Iron indices in chronic kidney disease in the National Health and Nutritional Examination Survey 1988-2004

Abstract

Background and objectives: Anemia is a common and early complication of nondialysis chronic kidney disease (CKD). One contributing factor is iron deficiency, which may be particularly problematic during erythropoietin replacement therapy. The aim of this study was to examine the prevalence of iron deficiency in nondialysis CKD.

Design, setting, participants, & measurements: The National Health and Nutritional Examination Survey (NHANES) data for NHANES III (1988 to 1994) and subsequent NHANES 2-yr datasets, 1999 to 2000, 2001 to 2002, and 2003 to 2004 were analyzed for individuals >18 yr old.

Results: It was found that low levels of iron tests [either serum ferritin < 100 ng/ml or transferrin saturation (TSAT) < 20%] were present in most patients with reduced creatinine clearance (CrCl). The percentage of low iron tests was higher among women than men, present in 57.8 to 58.8% of men and 69.9 to 72.8% of women (P < 0.001). With declining levels of CrCl, in women, TSAT levels decreased, whereas, surprisingly, serum ferritin tended to progressively increase. The percentage of anemic subjects increased progressively with declining quartiles of TSAT but was unrelated to serum ferritin quartiles.

Conclusions: It was found that low levels of iron tests, following National Kidney Foundation/Kidney Disease Outcomes Quality Initiative guidelines (either serum ferritin < 100 ng/ml or TSAT < 20%) were present in most patients with reduced CrCl.

Figure 1.

Percentage of subjects in each creatinine clearance (CrCl) classification for the combined cohorts (n = 34,782), chronic kidney disease (CKD) stage 5, CrCl 0 to 14.9, 0.2%; CKD stage 4, CrCl 15 to 29.9, 0.8%; CKD stage 3, CrCl 30 to 59.9, 9.9%; CrCl 60 to 90 (may be confused with CKD stage 2), 20.7%; CrCl > 90, 68.4%.

Figure 2.

The percentage of men and women with either serum ferritin < 100 ng/ml or transferrin saturation (TSAT) < 20% at different levels of CrCl for the combined National Health and Nutritional Examination Survey (NHANES) cohorts. National Kidney Foundation (NKF) CKD stages relative to CrCl are stage 5, 0 to 14.99; stage 4, 15 to 29.99; and stage 3, 30 to 59.99. Patients with CrCl 60 to 90 ml/min may have CKD stage 2. Patients with CrCl > 90 ml/min may have CKD stage 1 if other renal abnormalities are present.

Figure 3.

Mean (a) serum ferritin and (b) TSAT as a function of CrCl for the combined NHANES cohorts (error bars are SD). The trend for both TSAT and ferritin is NS for men but for women P < 0.0001 for serum ferritin and P < 0.02 for TSAT. NKF CKD stages relative to CrCl are stage 5, 0 to 14.99; stage 4, 15 to 29.99; and stage 3, 30 to 59.99. Patients with CrCl 60 to 90 ml/min may have CKD stage 2. Patients with CrCl > 90 ml/min may have CKD stage 1 if other renal abnormalities are present.

Figure 4.

Percentage of individuals defined as iron deficient using different threshold combinations of serum ferritin and TSAT. The NKF Kidney Disease Outcomes Quality Initiatives (KDOQI) thresholds of serum ferritin 100 ng/ml and TSAT 20% are different than indices of iron deficiency in the non-CKD population in which lower thresholds are generally used. The light blue bars indicate AND logic, both test results below the specified threshold, whereas the dark blue bars indicate OR logic, with either test result being below the threshold.

Figure 5.

There was no observable trend for mean hemoglobin (Hgb) by quartiles of serum ferritin (dark bars) (P = NS). The trend for mean Hgb by quartiles of TSAT (light bars) was significant, P < 0.0001 in the combined NHANES cohorts for patients with CrCl < 60 ml/min.