Diabetes mellitus increases the prevalence of anemia in patients with chronic kidney disease:A nested case-control study

AIM: To compare anemia prevalence between matched chronic kidney disease(CKD) patients with and without diabetes mellitus(DM) and to assess factors associated with anemia development.METHODS: This is a nested case-control study of 184 type-2 diabetic and 184 non-diabetic CKD patients from a prospectively assembled database of a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate(eG FR). Prevalence of anemia(hemoglobin: Men: < 13 g/dL, women: < 12 g/dL and/or use of recombinant erythropoietin) was examined in comparison, in the total population and by CKD Stage. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with anemia.RESULTS: The total prevalence of anemia was higher in diabetics(47.8% vs 33.2%, P = 0.004). Accordingly, prevalence was higher in diabetics in CKD Stage 3(53.5% vs 33.1%, P < 0.001) and particularly in Stage 3a(60.4% vs 26.4%, P < 0.001), whereas it was nonsignificantly higher in Stage 4(61.3% vs 48.4%; P = 0.307). Serum ferritin was higher in diabetics in total and in CKD stages, while serum iron was similar between groups. In multivariate analyses, DM(OR = 2.206, 95%CI: 1.196-4.069), CKD Stages 3a, 3b, 4(Stage 4: OR = 12.169, 95%CI: 3.783-39.147) and serum iron(OR = 0.976, 95%CI: 0.968-0.985 per mg/d L increase) were independently associated with anemia.CONCLUSION: Prevalence of anemia progressively increases with advancing stages of CKD and is higher in diabetic than matched non-diabetic CKD patients and diabetes is independently associated with anemia occurrence. Detection and treatment of anemia in diabetic CKD patients should be performed earlier than non-diabetic counterparts.

Effects of hypoxia on bone metabolism and anemia in patients with chronic kidney disease

BACKGROUND Abnormal bone metabolism and renal anemia seriously affect the prognosis of patients with chronic kidney disease(CKD).Existing studies have mostly addressed the pathogenesis and treatment of bone metabolism abnormality and anemia in patients with CKD,but few have evaluated their mutual connection.Administration of exogenous erythropoietin to CKD patients with anemia used to be the mainstay of therapeutic approaches;however,with the availability of hypoxia-inducible factor(HIF)stabilizers such as roxadustat,more therapeutic choices for renal anemia are expected in the future.However,the effects posed by the hypoxic environment on both CKD complications remain incompletely understood.AIM To summarize the relationship between renal anemia and abnormal bone metabolism,and to discuss the influence of hypoxia on bone metabolism.METHODS CNKI and PubMed searches were performed using the key words“chronic kidney disease,”“abnormal bone metabolism,”“anemia,”“hypoxia,”and“HIF”to identify relevant articles published in multiple languages and fields.Reference lists from identified articles were reviewed to extract additional pertinent articles.Then we retrieved the Abstract and Introduction and searched the results from the literature,classified the extracted information,and summarized important information.Finally,we made our own conclusions.RESULTS There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Abnormal vitamin D metabolism and hyperparathyroidism can affect bone metabolism,blood cell production,and survival rates through multiple pathways.Anemia will further attenuate the normal bone growth.The hypoxic environment regulates bone morphogenetic protein,vascular endothelial growth factor,and neuropilin-1,and affects osteoblast/osteoclast maturation and differentiation through bone metabolic changes.Hypoxia preconditioning of mesenchymal stem cells(MSCs)can enhance their paracrine effects and promote fracture healing.Concurrently,hypoxia reduces the inhibitory effect on osteocyte differentiation by inhibiting the expression of fibroblast growth factor 23.Hypoxia potentially improves bone metabolism,but it still carries potential risks.The optimal concentration and duration of hypoxia remain unclear.CONCLUSION There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Hypoxia may improve bone metabolism but the concentration and duration of hypoxia remain unclear and need further study.

Anemia treatment and left ventricular hypertrophy in non-dialysis chronic kidney disease

To this day, the target hemoglobin level that minimizes cardiovascular risk in chronic kidney disease (CKD) patients remains unclear. When one examines the many randomized trials of epoetin therapy in aggregate, enhanced quality of life provides the most cogent argument for hemoglobin levels above 110 g/L. It remains unclear whether treatment of anemia improves longevity, or even a surrogate marker (such as left ventricular [LV] mass index), especially when applied at earlier phases of CKD.

Sickle Cell Trait, Hemoglobin Levels and Anemia among Black Patients with Predialysis Chronic Kidney Disease: A Post Hoc Analysis

Objective: To assess the relationship between SCT, hemoglobin levels and anemia in CKD black patients. Method: A post-hoc analysis of data from 188 patients, enrolled in a cross-sectional study of sickle cell trait (SCT) and chronic kidney disease (CKD), was performed to assess the relationship between SCT, hemoglobin (Hb) levels and anemia defined as Hb < 12 g/dl in men and <11 g/dl in women. Student t test, Mann Whitney and Chi square test were used as appropriate for different comparisons. P < 0.05 defined the level of statistical significance. Results: SCT (HbAS) and normal hemoglobin (HbAA) were present in 39 (21%) and 149 (79%) CKD patients, respectively. Despite similar estimated GFR (eGFR) and age, HbAS patients had significantly lower Hb levels (8.8 ± 1.8 vs 10 ± 2.2 g/dl;p = 0.001) and a higher proportion of anemia (95% vs 72%, p = 0.001). In multiple linear regression analysis, eGFR, BMI, SBP and SCT emerged as independent determinants of Hb levels. The presence of SCT was associated with 1.185 g/dl decrease in Hb levels. Conclusion: In the present case series, SCT was associated with lower Hb levels suggesting its potential contribution to the pathogenesis of CKD-associated anemia.

Assessment of Patient Perceptions about Use of Wepox Pen^TM(Recombinant Erythropoietin Delivery Device with 30,000 IU Cartridge) in the Management of Anemia in Chronic Kidney Disease Patients

Objective: To assess perceptions about ease of use and other benefits of Wepox PenTM (loaded with 30,000 IU cartridge of recombinant erythropoietin) in the management of anemia in adult chronic kidney disease (CKD) patients. Material and methods: In this prospective, observational, multicentric post marketing surveillance, adult CKD patients treated with erythropoietin were enrolled from November 2015 to December 2016 to understand their opinions about Wepox PenTM. Ease of use of pen, ease of administering accurate dose, confidence in administration and ease of storage and disposal of cartridge were assessed on five points Likert scale: 1. very easy;2. somewhat easy;3. neither easy nor difficult;4. somewhat difficult;5. very difficult. Global assessment was performed on five points scale: 1. excellent;2. very good;3. good;4. average;5. not good. Safety was recorded by checking pain and discomfort and adverse events. Results: A total of 263 patients (mean age 32.87 years;66% male;34% female) were enrolled. Number of patients reporting ease of use as “very easy” from 209 (80.7%) at baseline increased to 245 (94.6%) and 249 (96.1%) at visit 2 (p = 0.001) and visit 3 (p = 0.001) respectively. Number of “very easy” response for accurate dose increased from 236 (91.1%) at visit 1 to 246 (95%) at visit 2 (p = 0.84) and 249 (96.1%) at visit 3 (p = 0.001). Number of the patients with “no pain” at injection site increased from 177 (68.3%) at visit 1 to 205 (79.2%) and 212 (81.9%) at visit 2 (p = 0.001) and visit 3 (p = 0.001) respectively. Improvement in number of patients with “no hurt” at visit 2 (p = 0.538) and visit 3 (p = 0.286) was not statistically significant. Number of patients reporting “somewhat easy” to “very easy” confidence in self injection increased from 251 (96.9%) at visit 2 to 255 (98.5%) at visit 3. Number of patients reporting ease of storage and disposal of cartridge as “somewhat easy” to “very easy” increased from 254 (98.1%) at visit 2 to 256 (98.9%) at visit 3. According to the global assessment, 144 (56.3%) cases reported “excellent” response. “Very good” and “Good” responses were reported by 106 (41.4%) and 6 (2.3%) patients respectively. A total of 230 (98.7%) patients said that they would prefer to use erythropoietin pen device for further treatment too. Conclusion: Wepox PenTM(recombinant erythropoietin) is easy to use and does not cause significant pain or discomfort. Ability to self-administer recombinant erythropoietin with Wepox PenTM is a great advantage which can make a significant difference for both CKD patients and doctors. Storage and disposal of cartridge is also easy.

Hyperuricemia in Hypertension and Chronic Kidney Disease: Risk Factors, Prevalence and Clinical Correlates: A Descriptive Comparative Study

Introduction: Uric acid is a product of purine metabolism and elevated serum concentration are very common in, and linked with hypertension and chronic kidney disease, conditions associated with heavy health burden and cardiovascular complications particularly in sub Sahara Africa. An assessment of factors relating hyperuricemia to hypertension and chronic kidney disease would therefore be necessary as way of mitigating the poor quality of life, morbidity and mortality associated with these diseases in low income nations. Methods: A single centre, descriptive comparative study in which the demographic, clinical and laboratory data of hypertensive and non-dialyzed chronic kidney disease (CKD) patients were analyzed. Serum biochemical parameters with uric acid, hematocrit and urine dip strip protein were assessed. Predictors of hyperuricemia were determined using multivariate analysis. Results: One hundred and thirty nine hypertensives and 69 CKD were studied. The mean age of the participants was 54.3 ± 11.7 years, hypertensives (52.9 ± 15.7 years) and CKD (57.3 ± 16.1 years). Both groups had more males, P = 0.8. Majority (78.3%) of the CKD cohorts had stage 4 or 5 (non-dialyzed) disease. The systolic and diastolic blood pressure, creatinine and uric acid were lower in hypertension than in CKD, P = 0.07, P = 0.05, P < 0.001 and P = 0.004 respectively. The hematocrit, albumin and GFR were higher in HTN than CKD, P < 0.001, P < 0.001 and P < 0.001 respectively. The prevalence of hyperuricemia was 56.2%. The mean uric acid was 505.9 ± 23.6 mmol/L, 382 7 ± 10.5 mmol/L for hypertensive and 755.9 ± 14.8 mmol/L for CKD, P < 0.001. The prevalence of systolic HTN, proteinuria, hypoalbuminemia and anemia were 51%, 75%, 46% and 59%, and were higher in males. Hyperuricemia was related to advancing age, proteinuria, elevated creatinine, hypoalbuminemia, anemia and hypertriglyceridemia. Proteinuria (OR—4.66, 95% CI—2.42 - 9.65), elevated creatinine (OR—3.12, 95% CI—2.40 - 6.92), hypoalbuminemia (OR—2.92, 95% CI—1.83 - 5.78) and anemia (OR—4.01, 95% CI—3.78 - 7.99) independently predicted hyperuricemia. Conclusion: Hyperuricemia is commoner in CKD than hypertension and was higher in males and positively correlated with the blood pressure, proteinuria and creatinine, but negatively related to hematocrit, albumin and glomerular filtration rate. Independent predictors of hyperuricemia were proteinuria, elevated creatinine, hypoalbuminemia and anemia. Measures are needed to prevent and treat hyperuricemia to reduce the health burden associated with hypertension and CKD.

Parathyroid Hormone as a Marker for the Red Cell Fragility in Different Stages of Chronic Kidney Disease

Objective: The aim of the work is to study the relationship between Red blood cell osmotic fragility and level of parathyroid hormone in patients with different stages of Chronic Kidney Disease including End Stage Renal Disease. Background: Anaemia is one of the common complications associated with Chronic Kidney Disease (CKD) responsible for the increase in the morbidity and mortality in such patients. Several factors have been attributed to causing renal anaemia, amongst which hyperparathyroidism is one of the less recognised reasons. The level of PTH in early stages of chronic kidney disease has not been much studied. The excess amount of Parathyroid Hormone (PTH) secondary to CKD has been suggested to be a causative factor for anaemia. Method: A number of chronic kidney disease patients were studied for the relationship between Red cell osmotic fragility and level of parathyroid hormone. Results: This study was conducted on a number of 111 patients with chronic kidney disease classified into three groups. The study revealed a significant fall in Hb%, along with a rise in Median Osmotic Fragility (MOF) and PTH in the CKD patients. iPTH and MOF were significantly lower in group 3 as compared with cases in group 1. Also, iPTH and MOF were significantly lower in cases in group 2 as compared with cases in group 1. Conclusions: Based on our findings, secondary hyperparathyroidism has considerable effects on erythrocyte survival, contributing to increased fragility and anemia.

Efficacy and safety of recombinant human erythropoietin(Hema-Plus®)for management of anemia in Thai patients on peritoneal dialysis

BACKGROUND Hema-Plus,a recombinant human erythropoietin(rHuEPO)or epoetin alfa has shown effectiveness in correction of anemia in Thai population in clinical practice.This study was aimed to demonstrate efficacy and safety under the evidencebased approach.AIM To evaluate the efficacy and safety of rHuEPO(Hema-Plus)for treatment of anemia over 12 wk in Thai patients with Stage V chronic kidney disease(CKD)on peritoneal dialysis(PD).METHODS This study was an open-label,multi-center study to enroll 30 CKD patients identified to start PD with hemoglobin(Hb)less than 9.5 g/dL,serum ferritin more than 100 ng/mL,serum transferrin saturation more than or equal to 20%and who had not previously received epoetin.Patients with conditions that could increase the risk of adverse effects from study participation or interfere with study outcomes,were using concomitant androgens or had secondary hyperparathyroidism were excluded.All eligible patients started Hema-Plus by SC injection at 4000 IU once or twice weekly(week 0)and with follow-up at weeks 2,4,8,and 12.Dosage adjustment could be done to achieve Hb level of 11-12 g/dL.Primary end point was mean change in Hb level from baseline to end of treatment(week 12).Safety was assessed throughout the study.Quality of life(QoL)was assessed using KDQOL-36.RESULTS All 30 enrolled patients completed the study.Mean(standard deviation)Hb at baseline(week 0)to the end of 12 wk was significantly increased from 7.39(1.29)g/dL to 11.15(1.73)g/dL(paired t-test,P value<0.001).Overall change of Hb means from baseline over the other 4 visits was statistically significantly increased(repeated measure ANOVA,P value<0.001).Ten out of 39 adverse events(AEs)were serious.Two serious AEs were probably related to study medication by investigators’assessment.At week 12,the QoL scores in all domains were significantly increased from baseline.CONCLUSION Hema-Plus administered for 12 wk for treatment of anemia in patients on PD effectively increased Hb levels with acceptable safety profile.

Roxadustat as treatment for a blood transfusion-dependent maintenance hemodialysis patient:A case report and review of literature

BACKGROUND Erythropoiesis-stimulating agents(ESAs)have revolutionized the therapeutic strategy for anemia in chronic kidney disease.However,some cases are resistant or hyporesponsive to ESAs.Roxadustat is an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism.Here,we describe a hemodialysis patient with refractory anemia who did not respond to traditional treatments and depended on blood transfusion for more than 1 year.After applying Roxadustat,the patient’s anemia improved significantly.CASE SUMMARY A 44-year-old man was diagnosed with uremia accompanied by severe anemia with a hemoglobin(Hb)level ranging from 30-40 g/L.His anemia did not improve after sufficient dialysis or high doses of active ESAs;other causes of anemia were excluded.The patient required approximately 600-1000 mL of red blood cell suspension every 15-30 d for more than 1 year.After accepting Roxadustat therapy,the patient’s anemia symptoms improved significantly;his Hb level gradually increased to 50 g/L,and no further blood transfusions were administered.His Hb level reached 69 g/L by the 34th week.Although a Hb level of 60-70 g/L cannot be considered satisfactory,he no longer required blood transfusions and his quality of life was substantially improved.Roxadustat showed good efficacy and safety in this case.CONCLUSION Roxadustat represents an innovative and effective agent for the clinical treatment of renal anemia caused by multiple complex factors.

Response to roxadustat in a patient undergoing long-term dialysis and allergic to erythropoiesis-stimulating agents:A case report

BACKGROUND Hypoxia-inducible factor prolyl hydroxylase inhibitor is a new class of drugs for treating renal anemia.It is a second-generation hypoxia-inducible factor prolyl hydroxylase-2(PHD2)inhibitor.Roxadustat can effectively increase hemoglobin in patients with dialysis-dependent chronic kidney disease,with an adverse events profile comparable to that of epoetin alfa.We administered roxadustat to a maintenance hemodialysis patient who was allergic to erythropoiesis-stimulating agents(ESAs)and depended on blood transfusion for five years.After applying Roxadustat,the patient’s anemia improved significantly.CASE SUMMARY A 77-year-old Chinese man had type 2 diabetes for 16 years,underwent maintenance hemodialysis for five years,and had fatigue for five years.Laboratory tests showed severe anemia(hemoglobin concentration of 42 g/L).The patient was administered a subcutaneous injection of ESAs before dialysis.He suffered an allergic shock immediately and fainted.His blood pressure dropped to undetectable levels.He was not administered ESAs henceforth.The patient was prescribed iron supplements and received blood transfusions occasionally for five years.His hemoglobin concentration ranged from 42-68 g/L.After taking six weeks of oral roxadustat three times weekly(100 mg TIW),the patient’s hemoglobin concentration increased significantly,and his symptoms decreased.We adjusted the doses of roxadustat,and the hemoglobin concentration was maintained between 97 and 126 g/L.CONCLUSION Oral roxadustat is effective in treating anemia in maintenance hemodialysis patients who cannot be administered ESAs.

Pharmacological Adjuvants to Limit Erythropoietin Stimulating Agents Exposure

Anemia in chronic kidney disease (CKD) is common, causing morbidity and mortality, and is primarily due to reduced erythropoietin (EPO) release and, to a lesser degree, shortened red cell survival. Erythropoietin Stimulating Agents like epoetin Alfa and darbepoetin alpha are used commonly to treat this form of anemia. Recent evidence suggests increased morbidity and mortality associated with higher hemoglobin in the setting of these agents use. Whether these complications are due to higher dose of erythropoietin or its resistance (i.e. inflammation), or achieving a higher hemoglobin remains unclear. Tightening restrictions on these agents has led to increase interest in the use of non-ESA adjuvants to improve erythropoiesis. This review will highlight the most promising of these agents.

Benefits and risks of erythrocyte-stimulating agents

Chronic kidney disease(CKD)is a common and serious clinical problem.Anemia in patients with advanced CKD,frequently called renal anemia,causes disabling fatigue and diminishes patients’quality of life.Frequent and excess transfusions or iron supplementation are potentially hazardous.Although it remains unclear whether the main factor in the development of renal anemia is the failure of erythropoietin(EPO)production in the kidney or a dysfunction in oxygen sensing exogenous EPO administration is considered a rational treatment.The advent of recombinant human erythropoietin(r Hu-EPO)products has dramatically changed the therapeutic strategy for renal anemia.Although rH u-EPO therapy has improved patients’quality of life and decreased the need for blood transfusions,some potential adverse effects have been reported till date.This brief review discusses the treatment of renal anemia with regard to the following:(1)historical background;(2)effectiveness of r Hu-EPO;(3)some topics regarding the treatment of anemia,including EPO resistance,hemoglobin(Hb)cycling,and adequate Hb levels;(4)major adverse effects of rH u-EPO,including hypertension,thrombotic complications,and pure red cell aplasia;and(5)future problems to be resolved.