Graft Rejection Episodes Research Articles

Infected Donors in Renal Transplantation: Expanding the Donor Pool

IntroductionThe shortage of suitable organ donors is now the most important limiting factor in the field of transplantation and more expanded criteria have been accepted to overcome this problem. ObjectiveThe objectives of this study were to evaluate the outcome of patients who received an organ from an infected donor and to compare them with patients who received organs from noninfected donors. MethodsRetrospective analysis of all patients who underwent transplantation in our unit between January 2008 and June 2011 was performed. The definition of infected donor included: (1) documented bacteremia at the time of transplantation; and (2) organ-related infection, either with or without isolation from biological products (urine, liquor, and bronchial secretions). ResultsNineteen of 77 transplant recipients (24.7%) received organs from infected donors. There were 9 cases of pneumonia, 4 cases of meningitis with bacteremia, 5 cases of urinary tract infection, 1 case of bacteremia due to Staphylococcus aureus, and 1 case of ventriculo-peritoneal shunt infection. All these recipients were prescribed antibiotic prophylaxis for 10.9 ± 3.2 days, according to the antibiotic administered to the donor. Significant differences between both groups were not observed concerning demographics features, graft thrombosis, arterial disruption, delayed graft function, rejection episodes, and renal graft and patient survivals at 12 months. The recipients of infected donor kidneys were mostly treated with basiliximab for induction therapy. There was a trend toward fewer infectious complications among patients who received organs from infected donors (21.1% vs 44.8%; P = .065) and shorter hospital stay durations (median, 11 vs 17.5 days; P = .041). DiscussionKidney transplantation using organs from infected donors did not seem to be associated with a greater risk of complications. Antibiotic therapy initiated in the donor and continued in the recipient may explain these results, perhaps by reducing infectious complications that necessarily prolong the hospital stay.

Deep Anterior Lamellar Keratoplasty for the Treatment of Stromal Corneal Dystrophies

To report the perioperative complications and clinical outcomes after deep anterior lamellar keratoplasty (DALK) using the big bubble technique in eyes with stromal corneal dystrophies. Seventy-four eyes of 65 patients who underwent DALK for stromal corneal dystrophies were evaluated in this retrospective interventional case series study. Main outcome measures were intraoperative and postoperative complications, postoperative uncorrected visual acuity, best spectacle-corrected visual acuity, spherical equivalent refraction, and topographic astigmatism. There were 44 eyes with macular corneal dystrophy, 18 eyes with lattice dystrophy, and 12 eyes with granular dystrophy. DALK was completed in 69 cases (94.6%). Descemet membrane microperforations occurred in 6 eyes (8.7%). The mean follow-up period was 43.5 ± 23.9 months, ranging from 12 to 96 months. Postoperative best spectacle-corrected visual acuity of 0.5 or better was present in 52 of 69 eyes (75.4%). There were 3 episodes of stromal graft rejection, which responded to topical therapy. Lattice dystrophy recurred in 6 eyes (35.3%). DALK using the big bubble technique is an effective procedure in the treatment of patients with corneal stromal dystrophies. Recurrence of lattice dystrophy was relatively high.

Impact of renal graft nephrectomy on second kidney transplant survival

To determine the impact of non-functional renal graft nephrectomy on second kidney transplantation survival. We performed a retrospective study on patients managed in our department from April 1989 to April 2011. We compared the number of acute graft rejections and graft survival between patients undergoing second transplantation with (Group I) or without (Group II) prior graft nephrectomy. A total of ninety-one patients received a second renal graft: 43 underwent graft nephrectomy and 48 kept their non-functional renal graft. There were 5 episodes of acute graft rejection in Group I and 12 in Group II (p = 0.3). Six (13.9 %) grafts failed in Group I and eight (16.6 %) in Group II. Five and 10 years actuarial graft survival in Group I were, respectively, 91 and 85 %, while in Group II were 82.7 % and 69 % (p = 0.2). PRA level and number of acute rejection episodes did not have a statistically significant influence on graft survival, whether the patient had a nephrectomy or not (p = 0.2). Nephrectomy of a failed allograft did not significantly improve the survival of a subsequent graft. Graft nephrectomy should be indicated in case of graft-related pain or a chronic inflammation syndrome.

Anti-HLA and Anti-MICA Antibodies in Liver Transplant Recipients: Effect on Long-Term Graft Survival

Objective. Presence of anti-HLA antibodies has a well-known impact on kidney grafts survival; however their role in liver transplantation has not been fully elucidated. We conducted a 7-year prospective study to show correlation between presence of anti-HLA and anti-MICA antibodies and liver graft survival. Methods. Blood samples from 123 liver transplant recipients were collected during patients routine visits. Time from transplantation to blood sample collection was different for each patient. Blood samples were tested for anti-HLA (separately class I and II) and MICA antibodies using Luminex assays. Results. There were 32 (26%) patients with positive anti-HLA and 37 (30%) with positive anti-MICA antibodies. Graft loss occurred in 7 cases (23%) in anti-HLA positive group compared to 20 (22%) in anti-HLA negative group (P = ns) and in 8 cases (22%) in anti-MICA positive group but 19 (23%) in anti-MICA negative group (P = ns). No correlations were detected between presence of antibodies and acute graft rejection (AGR). Presence of any antibodies (anti-HLA or anti-MICA antibodies) correlated with late graft rejection (P = 0.04). Conclusion. Presence of anti-HLA or anti-MICA had no impact on long-term liver graft survival; however, detection of any antibodies was correlated with episodes of late graft rejection.

Red cell and human leukocyte antigen alloimmunization in candidates for renal transplantation: a reality

Red cell and human leukocyte antigen alloimmunization in candidates for renal transplantation: a reality

Once– versus twice–daily tacrolimus: are the formulations equivalent?

Tacrolimus is one of the most often used immunosuppressive drugs in organ transplantation. It was first approved in 1994 for use in liver transplantation, replacing cyclosporine A, due to better absorption properties regardless of bile secretion. Then it use was extended to other organs and nowadays more that 90% of kidney graft recipient in the United States receive tacrolimus as a basic immunosuppressant [1]. The use of tacrolimus is complicated by its narrow therapeutic index and wide intra– and interpatient pharmacokinetics variability, thus it dosage should be based on monitoring trough drug blood concentration. The main complications of drug overdosage are nephro– and neurotoxicity and metabolic disturbances like posttransplant diabetes mellitus and hyperlipidemia. On the other hand low, non–therapeutic drug blood level can lead to graft rejection and loss. Patients’ noncompliance is the main cause of fluctuating tacrolimus blood concentration and in many cases could be the reason of acute graft rejection episodes. It is an important problem both in young, active but also in older kidney graft recipients and reduction of immunosuppressive drugs daily doses is one method to overcome this problem [2]. The once–daily (OD) extended–release formulation of tacrolimus (Advagraf, Astellas) was launched in 2007 in 0.5, 1, 3, and 5 mg doses. This drug formulation allows most of liver transplant and some kidney transplant recipients (on tacrolimus monotherapy or in dual therapy with prednisone) to use only one morning dose of immunosuppressants. Such therapy simplifies treatment protocol and increases patient compliance. Converting patients from twice daily (BID) to OD tacrolimus was proposed on equivalent daily dose but there was a concern of adequate blood levels after treatment switch. We observed in our center that OD tacrolimus doses had to be 10–15% higher than BID formulation to get the same trough blood drug concentration after conversion. In a multicenter, open–label, phase III study in stable adult liver transplant recipients converted from tacrolimus BID to OD (1:1 [mg:mg] total daily dose basis). Following conversion, mean tacrolimus trough levels were reduced by approximately 15% (7.5 ng/ml vs. 6.5 ng/ml; P <0.0001) but were more consistent, showing reduction between– and within–patient variability in trough levels [3]. However, in our retrospective analysis of 60 kidney graft recipients converted from tacrolimus BID to OD formulation in identical (1:1) daily doses in late posttransplant period trough blood drug concentration did not significantly differ pre and after conversion. OD tacrolimus doses were increased in 11 patients and decreased in 13 patients based on trough blood concentration during consecutive patient visits (unpublished data). OD tacrolimus is non inferior to BID formulation in long term effect in kidney transplant recipients. A systematic review of 6 randomized controlled trials and 15 observational studies revealed no significant differences in biopsy–proven acute rejection, patient and graft survival between the two formulations at 12 months [4]. However, there are some disadvantages of OD tacrolimus therapy. First, risk of overdose–related side effects is very high in first postransplant days and with BID tacrolimus formulation dose correction can be made with the evening dose. Secondly, only 1 mg OD tacrolimus capsules are reimbursed in Poland, making treatment rather difficult in case of higher daily doses. In the present paper authors describe their experience with kidney transplant recipients from living donors who received OD tacrolimus [5]. They investigated tacrolimus pharmacokinetics and compared the dose of OD tacrolimus OD TAC to BD drug formulation. The study group is relatively small and there are some demographic differences between the groups that could affect pharmacokinetic parameters of the study drug: patients on OD tacrolimus were younger and were shorter time on dialysis. The authors compare daily doses and minimal concentration (Cmin) of both formulations, what is most important in clinical practice. However, detailed pharmacokinetic parameters are presented only for OD tacrolimus. In conclusions OD tacrolimus appears to have efficacy and safety equivalent to that of BD formulation but a larger dose of OD tacrolimus compared to that of BD drug form may be required during the early period after kidney transplantation [5].

Tumor necrosis factor-alfa and monocyte chemoattractant protein-1 gene polymorphisms in kidney transplant recipients

Tumor necrosis factor-alfa (TNF-α) gene polymorphism is supposed to have a significant influence on the incidence of acute rejection in renal transplantation. The monocyte chemoattractant protein-1 (MCP-1) is another factor supposed to modulate graft rejection. We studied TNF-α and MCP-1 gene polymorphisms in 84 kidney allograft recipients with polymerase chain reaction and restriction fragment length polymorphism and their serum levels by enzyme-linked immunosorbent assay. The patients were classified into two groups based on their outcomes: Group I (n = 47) recipients with stable graft function as the control group and group II (n=37) recipients who experienced acute graft rejection episodes in the first 30 days post-transplantation. A significantly higher incidence of TNF 2 /TNF 2 genotype was observed among patients with acute graft rejection in comparison with the control group (40.5% and 19.2% respectively, P <0.05), while no statistically significant differences were observed in the TNF 1 /TNF 1 genotype between the groups (59.4% and 80.8%, respectively, P >0.05). A significant elevation of serum TNF-α levels was found in group II than group I and between TNF 2 genotype compared with that of TNF1 genotype within group II recipients. Distribution of MCP-1 genotypes in patients with and without acute rejection episodes was not significantly different (70.2% and 76.6% for MCP-1 A/A and 29.7% and 23.4% for MCP-1 G/G, respectively, P >0.05). The serum MCP-1 levels were not significantly different between the groups and between MCP-1 G/G genotype and MCP-1 A/A genotype in group II recipients. In conclusion, TNF-α gene polymorphism or its serum levels may identify patients at risk of acute rejection, where patients with TNF 2 /TNF 2 genotype or high serum TNF-α levels are more likely to have acute rejection episodes, while there was no relation between MCP-1 genotype or its serum levels and acute rejection.

Risk Factors for Surgical Complications After Renal Transplantation and Impact on Patient and Graft Survival

PurposeWe report herein the incidence of and factors predisposive to surgical complications (SC) after renal transplantation. MethodsBetween 2004 and 2008, we performed 200 renal transplantation. We retrospectively studied recipient and donor characteristics, cold ischemia time, surgical revision in the month after transplantation, delayed graft function, surgical complications (vascular, urologic, wound, or bleeding), as well as graft and patient 5-year survival rates. ResultsSixty-six surgical complications were reported among 49 patients with a preponderance of urologic complications. We noted 6.1% Clavien I, 1.5% Clavien II, 30.3% Clavien IIIa, 53% Clavien IIIb, and 9.1% Clavien IVa SCs. Vascular complications showed a worse prognosis. Among recipients, dialysis duration before transplantation (40.3 ± 50.8 months in SCs versus 28 ± 26.5 months in the control unaffected group, P = .032) and anti-HLA immunization (34.7 ± 48% versus 21.2 ± 41%, P = .05) appeared to be risk factor. No significant factor was identified among donors, although patients with surgical complications received older transplants than the control popuation (49.7 ± 14.5 years versus 45.5 ± 15.1 years, P = .08). A greater percentage of delayed graft function (30.6 ± 46.6% versus 11.4 ± 31.9%; P = .001) and graft rejection episodes (34.7 ± 48.1% versus 17.9 ± 38.4%, P .013) were observed among the SC compared with the control group. No significant difference in patient (89.5% versus 95.6% confidence interval, CI 95% [0.7–10.0]; P = .14) or graft survival (88.7% versus 91.8%, CI 95% [0.4–3.9] P = .63) was observed between the groups. ConclusionSurgical complications, especially urologic complications appear frequently after renal transplantation. Dialysis duration and pre-transplant immunization were linked to the occurrence of a surgical complication, which did not affect graft or patient survival.

The Diagnostic Value of Systolic Acceleration Time (SAT) and Resistance Index (R/I) as Non-Invasive Modality for Detection of Graft Rejection after Orthotopic Liver Transplantation

Background: Graft rejection (acute cellular rejection, chronic rejection) belongs to the major disorders in the postoperative setting after orthotopic liver transplantation (LT) and the immediate diagnosis and successful therapy are essential for graft survival. Aim of this study was to determine whether quantitative and qualitative analysis of Doppler sonography data are predictive and sensitive as non-invasive diagnostic tool for rejection episodes after LT. Material and methods: We reviewed the medical records of patients underwent LT between January 2000 and November 2011. Patients' data were prospectively recorded and retrospectively analyzed. Patients with an acute cellular rejection (ACR) and chronic rejection (CR) were identified and the grade of rejection was classified by use of rejection activity index (RAI) according to BANFF criteria. Parameters analyzed included R/I, SAT, laboratory liver values, histopathological grade of rejection, therapy, graft and patients' survival. Results: Patient follow up as of December 2011 or till time of death ranged from 2 to 132 months (median follow-up: 79 months, mean= 83 months). We registered 29 rejection episodes (ACR n=20 and CR n=9) in 20 patients. The majority of these patients had an Tacrolimus-based immunsuppressive regimen (n=14, trough levels: 7-12 ng/ml). All of them underwent immunsuppressive therapy based on administration of high dose cotricosteroids, followed by dual or triple immunsuppression. In one patient a coricosteroid-resistant ACR has been developed and in 4 patients with CR a graft loss was registered, followed by retransplantation. R/I was calculated in all patients and SAT in patients underwent LT since 2009. As control group patients with delayed SAT and high R/I without a graft rejection were used. In all patients a high R/I (>0.7, range: 0.71-0.91) and in all patients suffered graft rejection since 2009 (n=) a delayed SAT (≥ 0.08, range: 0.08-0.18 s) were registered. The sensitivity and specificity for R/I were 100%, and 54.9% and for SAT 100% and 72.8% respectively Conclusion: Delayed SAT (≥ 0.08 s) and high R/I (>0.7) are according to our results highly sensitive as far as the diagnosis of graft rejection episodes are concerned. Limitation of these diagnostic parameters is their specificity, especially in the immediate postoperative period, where early vascular disorders could trigger equal sonographic results. Nevertheless SAT and R/I could consider as important diagnostic tools and in combination with laboratory liver values can lead to early diagnosis of graft rejection.

Co-infection and Clinical Impact of Human Herpesvirus 5 and 6 in Liver Transplantation

BackgroundHuman herpesvirus (HHV) 5 and 6 remain latent after primary infection and can be reactivated after immunosuppression for organ transplantation. An association between HHV-5 and HHV-6 has been reported in liver transplant patients. The coinfection is associated with clinical manifestations and graft dysfunction. ObjectiveThe aim of this study was to monitor herpesviruses in liver transplant recipients to better understand issues involving coinfection with HHV-5/6 and correlations with acute cellular rejection episodes and bacterial infections. MethodsForty-five adult liver transplant patients of median age 47 years (range, 18–66), gave blood samples and liver biopsies in the first 6 months after their surgeries. Viremia was detected with the use of nested PCR and antigenemia; the Banff classification was used to detect allograft rejection. ResultsIgG positive for HHV-5 was observed in 94% of subjects whose main indication (67%) for transplantation was hepatitis C. Twenty-three (51.1%) displayed cytomeg virus (CMV) infections and 12 (26.7%) HHV-6 infection. There were 6 patients (13.3%) with HHV-5/6 coinfections. Eighteen of the 23 patients had CMV disease, showing a strong correlation between a positive test and CMV disease; 6 displayed an acute cellular rejection episode in the same period (χ2 = 6.62; P < .03). Four out of 6 patients who displayed coinfections (HHV-5/6) had concomitant bacterial infections; 3/6 experienced graft rejection episodes. During follow-up, 1 patient had HHV-6 infection diagnosed as encephalitis followed by fever on the 24th day after surgery. The median 32 days for HHV-6 detection by nested PCR positivity was shorter than 38 days for HHV-5. ConclusionsHHV-5/6–infected patients displayed more allograft rejection episodes, coinfections, and concomitant bacterial infections, besides an higher risk for CMV disease.

Assessment of different biomarkers provides valuable diagnostic standards in the evaluation of the risk of acute rejection

Acute rejection (AR) is a strong risk factor for chronic rejection in renal transplant recipients. Accurate and timely diagnosis of AR episodes is very important for disease control and prognosis. Therefore, objectively evaluated the immune status of patients is essential in the field of post-transplantation treatment. This longitudinal study investigated the usefulness of five biomarkers, human leukocyte antigen (HLA)-G5 and sCD30 level in sera, intracellular adenosine triphosphate (iATP) release level of CD4(+) T cells, and granzyme B/perforin expression in peripheral blood mononuclear cells (PBMCs) and biopsies, to detect AR and the resolution of biomarkers in a total of 84 cases of renal transplantation. The data demonstrated that recipients with clinical or biopsy proven rejection significantly increased iATP release level of CD4(+) T cells, and elevated sCD30 but lowered HLA-G5 level in sera compared with individuals with stable graft function. Expression levels of granzyme B and perforin were also elevated in PBMCs and graft biopsies of AR patients. Taken together, we identified that upregulation of sCD30, iATP, granzyme B, perforin, and downregulation of HLA-G5 could provide valuable diagnostic standards to identify those recipients in the risk of AR. And iATP may be a better biomarker than others for predicting the graft rejection episode.

Long‐term results of deep anterior lamellar keratoplasty in patients with keratoconus

AbstractPurpose Long‐term endothelial cell density changes and visual and refractive outcomes after descemetic (d) and predescemetic (pd) deep anterior lamellar keratoplasty (DALK) using the big‐bubble technique in eyes with keratoconus.Methods Retrospective, consecutive, non‐comparative, case series analysis of 95 eyes that have undergone DALK for keratoconus using the big‐bubble technique with at least 1 year of follow‐up. Big‐bubble was achieved in 74 (77.9%) eyes (dDALK), whereas 21 (22.1%) eyes underwent manual lamellar dissection (pdDALK) because of failed big‐bubble.Results Descemet ruptures occurred in 13 of 95 cases (13.7%). Five ruptures (5.3%) were converted to penetrating keratoplasty. Mean length of follow‐up was 5.3 years (range, 1‐8 years). Postoperative best spectacle‐corrected visual acuity was significantly better in dDALK group than in pdDALK group at years 1 and 2. But, at the final examinations, there was no significant difference between the study groups (0.25 ± 0.22 logarithm of the minimum angle of resolution in dDALK group and 0.33 ± 0.15 logarithm of the minimum angle of resolution in pdDALK group; p = 0.12). The 2 groups were comparable regarding astigmatism and spherical equivalent refractive error throughout the follow‐up period. Mean endothelial cell loss was 22.5 ± 17.9% at last follow‐up with most of the loss occurring in the first year (8.7% ± 5.6%). Stromal graft rejection episodes occurred in 3 eyes (3.2%), which resolved with appropriate therapy.Conclusion DALK using the big‐bubble technique is effective in patients with keratoconus. In DALK, manual lamellar dissection is a reasonable alternative when big‐bubble separation of the Descemet membrane is not achieved.

Long term visual outcomes, graft survival and complications of deep anterior lamellar keratoplasty in patients with herpes simplex related corneal scarring

AimsTo report long term visual outcomes, complications and graft survival of patients undergoing deep anterior lamellar keratoplasty (DALK) to treat corneal scarring secondary to herpes simplex virus (HSV) keratitis.MethodsRetrospective, non-comparative...

Safety and feasibility of sleeve gastrectomy in morbidly obese patients following liver transplantation

Obesity, steroid-induced diabetes, hypercholesterolemia, and steatohepatitis can occur after liver transplantation and may respond to bariatric surgery. The safety and feasibility of bariatric surgery after liver transplantation is unknown. Nine morbidly obese patients with prior liver transplants underwent sleeve gastrectomy in a pilot program. Sleeve gastrectomy was chosen over gastric banding to avoid foreign body implantation, and over gastric bypass to maintain endoscopic access to the biliary system and reduce surgical complexity. We reviewed patient demographics, operative details, 30-day complications, weight loss, postoperative hepatic and renal functions, and resolution of comorbidities. Sleeve gastrectomy was performed laparoscopically in eight patients and as an open procedure in one patient. The mean operative time was 165 min and mean postoperative length of stay was 5 days. Follow-up ranged from 3 to 36 months. In the first 30 days, there were three complications in three patients: mesh dehiscence after a synchronous incisional hernia repair, bile leak from the liver surface requiring laparoscopic drainage, and postoperative dysphagia that required reoperation. Calcineurin inhibitor levels and hepatic and renal functions remained stable. There were no episodes of graft rejection. At 3 months liver function tests remained stable. Excess weight loss averaged 55.5% at 6 months. Sleeve gastrectomy is technically feasible after liver transplantation and resulted in weight loss without adversely affecting graft function and immunosuppression. Early complications may be more frequent as a result of adhesions of the left upper quadrant. Late complications were rare.

Follicular carcinoma of thyroid following successful liver transplantation – A report

Follicular carcinoma of the thyroid is a relatively rare malignancy in childhood even in paediatric solid organ transplant recipients. The risk of developing de novo malignancies after liver transplantation is higher compared to the general population. We report an 18-yr-old girl who had successfully undergone liver transplantation five yr earlier for neonatal sclerosing cholangitis complicated by the development of dysplastic nodules. Baseline immunosuppression was with tacrolimus and prednisolone. Mycophenolate mofetil was later added in view of steroid-resistant episodes of graft rejection. She subsequently suffered from marked obesity and essential hypertension needing antihypertensive medication. Five yr after liver transplantation, she presented with a right-sided thyroid swelling that was rapidly progressive with no associated lymphadenopathy and normal systemic examination. Ultrasound of her neck revealed a solid lesion in the right lobe of the thyroid gland with ill-defined margins, and a diagnostic right thyroid lobectomy confirmed the diagnosis of follicular carcinoma with focal capsular and vascular invasion. She underwent total thyroidectomy and currently remains well on thyroxine supplements. Our report highlights the need for high level of suspicion and prompt investigation into any abnormal lesion in the long-term follow-up of solid organ transplant recipients.

Role of Human Leukocyte Antigen, Donor-Specific Antibodies, and Their Impact in Renal Transplantation

IntroductionThe clinical significance of the presence of antibody against human leukocyte antigen (HLAb) and donor-specific antibodies (DSAb) prior to renal transplantation remains unclear. This study was done to assess the impact of HLAb and DSAb on graft function, rejection episodes, and graft survival in renal transplantation. MethodsThe Luminex (Luminex, Austin, Texas, United States) is a solid-phase assay using micro-spheres and it is more sensitive at detecting human leukocyte antigen (HLA) antibodies than conventional tests. This retrospective analysis involved 141 consecutive renal transplant recipients between May 2007 and 2009 and with a minimum of 2 years of follow-up. ResultsLuminex was positive for HLA class I in 35 and negative in 106; similarly class II positivity was noted in 23 and negative in 118. The DSAb were positive in 33 and negative in 108 recipients. The HLA class I, class II, and DSA-positive groups showed no difference in renal function assessed by estimated glomerular filtration rate (eGFR) at 2 years (52 ± 29 vs 52 ± 22; 56 ± 29 vs 51 ± 29; 48 ± 18 vs 53 ± 19; P = not significant [NS]). But rejection episodes at 1 year were significantly high in HLA class I and DSAb-positive group (17/35 vs 27/106; P = .019 and 16/33 vs 29/108; P = .035). The rejection episodes in the HLA class II–positive group did not show any difference when compared with the negative group (9/23 vs 40/118; P = .63). Graft survival was not affected by positivity to any of these antibodies at 2 years. ConclusionHaving HLA class I, class II, and DSAb does not have any influence on early and intermediate graft function. The HLA class I and DSAb positivity increases rejection episodes within 1 year in renal transplantation. Graft survival was not affected by class I, class II, and DSAb at 2 years.

Descemet stripping automated endothelial keratoplasty in pediatric age group

PurposeTo report the outcomes of DSAEK surgery performed in pediatric patients. DesignNoncomparative interventional case series. Subjects and methodsAll pediatric patients (age up to 16years) undergoing Descemet automated stripping endothelial keratoplasty (DSAEK) at our Institution since January 2008 have been enrolled in a prospective study. A standard DSAEK, involving delivery of an 8.5–9.5mm graft by Busin glide, was performed under general anesthesia in 19 eyes of 11 pediatric patients (congenital hereditary endothelial dystrophy n=13; congenital glaucoma n=2; posterior polymorphous dystrophy n=2, and failed penetrating keratoplasty n=2). Slit-lamp examination, refraction and visual acuity as well as endothelial cell density were evaluated preoperatively as well as 1, 3, 6, 12, and 18months postoperatively. ResultsAll surgical procedures were uneventful. Graft detachment occurred in 4 cases and was managed successfully with repeat air injection. All corneas cleared within a week from surgery. Follow-up was 3–18months. At last follow-up examination, best-corrected visual acuity (BCVA) was better than 20/40 in 8 of the 13 cases of patients old enough to assess vision. A graft rejection episode was seen in 1 case within 3months from surgery but was reverted with steroidal treatment. No graft failures were observed. ConclusionsDSAEK is an appropriate surgical intervention for children with corneal endothelial failure. In contrast to penetrating keratoplasty (PK), DSAEK is performed under “closed system” conditions, thus minimizing intraoperative risks. Finally, healing is much faster than with PK and all sutures can be removed within 2–4weeks from surgery, thus allowing fast visual recovery and prompt starting of amblyopia treatment.

Graft Rejection After Descemet's Stripping Automated Endothelial Keratoplasty: Graft Survival and Endothelial Cell Loss

To evaluate the effects of graft rejection episodes after Descemet's stripping automated endothelial keratoplasty surgery (DSAEK) on long-term endothelial cell density (ECD) decline and graft survival. Retrospective, comparative analysis of an interventional case series. We included 615 eyes of 415 Fuchs' dystrophy patients at a single institution with ≥ 6 months follow-up and without comorbidities known to influence postoperative ECD. All patients were enrolled as part of an ongoing, institutional review board-approved clinical protocol for a long-term, prospective study of endothelial keratoplasty in patients with endothelial dysfunction. Preoperative specular microscopy of donor corneal tissue was performed. Postoperative specular microscopy measurements were recorded at 6 and 12 months, and yearly thereafter. The percentages of endothelial cell loss recorded at 1, 2, 3, and 4 years were compared with the Mann-Whitney U test. Percentage ECD declines were calculated at each time point from the results of the preoperative and postoperative specular microscopy. Patients with graft rejection episodes and late endothelial failure were identified. Graft rejection was defined as findings of keratic precipitates with or without corneal edema, or anterior chamber cell and flare with or without corneal edema after the initial resolution of perioperative inflammation. We identified 45 cases of graft rejection. The greatest number of rejections occurred between postoperative months 12 and 18. Eyes with a graft rejection episode had a higher median percentage decline in ECD at all time points compared with eyes without graft rejection episodes. This was statistically significant at 2 and 3 years postoperatively. There is a trend toward a greater percentage of ECD loss with time in eyes experiencing graft rejection after DSAEK surgery. Proprietary or commercial disclosure may be found after the references.

The Role of Atopy in Corneal Graft Survival in Keratoconus

To compare the prevalence of endothelial rejection episodes and the probability of graft survival after initial and repeat penetrating keratoplasty (PK) in patients with keratoconus with and without atopy. A retrospective review was conducted of all patients receiving PK for keratoconus at the University of Texas Southwestern Medical Center at Dallas from 1988 to 2009. Inclusion criteria involved those with both an International Classification of Diseases-9 code for keratoconus and a Current Procedural Terminology code for PK based on a computer database search. Patients younger than 18 years were excluded. These records were then reviewed for a history of atopic disorders. The main outcome measures included the prevalence of endothelial rejection episodes and the probability of graft survival. The probability of corneal graft survival in patients with and without a history of atopy was compared using the Kaplan-Meier method. There were 168 grafts in 122 patients. There were 66 (39.2%) and 102 (60.8%) grafts with and without a history of atopy, respectively. Bilateral first grafts were required in 32 patients, 14 and 18 patients with and without a history of atopy, respectively. The atopic and nonatopic groups had no significant differences with respect to age, preexisting ocular conditions, concomitant surgical procedures, and length of follow-up. Men received first grafts significantly more frequently than women in the nonatopic group (P = 0.029); however, there was no sex difference in repeat grafts. There were no significant differences in the prevalence of endothelial rejection episodes after the first (P = 0.716), second (P > 0.999), and third or further grafts (P > 0.999). Graft survival between the atopic and nonatopic groups did not differ significantly in the first (P = 0.881), second (P = 0.752), or third or further graft (P = 0.157). Among first grafts in the atopic group, no statistically significant difference in survival existed among patients analyzed with different manifestations of atopy (P = 0.061). One episode of allograft endothelial rejection created a statistically significant difference in ultimate graft survival probability in both the atopic (P = 0.003) and nonatopic (P = 0.002) groups. Among patients with keratoconus receiving PK, there is no statistically significant difference in the prevalence of endothelial graft rejection episodes or probability of graft survival between patients with and without a clinical history of atopy.

Conversion to Everolimus in Liver Transplant Patients With Renal Dysfunction

Calcineurin inhibitor (CNI) immunosuppressive therapy post–liver transplantation (OLT) is important to reduce graft rejection episodes. However, these drugs show important side effects, particularly renal dysfunction (RDF). Changing from CNI to a nonnephrotoxic drug, as mammalian target of rapamycin (mTOR) inhibitor may solve the problem. Our objective was to evaluate renal function (RF) among liver transplant patients initially receiving CNI, among whom the patients with RDF were converted completely or partially to an mTOR inhibitor like everolimus (EVE). We performed a prospective study in liver transplant patients from 2000 to 2009. Creatinine levels and creatinine clearances (Cockroft-Gault) expressed as mean values ± standard deviations were measured pre- and postswitch for comparisons using Wilcoxon nonparametric tests. Six patients were converted fully or partially to EVE. Their mean age at the moment of introducing the new therapy was 52.2 ± 13.6 years (range = 28–60). Immunosuppression time prior to switching from CNI to EVE was 23.8 ± 26.6 months (range = 6–70). Postconversion follow-up was 25.8 ± 16.5 months (range = 8–42). All patients showed improvement in RF. The creatinine level improvement was significant (P = .03) namely, from a mean of 2.26 ± 0.49 to 1.21 ± 0.57 mg/dL. Glomerular filtration rate improved from a mean of 40 ± 15.13 to 72.60 ± 17.3 mL/min/m2 (P = .03). Conversion from CNI to EVE improved creatinine concentrations and creatinine clearances with long-term effects free of graft rejection.