Elevated levels of C-reactive protein independently predict accelerated deterioration of graft function in renal transplant recipients

Chronic transplant dysfunction is characterized by a gradual decline in renal function with slowly rising serum creatinine. The underlying mechanism is thought to include inflammation and atherosclerosis. C-reactive protein (CRP) is a well-established marker of both inflammation and atherosclerosis. In this prospective study, we investigated whether CRP could be of use as a clinical marker for early identification of renal transplant recipients at increased risk of deterioration of graft function. In this prospective study, all participating patients (n = 606) visited the out-patient clinic at least once a year, and serum creatinine was assessed at every visit. Subjects with a follow-up of <1 year (n = 31) were excluded from analysis. A total of 575 patients participated at a median (interquartile range) time of 5.9 (2.6-11.3) years post-transplantation. Median time of follow-up was 3.0 (2.4-3.4) years. Changes in serum creatinine during follow-up were -0.45 (-4.83-4.76) micromol/l/year in 172 subjects with CRP <1.0 mg/l, 1.04 (-3.36-6.12) micromol/l/year in 184 subjects with CRP 1.0-3.0 mg/l and 2.34 (-3.33-9.07) micromol/l/year in 219 subjects with CRP >3.0 mg/l (P <0.05 for comparison of the three groups). Proteinuria (P = 0.003), CMV IgG titre (P = 0.01), donor age (P = 0.01), CRP concentration (P = 0.02), recipient age (P = 0.02) and recipient gender (P = 0.047) were independently associated with change in serum creatinine during follow-up in a multivariate analysis. Elevated levels of CRP independently predict accelerated deterioration of graft function in renal transplant recipients >1 year post-transplantation. Further prospective studies are required to investigate whether early intervention can prevent deterioration of graft function in subjects with elevated levels of CR

N-Terminal Pro-B-Type Natriuretic Peptide and Mortality in Renal Transplant Recipients Versus the General Population

Background. Mortality rates are higher in renal transplant recipients (RTR) than in the general population (GP). It is unknown what risk factors account for this difference. Methods. We prospectively followed a cohort of 606 RTR for 3026 person-years, during which 95 died. A GP cohort of 3234 subjects was followed for 24,940 person-years, during which 130 died. Results. All investigated risk factors, except ethnicity, body mass index, and total cholesterol, differed significantly between cohorts, with an adverse risk profile in the RTR. The age-adjusted and gender-adjusted hazard ratio for mortality in RTR was 6.2 (95% confidence interval [Cl] 4.6-8.3) compared with GP, which was reduced to 2.4 (95% Cl 1.6-3.6), 4.3 (95% Cl 3.0-6.1), and 5.0 (95% Cl 3.5-7.3) after additional adjustment for differences in N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatinine clearance, and need for antihypertensive medication, respectively (all P Conclusions. Elevated NT-proBNP, low creatinine clearance, and need for antihypertensive medication are stronger risk factors for mortality in RTR than in GP. The increased mortality seen in the RTR population may well be related to cardiac failure rather than "accelerated atherosclerosis.

Plasma Procalcitonin Is an Independent Predictor of Graft Failure Late After Renal Transplantation

Background. Chronic low-grade inflammation is involved in chronic transplant dysfunction after renal transplantation. Procalcitonin (PCT), known to reflect microbial inflammation, may also reflect ongoing noninfectious chronic low-grade inflammation in organ parenchyma, including transplanted kidneys. We aimed to compare predictive performance of plasma PCT for development of graft failure in renal transplant recipients (RTR) with that of high-sensitivity C-reactive protein (hsCRP), an established marker of systemic chronic low-grade inflammation. Methods. We included 575 RTR with functioning grafts for more than or equal to 1 year at a median (interquartile range) time of 6.1 (2.9-11.7) years posttransplant. PCT was determined using an Ultrasensitive immunoluminometric assay and hsCRP using high-sensitivity enzyme-linked immunosorbent assay. Results. Median (interquartile range) plasma PCT and hsCRP concentrations were 0.023 (0.017-0.036) ng/mL and 2.1 (0.8-4.9) mg/L, respectively. After a median (interquartile range) of 5.2 (4.5-5.7) years of follow-up, incidence of graft failure was 0.5%, 2.6%, and 18.5% according to increasing PCT tertiles (P Conclusion. We identified plasma PCT as a strong and an independent predictor of graft failure in RTR. These data suggest that PCT in RTR reflects ongoing inflammation in parenchyma of transplanted kidneys. Further studies are required to investigate whether PCT could be of use as an early biomarker for chronic transplant dysfunction

Abdominal obesity and smoking are important determinants of C-reactive protein in renal transplant recipients

C-reactive protein (CRP) is a predictor of coronary heart disease, total mortality and chronic allograft nephropathy in renal transplant recipients. The determinants of CRP have been investigated in the general population, but not in renal transplant recipients. CRP might reflect metabolic aberrations in association with central obesity and systemic atherosclerosis. However, it may also reflect a low-grade immune-mediated response to the graft. In this study we investigated the factors associated with CRP in a renal transplant population. Between August 2001 and July 2003, renal transplant recipients with a functioning graft for more than 1 year (n = 847) were eligible for investigation at their next visit to the outpatient clinic. A total of 606 patients (55% male, aged 51+/-12 years) participated at a median (interquartile range) time of 6.0 (2.6-11.4) years post-transplant. Median CRP concentration was 2.0 (0.80-4.8) mg/l and mean 24 h creatinine clearance was 62+/-22 ml/min. CRP was significantly associated with body mass index, waist circumference and waist-to-hip ratio (P-value <0.0001). None of the transplant characteristics except creatinine clearance was associated with CRP. In multiple regression analysis, waist circumference, log sICAM-1 concentration, gender, creatinine clearance and current smoking were independently associated with CRP. In renal transplant recipients waist circumference and smoking are the two most important modifiable independent determinants of CRP. Furthermore, CRP is independently associated with the endothelial function parameter sICAM-1 and, in univariate analyses, associated with multiple cardiovascular risk factors. CRP is not associated with any of the transplant-related factors, except for renal transplant functio