Weight Loss Surgery Increases Kidney Transplant Rates in Patients With Renal Failure and Obesity.

OBJECTIVE: To describe the outcomes of kidney transplant (KT) candidates with obesity undergoing sleeve gastrectomy (SG) to meet the criteria for KT. METHODS: Retrospective analysis was conducted of electronic medical records of KT candidates with obesity (body mass index >35 kg/m2) who underwent SG in our institution. Weight loss, adverse health events, and the listing and transplant rates were abstracted and compared with the nonsurgical cohort. RESULTS: The SG was performed in 54 patients; 50 patients did not have surgery. Baseline demographic characteristics were comparable at the time of evaluation. Mean body mass index ± SD of the SG group was 41.7±3.6 kg/m2 at baseline (vs 41.5±4.3 kg/m2 for nonsurgical controls); at 2 and 12 months after SG, it was 36.4±4.1 kg/m2 and 32.6±4.0 kg/m2 (P<.01 for both). In the median follow-up time of 15.5 months (interquartile range, 6.4 to 23.9 months), SG was followed by active listing (37/54 people), and 20 of 54 received KT during a median follow-up time of 20.9 months (interquartile range, 14.7 to 28.3 months) after SG. In contrast, 14 of 50 patients in the nonsurgical cohort were listed, and 5 received a KT (P<.01). Three patients (5.6%) experienced surgical complications. There was no difference in overall hospitalization rates and adverse health outcomes, but the SG cohort experienced a higher risk of clinically significant functional decline. CONCLUSION: In KT candidates with obesity, SG appears to be effective, with 37% of patients undergoing KT during the next 18 months (P<.01). Further research is needed to confirm and to improve the safety and efficacy of SG for patients with obesity seeking a KT.

BK polyomavirus DNAemia in pancreas transplant recipients compared to pancreas-kidney recipients.

BACKGROUND: BK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non-kidney transplant recipients, data are limited regarding its epidemiology and outcomes in pancreas transplant recipients. METHODS: We conducted a retrospective cohort study of adults who underwent pancreas transplantation from 2010-2020. The primary outcome was BKV DNAemia. Secondary outcomes were estimated glomerular filtration rate (eGFR) reduction by 30%, eGFR < 30 mL/min/1.73 m2 , endstage kidney disease, and pancreas allograft failure. Cox regression with time-dependent variables was utilized. RESULTS: Four hundred and sixty-six patients were analyzed, including 74, 46, and 346 with pancreas transplant alone (PTA), pancreas-after-kidney, or simultaneous pancreas-kidney transplants, respectively. PTA recipients experienced a lower incidence of BKV DNAemia (8.8% vs. 32.9%; p < .001) and shorter duration of DNAemia (median 28.0 vs. 84.5 days). No PTA recipients with BKV DNAemia underwent kidney biopsy or developed endstage kidney disease. Lymphopenia, non-PTA transplantation, and older age were associated with BKV DNAemia, which itself was associated with pancreas allograft failure (adjusted hazard ratio 2.14, 95% confidence interval 1.27-3.60; p = .004). Among PTA recipients, BKV DNAemia was not associated with eGFR reduction or eGFR < 30 mL/min/1.73 m2 . CONCLUSIONS: BKV DNAemia was common among PTA recipients, though lower than a comparable group of pancreas-kidney recipients. However, BKV DNAemia was not associated with adverse native kidney outcomes and no PTA recipients developed endstage kidney disease. Conversely, BKV DNAemia was associated with pancreas allograft failure. Further studies are needed to estimate the rate of BKV nephropathy in this population, and further evaluate long-term kidney outcomes.

Impact of Perioperative Prophylaxis With Enterococcus Activity on Risk of Surgical-Site Infection After Pancreas Transplantation.

Surgical-site infection (SSI) is the most common early infectious complication after pancreas transplantation (PT). Although SSI has been shown to worsen outcomes, little data exist to guide optimal choices in perioperative prophylaxis. Methods: We performed a retrospective cohort study of PT recipients from 2010-2020 to examine the effect of perioperative antibiotic prophylaxis with Enterococcus coverage. Enterococcus coverage included antibiotics that would be active for penicillin-susceptible Enterococcus isolates. The primary outcome was SSI within 30 d of transplantation, and secondary outcomes were Clostridioides difficile infection (CDI) and a composite of pancreas allograft failure or death. Outcomes were analyzed by multivariable Cox regression. Results: Of 477 PT recipients, 217 (45.5%) received perioperative prophylaxis with Enterococcus coverage. Eighty-seven recipients (18.2%) developed an SSI after a median of 15 d from transplantation. In multivariable Cox regression analysis, perioperative Enterococcus prophylaxis was associated with reduced risk of SSI (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.35-0.96; P = 0.034). Anastomotic leak was also significantly associated with elevated risk of SSI (HR 13.95; 95% CI, 8.72-22.32; P < 0.001). Overall, 90-d CDI was 7.4%, with no difference between prophylaxis groups (P = 0.680). SSI was associated with pancreas allograft failure or death, even after adjusting for clinical factors (HR 1.94; 95% CI, 1.16-3.23; P = 0.011). Conclusions: Perioperative prophylaxis with Enterococcus coverage was associated with reduced risk of 30-d SSI but did not seem to influence risk of 90-d CDI after PT. This difference may be because of the use of beta-lactam/beta-lactamase inhibitor combinations, which provide better activity against enteric organisms such as Enterococcus and anaerobes compared with cephalosporin. Risk of SSI was also related to anastomotic leak from surgery, and SSI itself was associated with subsequent risk of a poor outcome. Measures to mitigate or prevent early complications are warranted.

Guiding Kidney Transplantation Candidates for Effective Weight Loss: A Clinical Cohort Study.

Background: Obesity is increasingly common in kidney transplant candidates and may limit access to transplantation. Obesity and diabetes are associated with a high risk for post-transplant complications. The best approach to weight loss to facilitate active transplant listing is unknown, but bariatric surgery is rarely considered due to patient- and physician-related apprehension, among other factors. Methods: We aimed to determine the magnitude of weight loss, listing, and transplant rates in 28 candidates with a mean BMI of 44.4±4.6 kg/m2 and diabetes treated conservatively for 1 year post weight-loss consultations (group 1). Additionally, we evaluated 15 patients (group 2) who met the inclusion criteria but received bariatric intervention within the same time frame. All patients completed a multidisciplinary weight management consultation with at least 1 year of follow-up. Results: In the conservatively managed group (group 1), the mean weight at the time of initial consultation was 126.5±18.5 kg, and the mean BMI was 44.4±4.6 kg/m2. At 1 year post weight-loss consultation, the mean weight decreased by 4.4±8.2 kg to 122.9±17 kg, and the mean BMI was 43±4.8 kg/m2, with a total mean body weight decrease of 3% (P=0.01). Eighteen patients (64%) did not progress to become candidates for active listing/transplantation during the follow-up time of 4±2.9 years, with 15 (54%) subsequently developing renal failure/diabetes-related comorbidities prohibitive for transplantation. In contrast, mean total body weight decreased by 19% at 6 months post bariatric surgery, and the mean BMI was 34.2±4 and 32.5±3.7 kg/m2 at 6 and 12 months, respectively. Bariatric surgery was strongly associated with subsequent kidney transplantation (HR=8.39 [95% CI 1.71 to 41.19]; P=0.009). Conclusions: A conservative weight-loss approach involving multidisciplinary consultation was ineffective in most kidney transplant candidates with diabetes, suggesting that a more proactive approach is needed.

Complications After Hand-Assisted Laparoscopic Living Donor Nephrectomy.

OBJECTIVE: To study the complications of hand-assisted laparoscopic living donor nephrectomy (HALLDN) with an emphasis on complications occurring early after hospital discharge up to 120 days after surgery. PATIENTS AND METHODS: We retrospectively categorized complications using the Clavien-Dindo classification in 3002 HALLDNs performed at 1 center from January 1, 2000, through December 31, 2019. In addition to overall summaries, modeling was used to identify correlates of complications before and after living donation. RESULTS: Of these donors, 87% were White, 59% were female, the mean age was 45 years (range, 18-77 years), 30.3% had a body mass index of at least 30, and 36.3% had previous abdominopelvic surgery. There were no deaths related to the surgery. The incidence of major complications (intraoperative complications plus Clavien-Dindo grade ≥III postoperatively) was 2.5% (n=74). The overall complication rate was 12.4% (n=371), including 15 intraoperative, 76 postoperative before discharge, and 280 after discharge to 120 days. Reoperation was required in 1.8% of patients (n=54), and all but 1 of these were incision-related problems. Seventy-six percent of all complications occurred after discharge, including 85% of the reoperations. For major complications, no risk factor was found. Risk factors for any complication included paramedian incision (hazard ratio [HR], 2.54; 95% CI, 1.49 to 4.34; P<.001); a history of abdominopelvic surgery (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), male sex (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), non-White race (HR, 1.40; 95% CI, 1.05 to 1.88; P=.02), and early era of the experience. CONCLUSION: Most major complications of HALLDN occur after discharge, suggesting that close follow-up is warranted and that the current literature may underestimate the true incidence.

Long-term Outcomes of Sequential Hematopoietic Stem Cell Transplantation and Kidney Transplantation: Single-center Experience.

BACKGROUND: Experience with sequential hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) is limited. METHODS: We conducted a retrospective observational study of adult patients who underwent both HSCT and KT at our center, with a median follow-up of 11 y. RESULTS: In our 54 patients cohort (94% autologous HSCT), 36 (67%) patients received HSCT first followed by KT, while 18 (33%) received KT before HSCT. In both groups, AL amyloidosis represented 50% of hematologic diagnosis. Only 4 patients expired due to hematologic disease relapse (2 patients in each group) and only 3 allografts were lost due to hematologic disease recurrence (HSCT first n = 1 and KT first n = 2). Overall 1, 5, and 10 y death-censored graft survival rates were 94%, 94%, and 94%, respectively, for the HSCT first group and 89%, 89%, and 75%, respectively, for the KT first group. Overall 1, 5, and 10 y patients survival rates were 100%, 97% and 90%, respectively, for the HSCT first group and 100%, 76%, and 63%, respectively, for the KT first group. CONCLUSIONS: Our study supports safety of sequential KT and HSCT, with improved overall patient survival compared to recipients of HSCT remaining on dialysis and good long-term kidney allograft outcome.

A study from The Mayo Clinic evaluated long-term outcomes of kidney transplantation in patients with immunoglobulin light chain amyloidosis.

Longer survival using modern therapies has increased the number of patients with immunoglobulin light-chain amyloidosis receiving kidney transplantation. We evaluated 60 patients with immunoglobulin light chain amyloidosis who underwent kidney transplantation based on their hematologic response for outcomes of death, graft failure, and complications. Patient hematologic responses (light-chain in blood or urine) prior to kidney transplantation were three patients had no response, five had a partial response, six had a very good partial response, 37 had a complete response, and nine were treatment-naive patients (never treated for this disorder). After transplantation, seven of nine treatment-naive patients achieved a complete response. The median follow-up for the entire transplant cohort was 61 months. The estimated median overall survival from the time of kidney transplantation was 123 months for the entire group. Median overall survival was not reached for the very good partial response plus complete response groups, it was 47 months for no response plus partial response groups, and 117 months for the treatment-naive group (all significantly different). Median overall survival of very good partial response was 81 months, while the median was not reached in the complete response group (no significant difference). The time to amyloid recurrence was significantly longer in complete response compared to very good partial response (median 181 vs 81 months). Death-censored graft survival at one- and five-years was 98.3%, and 95.8%, respectively for all groups. Of the 60 patients, three had allograft failure, 19 died with a functioning graft, and 13 had an amyloid recurrence. Thus, outcomes after kidney transplant in patients with immunoglobulin light-chain amyloidosis seem acceptable if a very good partial response or complete response is achieved either before or after transplantation.

NASA-TLX Assessment of Surgeon Workload Variation Across Specialties.

OBJECTIVE: With advancements in surgical equipment and procedures, human-system interactions in operating rooms affect surgeon workload and performance. Workload was measured across surgical specialties using surveys to identify potential predictors of high workload for future performance improvement. SUMMARY BACKGROUND DATA: Surgical instrumentation and technique advancements have implications for surgeon workload and human-systems interactions. To understand and improve the interaction of components in the work system, NASA-Task Load Index can measure workload across various fields. Baseline workload measurements provide a broad overview of the field and identify areas most in need of improvement. METHODS: Surgeons were administered a modified NASA-Task Load Index survey (0 = low, 20 = high) following each procedure. Patient and procedural factors were retrieved retrospectively. RESULTS: Thirty-four surgeons (41% female) completed 662 surgery surveys (M = 14.85, SD = 7.94), of which 506 (76%) have associated patient and procedural data. Mental demand (M = 7.7, SD = 5.56), physical demand (M = 7.0, SD = 5.66), and effort (M = 7.8, SD = 5.77) were the highest rated workload subscales. Surgeons reported difficulty levels higher than expected for 22% of procedures, during which workload was significantly higher (P < 0.05) and procedural durations were significantly longer (P > 0.001). Surgeons reported poorer perceived performance during cases with unexpectedly high difficulty (P < 0.001). CONCLUSIONS: When procedural difficulty is greater than expected, there are negative implications for mental and physical demand that result in poorer perceived performance. Investigations are underway to identify patient and surgical variables associated with unexpected difficulty and high workload. Future efforts will focus on re-engineering the surgical planning process and procedural environment to optimize workload and performance for improved surgical care.

Use of Eculizumab for Active Antibody-mediated Rejection That Occurs Early Post-kidney Transplantation: A Consecutive Series of 15 Cases.

BACKGROUND: Active antibody-mediated rejection (AMR) that occurs during the amnestic response within the first month posttransplant is a rare but devastating cause of early allograft loss after kidney transplant. Prior reports of eculizumab treatment for AMR have been in heterogeneous patient groups needing salvage therapy or presenting at varied time points. We investigated the role of eculizumab as primary therapy for active AMR early posttransplant. METHODS: We performed a retrospective observational study of a consecutive cohort of solitary kidney transplant recipients who were transplanted between January 1, 2014, and January 31, 2018, and had AMR within the first 30 days posttransplant and treated with eculizumab ± plasmapheresis. RESULTS: Fifteen patients had early active AMR at a median (interquartile range [IQR]) of 10 (7-11) days posttransplant and were treated with eculizumab ± plasmapheresis. Thirteen cases were biopsy proven, and 2 cases were presumed on the basis of donor-specific antibody trends and allograft function. Within 1 week of treatment, the median estimated glomerular filtration rate increased from 21 to 34 mL/min (P = 0.001); and persistent active AMR was only found in 16.7% (2/12) of biopsied patients within 4-6 months. No graft losses occurred, and at last follow-up (median [IQR] of 13 [12-19] mo), the median IQR estimated glomerular filtration rate increased to 52 (46-60) mL/min. CONCLUSIONS: Prompt eculizumab treatment as primary therapy is safe and effective for early active AMR after kidney transplant or abrupt increases in donor-specific antibodies when biopsy cannot be performed for diagnosis confirmation.

Modeling graft loss in patients with donor-specific antibody at baseline using the Birmingham-Mayo (BirMay) predictor: Implications for clinical trials.

Predicting which renal allografts will fail and the likely cause of failure is important in clinical trial design to either enrich patient populations to be or as surrogate efficacy endpoints for trials aimed at improving long-term graft survival. This study tests our previous Birmingham-Mayo model (termed the BirMay Predictor) developed in a low-risk kidney transplant population in order to predict the outcome of patients with donor specific alloantibody (DSA) at the time of transplantation and identify new factors to improve graft loss prediction in DSA+ patients. We wanted define ways to enrich the population for future therapeutic intervention trials. The discovery set included 147 patients from Mayo Cohort and the validation set included 111 patients from the Paris Cohort-all of whom had DSA at the time of transplantation. The BirMay predictor performed well predicting 5-year outcome well in DSA+ patients (Mayo C statistic = 0.784 and Paris C statistic = 0.860). Developing a new model did not improve on this performance. A high negative predictive value of greater than 90% in both cohorts excluded allografts not destined to fail within 5 years. We conclude that graft-survival models including histology predict graft loss well, both in DSA+ cohorts as well as DSA- patients.

Frequency and Predictors of Renal Transplantation Among Patients Rendered Surgically Anephric for Sporadic Renal Cancer.

OBJECTIVE: To assess the frequency of renal transplantation in patients rendered surgically anephric during treatment of renal cancers as well as the clinicopathologic factors associated with receipt of transplantation. METHODS: A retrospective review was conducted to identify patients rendered surgically anephric between 2001 and 2016 due to cancer in both renal units or cancer in an anatomically or functionally solitary kidney. Patient demographics, comorbidities, and cancer features were compared between patients who subsequently received a renal transplantation and those who did not. Time-to-event analysis was used to compare time to transplantation across varied identified parameters. RESULTS: Among 27 patients rendered anephric, 4 (15%) received a renal transplantation over a median follow-up of 21.6 months (interquartile range 7.2, 53.3). All transplanted patients were less than 70 years of age and had cT1a renal parenchymal mass at the time of nephrectomy. No patient undergoing completion nephrectomy for upper tract urothelial carcinoma received transplantation. Patients who were evaluated by the transplant service prior to nephrectomy were more likely to eventually undergo transplantation (60% vs 5%; P < .01). On time-to-event analyses, a cT1a renal parenchymal mass (P < .01) and a pre-nephrectomy transplant evaluation (P < .01) were associated with receipt of a transplant. CONCLUSION: Patients rendered anephric via nephrectomy for cancer are more likely to receive renal transplantation if they are less than 70 years old, have a cT1a renal parenchymal mass, and receive transplant consultation before nephrectomy. These data may inform future patient counseling.

Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study.

BACKGROUND: Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. METHODS AND FINDINGS: We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures-including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue-the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. CONCLUSIONS: allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.

Effects of Aspirin Therapy on Ultrasound-Guided Renal Allograft Biopsy Bleeding Complications.

PURPOSE: To determine if patient aspirin exposure and timing affect bleeding risk after renal allograft biopsy. MATERIALS AND METHODS: Review of 6,700 renal allograft biopsies (in 2,362 unique patients) was performed. Median patient age was 53.0 years [interquartile range 43.0, 62.0]; 56.2% of patients were male. Of biopsies, 4,706 (70.2%) were performed in patients with no aspirin exposure within 10 days of biopsy; 664 (9.9%), were performed within 8-10 days of aspirin exposure; 855 (12.8%), within 4-7 days; and 475 (7.1%), within 0-3 days. Follow-up to 3 months after the procedure was completed in all patients. Biopsies were categorized as protocol or indication; 19.7% were indication biopsies. Bleeding complications were graded based on SIR criteria. Logistic regression models examined the association between aspirin use and bleeding events. RESULTS: Rate [95% confidence interval] of major bleeding complications was 0.24% [0.14, 0.39], and rate of any bleeding complication was 0.66% [0.46, 0.90]. Bleeding events were significantly associated with patients undergoing indication biopsies compared with protocol biopsies (odds ratio [OR] 2.27, P = .012). Patient factors associated with major bleeding complications in multivariate models included estimated glomerular filtration rate (OR 0.61, P = .016) and platelet count (OR 0.64, P = .033). Aspirin use was not significantly associated with increased risk of bleeding complication except for use of 325 mg of aspirin within 3 days of biopsy (any complication OR 3.87 [1.12, 13.4], P = .032; major complication OR 6.30 [1.27, 31.3], P = .024). CONCLUSIONS: Renal allograft biopsy bleeding complications are very rare, particularly for protocol biopsies. Use of 325 mg of aspirin within 3 days of renal allograft biopsy was associated with increased bleeding complications.

Early subclinical inflammation correlates with outcomes in positive crossmatch kidney allografts.

The aim of this study was to investigate correlations between early subclinical findings (10- and 90-day histology and gene expression data) and late outcomes (transplant glomerulopathy and graft loss) in positive crossmatch kidney transplants (+XMKTx). We compared 34 +XMKTx (19 receiving eculizumab and 15 receiving standard of care without eculizumab) to 13 -XMKTx (between August 2001 and August 2011). At 10 days, light microscopy identified subclinical inflammation in only 18% of +XMKTx, while intragraft gene expression identified inflammation in 79% (gene sets for activated macrophages, dendritic cells, NK cells or T cells). Inflammation persisted at 90 days and was associated with the development of transplant glomerulopathy by 2 years and graft loss. In contrast, endothelial cell (EC) changes present at 90 days by either electron microscopy or gene expression were not associated with transplant glomerulopathy or graft loss in this cohort. Eculizumab treatment did not appear to alter inflammation or EC changes. Therefore, intragraft inflammation might be an appropriate surrogate marker of progression and also a target of therapy to prevent chronic antibody-mediated rejection.

Acute renal allograft dysfunction due to cecal volvulus: a case report.

PURPOSE: Among kidney transplant recipients with acute kidney injury, the differential diagnosis must be broadened to include conditions such as rejection, immunocompromised host infections, anatomic pathologies, and recurrent or de novo glomerular diseases. In this case report, we describe an unusual cause of acute renal allograft injury due to external compression of the allograft ureter. METHODS: Retrospective review; case report. RESULTS: The patient developed acute kidney injury of the renal allograft due to external compression of the allograft ureter coincident with a cecal volvulus. The patient underwent lysis of adhesions, right hemicolectomy, and end ileostomy creation with resolution of acute kidney injury. CONCLUSIONS: Cecal volvulus is an uncommon cause of bowel obstruction and is often associated with adhesions following abdominal surgery. To our knowledge, cecal volvulus has not previously been reported as a direct contributor to acute kidney injury. This case highlights the need for a systematic approach to the patient with acute kidney injury and the special considerations involved in the diagnosis of renal failure in the kidney transplant population.

Outcomes of colorectal cancer arising in solid organ transplant recipients.

INTRODUCTION: The incidence of colorectal cancer posttransplantation is unclear. Limited reports exist and have conflicting conclusions. We aimed to review the clinical features and oncologic outcomes of colorectal cancer in transplant recipients at our institution. METHODS: A retrospective review of all patients diagnosed with colorectal cancer after solid organ transplantation between 2000 and 2011 was conducted. Clinical features and outcomes were reviewed. RESULTS: Twenty of 3,946 patients were identified. The most common single organ transplanted was the kidney (n = 8). Six patients had multiorgan transplantation. Median age of diagnosis of cancer was 64.3 years, and median time from transplant to diagnosis of cancer was 8.7 years. Ten patients were symptomatic at presentation. Cancer was identified on routine colonoscopy in seven patients. Tumors were most commonly found in the right colon (n = 14, 70%). Six patients had stage IV disease at presentation. Short-term morbidity was identified in 11 patients. Postoperative mortality occurred in one patient. Median follow-up was 2.47 years. Overall survival at 5 years was 69%, and disease-free survival was 68 %. Distant recurrence was seen in 3 (15%) patients. CONCLUSION: Colorectal cancer in these patients is rare, and surgery can be done safely. Vigilant screening must be maintained in this patient population.

Down-regulating humoral immune responses: implications for organ transplantation.

Alloantibody can be a major barrier to successful organ transplantation; however, therapy to control antibody production or to alter its impact on the allograft remains limited. The goal of this review is to examine the regulatory steps that are involved in the generation of alloreactive B cells, with a specific emphasis on how known mechanisms relate to clinical situations in transplant recipients. Thus, we will examine the process of activation of mature, naïve B cells and how this relates to de novo antibody production. The role of long-lived plasma cells in persistent antibody production and the factors regulating their longevity will be explored. The regulation of memory B cells and their possible roles in alloimmunity also will be assessed. Finally, we will review current therapeutic approaches aimed at controlling alloantibody and assess their efficacy. By examining the pathways to antibody production mechanistically, we hope to identify important gaps in our current knowledge and gain insight into possible new therapeutic approaches to overcoming antibody in transplant patients.

Using implantation biopsies as a surrogate to evaluate selection criteria for living kidney donors.

BACKGROUND: The acceptance criteria used for living kidney donors are largely theoretical, as they are not clearly linked to outcomes. The goal of this study was to use implantation biopsies as a surrogate outcome marker to evaluate our living kidney donor selection criteria. METHODS: One thousand six hundred sequential living kidney donor biopsies were performed between 2001 and 2011. Implantation biopsies were assessed by dedicated renal pathologists according to the Banff criteria. Biopsies with any chronic score of 2 or higher were deemed to have moderate to severe changes (MSC). RESULTS: MSC was present in 4% (n=65) of implantation biopsies and occurred across a wide range of age and other demographics. By multivariate analysis, donor age (odds ratio [95% confidence interval], 1.060 [1.035-1.086]; P<0.0001) and donor systolic blood pressure (SBP) (odds ratio [95% confidence interval], 1.022 [1.006-1.037]; P=0.0060) were associated with MSC. Donor gender, body mass index, diastolic blood pressure, glomerular filtration rate, and urinary microalbuminuria were not. MSC was further increased in donors older than 60 years with SBP>140 (30% [7 of 23]) and donors older than 60 years with SBP>140 and glomerular filtration rate above the 25th percentile (42.8% [3 of 7]). In donors younger than 60 years, combining factors did not show an increased prevalence of MSC. At follow-up, renal function was similar in donors with and without MSC. CONCLUSIONS: MSC occurred sporadically in donors with varied characteristics. Although we did not detect patterns to support specific changes in our acceptance criteria, certain subgroups of donors might benefit from close follow-up.