A case report on congenital hypothyroidism and alpha thalassemia in children with anemia and muscle damage as the main manifestation.

RATIONALE: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. PATIENT CONCERNS: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. DIAGNOSES: The child was diagnosed with CH with alpha thalassemia. INTERVENTIONS: The patient was treated with levothyroxine sodium and anemia correction. OUTCOMES: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CONCLUSIONS: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. LESSON: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.

The clinical efficacy of combined ESA and Roxadustat treatment for renal anemia in hemodialysis patients with secondary hyperparathyroidism: A case series.

RATIONALE: Pharmacological mechanism of Roxadustat in the treatment of renal anemia. PATIENT CONCERNS: To investigate the efficacy and safety of combined Roxadustat and erythropoiesis stimulator (ESA) treatment of renal anemia in hemodialysis patients with secondary hyperparathyroidism. DIAGNOSES: A retrospective analysis was conducted on hemodialysis patients with renal anemia and secondary hyperparathyroidism treated with ESAs alone, who were admitted to our hospital from March 2022 to December 2022. INTERVENTIONS: The patients were treated with Roxadustat combined with ESAs for 3 months, during which oral iron supplementation was given, and the changes in Hb levels and laboratory-related indicators before and after the combined treatment were analyzed. OUTCOMES: The results showed that a total of 13 patients received combination therapy, with a significant increase in Hb compared to ESAs alone (t = -3.955, P = .002). The Hb qualification rate was 38.46%, and the ∆Hb response rate was 76.92%. The parathyroid hormone significantly decreased with a statistically significant difference (Z = -2.062b, P = .039). Hemoglobin (RBC), total iron binding capacity, and serum ferritin (male) were significantly increased compared to ESAs alone. Total cholesterol and low-density lipoprotein were significantly lower than ESAs alone. The differences in the changes in the above indicators were statistically significant (P < .05). There was no statistically significant difference in changes in other laboratory-related indicators (P > .05). No adverse reactions were observed during the combined treatment of 13 patients. LESSONS SUBSECTIONS: The combination of Roxadustat and ESAs can effectively improve renal anemia in hemodialysis patients with secondary hyperparathyroidism, as well as improve indicators of hyperparathyroidism and blood lipid levels with high levels of safety. This combined treatment thus provides a new and safe treatment method for these patients.

A real-world analysis of roxadustat effectiveness and safety in managing renal anemia among patients on maintenance hemodialysis: An observational study.

We aimed to compare the clinical efficacy and safety of roxadustat with erythropoiesis-stimulating agents, particularly erythropoietin (EPO), in the treatment of maintenance hemodialysis patients with renal anemia. A prospective cohort study was carried out at the Nephrology Department of the Nantong First People's Hospital and Nantong University Affiliated Hospital from December 2020 to December 2021. We compared hemoglobin (Hb) levels, serum ferritin (SF) levels, and adverse cardiovascular events between the roxadustat and EPO groups at 1, 3, and 6 months into the treatment. A total of 209 patients participated in the study, with 112 in the roxadustat group and 97 in the EPO group. At baseline, no statistically significant differences were observed between the 2 groups in terms of age, gender, weight, dialysis modality and duration, previous EPO dosage, Hb levels, SF levels, transferrin saturation, heart function classification, and blood pressure levels (P > .05). After 1 month, Hb levels in the roxadustat group were significantly higher than those in the EPO group (P < .05). However, no statistically significant differences were found between the 2 groups at 3 and 6 months (P > .05). Additionally, there were no significant differences in SF levels and the occurrence of adverse cardiovascular events between the 2 groups after treatment (P > .05). Roxadustat was superior to EPO in the initial treatment phase, while its cardiovascular safety was comparable to that of EPO.

The effect of erythropoiesis­stimulating agents on lung cancer patients: a meta­analysis.

Previous studies have demonstrated that erythropoiesis-stimulating agents (ESAs) can reduce anemia and improve quality of life in cancer patients, but ESAs may increase mortality. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) comparing the effect and risk of ESAs about the prevention or treatment of anemia in cancer patients. Four databases including PubMed, Embase, Web of science and Cochrane Library were searched for published RCTS on ESAs in the treatment of anemia in lung cancer patients from 2000 to 2023. Endpoints including mortality, incidence of thrombotic vascular events, blood transfusion requirement, and incidence of adverse events. Our meta-analysis included 8 studies, with a sample size of 4240 patients, including 2548 patients in the ESAs group and 1692 patients in the control group. The risk of mortality was lower in patients using ESAs than control group (RR 0.96, 95% CI 0.92-0.99, P = 0.02). But there was no significant difference in the risk of mortality between the patients using ESAs and controls (RR 0.99, 95% CI 0.92-1.06, P = 0.69) after removing Pere 2020. Subgroup analysis found that patients diagnosed with small cell lung cancer (SCLC) (RR 1.00, 95% CI 0.92-1.08, P = 0.16) or non-small cell lung cancer (NSCLC) (RR 1.01, 95% CI 0.87-1.17, P = 0.13) were no significant difference in mortality rate. The thrombotic vascular events increase in patients using ESAs than control group (RR 1.40, 95% CI 1.13-1.72, P = 0.002). The blood transfusion requirement of ESAs group was lower than control group (RR 0.56, 95% CI 0.44-0.72, P < 0.00001). And the subgroups of Darbepoetin alfa (RR 0.57, 95% CI 0.41-0.79, P = 0.003) and Epoetin alfa (RR 0.68, 95% CI 0.47-0.99, P = 0.01) had lower transfusion requirements than the control group. In the SCLC subgroup (RR 0.51, 95% CI 0.40-0.65, P = 0.34), blood transfusion requirements were lower in the ESAs group, but there was no significant difference between the subgroup of patients with NSCLC (RR 0.61, 95% CI 0.36-1.04, P = 0.009). There was no statistically significant difference between the two groups in the incidence of adverse reactions (RR 0.98, 95% CI 0.95-1.00, P = 0.10). In conclusion, ESAs does not increase the mortality of lung cancer patients or may reduce the risk of death, and can reduce the need for blood transfusion, although ESA can increase the incidence of thrombotic vascular adverse events.Registration PROSPERO CRD42023463582.

Treatment of Anemia Associated with Chronic Kidney Disease: Plea for Considering Physiological Erythropoiesis.

Traditionally, the treatment of anemia associated with chronic kidney disease (CKD) involves prescribing erythropoiesis-stimulating agents (ESAs) or iron preparations. The effectiveness and safety of ESAs and iron have been established. However, several clinical issues, such as hyporesponsiveness to ESAs or defective iron utilization for erythropoiesis, have been demonstrated. Recently, a new class of therapeutics for renal anemia known as hypoxia-inducible factor (HIF)/proline hydroxylase (PH) inhibitors has been developed. Several studies have reported that HIF-PH inhibitors have unique characteristics compared with those of ESAs. In particular, the use of HIF-PH inhibitors may maintain target Hb concentration in patients treated with a high dose of ESAs without increasing the dose. Furthermore, several recent studies have demonstrated that patients with CKD with defective iron utilization for erythropoiesis had a high risk of cardiovascular events or premature death. HIF-PH inhibitors increase iron transport and absorption from the gastrointestinal tract; thus, they may ameliorate defective iron utilization for erythropoiesis in patients with CKD. Conversely, several clinical problems, such as aggravation of thrombotic and embolic complications, diabetic retinal disease, and cancer, have been noted at the time of HIF-PH inhibitor administration. Recently, several pooled analyses of phase III trials have reported the non-inferiority of HIF-PH inhibitors regarding these clinical concerns compared with ESAs. The advantages and issues of anemia treatment by ESAs, iron preparations, and HIF-PH inhibitors must be fully understood. Moreover, patients with anemia and CKD should be treated by providing a physiological erythropoiesis environment that is similar to that of healthy individuals.

Short-term effect of low-dose roxadustat combined with erythropoiesis-stimulating agent treatment for erythropoietin-resistant anemia in patients undergoing maintenance hemodialysis.

Background: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week). Methods: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO. Results: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased. Conclusion: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.

Discovery of DS-1093a: An oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of renal anemia.

Inhibition of the hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) represents a promising strategy for discovering next-generation treatments for renal anemia. We discovered DS44470011 in our previous study, which showed potent in vitro activity and in vivo efficacy based on HIF-PHD inhibition. However, DS44470011 was also found to exert genotoxic effects. By converting the biphenyl structure, which is suspected to be the cause of this genotoxicity, to a 1-phenylpiperidine structure, we were able to avoid genotoxicity and further improve the in vitro activity and in vivo efficacy. Furthermore, through the optimization of pyrimidine derivatives, we discovered DS-1093a, which has a wide safety margin with potent in vitro activity and an optimal pharmacokinetic profile. DS-1093a achieved an increase in hemoglobin levels in an adenine-induced rat model of chronic kidney disease after its continuous administration for 4 days.

Targeting HIF-2α and anemia: A therapeutic breakthrough for clear-cell renal cell carcinoma.

Renal cell carcinoma (RCC) is a heterogenous disease which the incidence is increasing worldwide. The identification and understanding of the role of the Von Hipple Lindau (VHP) in regulating the hypoxia-inducible factor signaling pathway has revolutionized the treatment of this disease. Belzutifan is an oral hypoxia-inducible factor (HIF)-2α inhibitor, which has demonstrated efficacy in treating von Hippel-Lindau (VHL) disease and for the treatment of adults with RCC who experienced disease progression after PD-1/PD-L1- and VEGFR-targeted therapies. One of the most common adverse effect of this drug is anemia; however, it is treatment is not well known. This review summarizes role of the VHL-HIF pathway in ccRCC aroused the interest of targeting HIF activity, the history of belzutifan development and their relationship to anemia as well as propose a management algorithm.

A spotlight on using HIF-PH inhibitors in renal anemia.

INTRODUCTION: Erythropoiesis-stimulating agents (ESAs) together with iron supplementation had been the standard treatment for anemia in chronic kidney disease (CKD) for the past decades. Recently, hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have attracted attention as a novel treatment option. AREAS COVERED: This review summarizes the effectiveness and the safety of HIF-PHIs based on previous clinical trials and discusses points to consider for their clinical use. EXPERT OPINION: The results from clinical trials demonstrate that HIF-PHIs are non-inferior to ESAs in terms of the efficacy to maintain or improve blood hemoglobin levels. However, concerns about adverse events including cardiovascular outcomes, thrombotic events, and tumor progression have prevented HIF-PHIs from being widely approved for clinical use. Also, long-term safety has not been demonstrated yet. Practically, HIF-PHIs should be used with caution in patients with a history of thrombosis or active malignancy. Patients without them may be preferable for HIF-PHIs if those are bothered with regular injections of ESAs or are hyporesponsive to ESAs without obvious reasons, provided that the drugs were approved in the country. Even so, clinicians must take caution for signs of adverse events such as heart failure after prescribing the drugs.

Efficacy of vitamin C on chemotherapy-related anemia in pancreatic cancer: study protocol for a randomized controlled trial.

BACKGROUND: In the treatment of advanced pancreatic cancer, chemotherapy plays a pivotal role. Despite its effectiveness, this regimen is often marred by side effects such as anemia, neuropathy, fatigue, nausea, and malnutrition, which significantly affect patients' tolerance to the treatment. Some studies have shown that vitamin C could potentially augment chemotherapy's tolerability, notably by boosting iron absorption, ameliorating anemia, and relieving pain and numbness in hands and feet. Nevertheless, the integration of vitamin C with chemotherapy to mitigate toxic side effects and enhance the quality of life for advanced pancreatic cancer patients has not been examined in any randomized controlled trials to date. METHODS: A prospective, single-center, open-label, randomized controlled trial will be conducted at Fudan University Shanghai Cancer Center from September 2023 to September 2026. A total of at least 100 patients with advanced pancreatic adenocarcinoma exhibiting distant metastases will be recruited and randomly assigned to the chemotherapy group or the chemotherapy plus vitamin C group. The primary endpoint is the rate of anemia. Secondary endpoints include the rate of grade 3 neuropathy, change of numeric rating scale, quality of life, and overall survival. DISCUSSION: This study aims to assess the impact of low-dose vitamin C on enhancing the quality of life for patients with metastatic pancreatic cancer undergoing gemcitabine and nab-paclitaxel chemotherapy. TRIAL REGISTRATION: The trial was registered with the ClinicalTrials.gov (NCT06018883) on August 31, 2023.

Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin ≥10 g/dL) who had received eculizumab or were naive to complement inhibitors.

BACKGROUND: Although complement component 5 inhibitors (C5is) eculizumab and ravulizumab improve paroxysmal nocturnal hemoglobinuria (PNH) outcomes, patients may experience persistent anemia. This post hoc analysis investigated whether the complement component 3-targeted therapy pegcetacoplan also improved hematologic outcomes and reduced fatigue in patients with PNH and mild/moderate anemia. METHODS: Patients with PNH and hemoglobin ≥10.0 g/dL at baseline of PADDOCK (N = 6), PRINCE (N = 8), and PEGASUS (N = 11) were included. Before receiving pegcetacoplan, PADDOCK and PRINCE patients were C5i-naive; PEGASUS patients had hemoglobin <10.5 g/dL despite stably dosed eculizumab. Hemoglobin concentrations, percentages of patients with concentrations ≥12 g/dL, and sex-specific normalization were assessed at baseline and after 16 weeks of pegcetacoplan, as were absolute reticulocyte counts (ARCs) and normalization and fatigue scores and normalization. RESULTS: From baseline to week 16, mean (SD) hemoglobin concentrations increased in C5i-naive patients (PADDOCK: 10.5 [0.4] to 12.7 [1.1] g/dL; PRINCE: 11.3 [1.0] to 14.0 [1.3] g/dL) and those with suboptimal eculizumab responses (PEGASUS: 10.2 [0.2] to 12.8 [2.6] g/dL). Percentage of patients with hemoglobin ≥12 g/dL increased (PADDOCK: 0 to 60.0% [3 of 5 patients]; PRINCE: 25.0% [2 of 8] to 87.5% [7 of 8]; PEGASUS: 0 to 72.7% [8 of 11]). Sex-specific hemoglobin normalization at week 16 occurred in 40.0% (2 of 5) (PADDOCK), 62.5% (5 of 8) (PRINCE), and 63.6% (7 of 11) (PEGASUS). In all studies, mean ARCs decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy-Fatigue scores improved from below to above or near normal. Two patients had serious adverse events (PEGASUS: post-surgery sepsis, breakthrough hemolysis); breakthrough hemolysis resolved without study discontinuation. CONCLUSION: Patients with PNH and mild/moderate anemia who were C5i-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan. TRIAL REGISTRATION: Trial registration numbers: PADDOCK (NCT02588833), PRINCE (NCT04085601; EudraCT, 2018-004220-11), PEGASUS (NCT03500549).

Update on iron supplementation in patients with cancer-related anemia.

INTRODUCTION: Numerous clinical trials affirm the efficacy and safety of IV iron to treat cancer-related anemia (CRA). Nonetheless, evaluation and treatment of CRA remains suboptimal. AREAS COVERED: This review summarizes CRA therapy with a focus on iron deficiency and its treatment. The literature search was conducted using the National Library of Medicine (PubMed) database from 2004 to 2024. Topics reviewed include CRA pathophysiology, laboratory diagnosis of iron deficiency, a summary of clinical trial results using IV iron to treat CRA, and safety aspects. EXPERT OPINION: Despite overwhelming positive efficacy and safety data, IV iron remains underutilized to treat CRA. This is likely due to persistent (unfounded) concerns about IV iron safety and lack of physician awareness of newer clinical trial data. This leads to poor patient quality of life and patient exposure to anemia treatments that have greater safety risks than IV iron. Solutions to this problem include increased educational efforts and considering alternative treatment models in which other providers separately manage CRA. The recent availability of new oral iron therapy products that are effective in treating anemia of inflammation has the potential to dramatically simplify the treatment of CRA.

Efficacy of daprodustat for patients on dialysis with anemia: systematic review and network meta-analysis.

Chronic kidney disease (CKD) is commonly complicated by anemia. Treating dialysis-dependent patients with anemia, including daprodustat and other inhibitors of prolyl hydroxylase of hypoxia-inducible factor, recombinant human erythropoietin (rhEPO), and iron supplements. We conducted this study to test our postulation; daprodustat is superior to rhEPO and other conventional treatments respecting efficacy and safety parameters. We made systematic search through PubMed, Web of Science, Scopus, and Cochrane. Seven unique trials were eventually included for systematic review; six of them with a sample size of 759 patients entered our network meta-analysis (NMA). Daprodustat 25-30 mg was associated with the greatest change in serum hemoglobin (MD=1.86, 95%CI= [1.20; 2.52]), ferritin (MD= -180.84, 95%CI= [-264.47; -97.20]), and total iron binding capacity (TIBC) (MD=11.03, 95%CI= [3.15; 18.92]) from baseline values. Dialysis-dependent patients with anemia had a significant increment in serum Hemoglobin and TIBC and a reduction in serum ferritin, in a dose-dependent manner, when administered daprodustat.

[HIF-ɑ: New Target For Treatment of Renal Anemia. Molecular Aspects and Activation of Pathway HREs].

Roxadustat, recently approved, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has demonstrated favorable safety and efficacy in the treatment of renal anemia. This article reviews main features and possible effects by activation of pathway sequences HREs.

Evaluating the safety and efficacy of vadadustat for the treatment of anemia associated with chronic kidney disease.

INTRODUCTION: The breakthrough in erythropoietin-stimulating agents in the 1990s improved the prognosis and treatment of complications in chronic kidney disease patients and renal anemia. Discovery of the novel molecular mechanisms for hypoxia-inducible factor (HIF) transcription factor under hypoxic conditions has led to the development of oral drugs, HIF-Prolyl Hydroxylase inhibitors (HIF-PHIs), that constantly activate erythropoietin by inhibiting prolyl hydroxylase. HIF-PHIs have gained rapid approval in Asian countries, including Japan, with six distinct types entering clinical application. AREAS COVERED: This article provides a comprehensive review of the latest literature, with a particular focus on the effectiveness and safety of vadadustat. EXPERT OPINION: A phase 3, randomized, open-label, clinical trial (PRO2TECT) demonstrated that vadadustat had the prespecified non-inferiority for hematologic efficacy as compared with darbepoetin alfa in non-dialysis-dependent patients not previously treated with ESA. However, vadadustat did not show non-inferiority in major adverse cardiovascular events in the non-US/non-Europe patients. It may partly because of imbalances of the baseline eGFR level in those countries. In dialysis-dependent patients, a phase 3 clinical trial (INNO2VATE) showed vadadustat was non-inferior to darbepoetin alfa in cardiovascular safety and maintenance of hemoglobin levels. Adverse events including cancer, retinopathy, thrombosis, and vascular calcification should be evaluated in future clinical studies.

Usage of Meropenem Continuous Infusion for Treatment of Infectious Complications in Orthopedic Elderly Patients with Anemia: A Case Series.

Background and Objectives: The prolonged infusion of meropenem is recommended by guidelines for the treatment of sepsis. However, studies provide controversial data on the advantages of prolonged infusions over intermittent ones. In our opinion, this can be related to age, which possibly distorts the final data, as older people have age-related characteristics. In our study, we analyzed the ventilatory status, laboratory tests and vital signs of the patient and carried out microbiological cultures. Materials and Methods: This was a prospective single-center case series investigation conducted from June 2022 to June 2023. The objective of this study was to evaluate the effectiveness of continuous infusion in elderly patients with severe infectious complications after orthopedic interventions. The primary endpoints were 28-day survival and the emergence of new multidrug-resistant strains. Secondary endpoints were long-term mortality and length of stay in the ICU. Results: Three patients (median age 65, 100% female) received a continuous infusion of meropenem. Two patients were alive at hospital discharge, and one patient died on the 105th day of hospitalization. Multi-resistant bacteria were observed in one patient. Conclusions: The use of a continuous meropenem infusion in the complex treatment of purulent-septic complications in elderly patients with periprosthetic infection and anemia probably led to clinical improvement in these case reports. However, the emergence of new pan-resistant strains and overall mortality using this infusion technique remains unclear. Further, high-quality RCTs for the elderly are needed.

In transfusion-dependent, angiodysplasia-related anemia, adding octreotide to usual care reduced transfusions at 1 y.

SOURCE CITATION: Goltstein LC, Grooteman KV, Bernts LH, et al. Standard of care versus octreotide in angiodysplasia-related bleeding (the OCEAN study): a multicenter randomized controlled trial. Gastroenterology. 2024;166:690-703. 38158089.

LACC1 deficiency leading to juvenile arthritis and anemia.

OBJECTIVE: Juvenile arthritis caused by loss-of-function LACC1 mutations is characterized by early onset of symmetric and chronic arthritis, associated with an elevation of inflammatory markers. We aimed to describe serum cytokine levels, explore the type I interferon pathway, and evaluate the efficacy of treatment in a patient presenting with polyarthritis and anemia caused by novel compound heterozygous variations in LACC1. METHODS: Clinical data of a patient with compound heterozygous variations in LACC1 was collected. Serum cytokine levels and IFN-stimulated cytokine genes were analyzed at diagnosis, at disease flare, and after treatment. Full-length cDNA of LACC1 was checked by RNA analysis. Single-cell RNA sequencing was performed in PBMCs. RESULTS: Two novel variants in the LACC1 gene were identified in a patient presenting with polyarthritis and anemia. LACC1-cDNA was normally expressed in the healthy control, the target production at 1384 bp was not observed in the patient. Compared to nine patient controls with non-systemic juvenile idiopathic arthritis, serum interleukin(IL)-6 level was significantly elevated in the affected patient. The median IFN score for the patient, her mother, and controls were 118, 8, and 4.9, respectively. The combined treatment of JAK inhibitors with prednisone or tocilizumab led to a complete response, including remission of joint symptoms, resolution of anemia, reduced expression of IFN-stimulated cytokine genes, and normalized levels of inflammatory markers, including CRP, ESR, SAA, and serum IL-6. CONCLUSION: LACC1 may play a crucial role in multiple inflammatory signaling pathways. The combination therapy of JAK inhibitors and tocilizumab may be effective for a subset of refractory patients.

Can we effectively manage chronic kidney disease with a precision-based pharmacotherapy plan? Where are we?

INTRODUCTION: In recent years, thanks to significant advances in basic science and biotechnologies, nephrology has witnessed a deeper understanding of the mechanisms leading to various conditions associated with or causing kidney disease, opening new perspectives for developing specific treatments. These new possibilities have brought increased challenges to physicians, who face with a new complexity in disease characterization and selection the right treatment for individual patients. AREAS COVERED: We chose four therapeutic situations: anaemia in chronic kidney disease (CKD), heart failure in CKD, IgA nephropathy (IgAN) and membranous nephropathy (MN). The literature search was made through PubMed. EXPERT OPINION: Anaemia management remains challenging in CKD; a personalized therapeutic approach is often needed. Identifying patients who could benefit from a specific therapy is also an important goal for patients with CKD and heart failure with reduced ejection fraction. Several new treatments are under clinical development for IgAN; interestingly, they target specifically the pathogenetic mechanisms of the disease. The understanding of MN pathogenesis as an autoimmune disease and the discovery of several autoantibodies allows a better characterization of patients. High-sensible techniques for lymphocyte counting open the possibility of more personalized use of anti CD20 therapies.