scholarly journals Npt2a as a target for treating hyperphosphatemia

2022 ◽  
Author(s):  
Linto Thomas ◽  
Jessica A. Dominguez Rieg ◽  
Timo Rieg
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Function ◽  
Ventricular Hypertrophy ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Potential Treatment ◽  
Elevated Plasma ◽  
Pi Homeostasis ◽  
Reduced Kidney Function

Hyperphosphatemia results from an imbalance in phosphate (Pi) homeostasis. In patients with and without reduced kidney function, hyperphosphatemia is associated with cardiovascular complications. The current mainstays in the management of hyperphosphatemia are oral Pi binder and dietary Pi restriction. Although these options are employed in patients with chronic kidney disease (CKD), they seem inadequate to correct elevated plasma Pi levels. In addition, a paradoxical increase in expression of intestinal Pi transporter and uptake may occur. Recently, studies in rodents targeting the renal Na+/Pi cotransporter 2a (Npt2a), responsible for ∼70% of Pi reabsorption, have been proposed as a potential treatment option. Two compounds (PF-06869206 and BAY-767) have been developed which are selective for Npt2a. These Npt2a inhibitors significantly increased urinary Pi excretion consequently lowering plasma Pi and PTH levels. Additionally, increases in urinary excretions of Na+, Cl− and Ca2+ have been observed. Some of these results are also seen in models of reduced kidney function. Responses of FGF23, a phosphaturic hormone that has been linked to the development of left ventricular hypertrophy in CKD, are ambiguous. In this review, we discuss the recent advances on the role of Npt2a inhibition on Pi homeostasis as well as other pleiotropic effects observed with Npt2a inhibition.

Continuous Ambulatory Peritoneal Dialysis in High-Risk Patients: Patients with Cardiovascular Diseases -Role of the Nurse

1999 ◽  
Vol 19 (2_suppl) ◽  
pp. 499-503
Author(s):  
Marie-Christine Z. Lambert ◽  
Holger Schilling
Keyword(s):  
Cardiovascular Disease ◽  
Peritoneal Dialysis ◽  
Ventricular Hypertrophy ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Therapeutic Success ◽  
Risk Patients ◽  
Continuous Peritoneal Dialysis ◽  
Artery Disease

Most patients receiving renal replacement therapy have cardiovascular disease. The most frequent conditions are left ventricular hypertrophy and coronary artery disease. Hemodialysis is associated with a characteristic spectrum of acute complications (such as hypotension, sudden death) that can be explained by typical dialysis -induced effects on the heart. With continuous peritoneal dialysis (CAPO) some of the cardiovascular complications are ameliorated owing to slow ultrafiltration and absence of an arteriovenous fistula. CAPO might be concluded to be the preferable option in patients with cardiovascular disease, but a few disadvantages, such as hyperlipidemia and hyperinsulinemia, also exist. Nurses also play an important role in the therapeutic success and outcomes of these patients.

The role of bone metabolism regulators sclerotin and osteoprotegerin in the development of cardiovascular complications in the late stages of chronic kidney disease

2021 ◽  
Vol 25 (6) ◽  
pp. 63-70
Author(s):  
F. U. Dzgoeva ◽  
O. V. Remizov ◽  
V. Kh. Botsieva ◽  
N. G. Malakhova ◽  
Z. R. Ikoeva ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Serum ◽  
Bone Metabolism ◽  
Vascular Calcification ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Enzyme Linked Immunosorbent Assay ◽  
Commercial Kits

BACKGROUND. Cardiovascular complications caused by vascular calcification in chronic kidney disease (CKD) are closely related to disorders of bone and mineral metabolism, the mechanisms of which require further study.THE AIM: to clarify the role of the regulatory proteins of bone metabolism of sclerostin and osteoprotegerin in the processes of vascular calcification and the development of cardiovascular complications in CKD.PATIENTS AND METHODS. 110 patients with stage 3-5D CKD (67 men) were examined. Median age is 47.0 (23.0-68.0) years. Osteoprotegerin (OPG), sclerostin, intact parathyroid hormone (IPTG), troponin I in blood serum were determined using commercial kits "Enzyme-linked Immunosorbent Assay Kit for Sclerostin" ("Cloud-Clone Corp.", USA) and commercial kits "ELISA kit" ("Biomedica" (Austria) by enzyme immunoassay (ELISA). Echocardiography with Dopplerography was performed on the device "ALOKA 4000" ("Toshiba", Japan). The left ventricular myocardial mass index (LVMI) and peak systolic blood flow velocity in the aortic arch (Vps, peak systolic velocity) were determined to quantify hemodynamic changes indirectly indicating the state of the aortic vascular wall.RESULTS. Analysis of the ratios of the calculated glomerular filtration rate (EGFR), IMLJ, Vps, OPG, and sclerostin showed that a decrease in excretory kidney function is accompanied by an increase in the concentrations of OPG and sclerostin in the blood serum. At the same time, there is an increase in IMLJ and Vps. During the correlation analysis, it was shown that the level of OPG was positively correlated with the level of sclerostin and negatively with the level of iPTG.CONCLUSION. In our study, we obtained data confirming the interactive interaction between the vascular and bone systems. Morphogenetic proteins-inhibitors of bone metabolism (sclerostin and OPG) play a significant role in the defeat of the cardiovascular system in patients with CKD, as they promotes the development of vascular calcification.

scholarly journals Assessment of Risk Factors for Cardiovascular Complications in Patients with Chronic Kidney Disease (CKD) Stage III-V before Dialysis

2014 ◽  
Vol 9 (1) ◽  
pp. 25-32
Author(s):  
MK Khan ◽  
HU Rashid ◽  
S Yesmine ◽  
IH Mahmoo ◽  
SMA Habib ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Small Sample ◽  
Stage Iii ◽  
Ckd Stage

Background: Chronic Kidney Disease is a major public health and clinical problem throughout the world including Bangladesh. The prevalence of cardiovascular complications is much higher in patients with CKD regardless of stages than normal population. Considering this view, a cross sectional study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, with an aim to assessing the cardiovascular complications & associated risk factors among the patients with chronic kidney disease (CKD) stage III-V before dialysis. Methods: A total of 109 patients were selected consecutively who had a diagnosis of CKD and an estimated GFR of less than 60 ml/min/1.73m2 of stages III to V and who had not received any form of renal replacement therapy, during a period of June 2006 to July 2007. Results: The study included 63 males and 46 females with age ranging from 18 to 65 years having a mean age 45.5±12.2 years. Left ventricular failure, left ventricular hypertrophy (by ECG and echocardiography), cardiomegally by X-ray were identified as significant cardiovascular complications among the patients of CKD stage V (p<0.05). However , logistic regression analysis revealed that hypertension and CKD stages appeared to be the important predictors of cardiovascular complications p<0.05). Data analysis found that hypertension, smoking and anemia appeared to be important risk factors for cardiovascular complications in CKD patients (p<0.05) by bi-variate analysis. Conclusion: Though the study findings did not generalize the CKD patients in Bangladesh due to small sample size, however, heart failure and left ventricular hypertrophy significantly appeared to be the main cardiovascular complications in CKD stage V compared to other two stages (stage III and IV)(p<0.05). Anemia, hypertension were identified as important risk factors (p<0.05). DOI: http://dx.doi.org/10.3329/uhj.v9i1.19508 University Heart Journal Vol. 9, No. 1, January 2013; 25-32

scholarly journals Homoarginine as a laboratory cardiovascular risk biomarker

2021 ◽  
Vol 27 (3) ◽  
pp. 341-350
Author(s):  
A. A. Zhloba ◽  
Tatyana F. Subbotina ◽  
Artem V. Tishkov ◽  
Tatyana Yu. Reypolskaya
Keyword(s):  
Cardiovascular Risk ◽  
Ventricular Hypertrophy ◽  
Risk Groups ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Control Group ◽  
Diagnostic Role ◽  
Design And Methods ◽  
Very High

Background. Low plasma concentration of L-homoarginine (hArg) is associated with the progression of cardiovascular disease. However, the association between plasma hArg and cardiovascular complications in hypertension is not established. Objective. To assess and compare hArg levels as a biomarker of cardiovascular risk in hypertension. Design and methods. We included 60 hypertensives with moderate (n = 12), high (n = 16) and very high (n = 32) cardiovascular risk. Blood plasma tests including hArg were assessed. The control group included 30 age-matched regular donors. Results. The level of hArg was significantly lower in hypertensives compared to ocontrols (р < 0,001). There were negative correlations between hArg and echocardiography parameters of left ventricular hypertrophy. In the higher cardiovascular risk groups hArg was lower (р = 0,042). ROC-analysis showed AUC 0,860 (95 % confidence interval 0,787–0,933) with the threshold for hArg ≤ 1,69 µM, sensitivity 72,0 % and specificity 93,3 %. Conclusion. The hArg plasma level is associated with the expression and enzyme activity of the protein arginine: glycinamidinetransferase in various tissues. The hArg level ≤ 1,69 µM can be considered a cumulative laboratory biomarker of high cardiovascular risk. Further studies of prognostic and diagnostic role of hArg are needed.

scholarly journals Relative overhydration is independently associated with left ventricular hypertrophy in dialysis naïve patients with stage 5 chronic kidney disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Byoung-Geun Han ◽  
Jun Young Lee ◽  
Seung Ok Choi ◽  
Jae-Won Yang ◽  
Jae-Seok Kim
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Early Stage ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Volume Status ◽  
Functional Evaluation ◽  
Status Assessment

Abstract Patients with chronic kidney disease (CKD) have a high prevalence of left ventricular hypertrophy (LVH), which increases as kidney function decreases. LVH pathophysiology is complex, making it difficult to generalise its evolution in CKD. Therefore, early detection and prevention of risk factors are critical. Assessment and management of volume status can minimise cardiovascular complications including LVH. We retrospectively investigated the associations between fluid overload and LVH in patients with stage 5 CKD not undergoing dialysis in prospective cohort of 205 patients (age: 59.34 ± 13.51 years; women: 43.4%). All patients, free of intrinsic heart disease, were assessed for relative overhydration/extracellular water (OH/ECW) by bioimpedance spectroscopy. Our results show that markers reflecting fluid balance were significantly higher in the LVH group and as OH/ECW increased, the left ventricular mass index (LVMI) trended higher. Furthermore, our results show that systolic blood pressure, serum phosphorus levels, and OH/ECW were independently associated with LVMI and that OH/ECW was independently associated with LVH. Structural and functional evaluation of the heart using echocardiography and volume status assessment using bioimpedance should be performed simultaneously in patients with early-stage CKD, even in those without evident cardiovascular disease.

Biochemical and Paraclinical Evaluation of Organ Damage in Arterial Hypertension with Associated Chronic Kidney Disease

2020 ◽  
Vol 71 (6) ◽  
pp. 194-204
Author(s):  
Teim Baaj ◽  
Ahmed Abu-Awwad ◽  
Mircea Botoca ◽  
Octavian Marius Cretu ◽  
Elena Ardeleanu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Ventricular Hypertrophy ◽  
Ankle Brachial Index ◽  
Intima Media Thickness ◽  
Organ Damage ◽  
Left Ventricular ◽  
Study Group ◽  
Group A

Organ damages, which contribute to the overall cardiovascular risk of hypertensive patients, should be early detected, prevented and treated. The study evaluated organ damage in a hypertensive study group with chronic kidney disease (CKD), compared with a study group of hypertension without CKD. Albuminuria was present in 41.2% and reduced estimated glomerular filtration rate [60 ml/min/m2 was present in 72.5% of hypertensive with CKD. The comparison of organ damage revealed in the CKD group a statistical significant higher prevalence of organ damage as follows: intima-media thickness ]0.9 mm in 39.9% vs 10.5%, carotid plaques in 28.2% vs 12.6%, left ventricular hypertrophy in 39.9% vs 31%, ankle brachial index in 6.2% vs 3.5%. Early detection and treatment of additional cardiovascular risk factors as dyslipidaemia and hyperglycaemia, that have significant role in the pathogenesis of organ damage, contribute to the better prevention of cardiovascular and renal complications in hypertension with CKD.

scholarly journals Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Guillaume Courbon ◽  
Connor Francis ◽  
Claire Gerber ◽  
Samantha Neuburg ◽  
Xueyan Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Fibroblast Growth Factor ◽  
Kidney Function ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Lipocalin 2

AbstractBone-produced fibroblast growth factor 23 (FGF23) increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2; LCN2 the murine homolog) is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD progression. We investigated bone FGF23 regulation by circulating LCN2. At 23 weeks, Col4a3KO mice showed impaired kidney function, increased levels of kidney and serum LCN2, increased bone and serum FGF23, anemia, and left ventricular hypertrophy (LVH). Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum FGF23. Lcn2 deletion specifically prevented FGF23 elevations in response to inflammation, but not iron deficiency or phosphate, and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone cells. These results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in CKD. LCN2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.

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