Anemia In Chronic Kidney Disease Patients Research Articles

#206 The effect of dapagliflozin on anemia in patients with CKD

Abstract Background and Aims SGLT2 inhibitors confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). Some studies have analyzed the effects of SGLT2is on hemoglobin levels. Potential mechanisms for rising hemoglobin include hypoxia-induced activation of HIF2α, hepcidin inhibition resulting in iron metabolism modulation, and hemoconcentration. We aimed to evaluate the effect of dapagliflozin on anemia in CKD patients. Method We conducted a prospective study in patients in a single center with eGFR 35-90 ml/min/1.73 m2 who received dapagliflozin 10 mg daily between 6/2022 and 10/2023. The primary outcome was the mean difference in hemoglobin levels 5 months prior and 8 months after initiation of SGLT2i therapy. Results Among 132 patients screened from 6/2022 to 10/2023, 53 were prescribed dapagliflozin 10 mg daily, with a mean eGFR of 53.2 ml/min/1.73 m2. Of those 53 patients, 28 (52.8%) were males and 25 (47.2%) females. No one received any iron supplements or erythropoietin therapy. The mean hemoglobin level 5 months before initiating SGLT2i therapy was 10.5 g/dL, with a mean drop of 0.10 g/dL (95% CI, –0.22 to + 0.06) in 5 months. Eight months following the addition of SGLT2is, patients experienced an increase in hemoglobin levels of 1.03 g/dL (95% CI, 0.84 to 1.14). Overall, we observed a mean hemoglobin difference of 1.13 g/dL (95% CI, 0.84 to 1.41, p < 0.01) before and after initiating SGLT2i therapy. Conclusion The use of dapagliflozin for eight months resulted in a significant elevation in hemoglobin levels in patients with CKD. Further studies can explore of better understanding of the effect and confirm the mechanisms that explain this finding. Elevation of hemoglobin with SGLT2is may be closely linked to the reduction of cardiovascular mortality and heart failure.

Iron biology.

Iron is a fundamental element for biological life, starting from bacteria till humans. Iron is essential for cell function and survival, energy production and metabolism, whereas increased levels cause oxidative stress. It is also a constituent of haemoglobin and thus it is necessary for oxygen transportation through the body. Given these multiple functions, the regulation of iron metabolism is complex and tight coupled with oxygen homeostasis at tissue and cellular levels, thanks to the interaction with the hypoxia inducible factor (HIF) system. In patients with chronic kidney disease (CKD), iron deficiency significantly contributes to anaemia development. This frequently overlaps with chronic inflammation, causing iron- restricted erythropoiesis. To add further complexity, metabolic hyperferritinemia may, on one side, increase the risk for CKD and, on the other, overlaps with functional iron deficiency. Excessive intracellular iron in certain cell types during CKD can also mediate cellular death (called ferroptosis), and contribute to the pathogenesis of kidney damage, atherosclerosis and vascular calcifications. This review is aimed at broadening the perspective of iron metabolism in the setting of CKD not just as a contributor to anaemia in CKD patients, but also as an important player with an impact on cell metabolism, renal fibrosis, and the cardiovascular system.

Evaluation of Folic Acid Deficiency Anaemia in Predialysis Chronic Kidney Disease Patients: A Hospital-based Study

Background: Chronic kidney disease (CKD) is defined as decreasing kidney function for more than 3 months. Anemia is a common complication of CKD due to a decrease in the hormone erythropoietin related to hemoglobin levels. Folic acid helps with the process of nucleoprotein synthesis and erythropoiesis maintenance.Objectives: The aim of the study was to determine the folic acid level in predialytic anaemic chronic kidney disease patients. Methodology: It was a cross-sectional study conducted in the department of Nephrology of Eastern Medical College & Hospital from September 2020 to August 2021 on predialysis CKD anaemic patient of stage-3 to stage-5. A total of 100 subjects were selected by purposive sampling. The age group was 18 to 70 years. Results: Among the 100 subjects mild, Moderate and Severe aneamia were found in 27%, 44% and 29% respectively. Maximum cases showed normocytic normochromic anaeamia (54%) and 7% cases showed macrocytic aneamia. Serum folic acid levels were found to have decreased in 1 (16.7%), 2 (8.33%) and 7 (10.0%) cases and increased in 2 (33.3%), 5 (20.83%) and 21 (30.0%) cases in stage-3, stage-4 and stage-5 respectively. Conclusion: Anemia is a frequent complication of chronic kidney disease. Inadequate production of erythropoietin by the failing kidneys leads to decreased stimulation of the bone marrow to produce red blood cells. Folic acid deficiency may represent an influential factor in renal anemia. Eastern Med Coll J. July 2023; 8 (2): 13-18

A novel scenario in the therapeutic management of anemia of chronic kidney disease: placement and use of roxadustat.

Anemia is a frequent and early chronic kidney disease (CKD) complication. Its management is currently based on oral or intravenous iron supplements, erythropoiesis-stimulating agents, and red blood cell transfusions, when the benefits of transfusion outweigh the risks. Anemia in CKD patients is underdiagnosed and undertreated. Current standard of care is associated with challenges and therefore new treatment approacheshave been sought. Hypoxia-inducible factor-prolyl-hydroxylase enzyme inhibitors are a new class of orally administered drugs used to treat anemia associated with CKD. Small-molecule hypoxia-inducible factor-prolyl-hydroxylase inhibitors have a novel mechanism of action that activates the hypoxia-inducible factor (oxygen-sensing) pathway resulting in a coordinated erythropoietic response, leading to increased endogenous erythropoietin production, improved iron absorption and transport, and reduced hepcidin. Roxadustat is the first hypoxia-inducible factor-prolyl-hydroxylase inhibitor approved by the European Medicines Agency (EMA) and reimbursed in Italy by the Italian Medicines Agency (AIFA) for the treatment of adult patients with symptomatic CKD-related anemia. This authorization was based on the outcome of a globally-conducted phase 3 clinical trial program comprising eight pivotal multicenter randomized studies. In the absence of up-to-date guidelines, we performed a critical appraisal of the placement and use of roxadustat in this therapeutic context.

PENGARUH ERITROPOETIN TERHADAP TINGKAT KEBERHASILAN TERAPI ANEMIA PADA PASIEN ANEMIA PADA PASIEN CHRONIC KIDNEY DISEASE DI RSUD ULIN BANJARMASIN

Chronic kidney disease (CKD) is kidney damage for more than 3 months. The medical in hospital taken was hemodialysis. The aim of this study was to determine the success rate of anemia therapy, the incidence of anemia in CKD patients, and determine the effect of erythropoietin administration on the success rate of anemia therapy in CKD patients at Ulin Hospital, Banjarmasin. This research is a non-experimental research, observational in nature. Data collection was carried out prospectively. The sample used in this study was patient hemoglobin data in medical records that met the inclusion and exclusion criteria. The sample selection method used was total sampling. The measurement of therapeutic success used is the patient's hemoglobin data after being given erythropoietin. The research data obtained is displayed descriptively analytically. The research results of 90 patients with CKD (Chronic Kidney Disease). The results obtained were that 50 patients (55.55%) achieved success in anemia therapy and 40 patients (45.45%) did not achieve success in anemia therapy. The incidence of anemia was 90 patients (100%). Based on the analysis of data obtained, there is an influence of erythropoietin on the success of anemia therapy in Chronic Kidney Disease (CKD) at Ulin Regional Hospital, Banjarmasin.

LEFT VENTRICULAR GEOMETRY AMONG CHRONIC KIDNEY DISEASE PATIENTS: THE ROLE OF ANEMIA

BACKGROUND: Anaemia and abnormal left ventricular (LV) geometric pattern are common findings in Chronic Kidney disease (CKD) patients.
 OBJECTIVES: To assess LV geometric pattern and its relationship with anaemia among CKD patients.
 METHODS: A cross sectional study of 163 subjects (102 and 61 CKD subjects with and without anaemia respectively). Echocardiography determined the LV geometric pattern while packed cell volume (PCV) levels determined anaemia.
 RESULTS: The mean age of subjects with and without anaemia was 54.04 ± 14.47 and 54.92 ± 15.67 years respectively (p = 0.717) while the prevalence of LVH among the two groups was 68.8% and 57.9% respectively (p = 0.174). The most frequent LV geometry in both groups was concentric LVH (53.8% and 43.9% respectively). Prevalence of LV systolic dysfunction was 45%, higher among anaemic subjects (58(61.7%) vs 10(17.5%)) p < 0.001. There was a strong negative correlation between PCV and left ventricular mass index (r = -0.345, p = 0.001) among anaemic subjects, but weak positive correlation among patients without anaemia (r = 0.001, p = 0.993).
 CONCLUSION: Anaemic CKD patients had a high prevalence of abnormal LV geometry with significant contribution from anaemia. Early management of anaemia may thus improve cardiovascular outcomes.

Effect of Recommended Dietary Intake versus Higher Doses of Supplemental Zinc on Iron and Copper Deficiency Anemia Among Patients with Chronic Kidney Diseases, A Double-Blinded, Randomized Clinical Trial

Background: Complex interplays happen in absorption and function of iron, zinc and copper. Both zinc deficiency and excess may lead to anemia. In Iran, commonly available supplements for chronic kidney disease (CKD) patients contain 25 mg-zinc (Zn). This study compared 25 mg versus 7.5 mg dose of zinc in anemia of CKD patients, the latter dose approximates to recommended dietary intake (RDI) of zinc. Methods: In this double-blinded clinical trial, 51 non-dialysis CKD patients were randomized to continue previous formulation (25 mg-Zn group) or change to a new preparation (7.5 mg-Zn group) for three months. Blood counts and serum iron, zinc and copper status were compared between and within the groups. Results: At the end of the study, serum copper and ceruloplasmin concentrations were significantly higher in 7.5 mg-Zn group compared with those in 25 mg-Zn arm (115.04± 23.05 vs. 102.48±14.98 µg/dL; P= 0.02 and 29.97±7.94 vs. 25.42±4.23 mg/dL; P= 0.01, respectively). Serum zinc levels did not differ between two groups (76.73±15.35 vs. 77.68±18.07 µg/dL for 7.5 mg-Zn and 25 mg-Zn groups, respectively; P= 0.84). After three months, patients in 7.5 mg-Zn group experienced increase in their Hb (11.11±1.17 vs. 10.72±1.03 g/dL; P= 0.04), HCT (35.28± 4.01 vs. 33.96± 3.74%; P= 0.03), MCV (86.30 (81.40-90.82) vs. 86.00 (80.35-88.77) ¦L; P= 0.01) and ferritin (202.60 (79.29-298.97) vs. 129.07 (42.25-225.87) ng/mL; P<0.001) compared to their baseline values. Conclusion: Reducing zinc content to its RDI value in supplement for CKD patients led to increased serum copper and ceruloplasmin concentrations. Moreover, patients who switched to RDI zinc-containing formula experienced a significant rise in blood hemoglobin. hematocrit, mean corpuscular volume (MCV), and ferritin concentration.

An Overview of Safety and Efficacy Between Hypoxia-Inducible Factor-Prolyl-Hydroxylase Inhibitors and Erythropoietin-Stimulating Agents in Treating Anemia in Chronic Kidney Disease Patients.

Anemia is one of the common complications in chronic kidney disease (CKD) patients. Erythropoietin and iron deficiencies are the major causes to develop anemia in CKD patients. Untreated anemia is associated with increased morbidity and mortality. Erythropoietin-stimulating agents (ESA) with iron supplementation are the standard for treating renal anemia. Although ESA with iron supplementation is an effective therapy in maintaining serum hemoglobin (Hb) levels, it increases the risk of several life-threatening adverse events such as hypertension, thromboembolism, cardiovascular morbidity, and mortality with long-term use. Therefore, effective alternate therapy with better safety and efficacy is needed to treat renal anemia. The newer oral therapy hypoxia-inducible factor-prolyl-hydroxylase inhibitors (HIF-PHI) can potentially be an effective alternative therapy in treating renal anemia. This review article compares the safety and efficacy between HIF-PHI and ESA in treating anemia in CKD patients. We conducted a comprehensive literature review of articles, including clinical trials, meta-analyses, and reviews, that compared the safety and efficacy between HIF-PHI and ESA. Studies have shown that the newer oral therapy, HIF-PHI, was non-inferior to ESA to maintain serum Hb levels in CKD patients. Moreover, the adverse event profile was almost similar in both groups. However, as the studies we reviewed have small sample sizes and short duration periods, the long-term effectiveness and safety of HIF-PHI over ESA in treating renal anemia cannot be established.

Prevalence and treatment of anemia in chronic kidney disease patients based on regional medical big data

Objective: To assess the prevalence, risk factors and treatment of anemia in patients with chronic kidney disease (CKD). Methods: A descriptive method was used to analyze the prevalence and treatment of anemia in CKD patients based on regional health data in Yinzhou District of Ningbo during 2012-2018. The multivariate logistic regression analysis was used to identify independent influence factors of anemia in the CKD patients. Results: In 52 619 CKD patients, 15 639 suffered from by anemia (29.72%), in whom 5 461 were men (26.41%) and 10 178 were women (31.87%), and anemia prevalence was higher in women than in men, the difference was significant (P<0.001). The prevalence of anemia increased with stage of CKD (24.77% in stage 1 vs. 69.42% in stage 5, trend χ2 test P<0.001). Multivariate logistic regression analysis revealed that being women (aOR=1.57, 95%CI: 1.50-1.63), CKD stage (stage 2: aOR=1.10, 95%CI: 1.04-1.16;stage 3: aOR=2.28,95%CI: 2.12-2.44;stage 4: aOR=4.49,95%CI :3.79-5.32;stage 5: aOR=6.31,95%CI: 4.74-8.39), age (18-30 years old: aOR=2.40,95%CI: 2.24-2.57, 61-75 years old: aOR=1.35,95%CI:1.28-1.42, ≥76 years old: aOR=2.37,95%CI:2.20-2.55), BMI (<18.5 kg/m2:aOR=1.29,95%CI: 1.18-1.41;23.0-24.9 kg/m2:aOR=0.79,95%CI: 0.75-0.83;≥25.0 kg/m2:aOR=0.70,95%CI: 0.66-0.74), abdominal obesity (aOR=0.91, 95%CI: 0.86-0.96), chronic obstructive pulmonary disease (aOR=1.15, 95%CI: 1.09-1.22), cancer (aOR=3.03, 95%CI: 2.84-3.23), heart failure (aOR=1.44, 95%CI: 1.35-1.54) and myocardial infarction (aOR=1.54, 95%CI:1.16-2.04) were independent risk factors of anemia in CKD patients. Among stage 3-5 CKD patients with anemia, 12.03% received iron therapy, and 4.78% received treatment with erythropoiesis-stimulating agent (ESA) within 12 months after anemia was diagnosed. Conclusions: The prevalence of anemia in CKD patients was high in Yinzhou. However, the treatment rate of iron therapy and ESA were low. More attention should be paid to the anemia management and treatment in CKD patients.

#4993 EFFECT OF ETELCALCETIDE TREATMENT ON ERYTHROPOIESIS-STIMULATING AGENTS (ESAS) REQUIREMENT IN HEMODIALYSIS PATIENTS: A SINGLE CENTER STUDY

Abstract Background and Aims Anemia is a common consequence of advanced chronic kidney disease (CKD). There are various causes of renal anemia like decreased production of and resistance to Erythropoietin, shortened survival of red blood cells and chronic blood loss. Secondary hyperparathyroidism is a potential cause of renal anemia in CKD patients due to direct effect on Erythropoietin synthesis, red cell survival and bone marrow fibrosis [1]. There are several reports of the beneficial effect of treatment of hyperparathyroidism on hemoglobin (Hb) levels. Etelcalcetide is a novel intravenous calcimimetic used for the treatment of secondary hyperparathyroidism in hemodialysis patients. However, there are very few reports of Etelcalcetide's effect on anemia management in hemodialysis patients. We aimed to study the effect of Etelcalcitide on ESAs requirement in our hemodialysis cohort. Method This is a retrospective study in Al Wakra Hospital hemodialysis unit conducted on patients with uncontrolled secondary hyperparathyroidism who needed to be started on Etelcalcetide. Mean Hb and mean ESAs dose were calculated for a period of 6 months before and 6 months after starting Etelcalcetide, while iPTH levels were measured at the beginning and 6 months after starting Etelcalcetide. Inclusion criteria: hemodialysis patients who are on Etelcalcetide for at least 6 months. Exclusion criteria: Patients’ age &amp;lt; 18 years, hemodialysis duration &amp;lt; 12 months and patients with acute blood loss. Results Out of 94 hemodialysis patients, 26 (27.6%) were on Etelcalcetide. 2 patients were excluded, one for acute hematuria and the other for erosive gastritis. 24 patients were included (13 females and 11 males). Mean age of the patients was 58.7 years. 15 patients were on Darbepoetin, 8 on Erythropoietin and 1 patient was switched from Darbepoetin to Erythropoietin due to poor response. There was no significant difference in mean Hb levels for all the patients before and after starting Etelcalcetide (10.6 g/dl and 10.8 g/dl, respectively). Out of 24 patients, 19 had reduction while 5 had increase in ESAs dose requirement. In total, the mean reduction of ESAs dose for all the patients was 17.3%. There was a mean of 33.4% reduction in ESAs requirement for the 19 patients while a mean of 44% increase in the requirement for the 5 patients. Mean iPTH for the cohort at the time of starting Etelcalcetide and 6 months after was 1036 pg/ml and 473 pg/ml respectively. The mean reduction of iPTH for those who had decreased ESAs requirement was 58% while it was 38.8% for those who had increased ESA requirement. Conclusion This study showed that control of severe secondary hyperparathyroidism with Etelcalcetide was associated with reduction in ESAs requirement in hemodialysis patients. The more the control of hyperparathyroidism, the more the reduction of ESAs requirement. These findings were observed also in a one case report [2]. We believe that our study has one of the largest number of patients to show such an observation, however larger controlled studies are needed to confirm these preliminary findings in the improvement of anemia after treatment of hyperparathyroidism by Etelcalcetide.

Relationships between blood bone metabolic biomarkers and anemia in patients with chronic kidney disease

Introduction Blood bone metabolic biomarkers are noninvasive indices for evaluating metabolic bone diseases. We investigated the relationships between blood bone metabolic biomarkers and anemia in chronic kidney disease (CKD) patients and analyzed the effects of parathyroidectomy (PTX) on the above indices. Methods In this cross-sectional study, 100 healthy controls and 239 CKD patients, including 46 secondary hyperparathyroidism (SHPT) patients with PTX, were enrolled. Moreover, a prospective study was conducted in which 28 PTX patients were followed up. The degree of anemia was classified as mild, moderate, or severe based on the tertiles of hemoglobin (Hb) levels of the anemic CKD patients, with cutoff values of 83 g/L and 102 g/L. Bone metabolic biomarkers, including calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23), and α-klotho, were tested. Results The mean estimated glomerular filtration rate (eGFR) in CKD patients was 25.7 ± 36.0 ml/min/1.73 m2, and 84.10% of CKD patients had anemia. The baseline Hb levels in the mild, moderate, and severe anemia subgroups were 110.86 ± 5.99 g/L, 92.71 ± 5.96 g/L, and 67.38 ± 10.56 g/L, respectively. CKD patients had higher adjusted Ca, P, alkaline phosphatase (ALP), iPTH, and FGF23 levels and lower α-klotho levels than controls. Baseline adjusted Ca, P, iPTH, and α-klotho levels were associated with Hb levels in CKD patients. Blood adjusted Ca, P, and iPTH levels were correlated with anemia severity. After PTX (median interval: 6.88 months), anemia and high blood adjusted Ca, P, iPTH, and FGF23 levels were ameliorated, while α-klotho levels were increased. Conclusions Blood adjusted Ca, P, iPTH, and α-klotho levels were correlated with Hb levels in CKD patients. Correction of bone metabolic disorders may be a therapeutic strategy for anemia treatment.

Prevalence of anemia in dialysis patients in Northwestern of Libya

Background. Chronic kidney disease (CKD) is renal dysfunction leads to failure in the body's ability to maintain metabolic, fluid electrolytes, and balance. It mostly results in uremia or azotemia and can be classified into stages 1 to 5 based on the deterioration of glomerular filtration rate (GFR. These complications lead to the deficiency of erythropoietin (EPO) possible iron loss in patients on hemodialysis are considered the main factors in contributing anemia in CKD patients.

The role of folic acid supplementation on lowering homocysteine level in chronic kidney disease

Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD) patients. Elevated homocysteine levels in CKD patients were thought to be one of the causes. Folic acid supplementation, which was known to improve anemia in CKD patients, can also reduce homocysteine levels, which would reduce cardiovascular events. In this review we will discuss the pathophysiology of hyperhomocysteinemia in CKD patients and studies that explain the role of folic acid to lower homocysteine levels that can also lower the risk of CVD in CKD patients. There are some conflicting results among available studies, but folic acid still seems reasonable to be considered as a suitable supplementary therapy in individuals with CKD after a thorough evaluation of the patient's folate status.

The impacts of hypoxia-inducible factor stabilizers on laboratory parameters and clinical outcomes in chronic kidney disease patients with renal anemia: a systematic review and meta-analysis.

Renal anemia in chronic kidney disease (CKD) is associated with poor outcomes. Hypoxia-inducible factor (HIF) stabilizer, which induces endogenous erythropoietin synthesis and enhances iron mobilization, is a novel treatment for anemia in CKD. We conducted a systematic review and meta-analysis to analyze the effect of HIF stabilizers in anemic CKD patients. This meta-analysis included 43 officially published articles and 3 unpublished studies (27 338 patients). HIF stabilizer treatment significantly increased hemoglobin (Hb) level when compared with placebo (mean difference 1.19g/dL; 95% confidence interval 0.94 to 1.44g/dL; P<.001). There was no significant difference in Hb level when compared with erythropoiesis-stimulating agents (ESAs). Significant reductions of ferritin and transferrin saturation (TSAT) were observed, while total iron-binding capacity was increased in the HIF stabilizer group compared with placebo or ESAs. HIF stabilizers significantly reduced hepcidin, high-density lipoprotein, low-density lipoprotein and triglyceride levels. Acute kidney injury and thrombotic events were significantly observed in patients receiving HIF stabilizers. There were no significant differences in myocardial infarction, stroke, dialysis initiation, pulmonary hypertension and mortality between HIF stabilizer and control groups. The present meta-analysis provided evidence that HIF stabilizers increased Hb and TIBC levels and reduced hepcidin, ferritin and TSAT in CKD patients with renal anemia. Long-term follow-up studies on clinical outcomes of HIF stabilizers are still needed.

Prevalence of Anemia in Chronic Kidney Disease (CKD) Patients on Conservative Treatment in Benghazi- 2022

Background: Anemia is one of the most common and significant complications of chronic kidney disease (CKD) which is related to decreases in the glomerular filtration rate (GFR). Anemia is generally defined as a hemoglobin count of less than 13.0 g/ld in men and less than 12.0 g/dL in premenopausal women. Anemia of CKD is of a multifactorial origin; the widely accepted etiology being decreased renal production of erythropoietin (EPO). Since the kidney's production of erythropoietin serves as the primary stimulus for the production of red blood cells, CKD patients have lower levels of erythropoietin, which in turn can cause anemia. Anaemia in CKD patients is normocytic, normochromic and hypoproliferative.&#x0D; Aim: Determination of proportion and risk factors of anemia in CKD patients.&#x0D; Materials and method: A cross-sectional sectional study with a sample size of 91 CKD patients on conservative treatment. A questionnaire was used to interview patients who had been enrolled in the study. It included sociodemographic data, body mass index (BMI), past medical history, drug history, and laboratory data. &#x0D; Results: The overall prevalence of anemia was 35.2% among CKD patients on conservative treatment. The mean age of patients was 62.9±14.65 SD years and the mean BMI was 27.65±5.5SD. Most of the patients were from the OPD clinic (GFR&gt;15 ml/min/1.73 m2). 60% of the patients were hypertensive and diabetic. Hemoglobin (HB) levels were 10.52 ± 2.7 SD. According to to mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), the type of anemia observed was normocytic and normochromic. Most of the patients were commonly prescribed an oral and an injectable iron supplement.&#x0D; Conclusion: Anemia was prevalent in CKD patients and the severity increased with the degree of renal damage; however, it is sub-optimally managed. Screening and management of anemia for patients with renal disease should focus more on patients with lower GFR.

Efficacy and Safety of Roxadustat in Patients with Chronic Kidney Disease: An Updated Meta-Analysis of Randomized Controlled Trials including 6,518 Patients.

Roxadustat is a newly listed oral hypoxia-inducible factor-proline enhancing enzyme inhibitor (HIF-PHI) in recent years. There have been some studies that have proved the efficacy of roxadustat on the treatment of renal anemia in patients with chronic kidney disease (CKD), but there are still different conclusions on its safety. PubMed, Embase, Cochrane, and ClinicalTrials were searched for randomized controlled trials (RCTs) that assess efficacy and safety of roxadustat treatment for anemia in CKD patients. The Cochrane Literature Quality Evaluation Scale was used to evaluate the quality of included literature. We choose fixed-effects model or random effects model for data processing based on heterogeneity. It was considered statistically significant when p value <0.05. A total of 842 articles were retrieved, and 16 trials in the 15 articles were finally included. Roxadustat treatment significantly increased Hb levels. Iron (SMD 1.43, 95% CI 0.31 to 2.55), total iron-binding capacity (SMD 2.06, 95% CI 0.91 to 3.22), ferritin (WMD 21.33, 95% CI 3.04 to 39.62), transferrin saturation (SMD 4.17, 95% CI 3.90 to 4.45), and LDL-cholesterol (SMD -0.64, 95% CI -0.73 to -0.55) showed statistical significance in dialysis-dependent (DD) study. And hepcidin (SMD -1.56, 95% CI -2.63 to -0.50), transferrin (SMD 1.80, 95% CI 1.53 to 2.06), total iron-binding capacity (SMD 1.62, 95% CI 1.39 to 1.86), total cholesterol (SMD -0.88, 95% CI -1.68 to -0.09), ferritin (WMD -52.68, 95% CI -62.68 to -42.67), transferrin saturation (SMD -5.57, 95% CI -7.47 to -3.68), and LDL-cholesterol (SMD -0.85, 95% CI -1.37 to -0.34) showed statistical significance in not dialysis-dependent (NDD) study. In terms of safety, roxadustat treatment did not increase risk of total adverse events either in dialysis-dependent or not dialysis-dependent patients. Roxadustat can effectively improve anemia in patients with chronic kidney disease. There was no significant difference in total adverse events compared with the control group.

Role of prolyl hydroxylase/HIF-1 signaling in vascular calcification.

Morbidity and mortality of chronic kidney disease (CKD) patients are largely associated with vascular calcification, an actively regulated process in which vascular smooth muscle cells (VSMCs) change into cells similar to osteocytes/chondrocytes, known as trans-differentiation. Cellular and systemic response to low oxygen (hypoxia) is regulated by the prolyl hydroxylase/hypoxia-inducible factor (HIF)-1 pathway. Recent studies highlighted that hypoxia-mediated activation of HIF-1 induces trans-differentiation of VSMCs into bone-forming type through an increase in osteo-/chondrogenic genes. Inhibition of the HIF-1 pathway abolished osteochondrogenic differentiation of VSMCs. Hypoxia strongly enhanced elevated phosphate-induced VSMC osteogenic trans-differentiation and calcification. HIF-1 was shown to be essential for phosphate enhanced VSMC calcification. O2-dependent degradation HIF-1 is triggered by the prolyl hydroxylase domain proteins (PHD). Prolyl hydroxylase inhibitors, daprodustat and roxadustat, increase high phosphate-induced VC in VSMCs, stabilizing HIF-1α and activating the HIF-1 pathway in these cells. Whether the use of these PHD inhibitors to treat anemia in CKD patients will favor the development and progression of vascular calcification remains to be explored.

FREQUENCY OF IRON DEFICIENCY ANEMIA IN NON-DIALYSIS CHRONIC KIDNEY PATIENTS

Background: Iron deficiency anemia (IDA) is the most common type of anemia. In chronic kidney disease (CKD) patients, it’s a significant burden and becomes more prevalent with decreasing GFR. Though, erythropoietin deficiency remains the major cause of anemia in CKD patients due to decreased renal erythropoietin production, yet the frequency of IDA in pre-dialysis CKD patients has not been well established in Pakistan. Objective: To determine the frequency of IDA in pre-dialysis CKD patients. Materials and Methods: 188 pre-dialysis CKD patients of age 18-75 and both genders were included. Patients having obvious causes of anemia were excluded. The percentage of patients with IDA in pre-dialysis CKD was then determined during OPD follow up. Results: Mean age was 46.03±12.24 years. Out of 188 patients, 102 (54.26%) were males with male-female ratio of 1.2:1. The frequency of IDA in pre-dialysis CKD patients was found in 73 (38.83%) patients. Conclusion: Study concluded that frequency of IDA in pre-dialysis CKD patients is high and close attention to the causes and its replacement may improve the patient outcome. Keywords: CKD, Pre-dialysis , IDA, anemia

Hypoxia-Inducible Factors and Diabetic Kidney Disease-How Deep Can We Go?

Diabetes is one of the leading causes of chronic kidney disease (CKD), and multiple underlying mechanisms involved in pathogenesis of diabetic nephropathy (DN) have been described. Although various treatments and diagnosis applications are available, DN remains a clinical and economic burden, considering that about 40% of type 2 diabetes patients will develop nephropathy. In the past years, some research found that hypoxia response and hypoxia-inducible factors (HIFs) play critical roles in the pathogenesis of DN. Hypoxia-inducible factors (HIFs) HIF-1, HIF-2, and HIF-3 are the main mediators of metabolic responses to the state of hypoxia, which seems to be the one of the earliest events in the occurrence and progression of diabetic kidney disease (DKD). The abnormal activity of HIFs seems to be of crucial importance in the pathogenesis of diseases, including nephropathies. Studies using transcriptome analysis confirmed by metabolome analysis revealed that HIF stabilizers (HIF-prolyl hydroxylase inhibitors) are novel therapeutic agents used to treat anemia in CKD patients that not only increase endogenous erythropoietin production, but also could act by counteracting the metabolic alterations in incipient diabetic kidney disease and relieve oxidative stress in the renal tissue. In this review, we present the newest data regarding hypoxia response and HIF involvement in the pathogenesis of diabetic nephropathy and new therapeutic insights, starting from improving kidney oxygen homeostasis.

Indoxyl sulfate impairs in vitro erythropoiesis by triggering apoptosis and senescence.

Anemia is a major complication in over 50% of chronic kidney disease (CKD) patients. One of the main causes of anemia in CKD is the reduction of erythropoietin (EPO) synthesis from renal tubular cells. Therefore, first-line treatment of CKD is EPO administration; however, EPO unresponsiveness in several patients is frequently found. More undefined causes of anemia in CKD are under interest, especially uremic toxins, which are a group of solutes accumulated in CKD patients. The highly detectable protein-bound uremic toxin, indoxyl sulfate (IS) was investigated for its effects on in vitro erythropoiesis in this study. CD34+ hematopoietic stem cells were isolated from human umbilical cord blood and differentiated toward erythrocyte lineage for 14 days in various concentrations of IS (12.5, 25, 50, and 100 µg/mL). The effects of IS on cell proliferation, differentiation, apoptosis, and senescence were determined. Cell proliferation was investigated by manual cell counting. Cell surface marker expression was analyzed by flow cytometry. Wright's staining was performed to evaluate cell differentiation capacity. Apoptosis and senescence marker expression was measured using reverse transcription polymerase chain reaction (RT-PCR). TUNEL assay was performed to detect apoptotic DNA fragmentation. Our results demonstrated that IS reduced cell proliferation and impaired erythrocyte differentiation capacity. In addition, this study confirmed the effects of IS on cell apoptosis and senescence during erythropoietic differentiation. Therefore, the promotion of apoptosis and senescence might be one of the possible mechanisms caused by uremic toxin accumulation leading to anemia in CKD patients.