Anemia and Low-grade Inflammation in Pediatric Kidney Transplant Recipients

Background: Anemia and low-grade inflammation are reported to be associated with impaired long-term graft outcome in renal transplant (RTx) recipients. In this study, hemoglobin (Hb) and inflammation marker levels were correlated with measured glomerular filtration rate (GFR) in 128 pediatric RTx recipients over a median follow-up period of 10 years.

Methods: Serum levels of erythropoietin (EPO), hepcidin-25, high-sensitivity C-reactive protein (CRP) (hsCRP) and interleukin-6 (IL-6) were analyzed by enzyme-linked immunosorbent assays, and GFR was analyzed by Cr-EDTA clearance.

Results: The median levels of Hb (115 g/L), hsCRP (0.4 mg/L) and IL-6 (1.4 pg/mL) and the median erythrocyte sedimentation rate (ESR; 19 mm/h) remained stable after the first post-operative year. However, approximately half of the patients had a normocytic, normochromic anemia, and one-third had elevated levels of hsCRP (>1 mg/L) and ESR (>25 mm/h), indicating continuous low-grade inflammation. Low Hb levels preceded increased fibrosis in protocol biopsies taken at 1.5 and 3 years after transplantation and preceded decreased GFR by several years. Hb levels showed an inverse correlation with EPO levels (r = -0.206, p = 0.038) and ESR (r = -0.369, p < 0.001), but not with hepcidin-25, hsCRP or IL-6 levels. The levels of the major inflammatory markers IL-6 and hsCRP did not show a significant correlation with GFR at either the early maintenance phase or later. In the multivariable analysis, low Hb levels performed better than any other marker with respect to predicting concomitant and subsequent GFR.

Conclusions: Anemia, but not elevated inflammatory indices, was associated with poor concomitant and subsequent graft function during a 10-year follow-up in pediatric RTx patients.