Anemia develops in the majority of patients with chronic kidney disease (40-90%) in parallel with the progression of the pathology. In response to this growing challenge, the KDIGO 2026 guideline introduces updated standards of treatment. The new recommendations focus on diagnostic accuracy and the maximum effectiveness of therapeutic strategies.
Pathophysiology
The development of anemia during chronic kidney disease is a complex process in which several pathological mechanisms intersect. In patients with stage 5 of the disease, erythropoietin deficiency plays a leading role, while in the non-dialysis stage, the body exhibits a diminished response to this hormone.
Added to this is the increase in hepcidin levels caused by chronic inflammation. Its excess leads to the “locking” of iron in stores, due to which iron is no longer available for erythropoiesis. The overall picture is further aggravated by the uremic environment and blood loss, which significantly reduces the viability of erythrocytes.
These processes directly reflect on the patient’s clinical outcome. Anemia not only increases cardiovascular complications and the risk of hospitalization and mortality, but also sharply decreases the quality of life, causing cognitive impairments and often becoming the reason for red blood cell mass transfusion.
Diagnosis of Anemia
For the diagnosis of anemia, the threshold indicators for hemoglobin (Hb) are defined as:
<13.0 g/dL – in men;
<12.0 g/dL – in women and adolescents older than 15 years;
<11.0 g/dL – in pregnant women.
Primary screening of patients should be conducted immediately upon the diagnosis of CKD (chronic kidney disease), while subsequent periodicity should be determined according to the stage of the disease:
Every 3 months: in patients with stage III-V CKD and those on dialysis;
Every 6 months: during stage I-II CKD.
Assessment of Iron Deficiency
According to the recommendations, the types of iron deficiency are determined by the following criteria:
Absolute deficiency: transferrin saturation (TSAT) <20% and ferritin <100 ng/mL (patients not on dialysis) or <200 ng/mL (patients on dialysis). This condition represents a direct indication for intravenous (IV) iron therapy.
Functional deficiency: TSAT ≤30% and ferritin in the range of 100–500 ng/mL.
Recommendation: In the case of absolute deficiency, preference is given to intravenous forms, because they more quickly and effectively ensure the filling of iron stores (reserves) and the achievement of the target hemoglobin indicator.
Iron Therapy
For the management of iron therapy for the disease, the guideline offers a strictly defined protocol. In the case of absolute deficiency, conducting a trial course of intravenous (IV) iron is recommended. To evaluate the effectiveness of the treatment, it is necessary that hemoglobin monitoring occurs 4 weeks after the completion of the course.
In patients on dialysis (HD, PD, G5D), intravenous iron is the first-line choice, while in other patients, its use is recommended when oral preparations are contraindicated, ineffective, or the patient is unable to take them.
From a practical standpoint, starting treatment with a 1000 mg trial course of intravenous iron is recommended, which is followed by subsequent maintenance therapy. The dosage and periodicity of the latter are determined individually, based on the monitoring of iron indices (TSAT and ferritin), which implies rechecking at intervals of every 1 to 3 months.
For safety purposes, the guideline advises us to avoid the routine use of iron if the ferritin indicator exceeds 500 ng/mL, and transferrin saturation (TSAT) exceeds 30%. Also, treatment must be stopped if an increase in hemoglobin is not recorded even after two full courses.
Erythropoiesis-Stimulating Agents (ESA)
In adult patients who are on dialysis (G5D), starting ESA therapy is recommended if the hemoglobin level is lower than 10.0 g/dL. In children, this threshold is relatively higher and amounts to <11.0 g/dL. As for patients not on dialysis and persons with a kidney transplant, here the decision is individual and is made in the presence of hemoglobin in the range of 8.5–10.0 g/dL, taking into account symptoms, cardiovascular risks, malignant processes, and transplantation status.
Although ESA therapy effectively reduces the need for transfusion and improves the patient’s quality of life, its use requires caution. Research has shown that high target indicators of hemoglobin (comparison of 13 g/dL with 11 g/dL) increase the risk of stroke and other Major Adverse Cardiovascular Events (MACE), without improving the survival prognosis.
Dosage, Administration, and Monitoring
During therapy, the priority is to use the minimum effective dose to avoid a sharp increase in hemoglobin (>1-2 g/dL in 4 weeks). Correction of the dose is necessary no more than once every 4 weeks. In patients on hemodialysis, the route of drug administration (intravenous or subcutaneous) depends on the patient’s choice, although in persons on non-dialysis and peritoneal dialysis, preference is given to subcutaneous (SC) injection.
Hemoglobin monitoring is needed 2-4 weeks after a dose change, and during the stable period – at least once every 3 months. Stopping treatment in case of the development of stroke, thrombosis, or oncological diseases is discussed together with the patient.
HIF-PHI (Hypoxia-Inducible Factor Prolyl-Hydroxylase Inhibitors) Medications
HIF-PHI represents an alternative pathway of treatment, during which we should consider the following practical aspects:
Method of use: Combining HIF-PHIs with ESA is impermissible. When using them, the same threshold indicators of hemoglobin apply as in the case of ESA.
Dosage and monitoring: Treatment must start with the minimum effective dose, taking into account drug-to-drug interactions. Hemoglobin control is recommended once every 2-4 weeks in the initial stage, and subsequently – monthly.
Safety: When using Roxadustat, periodic checking of thyroid gland function is necessary. Therapy must be stopped if the patient does not exhibit an adequate response during 3-4 months, or if a cardiovascular complication or oncological process develops.
Diminished Sensitivity Toward ESA
Diminished sensitivity toward ESA is found in 12.5-30.3% of patients and is directly connected with the increase in mortality caused by cardiovascular reasons.
In approximately 60% of such cases, the main cause of resistance is represented by chronic inflammatory processes or iron deficiency. Accordingly, the therapeutic strategy must primarily be based on the identification and elimination of precisely these factors.
In the event that the correction of etiological factors is ineffective, prescribing a drug of the HIF-PHI class at a minimum dose is possible. The mentioned therapy is permissible only in those patients who do not exhibit an active oncological process or a recently experienced severe cardiovascular complication in their anamnesis.
A special clinical approach is required for pure red cell aplasia (PRCA) caused by ESA therapy – a rare immunological complication during which the body produces antibodies toward erythropoietin, which causes the complete selective disappearance of erythrocyte precursor cells in the bone marrow. In such a case, a strict treatment protocol is activated: immediate cessation of ESA intake, initiation of immunosuppressive therapy, and consideration of the possibility of switching to a medication of the HIF-PHI class.
Red Blood Cell Mass Transfusion
The decision regarding red blood cell mass transfusion must be based on a joint, informed agreement between the doctor and the patient. At this time, the balance of the benefit obtained from improving oxygen transport and the expected risks (transmission of infections, hemodynamic overload, and allo-sensitization) is critically important.
The decision regarding transfusion must be based on clinical manifestation and not only on laboratory indicators. Focusing on the threshold mark of hemoglobin, along with the incorrect management of anemia, increases the risk of unfounded use of transfusion.
Particular caution is needed with transplantation candidates to minimize the risk of sensitization (which amounts to 2-21%). Sensitization, especially in women who have given birth multiple times and in patients waiting for re-transplantation, significantly complicates receiving an organ from a living donor.
According to international guidelines (Cochrane/AABB), maintaining hemoglobin within the range of 7–8 g/dL is considered a safe norm. To reduce the number of transfusions, auxiliary strategies are prioritized: minimizing iatrogenic blood loss, optimizing current therapy, and managing asymptomatic patients without blood transfusion, under conditions of strict observation of hemoglobin dynamics.
This KDIGO guideline is developed with the GRADE methodology, which implies systematic reviews and qualitative assessment of evidence (GRADEpro). The recommendations are divided into strong (Graded 1) and probable (Graded 2) categories, according to the reliability of the evidence (A-D). It is noteworthy that the patients themselves participated in the formation of the guideline, so that their priorities would also be reflected in the therapeutic approaches. Despite the progress achieved, the lack of data in the pediatric population and transplanted patients remains relevant. Along with this, the in-depth study of the long-term safety profile of HIF-PHI class medications remains a priority direction.
Source: Kidney International
