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MANAGEMENT OF PATIENTS WITH ANAEMIA IN CHRONIC CARDIORENAL
SYNDROME
Dilafruz Abdikhalimovna Amerova
Assistant teachet of the Department of Hematology,
Samarkand State Medical University
Komilakhon Nuriddinovna Fatullaeva
Deputy Chief Physician for Outpatient Care,
Samarkand Regional Multidisciplinary Medical Centre
Abstract
. Anaemia is a common and clinically significant complication in patients with
chronic cardiorenal syndrome, negatively affecting functional capacity, quality of life, and
overall prognosis. This study aimed to evaluate the effectiveness of oral versus intravenous
iron therapy, each in combination with erythropoiesis-stimulating agents (ESAs), in the
outpatient management of anaemia in patients with coexisting chronic kidney disease and
chronic heart failure. A total of 80 patients were enrolled and divided into two equal groups:
one received oral iron with ESAs, while the other was treated with intravenous iron and
ESAs. Over a 16-week follow-up period, the group receiving intravenous iron demonstrated
significantly greater improvements in haemoglobin levels, functional status (NYHA class),
iron indices (ferritin, TSAT), and treatment satisfaction. They also required fewer ESA dose
adjustments and had a lower incidence of anaemia-related hospitalisations. These findings
support the superiority of intravenous iron supplementation in anaemia correction among
patients with chronic cardiorenal syndrome, particularly in the presence of inflammation or
poor gastrointestinal absorption.
Keywords:
Anaemia, chronic kidney disease, chronic heart failure, cardiorenal syndrome,
intravenous iron, oral iron, erythropoiesis-stimulating agents, haemoglobin, outpatient
management.
Introduction
Anaemia is a frequent and clinically significant complication in patients with chronic kidney
disease (CKD), particularly when it coexists with chronic heart failure (CHF), a condition
known as chronic cardiorenal syndrome. The interdependence between the kidneys and heart
in this syndrome creates a complex pathophysiological environment in which the
dysfunction of one organ exacerbates the other. Anaemia in such patients not only
contributes to fatigue and reduced quality of life but also worsens the prognosis by
accelerating the progression of both renal and cardiac dysfunction.
The prevalence of anaemia in patients with chronic cardiorenal syndrome is reported to be as
high as 60–70%, and its presence is independently associated with increased hospitalisation
rates and mortality. The pathogenesis of anaemia in this setting is multifactorial. It includes
reduced erythropoietin production due to renal impairment, chronic inflammation leading to
functional iron deficiency, hemodilution, nutritional deficiencies, and the suppressive effects
of uremic toxins on erythropoiesis. Additionally, the use of renin-angiotensin-aldosterone
system (RAAS) inhibitors, though essential for cardiorenal protection, may further impair
erythropoietin levels and contribute to anaemia.
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Given this complex interplay of factors, anaemia management in cardiorenal patients poses a
significant clinical challenge. A one-size-fits-all strategy is often inadequate, and
individualised treatment approaches are necessary. Current international guidelines
recommend a combination of therapies, including iron supplementation (preferably
intravenous), erythropoiesis-stimulating agents (ESAs), and correction of underlying
nutritional and inflammatory states. However, the timing, dosage, and combination of these
interventions must be carefully balanced to avoid complications such as hypertension,
thrombosis, or excessive erythropoiesis.
Recent studies also highlight the importance of novel agents such as hypoxia-inducible
factor prolyl hydroxylase inhibitors (HIF-PHIs), which stimulate endogenous erythropoietin
production and improve iron metabolism. These agents offer promise, especially for patients
who are hyporesponsive to conventional ESA therapy. Nevertheless, they are not yet widely
accessible in many regions, including Uzbekistan, and their long-term safety remains under
evaluation.
In Uzbekistan, the burden of cardiorenal syndrome is steadily increasing, paralleling global
trends in diabetes, hypertension, and aging populations. However, anaemia in these patients
often remains underdiagnosed and undertreated, particularly in outpatient settings. There is a
need for more structured protocols and awareness among general practitioners and
cardiologists regarding early screening, risk stratification, and comprehensive anaemia
correction strategies.
This study aims to investigate current clinical approaches and treatment outcomes for
anaemia in patients with chronic cardiorenal syndrome, with a particular focus on outpatient
care. The objective is to evaluate the effectiveness of combined iron and ESA therapy in
real-world conditions, assess factors influencing treatment response, and propose
recommendations for optimising anaemia management protocols in regional healthcare
settings.
The results of this study are expected to provide valuable insights into improving the quality
of care, reducing rehospitalisation, and enhancing the life expectancy of patients suffering
from this dual-organ failure syndrome. By aligning local practice with international
standards and adapting evidence-based strategies to regional realities, healthcare providers
can significantly mitigate the burden of anaemia in chronic cardiorenal patients.
Methodology
This prospective observational study was conducted between 2022 and 2024 at the
outpatient department of the Samarkand Regional Multidisciplinary Medical Centre in
collaboration with the Department of Hematology, Samarkand State Medical University.
The study aimed to assess the effectiveness of current anaemia management strategies in
patients with chronic cardiorenal syndrome and to identify key factors affecting treatment
response in real-world outpatient conditions.
A total of 80 patients were enrolled in the study based on the following inclusion criteria: a
confirmed diagnosis of chronic heart failure (NYHA Class II–IV), chronic kidney disease
(Stage 3–5, eGFR < 60 ml/min/1.73m²), and anaemia as defined by WHO criteria
(haemoglobin levels < 130 g/L in men and < 120 g/L in women). Exclusion criteria included
active bleeding, recent blood transfusion (within the past 3 months), malignancy, acute
infection, uncontrolled hypertension, or hypersensitivity to iron or erythropoiesis-
stimulating agents (ESAs).
All patients underwent a comprehensive baseline evaluation, including clinical examination,
NYHA functional classification, echocardiography, serum creatinine, estimated glomerular
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filtration rate (eGFR), haemoglobin level, ferritin, transferrin saturation (TSAT), C-reactive
protein (CRP), serum iron, total iron-binding capacity (TIBC), vitamin B12, and folate
levels. Based on their iron status and inflammatory profile, patients were stratified into two
therapeutic subgroups.
Group A (n=40) received oral iron supplementation (ferrous sulfate or fumarate) and
standard ESA therapy (epoetin alfa or beta) with dose titration according to the patient’s
response. Group B (n=40) was treated with intravenous iron (ferric carboxymaltose or iron
sucrose) combined with subcutaneous ESAs. The decision to use oral versus IV iron was
guided by ferritin levels (<100 ng/mL or TSAT <20%) and the presence of elevated
inflammatory markers (CRP > 5 mg/L), in which case IV iron was preferred due to poor
absorption of oral preparations.
The duration of follow-up was 16 weeks. Haemoglobin levels were monitored every 4
weeks, while iron parameters, renal function, and cardiovascular status were reassessed at 8
and 16 weeks. The primary endpoint was the increase in haemoglobin by ≥10 g/L from
baseline without the need for blood transfusion. Secondary endpoints included improvement
in functional capacity (NYHA class), reduction in ESA dosage, correction of iron deficiency,
and incidence of adverse events such as hypertension, thromboembolic events, or
intolerance to therapy.
Treatment response was evaluated using both absolute haemoglobin gain and composite
clinical improvement (including symptom reduction and hospital admission rates). Data
were analysed using SPSS software version 26.0. Continuous variables were expressed as
mean ± standard deviation and compared using Student’s t-test. Categorical data were
analysed using the chi-square test. A p-value <0.05 was considered statistically significant.
Ethical approval for the study was obtained from the Institutional Review Board of
Samarkand State Medical University, and informed consent was obtained from all
participants. Patients were educated about their anaemia condition, treatment options,
potential side effects, and the importance of adherence to therapy during regular outpatient
visits.
This methodology ensured a structured and comparative evaluation of real-world anaemia
management practices and aimed to generate evidence for improving protocol-based care for
patients suffering from anaemia in the context of chronic cardiorenal syndrome in
Uzbekistan.
Results
The 16-week follow-up period revealed distinct differences in treatment response between
the two patient groups. Among the total 80 patients enrolled, 76 (95%) completed the study,
while 4 were lost to follow-up due to relocation or unrelated health complications. Both
groups were comparable at baseline in terms of age, sex distribution, severity of anaemia,
eGFR, and NYHA class.
In Group A, which received oral iron therapy combined with subcutaneous erythropoiesis-
stimulating agents (ESAs), the mean baseline haemoglobin level was 96.4 ± 8.2 g/L. By the
end of the follow-up period, a mean haemoglobin increase of 7.8 ± 4.6 g/L was recorded.
However, only 47.5% of patients (19 out of 40) achieved the target haemoglobin increase of
≥10 g/L without the need for transfusion. Furthermore, 30% of patients required ESA dose
escalation, and 4 patients (10%) experienced gastrointestinal side effects such as nausea or
constipation, which impacted adherence to oral iron therapy.
In contrast, Group B, which received intravenous iron (ferric carboxymaltose or iron sucrose)
in addition to ESA therapy, demonstrated significantly better outcomes. The mean baseline
haemoglobin level in this group was 95.7 ± 7.9 g/L, and the mean increase by week 16 was
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13.1 ± 5.2 g/L (p < 0.01 compared to Group A). A total of 77.5% of patients (31 out of 40)
in this group achieved the target haemoglobin response. Inflammatory markers (CRP) also
declined modestly in this group, suggesting improved systemic iron availability and reduced
anaemia of chronic disease.
Additionally, functional improvement was more evident in Group B, with 65% of patients
moving up at least one NYHA class compared to 40% in Group A. Fewer ESA dose
adjustments were needed in Group B, indicating better erythropoietic responsiveness. No
serious adverse events were reported in either group, though mild infusion-related reactions
(such as transient flushing and dizziness) occurred in 3 patients in Group B, resolving
spontaneously without intervention.
Iron parameters also differed significantly between the two groups by week 16. In Group A,
only 55% of patients normalised ferritin and transferrin saturation, whereas in Group B, 85%
of patients reached target iron indices (ferritin > 100 ng/mL and TSAT > 20%). This
confirmed superior bioavailability and utilisation of intravenous iron in the presence of
inflammation.
The overall treatment satisfaction reported by patients, based on standardised questionnaires,
was higher in Group B, primarily due to faster symptom relief, fewer side effects, and
reduced fatigue. Hospital admission rates related to anaemia or CHF decompensation during
the follow-up were lower in the IV iron group (2 cases) compared to the oral iron group (6
cases), although this difference was not statistically significant (p = 0.08).
In summary, the results indicate that intravenous iron therapy, when combined with ESAs, is
more effective than oral iron in correcting anaemia, improving functional capacity, and
enhancing quality of life in patients with chronic cardiorenal syndrome. These findings
support the early use of IV iron in outpatient management protocols, particularly in patients
with inflammation, low iron stores, or poor tolerance to oral supplementation.
Discussion
The findings of this study demonstrate that anaemia in patients with chronic cardiorenal
syndrome requires a strategic, individualised management approach that goes beyond
standard oral iron supplementation. The superiority of intravenous (IV) iron therapy,
observed in Group B, aligns with a growing div of international evidence suggesting that
in the presence of inflammation and reduced gastrointestinal absorption—common in
patients with chronic kidney disease and heart failure—IV iron is not only more effective
but also better tolerated than oral preparations.
The enhanced haemoglobin response in Group B patients is largely attributable to the
increased bioavailability of parenteral iron, which bypasses the regulatory blockades caused
by hepcidin overexpression, a peptide hormone that inhibits intestinal iron absorption in
states of chronic inflammation. This mechanism is particularly relevant in the context of
chronic kidney disease and heart failure, where inflammation-induced functional iron
deficiency is a key contributor to treatment-resistant anaemia. Our study’s data supports
previous findings that IV iron, particularly ferric carboxymaltose or iron sucrose, achieves
faster replenishment of iron stores, increases transferrin saturation more efficiently, and
improves erythropoietin responsiveness [Macdougall et al., 2020, p. 118].
The improved NYHA functional class observed in Group B further highlights the systemic
benefits of effective anaemia correction. As anaemia impairs oxygen delivery to tissues and
increases cardiac workload, its correction can relieve cardiac stress, enhance exercise
tolerance, and improve overall quality of life. Patients in Group B not only achieved better
haemoglobin targets but also required fewer ESA dose adjustments, which is clinically
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important given the risks associated with high ESA dosages, including thrombosis and
hypertension.
Interestingly, despite a statistically non-significant difference, Group B also experienced
fewer hospitalisations for anaemia-related complications or heart failure decompensation.
This suggests that better anaemia control may contribute to improved clinical stability,
although longer follow-up is needed to confirm this association. Moreover, treatment
satisfaction was higher among patients receiving IV iron, underlining the practical
importance of symptom relief and reduced side effects, such as gastrointestinal intolerance,
which often limits the use of oral iron.
These findings are highly relevant for outpatient settings in Uzbekistan and other similar
healthcare environments, where anaemia is frequently underdiagnosed or treated
conservatively due to cost or resource limitations. This study highlights the need for greater
awareness among outpatient clinicians about the limitations of oral iron and the benefits of
early transition to IV iron in appropriate patients. At the same time, the data call for the
development of local clinical protocols and treatment pathways to standardise anaemia
screening and ensure timely correction based on evidence-based criteria.
However, the study has certain limitations. The follow-up period was limited to 16 weeks,
and the long-term sustainability of haemoglobin response and cardiovascular outcomes
could not be assessed. Additionally, although the study was conducted under real-world
outpatient conditions, it was restricted to a single centre and a moderate sample size. Future
multicentre studies with extended follow-up and the inclusion of newer therapeutic agents,
such as hypoxia-inducible factor stabilisers, would provide more comprehensive insights.
In conclusion, this study confirms that intravenous iron therapy, in combination with
erythropoiesis-stimulating agents, is a more effective strategy for managing anaemia in
patients with chronic cardiorenal syndrome than oral iron supplementation. This approach
leads to faster haemoglobin recovery, better iron repletion, improved functional status, and
higher patient satisfaction. Integration of these findings into routine outpatient practice can
significantly improve outcomes for a growing population of patients with dual kidney and
heart failure complications.
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