Chronic kidney disease (CKD) is a progressive disorder characterized by structural or functional abnormalities of the kidneys, lasting for more than three months, with implications for overall health [1]. CKD affects approximately 10–15% of adults worldwide, with higher prevalence in developing countries due to rising rates of diabetes and hypertension [2]. As CKD progresses, patients are at increased risk of complications such as cardiovascular disease, mineral bone disorder, and anemia. Anemia in CKD is a common and serious complication, defined by reduced hemoglobin concentration, and its prevalence increases with declining kidney function. The primary mechanism is erythropoietin deficiency, a hormone produced by the kidneys that stimulates red blood cell production. Secondary contributing factors include iron deficiency, chronic inflammation, blood loss, and accumulation of uremic toxins, which collectively impair erythropoiesis and reduce red blood cell lifespan [3,4]. Patients with CKD stages 4 (eGFR 15–29 mL/min/1.73 m²) and 5 (eGFR <15 mL/min/1.73 m²) are at particularly high risk of anemia due to the progressive loss of renal function [5]. Anemia in advanced CKD is associated with fatigue, reduced exercise tolerance, cognitive impairment, increased hospitalization rates, and higher cardiovascular mortality [6]. Global and regional prevalence: Studies report wide variation in anemia prevalence among CKD patients, ranging from 20–70% depending on population, CKD stage, and definitions used. Bishaw et al. reported anemia prevalence of 41% in stage 4 and 72% in stage 5 CKD patients [7]. Wittbrodt et al. observed severe anemia in 41% of stage 4 and 72.8% of stage 5 patients [8]. Such high prevalence underscores the importance of early recognition and intervention, especially in developing countries where routine screening may be limited. Rationale of the study: Despite the high burden of CKD and its complications, there is a paucity of region-specific data on anemia prevalence in advanced CKD stages. Understanding the prevalence, severity, and contributing factors can guide clinicians in timely intervention and improve patient outcomes. Objectives: To determine the prevalence of anemia in adult CKD patients with stages 4 and 5. To assess the severity of anemia and associated hematological parameters. To identify potential risk factors contributing to anemia in advanced CKD.

Study Design: This cross-sectional study was conducted over 12 months at the Department of Nephrology, Konaseema institute of medical science Amalapuram AP India. Ethical approval was obtained from the institutional ethics committee, and informed consent was obtained from all participants. Study Population: Adult patients (>18 years) with confirmed CKD stage 4 or 5 were included. CKD staging was based on KDIGO 2021 guidelines using estimated glomerular filtration rate (eGFR) [1]. Patients already on long-term dialysis (>3 months), those with hematological malignancies, hemolytic anemia, or acute blood loss, were excluded to avoid confounding results. Sample Size: A total of 120 patients were enrolled (stage 4: 70; stage 5: 50), calculated based on previous prevalence studies and assuming a 95% confidence interval and 10% margin of error. Data Collection: Demographics: Age, sex, comorbidities (diabetes, hypertension). Laboratory Parameters: Hemoglobin (Hb), hematocrit, mean corpuscular volume (MCV), serum ferritin, transferrin saturation (TSAT), serum creatinine, blood urea nitrogen (BUN), eGFR. Definition of Anemia: Per KDIGO 2021, Hb <13 g/dL in men and <12 g/dL in women. Iron Deficiency: Ferritin <100 ng/mL or TSAT <20%. Statistical Analysis: Data were analyzed using SPSS v25. Continuous variables were expressed as mean ± SD; categorical variables as percentages. Comparisons between stages 4 and 5 were performed using independent t-tests for continuous variables and chi-square tests for categorical variables. Statistical significance was set at p<0.05.

Demographic and Clinical Characteristics The study population included 120 patients with a mean age of 59.1 ± 12.1 years. Males constituted 60% (n=72) of the study population. Diabetes was present in 60% of patients, and hypertension in 79.2% (Table 1). There were no statistically significant differences in age, sex distribution, or comorbidities between stage 4 and stage 5 patients. Table 1. Demographic and clinical characteristics of study population Parameter CKD Stage 4 (n=70) CKD Stage 5 (n=50) Total (n=120) Age (years) 58.3 ± 12.4 60.1 ± 11.8 59.1 ± 12.1 Male/Female 42/28 30/20 72/48 Diabetes (%) 40 (57.1%) 32 (64%) 72 (60%) Hypertension (%) 55 (78.5%) 40 (80%) 95 (79.2%) Prevalence of Anemia Anemia was highly prevalent, affecting 78.3% (n=93) of the total study population. Among stage 4 patients, 62.9% were anemic, whereas almost all stage 5 patients (98%) were anemic (Table 2). The prevalence of moderate to severe anemia increased with CKD progression. Table 2. Prevalence of anemia in CKD stages 4 and 5 CKD Stage Number of Patients Number Anemic Prevalence (%) 4 70 44 62.9 5 50 49 98 Total 120 93 78.3 Hematological and Iron Parameters Mean hemoglobin was significantly lower in stage 5 patients (8.9 ± 1.6 g/dL) compared to stage 4 (10.5 ± 1.8 g/dL, p<0.001). Ferritin levels were slightly lower in stage 5 (160 ± 60 ng/mL) than stage 4 (180 ± 75 ng/mL), though not statistically significant (p=0.08). Transferrin saturation (TSAT) was lower in stage 5 patients (20 ± 5%) compared to stage 4 (22 ± 6%), approaching statistical significance (p=0.05) (Table 3). Table 3. Hematological and iron parameters Parameter CKD Stage 4 CKD Stage 5 p-value Hb (g/dL) 10.5 ± 1.8 8.9 ± 1.6 <0.001 Ferritin (ng/mL) 180 ± 75 160 ± 60 0.08 TSAT (%) 22 ± 6 20 ± 5 0.05

The present study demonstrated a high prevalence of anemia among adults with CKD stages 4 and 5, with an overall prevalence of 78.3%. This finding is in agreement with previous reports showing that anemia becomes increasingly common as kidney function declines, particularly in advanced non-dialysis CKD. Stauffer and Fan reported a substantial burden of anemia among CKD patients in the United States, with prevalence rising markedly in later stages of disease [6]. Similar observations were reported in the MICENAS I study from Catalonia, where Cases-Amenós et al. documented a high prevalence of anemia in patients with stages 3–5 CKD not on dialysis, emphasizing that anemia is a frequent and clinically relevant complication in advanced renal impairment [7]. Our findings also support the well-established stage-wise progression of anemia severity in CKD. Ryu et al., in the KNOW-CKD cohort, showed that anemia prevalence increased with worsening CKD stage and that many patients remained undertreated despite the recognized burden of disease [8]. Likewise, Wong et al. found that anemia and iron deficiency were common among patients with CKD stages 3–5ND, and that these abnormalities were often under-evaluated and variably managed in routine clinical practice [10]. The higher prevalence observed in our stage 4 and stage 5 population is therefore biologically and clinically expected, as advanced nephron loss leads to a progressive decline in erythropoietin production and impaired maintenance of hemoglobin levels [8,10]. The present study also identified iron deficiency in a considerable proportion of patients, which is consistent with existing literature. Ryu et al. demonstrated that anemia in CKD is frequently accompanied by disordered iron homeostasis, contributing substantially to reduced hemoglobin levels [8]. Wong et al. similarly reported that iron deficiency, both absolute and functional, was common in non-dialysis CKD and often insufficiently assessed [10]. These findings support our observation that iron deficiency is an important coexisting factor in CKD-associated anemia and should be actively evaluated in advanced-stage patients. Comparable epidemiological data have been reported across different healthcare settings. St Peter et al. showed that anemia in non-dialysis CKD was associated not only with a high prevalence but also with significant treatment burden and healthcare resource utilization, underlining its clinical and economic importance [9]. Alagoz et al. reported a high prevalence of anemia in predialysis CKD and further suggested that center-specific and population-specific factors may influence the observed burden [11]. Sofue et al., using a large Japanese CKD database, also confirmed that anemia is highly prevalent in CKD patients and becomes more frequent with advancing stage, further reinforcing the consistency of our findings with global evidence [12]. The pathophysiology of anemia in CKD is multifactorial. The principal mechanism is erythropoietin deficiency due to progressive loss of functional renal mass. In addition, iron deficiency, chronic inflammation, and uremic toxin accumulation play major roles in suppressing erythropoiesis and shortening red blood cell survival [8,10]. Inflammatory pathways may impair iron mobilization and utilization, producing a state of functional iron deficiency even when total body iron stores are not severely depleted [10]. Advanced CKD is also commonly accompanied by comorbid conditions such as diabetes and hypertension, which may further aggravate renal damage and contribute indirectly to worsening anemia [9,12]. Taken together, the findings of the present study confirm that anemia is highly prevalent in adults with CKD stages 4 and 5 and closely parallels the severity of renal dysfunction. The similarity of our results with those reported in different populations and healthcare systems highlights that anemia remains a major complication of advanced CKD worldwide [6]-[12]. Early recognition and systematic evaluation of hemoglobin status and iron parameters in patients with advanced CKD are therefore essential to reduce morbidity and improve overall disease management. Clinical Implications: Early detection and management of anemia in CKD are crucial. KDIGO guidelines recommend regular monitoring of hemoglobin, iron studies, and the judicious use of erythropoiesis-stimulating agents (ESAs) alongside iron supplementation [1,8]. Our findings emphasize that almost all stage 5 CKD patients require intervention to prevent cardiovascular complications and improve quality of life. Limitations: Single-center, cross-sectional design limits generalizability. Laboratory markers like hepcidin and reticulocyte count were not measured. Longitudinal follow-up to assess response to treatment was not included. Future Directions: Multicenter prospective studies are needed to assess the impact of anemia correction on cardiovascular outcomes and mortality in advanced CKD patients. Additionally, studies evaluating novel therapies, such as hypoxia-inducible factor prolyl hydroxylase inhibitors, could be valuable.

Anemia is a prevalent and clinically significant complication in adults with CKD stages 4 and 5. The prevalence increases markedly with worsening kidney function, and iron deficiency is a common contributing factor. Early identification and comprehensive management, including iron supplementation and ESAs, are essential to improve patient outcomes, reduce morbidity, and enhance quality of life. Regular monitoring of hematological parameters should be incorporated into routine CKD care.

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