Predicting outcome of IgA nephropathy by use of urinary epidermal growth factor: monocyte chemotactic peptide 1 ratio.

BACKGROUND. Tubulointerstitial damage in patients with IgA nephropathy is associated with increased urinary levels of monocyte chemotactic peptide 1 (MCP1; CCL2) and reduced urinary levels of epidermal growth factor (EGF). OBJECTIVE. To determine whether the ratio of EGF to MCP1 in the urine predicts progression of IgA nephropathy. DESIGN AND INTERVENTION. Consecutive patients who had undergone renal biopsy at the Renal Unit of the University of Bari, Italy and who were diagnosed with IgA nephropathy between January 1995 and December 2000 were recruited for this prospective cohort study. Secondary IgA deposition and use of corticosteroids or immunosuppressants were exclusion criteria. Levels of EGF and MCP1 were determined by enzyme-linked immunosorbent assay in morning urine samples obtained at the time of biopsy. Follow-up visits took place every 3-6 months until December 2005. OUTCOME MEASURE. The end point was a composite of doubling of baseline serum creatinine level and development of end-stage renal disease (i.e. need for dialysis or transplantation). RESULTS. The cohort comprised 132 patients, of whom 91 (69%) were male and 41 (31%) were female. The mean age at biopsy was 31.6+11.4 years, and follow-up continued for a median of 54 months (range 35-84 months). The majority of participants (74%) received angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers during followup. When the cohort was divided into tertiles according to EGF:MCP1 ratio, the lowest tertile had a higher prevalence of macrohematuria, hypertension, and severe nephropathy, higher mean levels of serum creatinine and proteinuria, and lower mean estimated creatinine clearance at baseline, than the highest tertile (P=0.03, P<0.0001, P<0.0001, P<0.0001, P=0.003 and P<0.0001, respectively). The rate of renal survival was greater in the highest tertile than in the middle or lowest tertiles (100% vs 94% vs 73% at 4 years and 100% vs 94% vs 36% at 7 years). In multivariate Cox regression analysis, the urinary EGF:MCP1 ratio was significantly associated with the composite end point after adjustment for factors including age proteinuria and histologic grade (P= 0.002). The area under a receiver operating characteristic (ROC) curve for prediction of the composite end point was 0.91 (95% CI 0.85-0.96) for urinary EGF:MCP1 ratio, 0.83 (95% CI 0.76-0.89) for urinary EGF level and 0.57 (95% CI 0.49-0.66) for urinary MCP1 level, indicating that urinary EGF:MCP1 ratio predicted renal outcome better than either EGF level or MCP1 level alone (P=0.01 and P<0.001, respectively). Urinary EGF:MCP1 ratio was also a better outcome predictor than estimated creatinine clearance, histologic grade and proteinuria in the ROC analysis (P=0.002, P=0.005 and P=0.004, respectively). At a cutoff of 23.2, urinary EGF:MCP1 ratio had a sensitivity and specificity of 88.9% and 86.4%, respectively, for prediction of the composite end point. CONCLUSION. Urinary EGF:MCP1 ratio seems to reliably predict renal outcome in IgA nephropathy and could identify patients who require more-intensive follow-up and treatment. [ABSTRACT FROM AUTHOR]