Incidence, determinants and outcome of chronic kidney disease after adult heart transplantation in the United Kingdom

Background: We investigated the incidence of chronic kidney disease (CKD) in the United Kingdom heart transplant population, identified risk factors for the development of CKD, and assessed the impact of CKD on subsequent survival.

Methods: Data from the UK Cardiothoracic Transplant Audit and UK Renal Registry were linked for 1732 adult heart transplantations, 1996 to 2007. Factors influencing time to CKD, defined as National Kidney Foundation CKD stage 4 or 5 or preemptive kidney transplantation, were identified using a Cox proportional hazards model. The effects of distinct CKD stages on survival were evaluated using time-dependent covariates.

Results: A total of 3% of patients had CKD at transplantation, 11% at 1-year and more than 15% at 6 years posttransplantation and beyond. Earlier transplantations, shorter ischemia times, female, older, hepatitis C virus positive, and diabetic recipients were at increased risk of developing CKD, along with those with impaired renal function pretransplantation or early posttransplantation. Significant differences between transplantation centers were also observed. The risk of death was significantly higher for patients at CKD stage 4, stage 5 (excluding dialysis), or on dialysis, compared with equivalent patients surviving to the same time point with CKD stage 3 or lower (hazard ratios of 1.66, 8.54, and 4.07, respectively).

Conclusions: CKD is a common complication of heart transplantation in the UK, and several risk factors identified in other studies are also relevant in this population. By linking national heart transplantation and renal data, we have determined the impact of CKD stage and dialysis treatment on subsequent survival in heart transplant recipients.

Epigenetics:Time to translate into transplantation

Substantial progress has been made in identifying genetic loci associated with multifactorial disorders, including variants that seem to impact outcomes following solid organ transplantation. Despite these advances, much of the heritability and susceptibility to chronic disease processes remains unexplained. Epigenetic modifications may exert their effect independently or complementary to genetic variants. Epigenetic modifications can change gene expression without altering the DNA sequence. These modifications are dynamic, potentially heritable, and can be induced by environmental stimuli or drugs. The impact of epigenetic phenomena on the outcomes of organ transplantation is currently poorly understood. Epigenetic modifications can occur during periods of illness; these may persist and potentially influence allograft outcomes. Epigenetic mechanisms influence the activation, proliferation, and differentiation of the immune cells involved in allograft rejection. The donor's epigenome may also impact transplant survival, and initial research has demonstrated that peritransplant conditions induce rapid epigenetic modification within the allograft. Further research will help to define the importance of epigenetic modifications in transplantation. This will potentially lead to the identification of useful biomarkers and the development of novel pharmacotherapies. This review explores the nature of epigenetic modification in disease and the emerging evidence for epigenetic influences on allograft survival.

Outcome of pregnancy following renal transplantation

Successful renal transplantation improves fertility with 1 in 50 women of childbearing age becoming pregnant. Pregnancy following renal transplantation is associated with increased maternal and fetal complications. In Belfast 118 women of childbearing age (15-45 yrs) have received a renal allograft and of these 14 (12%) have become pregnant. Twenty-seven pregnancies have resulted in 23 live births (including one set of identical twins), 1 still birth and 4 first trimester abortions. The most frequent complications were hypertension and prematurity. In this group of patients, whose sole immunosuppressive therapy was azathioprine and prednisolone, pregnancy post transplantation was associated with frequent successful outcome and a low incidence of maternal and fetal complications.

Autologous limbal transplantation in patients with unilateral corneal stem cell deficiency

Aim - To describe a surgical technique for autologous limbal stem cell transplantation and the outcome of a series of patients with unilateral stem cell deficiency. Methods - A report of six consecutive patients who underwent autologous limbal stem cell transplantation is presented. The primary diagnosis included alkali burn (n = 3), conjunctival intraepithelial neoplasia (CIN) (n = 1), recurrent pterygium (n = 1), and contact lens induced keratopathy (n = 1). The autologous transplanted tissue consisted of peripheral cornea, limbus, and conjunctiva obtained from the contralateral eye. Three of the above patients underwent penetrating keratoplasty in association with autolimbal transplantation. A significant modification to established techniques was the close monitoring of conjunctival epithelial migration in the immediate postoperative period. If conjunctival epithelium threatened to migrate on to the corneal surface, it was mechanically removed at the slit lamp and prevented from crossing the limbus. This was required in three patients. Results - The mean follow up was 18.8 months. The outcome was satisfactory in all cases: a stable corneal surface was restored and there was a substantial improvement in vision and symptoms. One patient had a primary failure of the corneal allograft associated with glaucoma, and 6 months later developed a retinal detachment. No complications were noted in the donor eye with the exception of one patient who developed filamentary keratitis along the edge of the donor site. Conclusion - Autologous limbal transplantation with corneal, limbal, and conjunctival carriers was found to be useful for ocular surface reconstruction, over a mid-term follow up, in patients with unilateral stem cell deficiency. Close monitoring of the migration of conjunctival epithelium in the immediate postoperative period, and preventing it from crossing the limbus, ensured that the corneal surface was re-epithelialised exclusively from epithelial cells derived from the transplanted limbal tissue. This approach should improve the success of this procedure.

Allo-limbal transplantation in patients with limbal stem cell deficiency

Aim - To report the outcome of a series of patients with stem cell deficiency who underwent allo-limbal transplantation and to describe a technique for this procedure. Methods - Six consecutive patients underwent allo-limbal stem cell transplantation. The primary diagnosis included alkali burn (n = 2), trachoma (n = 1), chronic rosacea blepharitis and keratoconjunctivitis (n = 1), aniridia (n = 1), and Stevens-Johnson syndrome (n = 1). The limbal rim consisted of peripheral cornea and perilimbal sclera, FK-506 was used postoperatively for immunosuppression. Results - The length of follow up ranged from 3 to 24 months (mean follow up 11.8 (SD 9.3) months). The outcome was considered satisfactory in five of six cases. The corneal surface was completely epithelialised within 2 weeks, and there was a substantial improvement in vision and symptoms. One patient had recurrent epithelial defects related to eyelid abnormalities. No side effects associated with systemic immunosuppression were noted. Conclusion - Allo-limbal transplantation, with systemic immunosuppression with FK-506 is useful in reconstruction of the ocular surface with improvement in vision in patients with severe stem cell deficiency.

Amniotic membrane transplantation for ocular surface reconstruction

Aims - To evaluate the efficacy of amniotic membrane transplantation (AMT) for ocular surface reconstruction. Methods - 10 consecutive patients who underwent AMT were included. The indications were: group A, cases with persistent epithelial defect after corneal abscess (n = 1), radiation (n = 1), or chemical burn (n = 3); group B, cases with epithelial defect and severe stromal thinning and impending or recent perforation, due to chemical burn (two patients, three eyes) or corneal abscess (n = 2); group C, to promote corneal epithelium healing and prevent scarring after symblepharon surgery with extensive corneo-conjunctival adhesion (n = 1). Under sterile conditions amniotic membrane was prepared from a fresh placenta of a seronegative pregnant woman and stored at -70°C. This technique involved the use of amniotic membrane to cover the entire cornea and perilimbal area in groups A and B, and the epithelial defect only in group C. Results - The cornea healed satisfactorily in four of five patients in group A, but the epithelial defect recurred in one of these patients. After AMT three patients underwent limbal transplantation and one penetrating keratoplasty and cataract extraction. In group B amniotic membrane transplantation was not helpful, and all cases underwent an urgent tectonic corneal graft. Surgery successfully released the symblepharon, promoted epithelialisation and prevented adhesions in the case of group C. Conclusion - AMT was effective to promote corneal healing in patients with persistent epithelial defect, and appeared to be helpful after surgery to release corneo-conjunctival adhesion. Most surgery for further surface rehabilitation. Amniotic membrane used as a patch was not effective to prevent tectonic corneal graft in cases with severe stromal thinning and impending or recent perforation.