Implant treatment in immunosuppressed renal transplant patients: A prospective case-controlled study.

OBJECTIVES: The aim of this clinical study was to evaluate long-term outcomes of implant therapy in a cohort of immunosuppressed renal transplant patients compared with a matched control group. MATERIAL AND METHODS: Pharmacologically immunosuppressed renal transplant patients received dental implant treatment between 2001 and 2011. Periodontal, clinical and radiographic parameters were prospectively measured with a mean follow-up of 116.8 months (range from 84 to 192 months). A matched controlled non-transplant sample receiving similar implant treatment in the same time was included as a control group. RESULTS: Implant survival rate was over 98% in both test and control groups (100% and 98.84%, respectively). Peri-implant mucositis was diagnosed in 46.80% of the implants in the study group and in 48.80% in the control group. Peri-implantitis occurred in 5.10% of the implants in the study group and in 8.10% of the controls. Wound healing and post-operative pain were similar in both groups. CONCLUSIONS: Despite the limitations of this study, pharmacological immunosuppression in renal transplant patients did not affect implant outcomes. Renal transplant patients should be carefully controlled periodically after implant treatment. CLINICAL IMPLICATIONS: The results from this investigation justify the use of dental implants for the dentalrehabilitation of immunosuppressed patients after renal transplantation provided they follow the necessarylong-term monitoring and regular maintenance of their oral and systemic health.

Isolated De Novo Antiendothelial Cell Antibodies and Kidney Transplant Rejection.

BACKGROUND: Studies analyzing the role of antiendothelial cell antibodies (AECAs) in large series of kidney transplant recipients are scarce, and HLA, MHC (major histocompatibility complex) class I-related chain A (MICA), and angiotensin II type 1 receptor have not been formally excluded as targets. STUDY DESIGN: Retrospective study of a cohort of kidney transplant recipients. SETTING & PARTICIPANTS: 324 kidney transplant recipients who were negative for anti-HLA, anti-MICA, and anti-angiotensin II type 1 receptor antibodies were tested for AECAs in pre- and posttransplantation serum samples. PREDICTORS: AECA-positive (preformed [pre+/post+] vs de novo [pre-/post+]) versus AECA-negative (pre-/post-) before or after transplantation. OUTCOMES: Patient mortality, transplant loss, and acute rejection events. RESULTS: 66 (20%) patients were AECA positive (39 [12%] preformed, 27 [8%] de novo) and 258 (80%) were AECA negative. During a follow-up of 10 years, 7 (18%) AECA pre+/post+ patients had rejections compared with 14 (52%) AECA pre-/post+ and 57 (22%) AECA pre-/post- recipients (OR, 3.80; P=0.001). AECA pre-/post+ status emerged as an independent risk factor for transplant rejection compared to the AECA pre-/post- group (OR, 5.17; P<0.001). However, AECA pre+/post+ and AECA pre-/post+ patients did not show higher risk for either patient death (ORs of 1.49 [P=0.7] and 1.06 [P=0.9], respectively) or transplant loss (ORs of 1.22 and 0.86, respectively; P for both = 0.8) compared to the AECA pre-/post- population. LIMITATIONS: Retrospective study. Posttransplantation sera were collected before or after rejection, entailing a nearly cross-sectional relationship between the exposure and outcome. Lack of identification of precise antigens for AECAs. CONCLUSIONS: De novo AECAs may be associated with rejection. These antibodies might serve as biomarkers of endothelium damage in kidney transplant recipients.

Early renal graft function deterioration in recipients with preformed anti-MICA antibodies: partial contribution of complement-dependent cytotoxicity.

BACKGROUND: We previously reported that preformed anti-MHC class I-related chain A (MICA) antibodies increase the risk for renal graft rejection and enhance the deleterious effect of PRA(+) status early after transplantation. METHODS: We studied 727 kidney recipients. Days to reach optimal serum creatinine level, estimated glomerular filtration rate (eGFR) at Month 3 and chronic kidney disease (CKD) stages were recorded. Anti-MICA specificities and C1q binding were tested by solid-phase assay. Complement-dependent cytotoxicity (CDC) and flow cytometry (FC) cross-matches with HeLa and PMA/CD28-T-blasts were performed. RESULTS: PRA(+)MICA(+) recipients exhibited longer time to reach optimal serum creatinine level after transplantation (P = 0.005) and had the lowest eGFR at Month 3 (P = 0.006). PRA(+)MICA(+) status independently increased the risk for CKDT stage 5 at Month 3 [hazard ratio (HR) 4.92, P = 0.030]. Pre-transplant anti-MICA antibodies were polyspecific and showed stronger reactions when coexisting with anti-HLA antibodies (mean standard fluorescent intensity 112 157 ± 44 426 in HLA(+)MICA(+) sera versus 49 680 ± 33 116 in HLA(-)MICA(+) sera, P = 0.0006). Anti-AYVE supereplet reactivity was significantly higher in HLA(+)MICA(+) versus HLA(-)MICA(+) patients (P < 0.001) and significantly superior than anti-CMGWS supereplet within HLA(+)MICA(+) patients (P = 0.001). Three of 13 anti-MICA(+) pre-transplant sera were positive for the C1q binding assay; one of them (serum 3) exclusively recognized AYVE supereplet with a strong reactivity against MICA*027 antigen (same as MICA*008). Anti-MICA antibodies in anti-HLA-absorbed serum 3 bound native MICA molecules in MICA*008(+) HeLa and PMA/CD28-T-blasts and mediated cell death by activating complement. CONCLUSION: Preformed anti-MICA antibodies may occasionally be cytotoxic by fixing and activating complement. This way they might contribute to worse early kidney graft function.

Oral candidiasis in patients with renal transplants.

OBJECTIVES: Oral candidiasis (OC) is a frequent oral lesion in renal transplant patients (RTPs). Despite the increased prevalence of OC in RTPs, no study has examined related risk factors. The aims of this study were to analyze the prevalence of and risk factors for OC in RTPs compared with age- and gender-matched healthy control group (HC) as well as determine the incidence of OC after transplantation. STUDY DESIGN: [corrected] We analyzed the prevalence and risk factors of OC in a group of 500 RTPs (307 men, 193 women, mean age 53.63 years) and 501 HC subjects (314 men, 187 women, mean age 52.25 years). Demographic and pharmacological data were recorded for all subjects. Incident cases of OC were ascertained retrospectively from outpatient clinical records only in the RTP group. RESULTS: The prevalence of OC was 7.4% in RTPs compared with 4.19% in HC (P<0.03). The most frequent type of OC in the two groups was denture stomatitis. Statistical association was found between OC and age, mycophenolate mofetil dose and blood levels, dentures and tobacco. The multiple logistic regression model only chose for denture variable. According to the outpatient clinical records, 24 RTPs suffered OC during the first moth post-transplant. Severe lesions affecting the oral cavity and pharynx appeared in 79% of the OC cases. CONCLUSIONS: This study shows a lower prevalence of OC in RTPs than previous reports. Denture stomatitis was the most frequent OC prevalence form described in RTPs. Severe candidiasis is more frequent in the immediate posttransplant period. The presence of denture is an important risk factor of OC. These results emphasise the importance of adequate pre- and post-transplant oral health and denture cleaning and adjustment is recommended for these subjects to prevent this infection.

Conversion from cyclosporin A to tacrolimus as a non-surgical alternative to reduce gingival enlargement: a preliminary case series.

BACKGROUND: Gingival enlargement (GE) is a frequent side effect that occurs in organ transplant recipients (OTR) after the administration of cyclosporin A (CsA). The availability of new drugs used to suppress graft rejection in OTR offers an opportunity to manage GE non-surgically. This preliminary case series aimed to analyze the effect of CsA withdrawal and its substitution by another immunosuppressant in OTR with severe GE. METHODS: Four organ transplant recipients who had received a liver or renal allograft were recruited for this study. All OTR had developed clinically severe CsA-induced GE. GE scores were assessed for each patient at baseline and at weeks 2, 4, 8, 12, 16, and 54 following conversion to tacrolimus. Scaling and root planing were initially performed and repeated monthly during the first 6 months. Careful polishing of the teeth was carried out once every 2 weeks until month 6 and then monthly until month 12. Hygiene instructions and reinforcement to optimize oral hygiene were maintained throughout the study. RESULTS: The four patients showed a rapid decrease in their gingival symptoms and in the size of the gingivae. This change was clinically evident 8 weeks after conversion to tacrolimus. One year later, all the patients experienced GE regression, although some anatomic irregularities persisted in the interdental papillae of one of the patients. No adverse effects from tacrolimus were observed during the study except in one patient who presented headaches. CONCLUSION: It seems that CsA withdrawal and its conversion to tacrolimus in organ transplant recipients who develop severe gingival enlargement, together with an extensive plaque control program, provide an effective means to control/eliminate gingival hyperplasia, with minimal risk of graft dysfunction.

Lip cancer in renal transplant patients.

The aims of this study were to establish the incidence of lip cancer (LC) in a population of renal transplant patients (RTPs), identifying possible risk factors and predictable variables, and to describe the clinical appearance, treatment, and course of LC in this group. The study included 500 patients (307 men, 193 women; mean age 53.63±13.42 years, range 19-95 years; mean period since transplant 59.66±55.81 months, range 4-330 months). Incident cases of LC were ascertained retrospectively from outpatient records. All LC lesions were sampled by biopsy and examined histopathologically. Six of the men (1.2%) suffered lower LC, and LC cases showed significant differences on univariate analysis for tobacco habit, tobacco consumption, and sun exposure. All patients who had LC were taking prednisolone and cyclosporine A (CsA) at the time of LC diagnosis. The median interval for LC incidence after renal transplant was 80.50±31.25 months. Five of six LCs were squamous cell carcinomas. Multiple logistic regression showed that the LCs were not significantly associated with any independent risk factor. The results show that the appearance of LC in RTPs is associated with immunosuppressant treatment, sun exposure, and tobacco and indicate that these patients should avoid unprotected exposure to sunlight and smoking. Because of the high incidence of LC in RTPs, periodic checking of the lips is important to ensure prompt diagnosis and correct management of LC. Our data suggest that the clinical profile of LC in this patient group is similar to that of the general population.

Interleukin-2 receptor antagonist induction in modern immunosuppression regimens for renal transplant recipients.

Addition of interleukin-2 receptor antagonist (IL-2RA) induction to calcineurin inhibitor (CNI)-based regimens reduces biopsy-proven acute rejection by 30-40%. IL-2RA induction facilitates early withdrawal of steroids, and supports the safe use of reduced-exposure CNI or delayed CNI introduction. IL-2RAs and rabbit antithymocyte globulin (Thymoglobulin) show comparable efficacy in patients at standard or low immunologic risk, but the adverse event profiles of lymphocyte-depleting agents are less favorable. IL-2RAs, uniquely, provide effective immunosuppression with similar tolerability to placebo.