Influence of C-reactive protein and urinary protein excretion on prediction of graft failure and mortality by serum albumin in renal transplant recipients

Hypoalbuminemia is an established predictor of poor outcome in renal transplant recipients (RTR). It is considered to reflect inflammation, poor nutritional status, or proteinuria. We explored the roles of high-sensitivity C-reactive protein (hsCRP) and urinary protein excretion in prediction of graft failure and mortality by serum albumin in RTR. We included 605 RTR at a median (interquartile range) time of 6.0 years (2.5-11.5 years) after transplantation for baseline measurements. At baseline, urinary protein excretion (beta=-0.242, P <0.0001), hsCRP concentration (beta=-0.207, P <0.0001), recipient age (beta=-0.115, P=0.004), living kidney donor (beta=0.100, P=0.01), and a history of myocardial infarction (beta=-0.084, P=0.03) were independently related to serum albumin. Prospectively, 94 RTR died and 42 had graft failure during 5.3 years (4.7-5.7 years) of follow-up. After adjustment for potential confounders, including hsCRP and urinary protein excretion in Cox-regression analyses, low serum albumin was significantly associated with graft failure (hazard ratio=0.34 [95% confidence interval=0.15-0.76] per g/dL, P=0.008) and mortality (hazard ratio=0.43 [95% confidence interval=0.24-0.78] per g/dL, P=0.005), with significant modification of the effect of serum albumin on graft failure by urinary protein excretion (P=0.003). Low serum albumin concentrations predict graft failure and mortality in RTR independent of hsCRP and urinary protein excretion. The effect of serum albumin on graft failure is strongly modified by urinary protein excretion. These results suggest that chronic low-grade inflammation is not an important mechanism underlying inverse associations of serum albumin with graft failure and mortality. They also suggest that proteinuria is involved in the association of low serum albumin with graft failure