Introduction The initiation of a kidney transplant program, in a low- and middle-income country, while striving to maintain excellent outcomes and adhere to high ethical, legal standards, is a formidable task. Herein, we review the outcomes and challenges of a living donor kidney transplant program from its inception to sustainability, in Guyana, South America. Methods This is a retrospective review of a living donor kidney transplant program instituted in Guyana in 2008. Data included recipient and donor demographics, cause of renal failure, donor-recipient matching and relationship, perioperative complications, timing and cause of death, graft failure, surgical technique, and laterality of organ procured. Patient and donor data were compared by phases and additionally compared to United States Renal Data Base System. Survival outcomes were compared by phases and by Kaplan-Meier curves. Results To date, 45 kidney transplants have been completed. Phase I (2007-2008) was the initiation of the program, which was comprised of upgrading hospital and operating rooms, obtaining antirejection medications, educating local providers, fostering a relationship with the government, and screening patients and living donors. We also began vascular access and peritoneal dialysis in the country, as well as introduced the companion public health service initiative: the SEVAK program. Phase II (2008-2014) involved completion of 25 living donor kidney transplants, of which there have been 11 confirmed deaths and 10 lost to follow-up. In Phase III (2015-present), 20 transplants have been completed to date, of whom only 1 died and none were lost to follow-up. In the third phase, we also introduced corneal transplantation to Guyana and have performed over 100 transplants. Conclusion Kidney transplantation can be safely and ethically performed in a low- and middle-income country. We applied lessons learnt from the first two phases to improve follow-up by appointing a local coordinator who goes to patient's homes in remote villages. Currently, there is a stable local team that is performing transplants and following the patients. We believe that our model of public-private partnership can sustain kidney, as well as corneal, transplantation and could be replicated in other countries.

BACKGROUND AND OBJECTIVES Before 2014, low-income individuals in the United States with non-dialysis-dependent CKD had fewer options to attain health insurance, limiting their opportunities to be preemptively wait-listed for kidney transplantation. We examined whether expanding Medicaid under the Affordable Care Act was associated with differences in the number of individuals who were pre-emptively wait-listed with Medicaid coverage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Using the United Network of Organ Sharing database, we performed a retrospective observational study of adults (age≥18 years) listed for kidney transplantation before dialysis dependence between January 1, 2011-December 31, 2013 (pre-Medicaid expansion) and January 1, 2014-December 31, 2016 (post-Medicaid expansion). In multinomial logistic regression models, we compared trends in insurance types used for pre-emptive wait-listing in states that did and did not expand Medicaid with a difference-in-differences approach. RESULTS States that fully implemented Medicaid expansion on January 1, 2014 ("expansion states," n=24 and the District of Columbia) had a 59% relative increase in Medicaid-covered pre-emptive listings from the pre-expansion to postexpansion period (from 1094 to 1737 listings), compared with an 8.8% relative increase (from 330 to 359 listings) among 19 Medicaid nonexpansion states (P<0.001). From the pre- to postexpansion period, the adjusted proportion of listings with Medicaid coverage decreased by 0.3 percentage points among nonexpansion states (from 4.0% to 3.7%, P=0.09), and increased by 3.0 percentage points among expansion states (from 7.0% to 10.0%, P<0.001). Medicaid expansion was associated with absolute increases in Medicaid coverage by 1.4 percentage points among white listings, 4.0 percentage points among black listings, 5.9 percentage points among Hispanic listings, and 5.3 percentage points among other listings (P<0.001 for all comparisons). CONCLUSIONS Medicaid expansion was associated with an increase in the proportion of new pre-emptive listings for kidney transplantation with Medicaid coverage, with larger increases in Medicaid coverage among racial and ethnic minority listings than among white listings.

Introduction: In 2008, we initiated the first Guyanese comprehensive kidney replacement program, comprising hemodialysis (HD), peritoneal dialysis (PD), vascular access procedures, and living-donor kidney transplantation. The government of Guyana, US-based philanthropists, US-based physicians, and Guyanese caregivers teamed up to form a public-private partnership. This pilot program was free of cost to the patients.Methods: From July 2010 to the time of writing, we placed 17 patients with end-stage kidney disease on PD, which was used as a bridge to living-donor kidney transplantation. During the same period, we placed 12 primary arteriovenous fistulae.Results: The 17 patients who received a PD catheter had a mean age of 43.6 years and a mean follow-up of 5.3 months. In that group, 2 deaths occurred (from multi-organ failure) within 2 weeks of catheter placement, and 2 patients were switched to HD because of inadequate clearance. Technical issues were noted in 2 patients, and 3 patients developed peritonitis (treated with intravenous antibiotics). An exit-site abscess in 1 patient was drained under local anesthesia. The peritonitis rate was 0.36 episodes per patient-year. Of the 17 patients who received PD, 4 underwent living-donor kidney transplantation.Conclusions: In Guyana, PD is a safe and cost-effective option; it may be equally suitable for similar developing countries. In Guyana, PD was used as a bridge to living-donor kidney transplantation. We have been able to sustain this program since 2008 by making incremental gains and nurturing the ongoing public-private partnership. Perit Dial Int 2013; 33(2): 116-123 www.PDIConnect.com doi:10.3747/pdi.2012.00001

This article reviews the field of donation after cardiac death, focusing on the history, ethicolegal issues, clinical outcomes, best practices, operative techniques, and emerging strategies to optimize utilization of this resource. Donation after cardiac death is one effective way to decrease the organ shortage and has contributed the largest recent increase in abdominal organ allografts. Currently, donation after cardiac death organs confer an increased risk of ischemic cholangiopathy after liver transplant and of delayed graft function after kidney transplant. As this field matures, risk factors for donation after cardiac death organ transplant will be further identified and clinical outcomes will improve as a result of protocol standardization and ongoing research. Mt Sinai J Med 2012 DOI: 10.1002/msj.21309

An emergency autologous islet transplant after a traumatic Whipple operation and subsequent total pancreatectomy was performed for a 21-year-old patient who was wounded with multiple abdominal gunshot wounds. After Whipple pancreatectomy, the remnant pancreas (63.5 g), along with other damaged organs, was removed by the surgeons at Walter Reed Army Medical Center (WRAMC) and shipped to Diabetes Research Institute (DRI) for islet isolation. The pancreas was preserved in UW solution for 9.25 h prior to islet isolation. Upon arrival, the organ was visually inspected; the pancreatic head was missing, the rest of the pancreas was damaged and full of blood; the tail looked normal. A 16-gauge catheter was inserted into the main duct and directed towards tail of the pancreas after the dissection of main duct in the midbody of the pancreas. The pancreas was distended with collagenase solution (Roche MTF) through the catheter. During 10 min of intraductal delivery of enzyme, the gland was distended uniformly. No leakage of the solution was observed. The pancreas was transferred to a Ricordi chamber for automated mechanical and enzymatic digestion. Islets were purified using a COBE 2991 cell processor. Islet equivalents (IEQ; 221,250) of 40% purity and 90% viability were recovered during the isolation, which were shipped back to WRAMC and infused by intraportal injection into the patient. Immediate islet function was demonstrated by the rapid elevation of serum C peptide followed by insulin independence with near normal oral glucose tolerance test (OGTT) 1 and 2 months later. It is possible to restore near normal glucose tolerance with autologous islet transplantation after total pancreatectomy even with suboptimal number of islets while confirming that islets processed at a remote site are suitable for transplantation.

Background. We investigated the effect of smoking on postkidney transplant outcomes in the United States Renal Data System. Methods. In a retrospective cohort of 41,705 adult Medicare primary renal transplant recipients in the United States Renal Data System database transplanted from January 1, 2000, to June 30, 2006, and followed through October 31, 2006, we assessed Medicare claims for smoking. The association between renal allograft loss and death and smoking as a time-dependent variable was assessed with Cox nonproportional hazards regression. Results. Of 41,705 Medicare primary adult renal transplant patients, there were 9.9% patients who had evidence of prior smoking and 4.6% patients with new claims for smoking after transplant. Incident smoking (new onset smokers) occurred at a mean of 1.29±0.88 years after transplant. In the adjusted analysis, factors associated with new smoking included male gender, history of drug or alcohol use, history of chronic obstructive pulmonary disease, and later year of transplant. Compared with never smokers, incident smoking after transplant was associated with increased risk of death-censored allograft loss (adjusted hazard ratio [AHR] 1.46 [95% confidence interval {CI}: 1.19–1.79]; P<0.001) and death (AHR 2.32 [95% CI: 1.98–2.72]; P<0.001). In a sensitivity analysis excluding patients with history of chronic obstructive pulmonary disease, similar results were obtained with increased risk of death-censored allograft loss (AHR 1.43 [95% CI: 1.16–1.76]; P=0.001) and death (AHR 2.26 [95% CI: 1.91–2.66]; P<0.001). Discussion. Incident smoking was detrimental to graft and patient survival. Transplant programs should screen those at risk during transplant follow-up and have smoking cessation programs.

PURPOSE: To report the uncommon occurrence of impetigo contagiosa in the setting of recurrent staphylococcal conjunctivitis.DESIGN: Interventional case report.METHODS: A 32-year-old patient had a recurrent painful red left eye and facial rash. Clinical examination revealed left bacterial conjunctivitis and facial bullous impetigo. Microbiology cultures were taken from the nose, conjunctiva, and facial lesions.RESULTS: Microbiologic cultures grew Staphylococcus aureus, and hematology findings demonstrated an elevated white cell count with neutrophilia. Complete resolution was achieved with topical chloramphenicol ointment and oral dicloxacillin.CONCLUSIONS: Although uncommon, bullous impetigo may be associated with recurrent staphylococcal conjunctivitis in adults. Recurrent infections may require nasal decolonization, systemic antibiotics, and antiseptic body wash.

Th1 derived cytokines IFN-gamma and IL-2, Th2 cytokine IL-4, and ICAM-1 have been implicated in liver allograft rejection. In order to determine whether monitoring of cytokine profiles during the first days post-liver transplant can predict early rejection we measured IFN-gg, IL-2, sIL-2 receptor, IL-4 and ICAM-1 in 22 patients, in plasma samples obtained within 4 h after liver perfusion (baseline) and between postoperative days (POD) 3-6. ICAM-1 and sIL-2R levels at POD 3-6 were significantly higher than at baseline but did not differ in presence or absence of rejection. Mean percentage increase of ICAM-1 levels was significantly lower in patients with Muromonab-C3 Orthoclone OKT3 (J.C. Health Care) (OKT3) whereas percentage increase of sIL-2R levels was higher in OKT3-treated patients. IFN-gamma levels at POD 3-6 increased from baseline while IL-4 levels were unchanged. Levels of IFN-gamma, IL-4 and their ratios did not correlate with rejection or immunosuppressive therapy. Thus, Th1/Th2 cytokine monitoring during the first week post-transplant does not predict early rejection and immunosuppressive therapy is the predominant factor affecting ICAM and sIL-2R levels after liver transplantation.

Leeser, David B.1; Jeevanandam, Valluvan2; Furukawa, Satoshi3; Eisen, Howard4; Mather, Paul4; Silva, Patricio5; Guy, Stephen6; III, Clarence E. Foster6 Author Information

OKT3 , a murine monoclonal antibody specific to the human CD3 complex, induces immunosuppression by depletion of T cells. Administration of OKT3 results in significant release of proinflammatory cytokines, such as TNFalpha and IL1beta. Liver recipients who experience rejection within 3 weeks after transplantation with OKT3 prophylaxis recover their T cells by postoperative day 10 despite complete initial clearance. We sought to analyze the role of proinflammatory and Th-1 cytokines in T cell recovery and rejection after liver transplantation with OKT3 prophylaxis. In plasma samples from 32 patients, we measured TNFalpha, IL1beta and IL6 (before transplant and on postoperative days 1, 2 and 3) and IL2, IFNgamma, sIL2R and slCAM (postoperative days 5, 7 and 10) and examined possible correlations with T-cell recovery and occurrence of rejection within 3 weeks. TNFalpha, IL1beta, and IL6 did not correlate with T-cell recovery. In patients who rejected, IL2 and IFNgamma on postoperative days 5 and 7 correlated with degree of T-cell recovery by day 10; a significant rise in sIL2R over time also correlated with T-cell recovery in this group. Our results emphasize the role of Th-1 cytokines in rejection following OKT3 induction and suggest that markers of T cell activation may predict risk.

Cold preservation/reperfusion leads to sinusoidal endothelial cell (SEC) activation and damage in nearly every liver transplantation; the extent of these changes influences early graft function. Upon reperfusion, activated SEC show increased expression of adhesion molecules, including von Willebrand factor (vWF) which is released into the circulation. This study was designed to evaluate the levels of vWF measured in the caval effluent and correlate these findings with known markers of SEC damage and early graft function. Data were obtained from 35 patients undergoing orthotopic liver transplantation (LTx). Two samples were taken from each patient for measurement of vWF: a) from the portal vein immediately prior to reperfusion; and b) from the first 50 ml of the caval effluent. Commercial assays were used to measure vWF, as well as hyaluronic acid (HA), thrombomodulin (TM), IL‐1β, IL‐6, IL‐8 and TNF‐α. Patients were divided into two groups based on early graft function. Poor early graft function (PEGF) was defined as a peak aspartate transaminase (AST) or alanine transaminase (ALT) level> 2500 U/L during the first three postoperative days (POD) and a prothrombin time (PT)> 16 s on POD 2 (n=8). The remaining 27 patients had good early graft function (GEGF). In patients with GEGF, vWF levels dropped significantly between the two time points. This change was not observed in those with PEGF. A positive linear correlation was observed in the PEGF group between vWF and HA and IL‐6. The different pattern of change in vWF between the two groups, as well as the positive correlation between HA, IL‐6 and vWF in PEGF, suggest that vWF may be a useful marker of early graft function.

The Liver is the primary site of synthesis for the majority of coagulation factors. There are published accounts of liver donor-to-recipient transmission of protein C deficiency with dysfibrinogenemia and factor XI deficiency In this article, we report what we believe to be the first observation, of transmission of factor VII deficiency, a rare, autosomal recessive coagulation disorder, from an affected Liver donor to a naive liver recipient. At 300 days after transplantation, the recipient remains with an isolated prolongation of the prothrombin time and a below-normal level of factor VII, and has had no bleeding complications.

201 Patients transplanted for hepatitis B virus (HBV) infection are treated with hepatitis B immune globulin (HBIg) to prevent posttransplant recurrence. When recurrence is documented, patients are treated with lamivudine or in combination with famciclovir. We report here our early results of rescue therapy with lamivudine and famciclovir in liver recipients with posttransplant HBV recurrence. Methods: We reviewed data on all patients at our center who underwent liver transplantation (LTx) for HBV and received HBIg immunoprophylaxis. We recorded the incidence of HBV recurrence in the allograft, interval to recurrence, pre- and post-recurrence serologies, and patient and graft survival post recurrence. HBV recurrence was diagnosed by either HbsAg positivity or by liver biopsy that stained positive for hepatitis B surface or core antigen. Patients with recurrence were treated with lamivudine, 150 mg/day; three patients also received famciclovir starting at diagnosis of recurrence. Results: Fifty-one patients (39 males, 12 females) were transplanted for HBV; recurrence was documented in 7 at a mean of 12±10 mos post-LTx (range, 1.5-32). In addition to lamivudine, 3/7 patients received famciclovir (500 mg TID). One of the 3 was unable to tolerate famciclovir (1 rash) and the drug was discontinued within 1 wk. Two patients remain on both agents. All 7 lamivudine-treated patients became HbsAg+ on recurrence; with treatment, 2 became negative at 6 and 13 mos. Five of 7 patients were also HBV-DNA+ (4538±8235 pg/ml, r:107-21000); 4 became negative within 1-12 mos and 1 had a decrease from 902 pg/ml to 17.5 pg/ml but died at 6 wk. Two patients have no detectable HBV-DNA. In 6/7 patients, ALT levels either improved or remained unchanged. Two of the 7 patients died: 1 of HBV recurrence and sepsis at 6 wk after recurrence, and the other of recurrent hepatocellular carcinoma at 1 yr post-LTx. Five patients are alive at a mean interval after recurrence of 20.2±4.9 mos (range, 16-28). One-yr patient survival after recurrence is 88%. Conclusions: Rescue treatment with lamivudine and famciclovir after HBV recurrence is well tolerated. It is effective in reducing HBV-DNA levels and in stabilizing liver function tests, which prolong patient and graft survival.

Background: With current early transplant patient and allograft survivals nearly optimized, long-term medical complications have become a significant focus for potential improvement in patient outcomes. Cardiovascular disease and associated risk factors have been shown in renal transplant patients to be related to the pharmacologic immunosuppression employed.Objective: The objective of this study is to investigate at 3 years postliver transplant (OLTx) the incidence of hypertension (HTN), hyperlipidemia (HLIP), diabetes mellitus (DM), nephrotoxicity (NTX), and cardiovascular disease (MI, angioplasty, CHF, CVA, and seborth) as well as rejection in two cohorts of liver transplant recipients who received either tacrolimus (FK-506) or cyclosporine (CSA) and to analyze the consequences of these complications on mortality following transplantation.Methods: Eighty-seven sequential patients (CSA: n = 50, mean age 48 years, M/F 32/18; and FK-506: n = 37, mean age 45 years, M/F 22/15) who underwent OLTx between 1994 and 1998, were ≥18 years, and had a minimum of 3 years of complete follow-up were included in the analysis. All OLTx candidates over age 50, who had a history of alcoholic cirrhosis, or had a history of cardiac conditions/events underwent complete cardiac consultation including an echocardiogram with additional cardiac investigation as indicated prior to OLTx.Results: At 3 years following OLTx, the incidence of acute rejection (40% versus 19%, P < 0.05), HTN (62% versus 38%, P < 0.05), HLIP (14% versus 5%, P = 0.08), and cardiovascular disease (18% versus 0%, P < 0.001), were significantly greater for the CSA patients compared with the FK-506 patients. Eight (20%) of the CSA patients who died before 3 years had their death attributed to cardiovascular events versus none in the FK-506 group.Conclusion: Compared with CSA, FK-506 was associated with significantly less rejection and a reduced incidence of HTN and cardiovascular disease.

Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin that lacks coagulating activity. The aim of this study was to determine if the presence of DCP in the donor could be used as a marker of post-transplant graft function. We collected data and serum samples on 90 organ donors. DCP level was correlated with donor-specific factors and with graft function intraoperatively and in the early post-transplant period. Twenty-seven donors (30.0 %) had positive DCP levels before harvesting. Although recipients were similar in demographics, preoperative liver function, and primary disease distribution, patients transplanted with livers from DCP-positive donors needed significantly more intraoperative transfusion. Furthermore, donor DCP positivity was identified as a preoperative risk factor for poor early graft function based on multivariate analysis (odds ratio = 6.58, P = 0.0032). Our findings suggest that DCP is another valuable marker for evaluating the quality of donor livers.

190 Recently, we demonstrated that patients receiving OKT3 induction who recover their T cells by post-operative day 10, despite complete initial clearance, experience rejection. The present study was designed to determine the role of pro-inflammatory and Th-1 cytokines in T cell recovery and rejection in patients receiving OKT3 induction. Methods: We analyzed plasma samples from 32 patients for TNFα, IL1β and IL6 (before surgery and on postoperative days 1, 2 and 3) and for IL2, IFNγ, sIL2R and sICAM (postoperative days 5, 7 and 10) using commercial ELISA kits obtained from Immunotech (Marseille, France) and from R&D Systems (Minneapolis, MN). Results: Mean TNFα and IL6 levels were highly variable among patients in both groups and no clear trends were appreciated between the preoperative sample and POD3. Detectable IL1β levels were only found in two samples. We found a correlation between IL2 and IFNγ levels on postoperative days 5 and 7 and the degree of T cell recovery on POD10 in the rejecting group (R2=0.7923 and 0.7079 respectively, p<0.05). A significant rise in the level of sIL2R over time strongly correlated with T cell recovery in the early rejection group only(Figure).Figure: Correlation between T cell recovery on POD10 and change in sIL2R POD5-7 in rejecting patientsConclusions: TNFα, IL1β, and IL6 levels did not correlate with T cell recovery. Our results emphasize the role of Th-1 cytokines in patients who experience rejection despite OKT3 induction. This data suggest that monitoring for markers of T cell activation may help identify those individuals at risk.