Iron Deficiency Is Prevalent in Patients With Non-Anemia, Non-Dialysis-Dependent-CKD

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Iron deficiency appears frequently in patients who have chronic kidney disease (CKD), including those without anemia. Despite this knowledge, the effects of iron deficiency on CKD progression and all-cause mortality in patients with non-dialysis-dependent (NDD)-CKD (NDD-CKD) without anemia are unknown. Authors of a study published in Nutrition Journal investigated the association between iron deficiency and the risks of CKD progression and all-cause mortality.

This multicenter, retrospective, nationwide cohort study included adult patients with non-anemia NDD-CKD from 24 hospitals across China from January 1, 2000, to December 31, 2022. The study investigated the associations between serum ferritin or transferrin saturation (TSAT) levels and the risks of CKD progression and all-cause mortality.

All enrolled patients were aged 18 years or older with CKD who underwent at least one serum ferritin test or TSAT test in the China Renal Data System. The investigators defined CKD based on 1 of the following criteria: International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes; estimated glomerular filtration rates (eGFR) less than 60 ml/min/1.73 m² for more than 3 months; or at least 2 abnormal urine protein tests for more than 3 months.

eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). Abnormal urine protein was defined as one of the following: qualitative urine protein detection greater than 1+; 24-hour urine protein quantitation over 0.3 g; or urine albumin to creatinine over 300 mg/g. Patients who had either ferritin or TSAT, or both, were included in the study. Additionally, baseline was defined as the first hospitalization with available ferritin or TSAT.

The investigators used 2 datasets for analytical purposes. The dataset for the analysis of kidney disease progression did not include patients without repeated eGFR measurement after discharge, and the dataset for the analysis of all-cause mortality did not include patients without identifiable information from the national electronic cause-of-death reporting system of the China Center for Disease Control and Prevention.

The primary outcome was the progression of CKD, which was defined as a composite of a sustained decrease in eGFR over 40% from baseline (excluding the occurrence of acute kidney injury) or the development of end-stage kidney disease (ESKD; eGFR < 15 ml/min/1.73 m² or the need for maintenance dialysis or kidney transplantation). Follow-up was discontinued when patients either reached the study outcome or when their last available serum creatinine measurement was recorded. The secondary outcome was all-cause mortality, which was determined using records from the national electronic cause-of-death reporting system. Follow-up commenced at discharge and continued until either death or the last date recorded in the electronic medical record.

Among the enrolled 18,878 patients with NDD-CKD, 9989 patients were included in the kidney outcome analysis, and 18,481 patients were included in the all-cause mortality analysis. Of the patients with the measurement, approximately 27.2% (n = 2450) had ferritin levels equal to or less than 100 ng/mL and 13.1% (n = 2440) had a TSAT level equal to or less than 20%. Compared with patients who had a TSAT level over 20%, those with TSAT level of equal to or less than 20% had significantly higher risks of both CKD progression (aHR: 1.66, 95% CI: 1.16–2.37; P = .005) and all-cause mortality (aHR: 2.21, 95% CI: 1.36–3.57; P = .001).

Interestingly, patients with ferritin levels at or below 100 ng/mL were younger, more likely to be female, had lower eGFR levels, and lower hemoglobin concentration. Patients with TSAT levels at or below 20% were also more likely to be female, and they had lower levels of both proteinuria and hemoglobin.

Iron deficiency was prevalent in patients with NDD-CKD and without anemia. Additionally, the authors believe that TSAT may be a modifiable risk factor of CKD progression and all-cause mortality. The screening of iron biomarkers—particularly in TSAT—in the early stage of NDD-CKD is significant to assess and improve prognosis. The strength of results was supported by subgroup analyses; however, there was no significant association found between ferritin levels and the risk of CKD progression or all-cause mortality (P > 0.05), according to the authors.

REFERENCE

Yu H, Shao X, Guo Z, et al. Association of iron deficiency with kidney outcome and all-cause mortality in chronic kidney disease patients without anemia. Nutr J. 2025;24(7). doi:10.1186/s12937-025-01072-1