Urinary cytokines after hematopoietic cell transplantation: Evidence for renal inflammation in the pathogenesis of proteinuria and kidney disease

Abstract

We compared urinary levels of cytokines in patients with and without albuminuria, proteinuria, and kidney disease (GFR < 60 ml/min/1.73m ²) after hematopoietic cell transplant (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, IL10, IL15, MCP1 and urine albumin to creatinine ratios (ACR). Cox-proportional hazards modeling examined associations between urinary cytokine levels and development of these renal endpoints. 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, HR=1.91; 95%CI:1.27-2.87; for ACR >300, HR=2.82; 95%CI:1.60-4.98).

After HCT, elevated urinary levels of proinflammatory cytokines are associated with development of albuminuria and proteinuria, suggesting early intrarenal inflammation as an important pathogenetic mechanism. Albuminuria and proteinuria within the first 100 days post-HCT are associated with decreased overall survival.