor ◽  
Renal Function ◽  
Kidney Disease ◽  
Serum Levels ◽  
Control Group ◽  
Vascular Endothelial ◽  
Stage 4 ◽  
Ckd Stage ◽  
Endothelial Growth Factor

Abstract Background and Aims Biomarkers associated with chronic kidney disease (CKD) may play a crucial role in patients with diabetic kidney diseases. Vascular endothelial growth factor (VEGF)-C and VEGF-D are lymphangiogenic growth factors. It has been well demonstrated that there is lympnagiogenesis in fibrotic kidney disease in human. Previously, we showed that renal VEGF-C and VEGF-D are involved in lymphangiogensis in renal fibrosis model. Recent studies have shown a relationship between sodium load and serum VEGF-C levels in hypertensive patients. Lymphatic endothelial proliferation has been detected in diabetic nephropathy. Thus, serum VEGF-C level has been introduced as a candidate marker of chronic kidney disease. However, until now, there have been few report about serum VEGF-D in patients with diabetic CKD. Thus, we evaluated the relationships between serum VEGF-D and renal function and albuminuria of diabetic CKD. Method We divided diabetic CKD patients into four groups: CKD stage 3, CKD stage 4, and CKD stage 5 (without dialysis). Total forty two Asian patients with diabetic CKD (14 patients with CKD stage 3, 14 patients with CKD stage 4 and 14 patients with CKD stage 5) and seven healthy controls without diabetes mellitus have been enrolled in this study. In this cross-sectional study, we performed comparative analysis with serum level of VEGF-D in patients with each group. We measured the levels of VEGF-D through the multiplexing using Luminex® technology. Results The serum levels of VEGF-D were higher in the CKD 3, CKD 4 and CKD 5 group compared with the control group (25.9±5.6 pg/ml in control group, 60.3±9.7in stage 3, 62.9±8.5 in stage 4, and 66.5±8.0 in stage 5). However, there was not a significant difference between CKD stage III or IV and CKD stage V in serum levels of VEGF-D. Serum VEGF-D level were negatively correlated with estimated glomerular filtration rate and positively correlated with serum creatinine. At GFR level ≥60 ml/min per 1.73 m2, serum VEGF-D were biomarkers in ROC analysis. There was a positive correlation between serum VEGF-D level and albuminuria in patient with diabetic CKD. We also found that serum VEGF-D level also correlated with urine protein-to-creatinine ratio in patient with diabetic CKD. Conclusion Serum VEGF-D is correlated with renal function in patients with diabetic CKD. VEGF levels in the serum correlate to the severity of proteinuria and albuminuria in diabetic CKD patients. Further large-scale studies are required to confirm these findings.

scholarly journals Serum-to-urine renalase ratio and its differences between healthy adults and chronic kidney disease patients

2019 ◽  
Author(s):  
Natalia Maria Serwin ◽  
Magda Wiśniewska ◽  
Elżbieta Cecerska-Heryć ◽  
Krzysztof Safranow ◽  
Edyta Skwirczyńska ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Statistical Significance ◽  
Fractional Excretion ◽  
Protective Role ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Significant Independent Factor ◽  
Two Parameters ◽  
Serum And Urine

Abstract Background: Renalase is a flavoprotein that plays a protective role in chronic kidney disease and cardiovascular diseases. The secretion and way of action of this protein are still discussed. The aim of our study was to estimate the balance between serum and urine renalase in healthy individuals and chronic kidney disease (CKD) patients, using two parameters: fractional excretion (FE) and serum-to-urine renalase ratio (StURR). Methods: Our study involved 28 healthy volunteers and 62 patients with CKD in stages I to IV. The concentration of renalase in serum and urine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (EIAab, Wuhan, China). We analyzed associations between renalase levels in urine and serum, and other parameters: sex, age, GFR, presence of hypertension, diabetes, and proteinuria, and determined the serum-to-urine renalase ratio and fractional excretion of renalase. Results: Renalase and serum-to-urine ratio were significantly higher in CKD patients in comparison with the control group. Fractional excretion was lower in CKD patients but this difference did not reach the statistical significance (p=0.092). Multivariate analysis performed in the CKD group showed, that from mentioned parameters, serum renalase was the only significant independent factor strongly positively associated with urinary renalase concentration. Conclusions: The serum-to-urine ratio is significantly and about 6.5-fold higher in CKD patients, and the fractional excretion of renalase is 3-fold, but not significantly lower in CKD patients. Renalase levels in both serum and urine are not related to glomerular filtration rate and not associated with blood pressure.

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