Pretransplant positivity for circulating thyroid antibodies and graft survival in patients undergoing kidney transplant.

BACKGROUND: Thyroid disturbances are common in kidney graft recipients and they may influence graft function. CXC chemokine ligand 10 plays a role in both autoimmune thyroiditis and graft rejection. Thyroid antibody (Ab) positivity has been regarded as a marker of imbalance of the immune system. AIM: To relate pretransplant positivity for antithyroperoxidase (TPO) Ab and antithyroglobulin (Tg) Ab with kidney graft outcome. METHODS: Pretransplant thyroid antibodies were measured in 211 kidney graft recipients. RESULTS: The 5-year death-censored graft survival rate was 91.5%. Pretransplant circulating Tg Ab and TPO Ab were detected in 12 (5.7%) and 13 (6.2%) patients, respectively. Lifetime analysis showed similar 5-year graft survival rates in patients negative or positive for Tg Ab and TPO Ab (91.5 vs. 91.7% for Tg Ab and 91.9 vs. 84.6% for TPO Ab). However, patients with pretransplant positivity for TPO Ab showed a significantly lower 5-year graft survival when early graft loss (12 months after transplant) was excluded (84.6 and 96.8% for TPO Ab+ and TPO Ab- patients, respectively; p < 0.05). Occurrence of acute rejection and chronic allograft nephropathy was unrelated to thyroid Ab positivity. Serum CXC chemokine ligand 10 levels were similar independent of Tg Ab and TPO Ab positivity. CONCLUSION: Pretransplant positivity for TPO Ab may affect long-term graft survival in kidney graft recipients independent of occurrence of acute rejections and chronic allograft nephropathy.

Predictive role of pretransplant serum CXCL10 for cardiac acute rejection.

BACKGROUND: The detection of acute rejection in heart transplantation remains an important feature of transplant management, especially in the early phase. Frequent surveillance with endomyocardial biopsy is necessary, even though it is an invasive procedure and carries a certain risk. Hence, noninvasive biomarkers able to predict acute rejection could be a further helpful tool in patient management. The interferon-gamma-inducible chemokine CXCL10 is required for initiation and development of graft failure caused by acute or chronic rejection. It has been reported that CXCL10 serum level is predictive of graft loss in kidney graft recipients. In the present study, we investigated whether pretransplant CXCL10 serum level may be a predictive noninvasive biomarker in heart transplant (HTx) recipients, as well. METHODS: Sera from 143 patients undergoing orthotopic heart transplantation were collected before surgery and tested for CXCL10 and CCL22 and compared with serum samples from healthy subjects. RESULTS: We found that basal CXCL10 serum levels in HTx recipients were significantly higher than in healthy subjects, whereas no difference was seen in CCL22 levels. Among HTx recipients, CXCL10 serum levels of rejectors were significantly higher than in nonrejectors. Our results showed that CXCL10 was a significant independent risk factor of several variables and had the highest predictive value for early acute heart rejection, with 160 pg/mL cutoff value. CONCLUSIONS: In HTx recipients, measurement of pretransplant CXCL10 serum levels could be a clinically useful tool for predicting cardiac acute rejection, especially in the early posttransplant period.

Pretransplant serum FT3 levels in kidney graft recipients are useful for identifying patients with higher risk for graft failure.

OBJECTIVE: End-stage renal disease (ESRD) is a condition associated with thyroid disturbances both in function and morphology. Recent studies demonstrated that serum free triiodothyronine 3 (FT3) levels are negatively correlated with serum markers of inflammation and endothelial activation in patients with ESRD. However, no previous research evaluated serum thyroid function parameters in relation to kidney graft outcome, as we aim to do so in this study. DESIGN: Serum FT3, free thyroxine 4 (FT4) and TSH levels were measured before transplantation in 196 kidney graft recipients. RESULTS: The graft survival rate at 5 years for all patients was 92.3%. Kidney graft recipients with normally functioning grafts showed serum pretransplant thyroid parameters similar to patients who experienced graft failure. Life-time analysis was performed after stratification of patients according to pretransplant serum FT3 levels < 3.1 pmol/l or > 3.1 pmol/l. A significantly different 5-year death-censored graft survival rate (93.9%vs. 76.5% for patients with normal or low FT3 levels, respectively; P < 0.01) and similar survival rate (death of patients with functioning grafts) (21.1%vs. 5.9%; P = 0.288) were observed. No similar feature was found for FT4 or TSH, suggesting that the effect is not related to hypothyroidism but rather dependent upon inappropriately low FT3 levels. Pretransplant serum FT3 levels were similar in patients who experienced early acute rejections as compared with nonrejector patients. CONCLUSIONS: The results of this study demonstrate that among patients with ESRD undergoing kidney transplantation, those displaying lower pretransplant serum FT3 levels are at higher risk for subsequent graft failure. The demonstration of a predictive value of serum FT3 levels for graft survival suggests that measurement of pretransplant serum FT3 levels might represent a clinically useful parameter to identify patients with increased risk for graft failure.

High CXCL10 expression in rejected kidneys and predictive role of pretransplant serum CXCL10 for acute rejection and chronic allograft nephropathy.

BACKGROUND: Several experimental models have shown that CXCL10 is required for initiation and development of graft failure caused by both acute and chronic rejection. METHODS: CXCL10 expression and distribution was investigated in tissue specimens obtained from 22 patients suffering from acute rejection (AR) or chronic allograft nephropathy (CAN) by using in situ hybridization. Furthermore, pretransplantation sera of 316 cadaveric kidney-graft recipients were tested retrospectively for serum CXCL10 levels by a quantitative sandwich immunoassay. RESULTS: Bioptic specimens obtained from patients with CAN were characterized by wide CXCL10 expression not only at level of infiltrating inflammatory cells but also of vascular, tubular, and glomerular structures. In addition, assessment of pretransplant serum CXCL10 levels in 316 graft recipients and stratification of patients in three groups according to serum CXCL10 levels (<100 pg/mL, n=163; 100-150 pg/mL, n=69; >150 pg/mL, n=84) showed highly significant differences in 5-year survival rates for the two extreme groups (95.7% vs. 79.7%, P=0.0002). Accordingly, patients who developed severe, early AR (277.14+/-65.08 p=0.004) and those who developed CAN also showed increased pretransplant serum CXCL10 levels (193.2+/-36.9, P=0.03). Multivariate analysis demonstrated that among the analyzed variables, CXCL10 (relative risk [RR] 2.801) and delayed graft function (RR 3.728) had the highest predictive power of graft loss. CONCLUSIONS: These results suggest that pretransplant serum CXCL10 levels greater than 150 pg/mL confer an increased risk of early, severe, AR and subsequent CAN, finally resulting in renal-allograft failure. This finding might be used for the individualization of immunosuppressive therapies.

High pretransplant serum levels of CXCL10/IP-10 are related to increased risk of renal allograft failure.

In experimental models, the chemokine CXCL10/IP-10 is required for graft failure owing to both acute and chronic rejection. In the present study, pretransplantation sera from 316 cadaver kidney graft recipients were tested for serum CXCL10 and CCL22/MDC levels by an ELISA assay. Kidney graft recipients with normally functioning grafts showed significantly lower serum CXCL10 levels than patients who experienced graft failure, whereas no differences for serum CCL22 levels were observed. After the assignment of all patients to four groups according to serum CXCL10 levels, the death-censored survival rates of grafts were 97.5%, 93.6%, 89.7%, 78.7% (p = 0.0006) at 5 years, while no influence was observed on patient survival. Accordingly, patients with the highest CXCL10 levels showed an increased frequency and severity of rejection episodes. Serum C-reactive protein (CRP) level was also assayed in the same samples. Increase of serum CRP levels represented a predictive parameter for death, but not for graft failure. Multivariate analysis demonstrated that among the analyzed variables, CXCL10 had the highest predictive power of graft loss (RR 2.787). Thus, measurement of pretransplant serum CXCL10 levels might represent a clinically useful parameter to identify subjects who are at high risk of severe rejection and graft failure.