Measuring and monitoring equity in access to deceased donor kidney transplantation.

The Organ Procurement and Transplantation Network monitors progress toward strategic goals such as increasing the number of transplants and improving waitlisted patient, living donor, and transplant recipient outcomes. However, a methodology for assessing system performance in providing equity in access to transplants was lacking. We present a novel approach for quantifying the degree of disparity in access to deceased donor kidney transplants among waitlisted patients and determine which factors are most associated with disparities. A Poisson rate regression model was built for each of 29 quarterly, period-prevalent cohorts (January 1, 2010-March 31, 2017; 5 years pre-kidney allocation system [KAS], 2 years post-KAS) of active kidney waiting list registrations. Inequity was quantified as the outlier-robust standard deviation (SDw ) of predicted transplant rates (log scale) among registrations, after "discounting" for intentional, policy-induced disparities (eg, pediatric priority) by holding such factors constant. The overall SDw declined by 40% after KAS implementation, suggesting substantially increased equity. Risk-adjusted, factor-specific disparities were measured with the SDw after holding all other factors constant. Disparities associated with calculated panel-reactive antibodies decreased sharply. Donor service area was the factor most associated with access disparities post-KAS. This methodology will help the transplant community evaluate tradeoffs between equity and utility-centric goals when considering new policies and help monitor equity in access as policies change.

New Insights Into the Alleged Kidney Donor Profile Index Labeling Effect on Kidney Utilization.

The Kidney Donor Profile Index (KDPI) became a driving factor in deceased donor kidney allocation on December 4, 2014, with the implementation of the kidney allocation system (KAS). On April 20, 2016, the annual recalibration of the Kidney Donor Risk Index into KDPI was incorrectly programmed in DonorNet, resulting in erroneously high KDPI values, by between 1 and 21 percentage points (e.g. actual KDPI of 70% was displayed as 86%). The error was corrected on May 19, 2016, <24 h after being recognized. During this 30-day period, the distribution of recipients largely resembled pre-KAS patterns. The observed discard rate of 22.9% was higher than the post-KAS average of 19.6% (odds ratio [OR]: 1.22) but far lower than the projected rate of 31.4% (OR: 1.96) based on the usual discard rate by KDPI relationship, suggesting clinicians and patients did not rely heavily on this single number (KDPI) in kidney-utilization decisions. Still, risk-adjusted analyses suggest the elevated discard rate was most likely attributable to the erroneously high KDPIs, not a shift in donor characteristics or random chance. The rise in discard rate was sharply higher for kidneys with inflated KDPI that crossed the 85% policy threshold (OR: 1.46; p = 0.049) versus those that did not (OR: 1.06; p = 0.631).

The Impact of the New Kidney Allocation System on Prior Living Kidney Donors' Access to Deceased Donor Kidney Transplants: An Early Look.

This study investigated the early effects of the new kidney allocation system (KAS) on the access of prior living kidney donors (PLDs) to deceased donor kidney transplants. Using data from the Organ Procurement and Transplantation Network, we compared prevalent and incident cohorts of PLDs in the 1-year periods before and after KAS implementation (pre-KAS group: December 4, 2013, to December 3, 2014, n = 50 [newly listed PLDs]; post-KAS group: December 4, 2014, to December 3, 2015, n = 39). We assessed transplant rates per active patient-year, waiting times, and Kidney Donor Profile Index (KDPI) of transplanted kidneys. Transplant rates were not statistically different before and after KAS implementation for either prevalent (2.37 vs. 2.29, relative risk [RR] 0.96; 95% confidence interval [CI] 0.62-1.49) or incident (4.76 vs. 4.36, RR 0.92; 95% CI 0.53-1.60) candidates. Median waiting time (MWT) to deceased donor kidney transplant for prevalent PLDs in the post-KAS cohort was 102.6 days compared with 82.3 days in the pre-KAS cohort (p = 0.98). The median KDPI for PLD recipients was 31% with KAS versus 23% before KAS (p = 0.02). Despite a sharp decrease in the MWT for highly prioritized candidates with calculated panel reactive antibodies of 98-100% (from >7000 to 1164 days), PLDs still had much shorter waiting times (MWT 102.6 days). The new system continues to provide quick access to high-quality organs for PLDs.

Changes in Deceased Donor Kidney Transplantation One Year After KAS Implementation.

After over a decade of discussion, analysis, and consensus-building, a new kidney allocation system (KAS) was implemented on December 4, 2014. Key goals included improving longevity matching between donor kidneys and recipients and broadening access for historically disadvantaged subpopulations, in particular highly sensitized patients and those with an extended duration on dialysis but delayed referral for transplantation. To evaluate the early impact of KAS, we compared Organ Procurement and Transplantation Network data 1 year before versus after implementation. The distribution of transplants across many recipient characteristics has changed markedly and suggests that in many ways the new policy is achieving its goals. Transplants in which the donor and recipient age differed by more than 30 years declined by 23%. Initial, sharp increases in transplants were observed for Calculated Panel-Reactive Antibody 99-100% recipients and recipients with at least 10 years on dialysis, with a subsequent tapering of transplants to these groups suggesting bolus effects. Although KAS has arguably increased fairness in allocation, the potential costs of broadening access must be considered. Kidneys are more often being shipped over long distances, leading to increased cold ischemic times. Delayed graft function rates have increased, but 6-month graft survival rates have not changed significantly.

The OPTN Deceased Donor Potential Study: Implications for Policy and Practice.

The Organ Procurement and Transplantation Network (OPTN) Deceased Donor Potential Study, funded by the Health Resources and Services Administration, characterized the current pool of potential deceased donors and estimated changes through 2020. The goal was to inform policy development and suggest practice changes designed to increase the number of donors and organ transplants. Donor estimates used filtering methodologies applied to datasets from the OPTN, the National Center for Health Statistics, and the Agency for Healthcare Research and Quality and used these estimates with the number of actual donors to estimate the potential donor pool through 2020. Projected growth of the donor pool was 0.5% per year through 2020. Potential donor estimates suggested unrealized donor potential across all demographic groups, with the most significant unrealized potential (70%) in the 50-75-year-old age group and potential Donation after Circulatory Death (DCD) donors. Actual transplants that may be realized from potential donors in these categories are constrained by confounding medical comorbidities not identified in administrative databases and by limiting utilization practices for organs from DCD donors. Policy, regulatory, and practice changes encouraging organ procurement and transplantation of a broader population of potential donors may be required to increase transplant numbers in the United States.

Trends and Patterns in Reporting of Patient Safety Situations in Transplantation.

Analysis and dissemination of transplant patient safety data are essential to understanding key issues facing the transplant community and fostering a "culture of safety." The Organ Procurement and Transplantation Network's (OPTN) Operations and Safety Committee de-identified safety situations reported through several mechanisms, including the OPTN's online patient safety portal, through which the number of reported cases has risen sharply. From 2012 to 2013, 438 events were received through either the online portal or other reporting pathways, and about half were self-reports. Communication breakdowns (22.8%) and testing issues (16.0%) were the most common types. Events included preventable errors that led to organ discard as well as near misses. Among events reported by Organ Procurement Organization (OPOs), half came from just 10 of the 58 institutions, while half of events reported by transplant centers came from just 21 of 250 institutions. Thirteen (23%) OPOs and 155 (62%) transplant centers reported no events, suggesting substantial underreporting of safety-related errors to the national database. This is the first comprehensive, published report of the OPTN's safety efforts. Our goals are to raise awareness of safety data recently reported to the OPTN, encourage additional reporting, and spur systems improvements to mitigate future risk.

Association of serum uric acid with graft survival after kidney transplantation: a time-varying analysis.

The association of serum uric acid (UA) with kidney transplant outcomes is uncertain. We examined the predictive value of UA during the first year posttransplant as a time-varying factor for graft survival after adjustment for time-dependent and independent confounding factors. Four hundred and eighty-eight renal allograft recipients transplanted from January 2004 to June 2006 and followed for 41.1 ± 17.7 months were included. Data on UA, estimated glomerular filtration rate (eGFR), tacrolimus level, mycophenolate mofetil (MMF) and prednisone doses, use of allopurinol, angiotensin-converting enzyme-inhibitor/angiotensin-receptor-blocker (ACEi/ARB) and diuretics at 1, 3, 6, 9 and 12 months were collected. Primary endpoint of the study was graft loss, defined as graft failure and death. Cox proportional hazard models and generalized estimating equations were used for analysis. UA level was associated with eGFR, gender, retransplantation, decease-donor organ, delayed graft function, diuretics, ACEi/ARB and MMF dose. After adjustment for these confounders, UA was independently associated with increased risk of graft loss (HR: 1.15, p = 0.003; 95% CI: 1.05-1.27). Interestingly, UA interacted with eGFR (HR: 0.996, p < 0.05; 95% CI: 0.993-0.999 for interaction term). Here, we report a significant association between serum UA during first year posttransplant and graft loss, after adjustment for corresponding values of time-varying variables including eGFR, immunosuppressive drug regimen and other confounding factors. Its negative impact seems to be worse with lower eGFR.

Guidelines for the diagnosis of antibody-mediated rejection in pancreas allografts-updated Banff grading schema.

The first Banff proposal for the diagnosis of pancreas rejection (Am J Transplant 2008; 8: 237) dealt primarily with the diagnosis of acute T-cell-mediated rejection (ACMR), while only tentatively addressing issues pertaining to antibody-mediated rejection (AMR). This document presents comprehensive guidelines for the diagnosis of AMR, first proposed at the 10th Banff Conference on Allograft Pathology and refined by a broad-based multidisciplinary panel. Pancreatic AMR is best identified by a combination of serological and immunohistopathological findings consisting of (i) identification of circulating donor-specific antibodies, and histopathological data including (ii) morphological evidence of microvascular tissue injury and (iii) C4d staining in interacinar capillaries. Acute AMR is diagnosed conclusively if these three elements are present, whereas a diagnosis of suspicious for AMR is rendered if only two elements are identified. The identification of only one diagnostic element is not sufficient for the diagnosis of AMR but should prompt heightened clinical vigilance. AMR and ACMR may coexist, and should be recognized and graded independently. This proposal is based on our current knowledge of the pathogenesis of pancreas rejection and currently available tools for diagnosis. A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions.

Banff schema for grading pancreas allograft rejection: working proposal by a multi-disciplinary international consensus panel.

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.

Safe pancreas transplantation in patients with coronary artery disease.

BACKGROUND: This study was conducted to determine the risk of clinically significant posttransplant cardiac events (PCEs) in a cohort of diabetic patients referred for pancreas transplantation. METHODS: Between April 1991 and December 1995, 316 insulin-dependent diabetics were evaluated for pancreas transplantation. Patients were assessed for risk factors for coronary artery disease (CAD), and underwent screening for significant CAD by a standardized algorithm that included selective coronary angiography. For the 3-year period following transplantation, PCEs were identified, and related to pretransplant cardiac risk factors. RESULTS: Only four patients (1.3%) were turned down for cardiac contraindications. Coronary angiography was done in 74 patients (27% of the active transplant candidates) during the evaluation period because of the patient's history or a positive stress test. Significant coronary artery stenoses were found in 54% of the patients catheterized. Twenty-five of these 40 patients (63%) underwent revascularization with percutaneous transluminal coronary angioplasty and/or coronary artery bypass grafting. A total of 359 organs were subsequently transplanted into 194 of these patients. No deaths occurred within 30 days of any of the transplants; four percent of transplant recipients died of cardiac causes within the follow-up period (median 23 months). Those with no pretransplant evidence of CAD had significantly lower rates of PCE (2% and 8% at 1 and 3 years, respectively) than those with pretransplant evidence of CAD (11% and 29% at 1 and 3 years, P<0.01; relative risk, 4.3). CONCLUSIONS: Routine cardiac screening of pancreas recipients with selective angiography and revascularization allows patients with significant CAD to safely undergo pancreas transplantation. Patients should rarely be excluded from pancreas transplantation for cardiac causes.

Histologic findings in islets of whole pancreas allografts: lack of evidence for recurrent cell-mediated diabetes mellitus.

Cell-mediated cytotoxicity directed toward pancreatic islets plays a significant role in the pathogenesis of type 1 diabetes mellitus. Histologically, autoimmune insulitis appears as mononuclear infiltrates that precede actual beta cell loss. Experimental studies by Bartlett et al. on the BB rat model suggest that whole pancreas transplants are not susceptible to recurrent autoimmune diabetes. To test this hypothesis on clinical grounds, we evaluated the islets in pancreatectomies and percutaneous needle biopsies from 55 whole pancreas allografts. In this material, islet inflammation was never seen independently of allograft rejection, but was always associated with inflammation of the surrounding acinar structures. The degree of islet inflammation and the occasional presence of islet necrosis correlated well with the degree of rejection and only occurred in the higher grades of the latter (grades III-V). We did not observe isolated insulitis as a histological indication of selective cell-mediated cytotoxicity against beta cells.

Isolated pancreas rejection in combined kidney pancreas tranplantation.

The clinical success of pancreas transplantation is limited by the difficulty in diagnosing rejection. In simultaneous pancreas kidney (SPK) transplantation, the diagnosis of pancreatic rejection is particularly difficult in the absence of clinical evidence of kidney rejection. Moreover, patients receiving only pancreas grafts will not have a concomitantly grafted kidney to serve as a "sentinel" for rejection. Percutaneous pancreas graft biopsy has been reported in a few small series but has not been adopted for broad clinical use. We describe the evaluation of 69 consecutive episodes of suspected isolated pancreas allograft rejection by percutaneous pancreas allograft biopsy. These rejection episodes occurred in 41 patients with bladder-drained pancreas transplants (25 SPK, 14 pancrease after kidney transplants [PAK], amd two pancreas transplant alone [PTA]). The indications for percutaneous pancreas biopsy were a twofold or greater increase in serum amylase or lipase, or a sustained 40% to 50% drop in urine amylase in the setting of no evidence of renal allograft dysfunction in SPK transplants. Biopsies were performed with color-flow Doppler ultrasound localization using an 18-gauge automated biopsy needle. Pancreatic tissue adequate for histologic evaluation was obtained in 61 of 69 cases (88%). There were two cases of intraabdominal bleeding, one of which required surgical intervention; the other resolved spontaneously. Histologic assessment of the biopsies demonstrated varying degrees of acute cellular rejection in 48 of 61 specimens (79%). Twelve specimens (20%) were free of histologic evidence of rejection, and one specimen (2%) showed acute pancreatitis. At the time of suspected rejection mean serum amylase and lipase values were increased 3.6 and 8.3-fold, respectively, and urine amylase was decreased by a mean of 45%. We conclude that the commonly used markers for pancreas allograft rejection are only about 80% specific for acute rejection. Percutaneous pancreas allograft biopsy is safe and allows the avoidance of unnecessary antirejection therapy with its attendant side effects and cost.

Histologic grading of acute allograft rejection in pancreas needle biopsy: correlation to serum enzymes, glycemia, and response to immunosuppressive treatment.

BACKGROUND: Allograft rejection continues to be the most common cause of graft failure in technically successful pancreas transplants. Early diagnosis and treatment of rejection is essential for long-term graft survival. Pancreas graft biopsies are now used routinely for the diagnosis of acute allograft rejection. The correlation between clinical evidence of graft dysfunction (increased serum enzymes and glucose), severity of acute rejection on biopsy (rejection grade), and response to treatment has not been previously studied. METHODS: A total of 151 pancreas transplant needle biopsy specimens from 57 patients were evaluated. Statistical correlation was done between the histologic rejection grade (O-V) and the peak level of enzymes in serum, glycemia, type of antirejection treatment instituted, and response to treatment. Differentiation between grades was also evaluated statistically. RESULTS: Response to antirejection treatment was 25%, 40%, 88%, 78%, 50%, and 17% for grades O-V, respectively. The response for grades II and III was better than for grades 0-I and IV-V (P=0.0003 and 0.0008, respectively). The response to corticosteroids alone was 36%, 86%, 68%, and 0% for grades I, II, III, and IV, respectively. The response to antilymphocyte regimen was 50%, 89%, 85%, 71%, and 17% for grades I, II, III, IV, and V, respectively. Overall correlation between the mean levels of enzymes and rejection grade was seen; the increase of lipase was statistically significant (r=0.24, P=0.012). Amylase and lipase correlated very well with each other (r=0.84, P=0.0001). No correlation was found in the mean values of blood glucose with the serum enzyme increase and with severity of rejection. Hyperglycemia was present in 12 patients; this abnormality in patients with grades II-IV responded promptly to treatment, whereas in patients with grade V, hyperglycemia persisted despite antirejection treatment. Other causes of increased enzymes were found in patients with biopsy specimens showing no rejection (grades 0 and I, 43% and 31%, respectively). CONCLUSIONS: Increased serum enzymes, particularly lipase, correlate with the grade of acute rejection, but their lack of specificity precludes their use as sole markers of acute rejection. Glucose levels are not a sensitive marker for acute rejection. Rejection grades II and III are the most responsive to treatment, and a significant proportion of these cases respond to treatment with corticosteroids only. The higher rejection grades (IV and V) require treatment with antilymphocytic regimens, and their overall response to treatment is moderate to poor, respectively.

Acute effects of intravenous cyclosporine on blood pressure, renal hemodynamics, and urine prostaglandin production of healthy humans.

The acute renal failure associated with cyclosporine may result from vasoconstriction of intrarenal arterioles. To evaluate the mechanism of cyclosporine-induced nephrotoxicity, we acutely administered cyclosporine to eight healthy female volunteers with normal blood pressure and renal function. Cyclosporine (4 mg/kg) in 250 ml of 5% dextrose in water (D5W) was administered as a steady intravenous infusion over 6 hr. Glomerular filtration rate and renal plasma flow were measured by serum disappearance of 99m TcDTPA and 131I hippuran, respectively, during the last 3 hr of the infusion. D5W was given to the patients on separate days before the cyclosporine infusion to obtain control data. Systolic and diastolic blood pressure measured every hour during the infusions and renal vascular resistance were slightly higher during cyclosporine administration, but the increases were not statistically significant. Renal plasma flow was not affected by cyclosporine, being 479.6 +/- 24.9 ml/min during the control infusion and 463.3 +/- 12.7 ml/min during the cyclosporine infusion. However, glomerular filtration rate was reduced by cyclosporine in all patients (control, 108.8 +/- 2.5 ml/min, vs. cyclosporine, 91.1 +/- 2.2 ml/min, P less than .01), except one who demonstrated no significant change. Urinary excretion of thromboxane B2 during cyclosporine administration was markedly increased in all patients, being 39.9 +/- 8.2 ng/hr in the control period and 85.8 +/- 22.3 ng/hr during cyclosporine infusion (P less than .05), except for the one patient in whom no decrease in GFR was noted. There was no significant change in the urinary excretion rate for 6-keto-prostaglandin F1a or prostaglandin E during cyclosporine infusion. Serum averaged levels of peripheral renin activity, angiotensin II, and aldosterone did not change during with the cyclosporine administration compared with the control. All patients demonstrated a decrease in 24-h urinary excretion of sodium and potassium on the day of the cyclosporine infusion. Verapamil SR (240 mg daily for 7 days prior to cyclosporine infusion) did not reverse the reduction in glomerular filtration rate induced by cyclosporine; however, a significant reduction in renal vascular resistance and an increase in renal plasma flow (P less than .05) were noted when the volunteers were treated with both verapamil and cyclosporine compared with cyclosporine alone. Intravenous infusion of Cremophor EL, the vehicle to dissolve cyclosporine, demonstrated no significant effects on blood pressure, renal hemodynamics or urinary prostaglandin excretion.(ABSTRACT TRUNCATED AT 400 WORDS)

CMV allograft pancreatitis: diagnosis, treatment, and histological features.

BACKGROUND: Cytomegalovirus (CMV) infection is a common problem in solid organ transplant recipients. CMV infection of pancreas allografts is not, however, well described. METHODS: We report the clinical presentation, histologic findings, treatment, and outcome in four patients with CMV allograft pancreatitis. These patients presented 18 weeks to 44 months after transplantation with elevated serum amylase and lipase and were suspected to have acute rejection. Percutaneous pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection. One patient had simultaneous CMV infection and acute rejection. RESULTS: Prolonged treatment with ganciclovir resulted in clinical and histologic resolution of the CMV disease. Rejection was successfully treated. Primary CMV infection in seronegative recipients seemed to be a risk factor. Three patients maintain normal allograft function; one patient lost function due to chronic rejection. The histology of tissue-invasive CMV pancreas allograft infection and its differentiation from acute rejection is described. CONCLUSION: Prompt diagnosis and prolonged therapy with antiviral agents can result in maintenance of allograft function.

Islet cell damage associated with tacrolimus and cyclosporine: morphological features in pancreas allograft biopsies and clinical correlation.

BACKGROUND: The introduction of the potent immunosuppressive drugs tacrolimus (FK) and cyclosporine (CSA) has markedly improved the outcome of solid organ transplantation. However, these drugs can cause posttransplantation diabetes mellitus. Abnormalities in the glucose metabolism are of particular significance in pancreas transplantation. METHODS: We studied 26 pancreas allograft biopsies, performed 1-8 months posttransplantation, from 20 simultaneous kidney-pancreas transplant recipients, randomized to receive either FK or CSA. The biopsies were studied by light microscopy, immunoperoxidase stains for insulin and glucagon, in situ DNA-end labeling for detection of apoptosis, and electron microscopy. The islet morphology was correlated with the mean and peak levels of CSA and FK in serum, with corticosteroid administration and with glycemia. RESULTS: On light microscopy cytoplasmic swelling, vacuolization, apoptosis, and abnormal immunostaining for insulin were seen in biopsies from patients receiving either FK or CSA. The islet cell damage was more frequent and severe in the group receiving FK than in the group receiving CSA (10/13 and 5/13, respectively) but the differences were not statistically significant. Significant correlation was seen between the presence of islet cell damage and serum levels of CSA or FK during the 15 days previous to the biopsy, as well as with the peak level of FK. Toxic levels of CSA or FK and administration of pulse steroids were associated with hyperglycemia when these occurred concurrently (P=0.005). Toxic levels of CSA or FK by themselves were associated with hyperglycemia in a minority of cases (8 and 26%, respectively). Electron microscopy showed cytoplasmic swelling and vacuolization, and marked decrease or absence of dense-core secretory granules in beta cells; the changes were more pronounced in patients on FK. Serial biopsies from two hyperglycemic patients receiving FK and evidence of islet cell damage demonstrated reversibility of the damage when FK was discontinued. CONCLUSIONS: The structural damage to beta cells demonstrated in this study is similar to morphological and functional abnormalities previously described in experimental animal models and can at least partially account for the glucose metabolism abnormalities seen in patients receiving these drugs. Toxic levels of CSA or FK and higher steroid doses potentiate each others' diabetogenic effects.

Late pancreas allograft rejection. Preliminary experience with factors predisposing to rejection.

A case series of 31 cadaveric pancreas transplant recipients who were insulin-independent at least for one year was analyzed for the factors predisposing to late acute rejection (> 12 months posttransplant). Sixty-two pancreas transplants were performed in 61 patients, of whom 53 had functioning allografts 3 months posttransplant; 31 of these had a follow-up > 12 months. Twenty had no evidence of late rejection, whereas 11 had evidence of acute rejection after 12 months. All patients received quadruple induction immunosuppression. No demographic or clinical factors-including donor age, organ cold time, HLA mismatch, age, sex, or race-could distinguish the late acute rejection group. The presence of acute rejection in the first year posttransplant was similar in the late rejectors (21 episodes in 9 of 11 patients) compared with patients without late rejection (31 episodes in 16 of 20 patients). Antilymphocyte induction therapy type had no influence, but the amount of immunosuppression with prednisone and cyclosporine (CsA) at 3 months posttransplant was significantly lower in those patients who experienced late rejection. After the first year posttransplant, CsA 12-hr trough levels were significantly lower in late rejection months (121 +/- 7 ng/ml) compared with each patient's own stable months (183 +/- 5 ng/ml, P < 0.0001). Neither prednisone nor azathioprine dosages differed between teh two groups after the first year posttransplant. Our preliminary results suggest that early under immunosuppression with prednisone and CsA in the first year and 12-hr trough CsA levels less than approximately 180 ng/ml after the first year posttransplant predispose to late pancreatic rejection.

Evaluation of pancreas transplant needle biopsy: reproducibility and revision of histologic grading system.

BACKGROUND: Tissue samples for the diagnosis of pancreatic allograft rejection are now obtained routinely through the application of the percutaneous needle biopsy technique. The availability of biopsy material (89% adequate for diagnosis in our setting) presents a challenge for pathologists who are asked to provide a fast and accurate diagnosis of rejection and its severity, while at the same time being able to differentiate rejection from other causes of graft dysfunction. METHODS: To differentiate rejection from other pathologic processes, 26 histologic features were assessed in 92 biopsies performed for confirmation of clinical diagnosis of rejection and the results were compared with 31 protocol biopsies, 12 allograft pancreatectomies with non-rejection pathology, and 30 native pancreas resections with various disease processes. RESULTS: Based on these comparisons, a constellation of findings relating to the vascular, septal, and acinar inflammation was identified for the diagnosis of rejection. Application of these features led us to revise our scheme for grading rejection (ranging from 0-normal to V-severe rejection) to include the categories of "inflammation of undetermined significance" and "minimal rejection." The scheme was used by five pathologist to grade 20 biopsies independently of any clinical data and the interobserver level of agreement was highly significant (kappa=0.83, P<0.0001). This grading scheme was applied blindly to all (183) biopsies from 77 patients with 6-52 months of follow-up. The correlation of the highest degree of rejection on each patient and ultimate graft loss (0% for grades 0-I, 11.5% for grade II, 17.3% for grade III, 37.5% for grade IV, and 100% for grade V) was highly statistically significant (P<0.002). The fraction of grafts lost due to pure immunologic causes increased proportionally to the grade of rejection (0, 50, 66, and 100% for grades II, III, IV, and V, respectively). CONCLUSIONS: This study provides strong support for the proposed pancreas rejection grading scheme and confirms its potential for practical use.

Double renal allografts successfully increase utilization of kidneys from older donors within a single organ procurement organization.

BACKGROUND: In 1994, a policy of double renal allografting (DUAL) was used at two centers within our local organ procurement organization to increase utilization of kidneys from older donors that would otherwise be discarded. Both kidneys from an older donor (age > 60 years) were selectively transplanted into a single adult recipient. METHODS: The relative impact of a DUAL policy on the utilization of older donor kidneys is examined for the period of April 1994 to April 1996. Actual utilization is compared with the hypothetical case in which a DUAL policy is not present. RESULTS: In the actual setting, a total of 75 kidneys from older donors (> 60 years) were accepted for transplantation. Thirty-six kidneys were transplanted as singlets, and 16 additional kidneys were transplanted as DUAL renal allografts. Thus, a 44% increase in transplantable kidneys, and a 22% increase in patients transplanted with kidneys from older donors, was realized. In the actual setting, 23 older kidneys were discarded; without the DUAL policy, 39 kidneys would have been deemed untransplantable. When compared with the actual (n = 52) and hypothetical number of kidneys transplanted without a policy of DUAL transplantation (n = 36), the DUAL policy significantly increased the utilization of older donor kidneys (P = 0.01). The actuarial 1-year graft survival rate of the dual kidneys was 100%, with a mean follow-up of 11.1 +/- 2.9 months. Mean 6-month and 1-year serum creatinine level were 1.76 +/- 0.4 and 1.63 +/- 0.6 mg/dl, respectively. CONCLUSIONS: A DUAL policy significantly increased the number of older donor kidneys transplanted in a single organ procurement organization and reduced the rate of discard of older donor kidneys over a 2-year period. Long-term follow-up is necessary to substantiate satisfactory graft function in DUAL from older donors.

A comparison of recipient renal outcomes with laparoscopic versus open live donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy (laparoNx) has the potential to increase living kidney donation rates by reducing the pain and suffering of the donor. However, renal function outcomes of a large series of recipients of laparoNx have not been studied. METHODS: We retrospectively reviewed the records of 132 recipients of laparoNx done at our center between 3/96 and 11/97 and compared them to 99 recipients of kidneys procured by the open technique (openNx) done between 10/93 and 3/96. RESULTS: Significantly more patients in the laparoNx group (25.2%) were taking tacrolimus within the first month than those in the openNx group (2.1%). Mean serum creatinine was higher in laparoNx compared with openNx at 1 week (2.8+/-0.3 and 1.8+/-0.2 mg/dl, respectively; P=0.005) and at 1 month (2.0+/-0.1 and 1.6+/-0.1 mg/dl, P=0.05) after transplant. However, by 3 and 6 months, the mean serum creatinine was similar in the two groups (1.7+/-0.1 versus 1.5+/-0.05 mg/dl, and 1.7+/-0.1 versus 1.7+/-0.1, respectively). By 1 year posttransplant, the mean serum creatinine for laparoNx was actually less than that for openNx (1.4+/-0.1 and 1.7+/-0.1 mg/dl, P=0.03). Although patients in the laparoNx compared to the openNx group were more likely to have delayed graft function (7.6 versus 2.0%) and ureteral complications (4.5 versus 1.0%), the rate of other complications, as well as hospital length of stay, patient and graft survival rates were similar in the two groups. CONCLUSION: Although laparoNx allografts have slower initial function compared with openNx, there was no significant difference in longer term renal function.