Mass spectrometry-based proteomic analysis of proteins adsorbed by hexadecyl-immobilized cellulose bead column for the treatment of dialysis-related amyloidosis.

BACKGROUND: Dialysis-related amyloidosis (DRA) is a severe complication in end-stage kidney disease (ESKD) patients undergoing long-term dialysis treatment, characterized by the deposition of ß2-microglobulin-related amyloids (Aß2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating ß2-microglobulin (ß2M). However, it is possible that the HICB also adsorbs other molecules involved in amyloidogenesis. METHODS: We enrolled 14 ESKD patients using HICB columns for DRA treatment; proteins were extracted from HICBs following treatment and identified using liquid chromatography-linked mass spectrometry. We measured the removal rate of these proteins and examined the effect of those molecules on Aß2M amyloid fibril formation in vitro. RESULTS: We identified 200 proteins adsorbed by HICBs. Of these, 21 were also detected in the amyloid deposits in the carpal tunnels of patients with DRA. After passing through the HICB column and hemodialyzer, the serum levels of proteins such as ß2M, lysozyme, angiogenin, complement factor D and matrix Gla protein were reduced. These proteins acted in the Aß2M amyloid fibril formation. CONCLUSIONS: HICBs adsorbed diverse proteins in ESKD patients with DRA, including those detected in amyloid lesions. Direct hemoperfusion utilizing HICBs may play a role in acting Aß2M amyloidogenesis by reducing the amyloid-related proteins.

Hypobilirubinemia might be a possible risk factor of end-stage kidney disease independently of estimated glomerular filtration rate.

BACKGROUND/AIMS: The relationship between serum total bilirubin (TB) and estimated glomerular filtration rate (eGFR) is controversial and there is no report on the association between TB and end-stage kidney disease (ESKD). METHODS: We examined the cross-sectional association between TB and eGFR and investigated whether TB can predict ESKD with multivariable logistic regression adjusted for age, sex, and baseline eGFR using hospital-based data. RESULTS: The geometric mean TB of patients with eGFR ≥ 90 mL/min/1.73 m2 (S1), 8960 mL/min/1.73 m2 (S2), 59-30 mL/min/1.73 m2 (S3), 29-15 mL/min/1.73 m2 (S4), and < 15 mL/min/1.73 m2 (S5 = ESKD) was 0.55 mg/dL, 0.59 mg/dL, 0.56 mg/dL, 0.47 mg/dL, and 0.36 mg/dL (all p<0.0001 except for S1 vs. S3 where p=0.3726), respectively excluding patients with hyperbilirubinemia (TB > 1.24 mg/dL). The odds ratio (95% confidence interval) of incident ESKD for each 0.1 mg/dL increase in TB and hypobilirubinemia defined as TB ≤ 0.34 mg/dL were 0.92 (0.80-1.07) (p=0.2804) and 3.51 (1.56-7.88) (p=0.0023), respectively in patients with baseline eGFR ≥ 15 mL/min/1.73 m2 and 0.59 (0.37-0.95) (p=0.0283) and 6.03 (1.63-22.30) (p=0.0071), respectively in patients with baseline eGFR 29-15 mL/min/1.73 m2. CONCLUSIONS: Hypobilirubinemia might be a possible risk factor of ESKD.