scholarly journals Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?”

2021 ◽  
Vol 22 (22) ◽  
pp. 12590
Author(s):  
Giuseppina Crugliano ◽  
Raffaele Serra ◽  
Nicola Ielapi ◽  
Yuri Battaglia ◽  
Giuseppe Coppolino ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Cardiovascular Events ◽  
Iron Supplementation ◽  
Hypoxia Inducible Factor ◽  
Current Treatment ◽  
Prolyl Hydroxylase ◽  
Individual Risk ◽  
Increased Risk ◽  
Gastrointestinal Side Effects ◽  
Iv Iron

Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients’ dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action.

MO547ASSOCIATION BETWEEN SERUM INDICES OF IRON METABOLISM AND CARDIOVASCULAR MORBIDITY IN PATIENTS WITH PREDIALYSIS CHRONIC KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Takahiro Imaizumi ◽  
Kenta Murotani ◽  
Takayuki Hamano ◽  
Masafumi Fukagawa
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Metabolism ◽  
Iron Supplementation ◽  
Transferrin Saturation ◽  
Cox Proportional Hazards ◽  
Function Evaluation ◽  
Iron Deficient ◽  
Increased Risk ◽  
Reduced Risk

Abstract Background and Aims Patients with predialysis chronic kidney disease (CKD) have a greater risk of developing cardiovascular disease (CVD) events than the general population. Anaemia is the most frequent comorbidity in pre-dialysis CKD patients and is associated with an increase in CVD events. Iron deficiency is the most frequent cause of erythropoiesis-stimulating agents (ESAs) resistant anaemia in CKD patients and is modifiable by therapeutic intervention. However, the optimal ranges of iron markers are uncertain in predialysis CKD patients. Therefore, we aimed to investigate the association between serum indices of iron metabolism and the incidence of CVD events in patients with predialysis CKD using the CKD-Japan Cohort (CKD-JAC) data. Method We prospectively followed 1550 CKD patients aged 20-75 years with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 for a mean of 4.21 years. We set serum transferrin saturation (TSAT) and ferritin levels as the main exposures to be tested. Our main outcome measures were any of the CVD events including fatal or non-fatal myocardial infarction, congestive heart failure (CHF), angina pectoris, arrhythmia, aorta dissection, cerebrovascular disorder, and peripheral artery diseases identified at each facility and adjudicated by the independent cardiac function evaluation committee. Multivariable Cox proportional hazards regression models were employed to examine the association between serum TSAT or ferritin levels with time to events. Death was considered as a competing risk with the Fine and Gray model. All models were stratified by facilities and adjusted for potential confounders as follows: age, sex, systolic blood pressure, diabetes mellitus, history of CHF, haemoglobin, serum calcium, serum phosphorus, intact parathyroid hormone, eGFR, proteinuria, ESAs, iron supplementation, renin-angiotensin system inhibitors, and beta-blockers. We also applied the multivariable fractional polynomial interaction (MFPI) approach to investigate whether TSAT levels are the effect modifier of the association between iron supplementation and the outcomes. Results In the overall cohort, 208 (13.4 %) patients developed CVD events (including 97 CHF) during the follow-up period (26.6 events/1000 person-year). The incidence rate of CVD events was the highest in the TSAT < 20% category (33.0 events/1000 person-year). Compared to patients in the TSAT > 40% category, those in the TSAT < 20% category demonstrated an increased risk of CVD events (adjusted hazard ratio (AHR): 1.86, 95% confidence interval (CI): 1.06-3.26) and CHF events (AHR: 2.82, 95% CI: 1.15-6.89), respectively. Meanwhile, there was no association between serum ferritin levels and the risk of developing CVD or CHF events. MFPI analyses showed a reduced risk of CVD in patients receiving iron supplementation only in patients with TSAT <20% (P for interaction=0.02). Conclusion Maintaining TSAT >20% could be effective to reduce the risk of developing CVD events (especially CHF) in patients with predialysis CKD. Our analyses also suggest that iron-deficient patients with predialysis CKD may benefit from iron supplementation for reduced risk of CVD events.

Special conditions: kidney disease

ESC CardioMed ◽  
2018 ◽  
pp. 947-950
Author(s):  
Drazenka Pongrac Barlovic ◽  
Per-Henrik Groop
Keyword(s):  
Risk Factors ◽  
Renal Failure ◽  
Kidney Disease ◽  
Life Expectancy ◽  
Renal Disease ◽  
Beneficial Effect ◽  
Cardiovascular Events ◽  
Treatment Strategies ◽  
Microvascular Damage ◽  
Increased Risk

Kidney disease is one of the most common and important consequences of microvascular damage in diabetes. Its occurrence largely determines the increased risk of cardiovascular events and remarkably shortens life expectancy. Therefore, protecting the kidney is one of the main aims of patient care in diabetes and should be based on implementation of the intensive treatment of risk factors that promote its progression to prevent renal failure, and even more importantly, cardiovascular events. Very recently, some new therapies with a beneficial effect on renal disease have emerged; however, there is still plenty of room for additional innovative treatment strategies to prevent, arrest, treat, and reverse kidney disease caused by diabetes and its devastating consequences.

scholarly journals SP334IRON REGULATION BY MOLIDUSTAT, BAY 85-3934, A DAILY ORAL HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITOR IN PATIENTS WITH CHRONIC KIDNEY DISEASE

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i457-i457 ◽  
Author(s):  
Tadao Akizawa ◽  
Iain C Macdougall ◽  
Jeffrey S Berns ◽  
Thomas Bernhardt ◽  
Megumi Taguchi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Prolyl Hydroxylase Inhibitor

scholarly journals Hyperphosphatemia in chronic kidney disease

2019 ◽  
pp. 78-85
Author(s):  
S. A. Martynov ◽  
M. Sh. Shamkhalova
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Cardiovascular Events ◽  
Cardiovascular Complications ◽  
Phosphate Binding ◽  
Renal Function Decline ◽  
Increased Risk ◽  
Binding Agents ◽  
Key Factor

Hyperphosphatemia in renal pathology is a key factor for developing mineral and bone disorders. It can develop even in the early stages of renal function decline and predict the formation of vascular calcification and an increased risk for developing cardiovascular complications in patients with chronic kidney disease, especially in those, who receive program hemodialysis. The use of calcium-free phosphate-binding agents that are not associated with the risk for developing hypercalcemia can slow the development of vascular calcification, reduce the incidence of adverse cardiovascular events and mortality in patients with chronic kidney disease.

Abstract 13234: The Association Between Serum Potassium and Major Adverse Cardiovascular Events in Patients With Chronic Kidney Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Alex Yang ◽  
Jiacong Luo ◽  
Donna E Jensen ◽  
Steven M Brunelli
Keyword(s):  
Kidney Disease ◽  
Serum Potassium ◽  
Cardiovascular Events ◽  
Beta Blockers ◽  
High Serum ◽  
Major Adverse Cardiovascular Events ◽  
Channel Blockers ◽  
Increased Risk ◽  
Rate Ratios ◽  
Stage Renal Disease

Introduction: Patients with kidney disease often have high serum potassium (K) due to diminished excretory capacity. Hypothesis: We evaluated the association of high K with rates of arrhythmia and major adverse cardiovascular events (MACE; composite of myocardial infarction, stroke, heart failure, and arrhythmia). Methods: We studied a retrospective cohort of patients with eGFR <60 mL/min/1.73m 2 between Jan-2009 and Jun-2013 (N=55,266). Patients were followed until the end of study (30-Jun-2013), death, end-stage renal disease, or transfer of care. Serum K, eGFR, and 13 covariates including demographics, prevalent comorbidities, and medication use (beta blockers, centrally acting calcium channel blockers, and loop and thiazide diuretics) were considered on a time-varying basis, updated for each K measurement. Results: At baseline, 15%, 4%, and 1% of patients had serum K 5.0-5.4, 5.5-5.9, and ≥6.0 mEq/L, respectively. Prevalence was greater in lower eGFR strata. Within each eGFR stratum serum K demonstrated U-shaped associations with rates of MACE and arrhythmia, displayed for eGFR <30 mL/min/1.73m 2 . Compared to K 4.5-4.9 mEq/L, incidence rate ratios (IRRs) of MACE for K ≥6.0 mEq/L were 2.11 [95%CI, 1.68-2.65], 1.44 [1.12-1.84], 1.56 [1.11-2.17], and 2.11 [1.53-2.89] in the eGFR <30, 30-39, 40-49, and 50-59 strata, respectively. K ≥6.0 mEq/L was associated with increased rate of arrhythmia in the lowest eGFR stratum (Figure); point estimates in other eGFR strata ranged from 1.39 to 1.53, but were not significant. Conclusions: K ≥6.0 mEq/L is associated with increased risk of MACE among patients with eGFR <60 mL/min/1.73m 2 and with arrhythmia among patients with eGFR <30 mL/min/1.73m 2 . Renal impairment should be considered when determining serum K targets with respect to cardiovascular risk.

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