A Variety Of New Drugs And Prediction Methods Support The Diagnosis, Treatment And Management Of Renal Anemia

Renal anemia has always been a heavy burden for patients with chronic kidney disease (CKD) in my country and is one of the problems that needs to be solved urgently. So, what new diagnostic and treatment methods have been available in recent years that can help Chinese doctors manage renal anemia in CKD patients?

Click to Cistanche for kidney disease

From April 13 to 16, 2024, the 2024 World Congress on Nephrology (WCN) opened in Argentina, the country farthest from our country. At this conference, a total of more than 1,000 abstracts were exhibited. Among these abstracts, there are 5 abstracts related to the progress of diagnosis and treatment of renal anemia.

   Important information  

The hemoglobin (Hb) target level of hemodialysis patients should be related to altitude;

②Rare causes of renal anemia, immune globulin injection;

③ New drug for treating renal anemia - LP001;

④ It is no longer a rumor, that lactoferrin injection can treat iron deficiency renal anemia;

⑤Thalidomide may improve gastrointestinal bleeding/discomfort caused by the treatment of renal anemia.

Hb levels in hemodialysis patients should be related to altitude1

Research background: Bolivia is an underdeveloped country with obvious geographical differences. Normal Hb levels increase in high-altitude areas, and uncontrolled anemia is an important cause of other comorbidities in chronic dialysis patients. It is worth noting that my country also has obvious differences in altitude. Compared with western regions such as Tibet, the altitude in the eastern region is significantly lower. So, how to manage Hb in patients from different regions?

STUDY DESIGN: We describe the outcomes of anemia management in a moderately high altitude area (2500 m above sea level) with a mean Hb of 13 gr/L in a retrospective cross-sectional study up to July 2023.

Research results: A total of 51 patients were treated from January 2015 to July 2023, aged between 17 and 78 years old. Women account for 63%. The causes of hemodialysis were: diabetes (43%), hypertension (24%), unknown causes (20%), glomerular disease (6%), and other causes (8%). All patients received conventional hemodialysis treatment for 3 to 114 months, using reverse osmosis treatment, 3 times a week, 4 hours each time. There was no history of infection or recent blood transfusion. Patients' dry weight ranged from 36 to 90 kg. Hb level was 13.1 g/l. The ferritin level was 732.8 mg/dl. Transferrin saturation was 26.2%. Received erythropoietin therapy with a weekly dose of 2,787 IU for the final month and a total dose of 74.5 mg intravenous iron sucrose for the final month.

Research conclusion: Hb levels vary at different altitudes. For areas above 4000 meters above sea level, a more stringent Hb target should be adopted, that is, Hb should be ≥18gr/L.

SGLT-2 inhibitors, a rare cause of renal anemia, immunoglobulin 2 injection

Case Background: Intravenous immune globulin (IVIg) is a treatment modality for a variety of medical and renal diseases. Although IVIg is generally safe, there are some side effects and potentially serious complications, including anemia, especially hemolytic anemia.

Case Report: This is a case report on the onset and progression of anemia in a 42-year-old female renal transplant recipient. The patient underwent renal suppression for type 1 diabetes and 4 years later was found to have a persistent increase in serum creatinine a renal biopsy showed antibody-mediated rejection, so he was treated with steroids and treated with IVIg (2 g/kg). The patient's creatinine continued to improve and stabilized over several days. However, the patient developed significant anemia, with Hb falling from 12 mg/dL to 7 mg/dL. After careful examination, the patient had no bleeding, no gastrointestinal bleeding, no gynecological bleeding, and the hemolytic function was normal. Although the Hb level gradually stabilized after a few days, it was too low and required blood transfusion treatment.

In 2023, her creatinine gradually increased again and she underwent another renal transplant biopsy, which showed antibody-mediated rejection. She was again treated with IVIg and, not surprisingly, she became anemic again with no evidence of bleeding. Hemolysis tests were also normal.

We believe that IVIg may be the cause of anemia in this patient.

Case Discussion: IVIg is used in the management of a variety of immune-mediated diseases. For desensitization and treatment of antibody-mediated rejection (AMR) in kidney transplant recipients. Anemia, especially hemolytic anemia, may be related to high-dose IVIg, but its incidence and mechanism are unclear. High titers of anti-a/B IgG antibodies, non-O blood type, and first-time use are risk factors. It is recommended to monitor Hb after IVIg treatment. If Hb decreases, further hemolysis examination is required. In suspicious cases, an anti-globulin test can be performed directly to look for antibodies related to the patient's blood type. Previous studies have shown that 12 of the 42 patients who received IVIg developed passive sensitization to antibodies to their own blood group antigens after receiving IVIg. As mentioned in another review, antibodies to blood group antigens are present in most commercially prepared IVIg. However, most patients will not develop clinically significant anemia. In our patient, she had severe anemia but no obvious hemolysis, which may be caused by another mechanism.

Case Conclusion: Overall, IVIg is a commonly used treatment option for kidney disease, but it may cause anemia. Increasing awareness among physicians of this complication will help in the early detection of anemia and early intervention.

New drug for the treatment of renal anemia--LP0013

Research background: CKD is a chronic disease with common complications including anemia. Anemia can increase patients' fatigue, reduce quality of life, and increase the risk of other complications, thereby increasing the overall burden of CKD.

LP001 is a safer, more cost-effective form of erythropoietin (EPO) that, in theory, could better improve the prognosis of patients with renal anemia.

Study design: This is a randomized, double-blind Phase I clinical study (CTR20221413). 48 healthy subjects were divided into 6 groups according to the random number table method and were given 0.5, 1.6, 5, 15, 30, and 50 μg/kg of LP001 respectively in a single intramuscular injection. 20 healthy subjects were randomly divided into 2 groups and received 4 intramuscular injections of 15 μg/kg and 30 μg/kg respectively to evaluate the safety, pharmacokinetics, and pharmacodynamic characteristics of LP001.

Research results: LP-001 has the same efficacy as alfadar in cell-based experiments (UT-7) and animal models (normal SD rats, carboplatin-induced SD rat anemia, and cyclophosphamide-induced cynomolgus monkey anemia). Bepoetin has considerable biological activity. The bioavailability of LP-001 in normal SD rats and monkeys is approximately 50%.

In the SAD of the Phase I study, LP-001 exhibited nonlinear PK characteristics similar to darbepoetin alfa, with T1/2 ranging from 65.8 hours to 107 hours. No drug immunogenicity (ADA) and grade ≥3 adverse reactions were observed.

Research conclusion: Both preclinical and phase I clinical studies of LP-001 have shown that this new long-acting EPO has a similar glycosylation form and half-life to darbepoetin alfa. In addition, it increases EPO levels more smoothly and is therefore potentially safe and cost-effective and may be an alternative for CKD treatment.

Lactoferrin injection can treat iron-deficiency renal anemia4

Research background: Renal anemia is one of the most common complications of CKD and is associated with complications such as increased hospitalizations, increased need for blood transfusions, and decreased quality of life. Many patients remain anemic despite receiving standard care of adequate dialysis, and anemia also affects perioperative outcomes during and after renal transplantation. Some scholars have found that lactoferrin is effective in treating anemia in pregnant women, but no studies have shown that lactoferrin is effective in adult patients with CKD and anemia. So, compared with standard treatment, can standard treatment combined with injection of lactoferrin improve patients' renal anemia?

Study design: Outpatient screening of CKD patients with anemia and receiving dialysis. CKD patients with stable creatinine for 3 months, Hb < 10 g/dL, stable EPO dose, and no new hematology drugs in the past 3 months were included. Patients with hematological malignancies, HBV, HCV, HIV, hematological renal disease, clinically significant bleeding, infection at the time of presentation, receiving systemic immunosuppressive therapy, and pregnancy/lactation during the study period were excluded. They were then randomly divided into two groups: the intervention group (lac arm), which received lactoferrin (100 mg twice daily) plus standard treatment; and the control arm (control arm), which received only standard treatment. The clinical data of the enrolled patients were recorded, and blood samples were collected from the patients at baseline and 3-month follow-up. General linear models were used for statistical analysis.

Research results: The effect of lactoferrin combined with standard treatment on anemia in CKD patients with anemia is better than standard treatment alone. However, the effect of lactoferrin on inflammatory markers was not statistically significant.

Study Conclusions: This study suggests that lactoferrin improves anemia regardless of its effects on ESR and CRP inflammatory markers. The etiology may be related to increased iron uptake and utilization. Larger cohort studies and long-term follow-ups are needed.

Thalidomide may improve gastrointestinal discomfort caused by the treatment of renal anemia5

Case background: Gastrointestinal bleeding (GIB) is one of the major complications in dialysis patients with CKD. We report an interesting and difficult-to-treat case of GIB in a patient on maintenance hemodialysis with diabetes mellitus and treated with a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).

Case report: A 60-year-old female patient with diabetes developed CKD stage 5 in 2019 and started receiving maintenance hemodialysis treatment. She underwent a hysterectomy due to endometrial cancer the following year. EPO-resistant anemia occurred at the end of 2020, and the ferritin was 756 mcg/L. The patient began to receive HIF-PHI treatment (Desidustat) 100 mg, 3 times/week, and Hb improved. During HIF-PHI treatment, doctors adjust the dose individually based on Hb levels. In 2022, she underwent surgery for an intertrochanteric fracture of the femur. In 2023, she underwent total hip replacement and took rivaroxaban. Disable HIF-PHI before surgery. Melena appeared 2 weeks after the operation, and Hb decreased. The patient required multiple transfusions of packed red blood cells (PRBC) and discontinuation of anticoagulation therapy. Upper gastrointestinal (UGI) endoscopy followed by colonoscopy and CT.

Case Discussion: Although the effectiveness of HIF-PHI in correcting renal anemia has been demonstrated in multiple randomized controlled trials, HIF-PHI may increase the digestive Risk of tract bleeding. Basic research shows that HIF can directly act on the VEGF pathway to regulate abnormal angiogenesis in the gastrointestinal tract. A few previous studies have shown that thalidomide is an effective and relatively safe treatment for preventing rebleeding in vascular dysplasia by inhibiting vascular endothelial growth factor (VEGF). No dose adjustment is required for hemodialysis patients.

Case summary: Refractory gastrointestinal bleeding caused by multiple telangiectasia is a rare complication of CKD, but it can pose diagnostic and treatment challenges. Thalidomide can be used in patients with refractory GIB who tolerate the drug. The possible etiological role of HIF-PHI in intestinal telangiectasia needs to be considered.

How Does Cistanche Treat Kidney Disease?

Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.

Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.

Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.

Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.

Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.

Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.

In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.

In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.