Effect of Thrombophilic Factors on Renal Graft Function: A Single-Center Experience.

BACKGROUND: Optimization of immunosuppressive therapy reduced the incidence of acute rejection, and therefore vascular complications, including graft thrombosis, which have emerged as the main cause of graft loss in the early post-transplant period. A thrombophilic condition may lead to renal graft loss. The aim of the study was to assess renal graft function in thrombophilic renal recipients receiving anticoagulation treatment. METHODS: This is a retrospective study including 29 renal recipients (ktx group) with a history of thrombosis and confirmed thrombophilic factor. Graft function was evaluated by median serum creatinine concentration at the third month after ktx (SCr1) and at the end of the observation (SCr2) with respect to hypercoagulability (factor V Leiden [FVL], mutation G20210A, antiphospholipid antibodies, deficiency of protein S [PS] or C [PC], factor VIII >200%). RESULTS: Recipients underwent retransplantation because of graft thrombosis (P < .001). They more often underwent urgent transplantation (P = .008), received induction therapy (P = .021), underwent an indication other than protocol biopsy (P = .001), or experienced acute rejection (P = .042). Differences in graft function (SCr2) were found at the end of observation (ktx group vs controls 1.9 mg/dL vs 1.3 mg/dL, respectively, P = .014). Multivariate analysis revealed inferior thrombophilic graft function in the model with SCr1 <2 mg/dL (odds ratio 0.07, 95% confidence interval 0.01-0.57, P = .014) and in the model with SCr2 <2 mg/dL (odds ratio 0.15; 95% confidence interval 0.04-0.54, P = .004). The incidence of antiphospholipid syndrome was 31%; FVIII, 31%; FVL, 24.1%; and PC/PS, 13.8%. After anticoagulation was introduced no thromboembolic events or bleeding complications occurred. CONCLUSION: Hypercoagulability is not a contraindication to ktx but may worsen graft function. Post-transplant care in thrombophilic recipients is demanding (retransplantation, immunization, protocol biopsy, anticoagulation), but is the only means by which to maintain a graft.

Human Pooled Immunoglobulin as Treatment of Active Antibody-Mediated Rejection of Transplanted Kidney.

BACKGROUND: Antibody-mediated rejection (ABMR) has emerged as the leading cause of renal graft loss. The optimal treatment protocol in ABMR remains unknown. This study aimed to assess the efficacy of intravenous immunoglobulin (IVIG) for treatment of ABMR in renal recipients. METHODS: Thirty-nine ABO-compatible cross-match-negative renal recipients with biopsy-proven ABMR composed the study group. Pulses of methylprednisolone (MP) and appropriate enhancement of net state of immunosuppression were applied in all individuals; 17/39 recipients were administered IVIG (IVIG group); the remaining 22/39 patients, identified to be nonadherent or unsatisfactorily immunosuppressed, were kept on the initial treatment (MP group). Serum creatinine concentration was obtained at each of 10 intended visits, and glomerular filtration rate (GFR) was estimated with the use of the standard Modification of Diet in Renal Disease (MDRD) formula. Generalized linear mixed model was used for statistical analysis. RESULTS: Renal function (modeled as linear slope of MDRD-based GFR change over time, separately for the pre- and post-intervention periods) improved significantly in IVIG-treated recipients. Pre-intervention slopes were -0.72 and -0.46 mL/min/mo for IVIG and MP groups, respectively (P = NS), whereas post-intervention the slopes changed to -0.03 and -0.47 mL/min/mo (IVIG and MP, respectively; P < .005). Within-group changes of slopes at the time of intervention were 0.69 and -0.01 mL/min/mo in IVIG (P < .01) and MP (P = NS) groups, respectively. The relative slope change (pre- to post-intervention) was 0.7 mL/min/mo in favor of the IVIG group (P < .033). None of the classic immunologic or nonimmunologic graft function predictors influenced GFR during 12 months of follow-up. CONCLUSIONS: IVIG improved graft function in renal recipients diagnosed with ABMR.

The significance of antiphospholipid antibodies in liver recipients.

BACKGROUND: The presence of antiphospholipid antibodies (APLAs) may be associated with increased thrombotic risk. Liver graft thrombosis may necessitate retransplantation. AIM: To determine the prevalence of APLAs among liver recipients and to investigate the relationship between APLAs and liver graft thrombosis. MATERIALS AND METHODS: We included 33 Caucasian patients aged 22 to 75 years who displayed stable liver graft function (21 women and 12 men). The patients were divided into 2 subgroups: high thrombotic risk subgroup T(-) and at low risk T(+) subgroups. The T(-) included 25 patients, T(+) included 8 recipients with a history of severe thrombosis. We investigated: lupus anticoagulant, anticardiolipin antibodies (aCL), anti-ß2-glycoprotein I antibodies (anti-ß2GPI), antiprothrombin antibodies (immunoglobulin (Ig)G and IgM isotype), protein C and S activities, factor VIII, antithrombin, ADAMTS-13 and anti-ADAMTS-13. The 2 determinations were performed at an interval of 6 months. The mean follow-up was 19.5 ± 4.6 months. RESULTS: The most commonly detected antibodies were anti-ß2GPI IgM (25%) and aCL IgG (15.63%). Comparing the prevalence of APLAs between T(-) and T(+), we observed a significant difference only for aCL IgM (P = .0183), which was not confirmed on a second determination after 6 months. We noted correlations between aCL IgM and number of thrombotic episodes (P = .0040) and between aCL IgM and anti-ß2GPI IgM (P = .0074; rho 0.45). Despite receiving low-molecular-weight heparin or aspirin recurrence of thrombosis occurred in 4 T(+) patients: 3 hepatic artery thrombosis and 1 splenic artery thrombosis. Only 1 patient had APLAs; the other 2, protein C or S deficiency and the fourth, a normal test. CONCLUSIONS: The prevalence of APLAs in liver recipients is greater than that in the general population. The usefulness of APLAs as a marker of thrombosis was not demonstrated suggesting multifactorial etiologies of liver graft thrombosis.

Antiphospholipid antibodies in renal allograft recipients.

BACKGROUND: Antiphospholipid antibodies (APLAs) are associated with an increased risk of thrombosis. The role of APLAs as a marker of thrombosis in renal recipients has not been established. We sought to determine the prevalence of APLAs in renal recipients and investigate their association with thrombosis. MATERIAL: The study included 37 renal recipients: 17 women and 20 men of ages 22-69 years. The 2 subgroups were one of patients without (n = 27; T-) and a second, with a history of severe thrombosis (n = 10; T+) subgroups, We determined lupus anticoagulant (coagulation methods) and anticardiolipin antibodies (ACL), anti-Beta2GlicoproteinI antibodies (anti-B2GPI), antiprothrombin antibodies (anti-PT) in immunoglobulin (Ig)G and IgM isotype using enzyme-linked immunosorbent assay. The determinations were made twice at a 6-months interval. The mean duration of follow-up was 12 months. RESULTS: The most commonly detected antibodies were anti-ß2GPI IgM (16.22%) and aCL IgG (13.8%). No differences were identified when the prevalence APLA was compared between T- and T+. A significant correlation was found between anti-ß2GPI IgM and aCL IgM (P = .0328); anti-ß2GPI IgM and aCL IgG (P = .0198) and aCL IgM and aCL IgG (P = .0252). No differences in serum creatinine were observed between the T- and T+ cohorts. During the follow-up, 2 female patients in the T+ produced APLAs and were treated with low-molecular-weight heparin. During follow-up one patient developed thrombosis (TMA), which led to graft loss. The other patient with normal renal graft function did not experience a recurrence of thrombosis. CONCLUSIONS: The prevalence of APLAs in renal transplant recipients was higher than in the general population. The study did not demonstrate any predictive value of APLAs as markers of thrombosis in renal recipients. Routine determination of APLAs is not necessary in all transplant recipients.