Table 1Study eligibility criteria

Key Question/PICOInclusion Criteria
Key Question 1 (Overarching Question)
Populations
  • Pediatric and adult nondialysis patients with stage 3, 4, or 5 CKD
  • Patients with CKD undergoing dialysis (hemo- or peritoneal dialysis)
  • Patients with a kidney transplant
Interventions
  • Newer laboratory biomarkers* to assess iron status and manage iron deficiency either as a replacement for or in addition to older laboratory biomarkers
Comparators
  • Older laboratory biomarkers to assess iron status and manage iron deficiency
Outcomes
  • Mortality
  • Morbidity (e.g., cardiac or liver toxicity and infection)
  • Quality of life, measured using standardized scales, including: Kidney Disease Quality of Life (KDQOL), Health Related Quality of Life (HRQOL), Medical Outcomes Study Short Form-36 (SF-36), and Pediatric Quality of Life Inventory (PQLI)
  • Adverse effects or harms associated with testing and associated treatments (e.g., test-related anxiety, adverse events secondary to venipuncture, effects of iron overload with iron treatments, and cardiovascular complications from use of erythropoietin at higher Hb levels)
Study designs
  • Randomized controlled trials
  • Nonrandomized controlled trials
  • Observational studies with concurrent comparison groups
Key Question 2, 3 and 4
Populations
  • Pediatric and adult nondialysis patients with stage 3, 4, or 5 CKD
  • Patients with CKD undergoing dialysis (hemo- or peritoneal dialysis)
  • Patients with a kidney transplant
Interventions
  • Newer laboratory biomarker alonea or in combination with older laboratory biomarkers of iron statusb
Comparators
  • Older laboratory biomarkers of iron status, which include bone marrow iron stores, serum iron, transferrin saturation, iron-binding capacity, and ferritin
OutcomesKey Question 2 and 4:
  • Measures of test performance (e.g., concordance, sensitivity, specificity, predictive values, AUC) comparing newer with older markers of iron status. We accepted any “reference standard” used by the study authors for the analyses of sensitivity and specificity in the original study, including functional iron deficiency as defined by response or nonresponse to treatment
  • Adverse effects or harms associated with laboratory testing
Key question 3 and 4:
  • Intermediate outcomes
  • Increase in Hb or hematocrit, or more consistent maintenance of Hb or hematocrit within the desired range
  • Use of ESA for maintenance of Hb within the desired range (stable dose in contrast to escalating dose resulting in net decreased ESA dose in hyporesponsive patients or actual decreased ESA dose in relatively responsive patients)
  • Adverse effects or harms associated with different management strategies
Study designsKey Question 2:
  • Any design
Key Question 3 and 4:
  • Randomized controlled trials
  • Nonrandomized controlled trials
  • Observational studies with concurrent comparison groups
Study settings
  • Any setting: primary or specialty care, in-facility or home, and inpatient or outpatient

AUC=area under the curve; CKD=chronic kidney disease; ESA= erythropoiesis stimulating agents; Hb=hemoglobin; HD=hemodialysis; IV=intravenous; RetHe=reticulocyte hemoglobin equivalent; sTfR= soluble transferrin receptor; TSAT=transferrin saturation; ZPP=erythrocyte zinc protoporphyrin.

a

Hemoglobin (Hb) content in reticulocytes, percentage of hypochromic red blood cells, erythrocyte zinc protoporphyrin, soluble transferrin receptor, hepcidin, and superconducting quantum interference devices.

b

Bone marrow iron stores, serum iron, transferrin saturation, iron-binding capacity, and ferritin.

Hemoglobin (Hb) content in reticulocytes, percentage of hypochromic red blood cells, erythrocyte zinc protoporphyrin, soluble transferrin receptor, hepcidin, and superconducting quantum interference devices.

Bone marrow iron stores, serum iron, transferrin saturation, iron-binding capacity, and ferritin.

From: Methods

Cover of Biomarkers for Assessing and Managing Iron Deficiency Anemia in Late-Stage Chronic Kidney Disease
Biomarkers for Assessing and Managing Iron Deficiency Anemia in Late-Stage Chronic Kidney Disease [Internet].
Comparative Effectiveness Reviews, No. 83.
Chung M, Moorthy D, Hadar N, et al.

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