Serum levels of anti-alphaGalactosyl antibodies predict survival and peritoneal dialysis-related enteric peritonitis rates in patients undergoing renal replacement therapy.
BACKGROUND
Anti-Galalpha1-3Gal antibodies (anti-alphaGal) represent a significant fraction of natural antibodies and were implicated in several disease states, yet their origin and physiological significance remain largely undisclosed.


METHODS
Under a prospective observational design, we estimated anti-alphaGal immunoglobulin G (IgG)/IgM and antipig hemolytic antibody (APA) levels in 133 patients starting dialysis therapy and again after a 1-year follow-up. We used baseline data to show correlations with demographic, nutritional, inflammatory, and anemia markers and analyzed their correlation with outcomes by using univariate and multivariate strategies of survival analysis.


RESULTS
Serum anti-alphaGal and APA levels showed wide baseline variability, but remained relatively stable in time. Both were measurable in dialysate of peritoneal dialysis (PD) patients, showing close correlation to serum levels. We observed no association between levels of anti-alphaGal/APA and nutritional markers, but showed direct correlations of anti-alphaGal IgM (P = 0.005) and APA levels (P = 0.001) with tumor necrosis factor alpha (TNF-alpha) levels. High APA levels also were associated with severe anemia (P = 0.006). High baseline anti-alphaGal IgM (P = 0.03) and APA levels (P = 0.045) predicted later risk for enteric peritonitis in PD patients. Finally, univariate and multivariate analyses showed a consistent association between high baseline anti-alphaGal IgM (P = 0.014) and APA (P = 0.021) levels and global risk for mortality during follow-up.


CONCLUSIONS
Anti-alphaGal IgM and APA levels at the start of dialysis therapy are significant predictors of later risk for mortality and, in PD patients, enteric peritonitis. Both correlate directly with TNF-alpha levels and, in the case of APA, severity of anemia in these patients.
Fontán
Miguel Pérez
MP
Division of Nephrology and Laboratory of Biochemistry, Hospital Juan Canalejo, Xubias 84, 15006 A Coruña, Spain. mfontan@canalejo.org
Máñez
Rafael
R
Rodríguez-Carmona
Ana
A
Peteiro
Javier
J
Martínez
Verónica
V
García-Falcón
Teresa
T
Domenech
Nieves
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000906:Antibodies / Q000097:blood*; D000910:Antibodies, Heterophile / Q000097:blood / Q000276:immunology; D001202:Ascitic Fluid / Q000276:immunology; D016009:Chi-Square Distribution; D002648:Child; D004187:Disaccharides / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000097:blood*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000628:therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010538:Peritonitis / Q000453:epidemiology* / Q000209:etiology / Q000382:microbiology / Q000401:mortality; D017582:Renal Replacement Therapy; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000906:Antibodies; D000910:Antibodies, Heterophile; D004187:Disaccharides; D000939:Epitopes; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C055075:galactosyl-(1-3)galactose