Urinary cytokines after HCT: evidence for renal inflammation in the pathogenesis of proteinuria and kidney disease

We compared urinary levels of cytokines in patients with and without albuminuria, proteinuria and kidney disease (glomerular filtration rate < 60 mL/min per 1.73m2) after HCT. Plasma and urine were collected at baseline and weekly through day 100 and monthly through year 1, for measurement of IL-6, gp130, sIL6r, IL-10, IL15, MCP-1 and urine albumin-to-creatinine ratios (ACRs). Coxproportional hazards modeling examined associations between urinary cytokine levels and development of these renal end points. The association of ACR with the hazard of overall mortality was assessed using Cox regression. Increasing urinary IL-6 and IL-15 were associated with an increased risk of developing proteinuria. Urinary MCP-1 during the first 100 days post HCT was associated with kidney disease at 1 year. The degree of albuminuria at any time point in the first 100 days post transplant was related to the subsequent risk of death (for ACR 30-299, hazard ratio (HR)=1.91; 95% confidence interval (CI): 1.27-2.87; for ACR > 300, HR=2.82; 95% CI: 1.60-4.98). After HCT, elevated urinary levels of pro-inflammatory cytokines are associated with development of albuminuria and proteinuria, suggesting early intra-renal inflammation as an important pathogenetic mechanism. Albuminuria and proteinuria within the first 100 days post HCT are associated with decreased overall survival.