The Use of Semaglutide in Patients With Renal Failure-A Retrospective Cohort Study.

OBJECTIVE: Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m2 (CKD stage 4), eGFR<15 mL/min/1.73 m2 (CKD stage 5) or on dialysis. METHODS: This is a retrospective electronic medical record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between January 2018 and January 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher's exact test, paired t test, linear mixed effects models and Wilcoxon signed rank test. RESULTS: Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of type 2 diabetes mellitus (96.0%), and most were males (53.9%). The mean age was 66.8 y (SD 11.5) with the mean body mass index was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1 mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2 (SD 24.2) to 101.3 (SD 27.3) kg (P < .001). Eight patients (16%) with type 2 diabetes mellitus T2DM discontinued insulin after starting semaglutide. Mean hemoglobin A1c (HbA1c) decreased from 8.0% (SD 1.7) to 7.1% (SD 1.3) (P < .001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints. CONCLUSIONS: Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6% of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity.

IFTA Foci Density: An Unrecognized Highly Prognostic Measurement of Fibrosis in Kidney Transplant Biopsies.

BACKGROUND: Contraction of interstitial fibrosis/tubular atrophy (IFTA) may cause %IFTA to under-represent the severity of nephron loss. Higher density of IFTA foci is an important predictor of progressive chronic kidney disease in native kidneys independent of %IFTA. METHODS: We studied kidney transplant recipients transplanted between 2000-2013 who had a 5-year surveillance kidney biopsy and subsequent follow-up. Banff ci score (interstitial fibrosis) was obtained from the pathology reports. After digitizing the biopsies, we traced cortex area and each distinct IFTA focus on a single trichrome-stained section. Percent IFTA area and IFTA foci density (count of IFTA foci/cortex area) were calculated. Cox models assessed the risk of death-censored graft failure after the 5-year biopsy with Banff ci score, morphometric %IFTA, and IFTA foci density. RESULTS: There were 58 death-censored allograft failures among 835 kidney recipients during the 5 years of follow-up. Biopsies from grafts that failed had higher mean Banff ci score (1.5 vs 0.7, p<0.0001), %IFTA (22.2% vs 7.0%, p<0.0001), and IFTA foci density (1.3 vs. 0.4 per mm2, p<0.001). After adjusting for other Banff scores or clinical variables, Banff ci did not correlate with allograft failure, but both higher %IFTA (HR=1.56, p<0.0001) and higher IFTA foci density (HR=2.34, p<0.001) did. All but 4 allograft failures by 10 years had biopsies in the top quartile of either %IFTA or IFTA foci density at 5 years. A model using just these two morphometric measures without clinical characteristics resulted in a c-statistic of 0.891 with respect to allograft failure. CONCLUSIONS: Morphometric characterization of IFTA foci density is a strong predictor of death censored allograft failure not captured in current Banff classification for grading of kidney fibrosis.

Bariatric surgery and the diseased kidney: a 5-year assessment of safety and postoperative renal outcomes.

BACKGROUND: Obesity and its related medical conditions are well-established contributors to the development of chronic kidney disease (CKD). Metabolic and bariatric surgery (MBS), including procedures such as sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), is a potential intervention for these individuals. However, the heightened risk of postoperative complications casts doubts on the suitability of MBS in this population. Our aim is to evaluate the long-term safety, anthropometric and renal outcomes of MBS in patients with CKD. METHODS: A retrospective review of patients who underwent primary laparoscopic MBS with a BMI ≥ 35 kg/m2 and a preoperative diagnosis of stage 2 to 5 CKD. Criteria for CKD diagnosis and staging were based on estimated glomerular filtration rate measurements in accordance with established guidelines. Anthropometric and renal outcomes were measured at 3-, 6-, 12-, 24- and 60-months postoperatively. RESULTS: A total of 302 patients (177 SG, 125 RYGB) were included. RYGB was preferred for patients with stage 3 CKD, while SG was more common in stages 4 and 5. At 5-year follow-up, percentage of total weight loss was higher in the RYGB cohort compared to SG (25.1% vs. 18.6%, p = 0.036). Despite SG patients having more advanced CKD, the incidence of late complications was significantly higher following RYGB, with 11 incidents (8.8%), compared to the SG cohort with only 4 cases (2.3%) (p = 0.014). In those with preoperative CKD stage 3, 76 patients (43.2%) improved to stage 2, with another 9 patients (5.1%) improving further to stage 1. Of all patients, 63 (20.8%) eventually received a successful renal transplant. CONCLUSIONS: MBS is an effective strategy for sustained weight loss in patients with CKD with acceptable complications rates. RYGB leads to a higher percentage of overall weight loss, albeit with an elevated likelihood of late surgical complications. Future studies are needed to determine the safety of MBS in this demographic.

Mesangial Expansion by Morphometry at 5 y After Kidney Transplantation: Incidence, Risk Factors, and Association With Graft Loss.

Background: Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff mm score is not reproducible and may miss important ME features. The study aimed to improve the quantification of ME using morphometry, assess changes over time, and determine its association with allograft loss. Methods: We studied ME in 1-y and 5-y surveillance biopsies in 835 kidney transplants performed between January 2000 and December 2013. ME was assessed using the Banff mm score by a central pathologist and by morphometry. We derived 3 different morphometric measures: (1) %ME mm (%glomeruli with ME in ≥2 lobules, like Banff mm); (2) %MEany (%glomeruli with any ME lesion); and (3) %ME area (sum of all ME areas/all glomerular tuft areas). Unadjusted and adjusted Cox models assessed the risk of death-censored allograft loss. Results: From 1- to 5-y biopsies, the mean Banff mm score increased from 0.18 to 0.34, whereas %ME mm increased from 2.5% to 13.3%. Banff mm score had modest correlations with morphometric ME measures. Moderate-severe %ME mm was present in 20.1% of 5-y biopsies, whereas only 6.6% of Banff mm scores were. In general, higher ME on both 1- and 5-y biopsies was associated with a deceased donor, older recipient age, recipient diabetes/obesity (present in >50% of severely affected biopsies), higher hemoglobin A1c at 5 y posttransplant, and recurrent kidney disease. Higher ME on 5-y biopsies was associated with delayed graft function. A higher Banff mm score at 1-y biopsy and morphometry ME measures at 5-y biopsy were associated with rejection during the first year posttransplant. Morphometric ME measures were associated with allograft loss independent of Banff scores and all clinical characteristics, including kidney function and recurrent disease. The model with %MEany had the highest c-statistic (0.872). Conclusions: Banff mm score underestimates the pervasiveness of ME in 5-y biopsies. ME is common and associated with alloimmune and nonalloimmune causes of graft loss.

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.

Highly Sensitized Candidates Remain at Risk for Microvascular Inflammation Even When Donor-specific Antibody Is Avoided: A Matched Cohort Study.

BACKGROUND: Microvascular inflammation (MVI) is a key feature of antibody-mediated rejection (AMR) among patients with HLA donor-specific antibody (DSA), but MVI at AMR thresholds (Banff glomerulitis [g] + peritubular capillaritis [ptc] score ≥ 2) without DSA has been increasingly recognized. We aimed to determine the incidence of MVI among highly sensitized kidney transplant recipients without DSA. METHODS: We performed a single-center, retrospective, matched cohort study comparing outcomes of kidney transplant recipients with cPRA ≥90% with preexisting DSA (n = 49), cPRA ≥90% without preexisting DSA (n = 47), and matched controls with cPRA = 0 without preexisting DSA (n = 49). Controls were matched by age, donor type, and transplant date. Indication and surveillance biopsies combined with annual de novo DSA screening were obtained. RESULTS: Kidney transplant recipients with a cPRA ≥90% and no evidence of preexisting or de novo DSA had a higher incidence of MVI (glomerulitis + peritubular capillaritis ≥ 2) than patients with cPRA = 0 [35% (17/49) versus 12% (6/49), P = 0.0003] over a median (interquartile range) follow-up of 5 (4-6) y posttransplant. Among this cPRA ≥90% group without DSA, MVI persisted in 54% of cases on follow-up biopsy (7/13), and 24% (4/13) of cases developed transplant glomerulopathy (Banff cg score > 0). CONCLUSIONS: Highly sensitized transplant recipients have a high incidence of persistent and progressive MVI, even without DSA. The mechanisms underlying these histologic features needs to be elucidated, but this information is important to consider when making decisions about transplantation among highly sensitized individuals.

Indications, Techniques, and Barriers for Pancreas Transplant Biopsy: A Consensus Perspective From a Survey of US Centers.

BACKGROUND: Pancreas transplant biopsy practices for the diagnosis of rejection or other pathologies are not well described. METHODS: We conducted a survey of staff at US pancreas transplant programs (March 22, 2022, to August 22, 2022) to assess current program practices and perceptions about the utility and challenges in the performance and interpretation of pancreas allograft biopsies. RESULTS: Respondents represented 65% (76/117) of active adult pancreas transplant programs, capturing 66% of recent pancreas transplant volume in the United States. Participants were most often nephrologists (52%), followed by surgeons (46%), and other staff (4%). Pancreas allograft biopsies were performed mostly by interventional radiologists (74%), followed by surgeons (11%), nephrologists (8%), and gastroenterologists (1%). Limitations in the radiologist's or biopsy performer's comfort level or expertise to safely perform a biopsy, or to obtain sufficient/adequate samples were the two most common challenges with pancreas transplant biopsies. Pancreas transplant biopsies were read by local pathologists at a majority (86%) of centers. Challenges reported with pancreas biopsy interpretation included poor reliability, lack of reporting of C4d staining, lack of reporting of rejection grading, and inconclusive interpretation of the biopsy. Staff at a third of responding programs (34%) stated that they rarely or never perform pancreas allograft biopsies and treat presumed rejection empirically. CONCLUSIONS: This national survey identified significant variation in clinical practices related to pancreas allograft biopsies and potential barriers to pancreas transplant utilization across the United States. Consideration of strategies to improve program experience with percutaneous pancreas biopsy and to support optimal management of pancreas allograft rejection informed by histology is warranted.

Management of Patients With Kidney Disease Undergoing Bariatric Surgery: A Multidisciplinary Approach.

Bariatric surgery is increasingly recognized as a safe and effective treatment for obesity in patients with chronic kidney disease (CKD), including stages 4, 5, and 5D (on dialysis). Among the available surgical methods, sleeve gastrectomy (SG) is the most commonly performed weight loss procedure and is mainly done to facilitate kidney transplantation (KT). However, many KT candidates treated with SG remain on the transplant waiting list for months to years, with some never receiving a transplant. Therefore, appropriate candidates for SG must be selected, and post-SG management should address the unique needs of this population, with a focus on sustaining the metabolic benefits of surgery while minimizing potential side effects related to rapid weight loss which may inadvertently lead to muscle and bone catabolism. Multidisciplinary post-SG care in this population may lead to overall better health on the transplant waiting list, resulting in a higher percentage of post-SG patients ultimately receiving KT. To tailor the effective treatment for these patients, clinicians should acknowledge that patients with CKD stage 4-5D have different nutritional needs and are metabolically and psychosocially distinct from the general bariatric surgery population. Sarcopenia is highly prevalent and may be exacerbated by muscle catabolism following SG if not adequately addressed. Blood pressure, glucose, and bone metabolism are all affected by the CKD stage 4-5D, and therefore require distinct diagnostic and management approaches. Long-standing chronic disease, associated comorbidities, and low adherence to medical therapies require ongoing comprehensive psychosocial assessment and support. This paper aims to review and consolidate the existing literature concerning the intersection of CKD stage 4-5D and the consequences of SG. We also suggest future clinical outcome studies examining novel treatment approaches for this medically complex population.

International consensus on post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

Outcomes of Kidney Transplantation in Patients That Underwent Bariatric Surgery: A Systematic Review and Meta-analysis.

The impact of bariatric surgery (BS) on kidney transplantation (KT) outcomes in patients with obesity remains controversial. We systematically searched MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials for studies reporting outcomes of KT recipients that underwent prior BS. Common/random effects meta-analyses were performed to obtain summary ratios of the postoperative outcomes. Eighteen eligible studies involving 315 patients were identified. Sleeve gastrectomy was the most common BS type (65.7%) followed by Roux-en-Y gastric bypass (27.6%) and gastric banding (4.4%). Across studies that provided the data, the %excess weight loss from BS to KT was 62.79% (95% confidence interval [CI], 52.01-73.56; range, 46.2%-80.3%). The rates of delayed graft function and acute rejection were 16% (95% CI, 7%-28%) and 16% (95% CI, 11%-23%) in 14 and 11 studies that provided this data, respectively. The rates of wound, urinary, and vascular complications following KT were 5% (95% CI, 0%-13%),19% (95% CI, 2%-42%), and 2% (95% CI, 0%-5%), in 12, 9, and 11 studies that provided this data, respectively. Follow-up time after KT was reported in 11 studies (61.1%) and ranged from 16 mo to >5 y. Graft loss was reported in 14 studies with an average of 3% (95% CI, 1%-6%). Four studies that included a comparator group of patients with obesity who did not undergo BS before KT showed comparable outcomes between the groups. We conclude that currently there is a paucity of robust evidence to suggest that pretransplant BS has a major effect on post-KT outcomes. High-quality studies are needed to fully evaluate the impact of BS on KT outcomes.

Risk of cytomegalovirus infection and subsequent allograft failure after pancreas transplantation.

Cytomegalovirus (CMV) is a common cause of infection after transplantation, but few studies have evaluated its epidemiology, risk factors, and outcomes among pancreas transplant recipients. We performed a retrospective cohort study of adults who underwent pancreas transplantation from January 1, 2010, through December 31, 2020, at 3 sites in Arizona, Florida, and Minnesota. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or infection requiring antiviral therapy. The secondary outcome was pancreas allograft failure. Among 471 pancreas transplant recipients, 117 (24.8%) developed csCMVi after a median of 226 (interquartile range 154-289) days. CMV donor (D)+/R- patients had a significantly higher incidence of csCMVi (hazard ratio [HR] 4.01, 95% confidence interval [CI] 2.10-7.64; P < .001). In adjusted analysis, a lower absolute lymphocyte count (ALC) was associated with a greater risk of csCMVi among seropositive recipients (HR 1.39 per 50% decrease, 95% CI 1.13-1.73; P = .002) but not among D+/R- patients (HR 1.04 per 50% decrease, 95% CI 0.89-1.23; P = .595). csCMVi, lower ALC, and acute rejection (P < .001) were independently associated with pancreas allograft failure. In conclusion, CMV D+/R- was associated with csCMVi in pancreas recipients, although ALC was associated with csCMVi only among seropositive patients. The development of csCMVi in pancreas recipients was associated with poor pancreas allograft outcomes.

Banff 2022 pancreas transplantation multidisciplinary report: Refinement of guidelines for T cell-mediated rejection, antibody-mediated rejection and islet pathology. Assessment of duodenal cuff biopsies and noninvasive diagnostic methods.

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.

Impact of pancreas transplantation alone on kidney function: A multicenter clinical cohort study.

Pancreas transplantation alone (PTA) is a ß cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m2 , and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10-year eGFR (mL/min/1.73 m2 ) were 76.3 (58.1-100.8) and 51.3 (35.3-65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post-transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post-PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death-censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.

Nutritional Considerations for Patients With Renal Failure Undergoing Sleeve Gastrectomy.

Obesity is highly prevalent in patients with renal disease, as it contributes to or accelerates the progression of kidney disease and is frequently a barrier to kidney transplantation. Patients with renal disease have unique dietary needs due to various metabolic disturbances resulting from altered processing and clearance of nutrients. They also frequently present with physical disability, resulting in difficulty achieving adequate weight loss through lifestyle modifications. Therefore, kidney transplant candidates may benefit from bariatric surgery, particularly sleeve gastrectomy (SG), as the safest, most effective, and long-lasting weight loss option to improve comorbidities and access to transplantation. However, concerns regarding nutritional risks prevent broader dissemination of SG in this population. No specific guidelines tailored to the nutritional needs of patients with renal disease undergoing SG have been developed. Moreover, appropriate monitoring strategies and interventions for muscle loss and functional status preservation, a major concern in this at-risk population, are unknown. We aimed to summarize the available literature on the nutritional requirements of patients with renal disease seeking SG as a bridge to transplantation. We also provide insight and guidance into the nutritional management pre and post-SG.

Intrauterine deaths - an unsolved problem in Polish perinatology.

OBJECTIVES: The Polish criteria for "intrauterine death" include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered. MATERIAL AND METHODS: An analysis using 142,662 births in the period between 2015-2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization. RESULTS: It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age. CONCLUSIONS: According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often.

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.

Effect of Maintaining Immunosuppression After Kidney Allograft Failure on Mortality and Retransplantation.

Few studies have addressed immunosuppression management after allograft failure (AF). Immunosuppression withdrawal to minimize complications must be balanced with the risk of sensitization and potentially reduced retransplantation. We aimed to determine relationships between immunosuppression, death, sensitization, and retransplantation among patients with AF. Methods: We performed a single-center retrospective study of patients transplanted from October 2007 to May 2017 with AF. We collected data on demographics, immunosuppression, calculated panel reactive antibody (cPRA) levels, death, retransplantation, and dialysis. Cox regression models were used to evaluate factors associated with death and retransplantation. Results: From October 2007 to May 2017, 1354 solitary ABO-compatible transplants were performed, of which 97 failed. Ten percent of patients received a preemptive retransplant. Among those who returned to dialysis (n = 87), 35% died, 25% received another transplant, and 30% remained on dialysis. After AF, 46% of patients discontinued immunosuppression. The cPRA was unchanged if immunosuppression was maintained, but immunosuppression discontinuation was associated with increased cPRA from a median (interquartile range) of 18 (0-99) to 96 (88.5-100.0; P = 0.003). Age at failure (hazard ratio, 1.1; confidence interval, 1.0-1.1) and cardiovascular disease were associated with death (hazard ratio, 2.9; confidence interval, 1.2-7.0) in multivariate analysis. Importantly, immunosuppression maintenance was not associated with increased death or retransplantation despite the increase in cPRA that occurred when immunosuppression was discontinued. Conclusions: Kidney transplant recipients with AF have a high mortality rate after dialysis initiation. Although immunosuppression withdrawal was associated with increased cPRA, it was not associated with reduced retransplantation. Therefore, it is reasonable to discontinue immunosuppression after AF despite sensitization if retransplantation is delayed.

Changes in Glomerular Volume, Sclerosis, and Ischemia at 5 Years after Kidney Transplantation: Incidence and Correlation with Late Graft Failure.

SIGNIFICANCE STATEMENT: Glomerular volume, ischemic glomeruli, and global glomerulosclerosis are not consistently assessed on kidney transplant biopsies. The authors evaluated morphometric measures of glomerular volume, the percentage of global glomerulosclerosis, and the percentage of ischemic glomeruli and assessed changes in these measures over time to determine whether such changes predict late allograft failure. All three features increased from transplant to five-year biopsy. Kidneys with smaller glomeruli at 5 years had more global glomerulosclerosis and a higher percentage of ischemic-appearing glomeruli. Smaller glomeruli and increasing percentages of global glomerulosclerosis and ischemic glomeruli at 5 years predicted allograft failure. Only increased percentage of ischemic glomeruli predicted allograft failure at 5 years independent of all Banff scores. Glomerular changes reflect pathologic processes that predicted allograft loss; measuring them quantitatively might enhance the current Banff system and provide biomarkers for intervention trials. BACKGROUND: Histology can provide insight into the biology of renal allograft loss. However, studies are lacking that use quantitative morphometry to simultaneously assess changes in mean glomerular volume and in the percentages of globally sclerosed glomeruli (GSG) and ischemic-appearing glomeruli in surveillance biopsies over time to determine whether such changes are correlated with late graft failure. METHODS: We used digital scans of surveillance biopsies (at implantation and at 1 and 5 years after transplantation) to morphometrically quantify glomerular volume and the percentages of GSG and ischemic-appearing glomeruli in a cohort of 835 kidney transplants. Cox proportional hazards models assessed the risk of allograft failure with these three glomerular features. RESULTS: From implantation to 5 years, mean glomerular volume increased by nearly 30% (from 2.8×10 6 to 3.6×10 6 µm 3 ), mean percentage of GSG increased from 3.2% to 13.2%, and mean percentage of ischemic-appearing glomeruli increased from 0.8% to 9.5%. Higher percentages of GSG and ischemic-appearing glomeruli at 5-year biopsy predicted allograft loss. The three glomerular features at 5-year biopsy were related; the percentage of GSG and the percentage of ischemic glomeruli were positively correlated, and both were inversely correlated to glomerular volume. At 5 years, only 5.3% of biopsies had ≥40% ischemic glomeruli, but 45% of these grafts failed (versus 11.6% for <40% ischemic glomeruli). Higher Banff scores were more common with increasing percentages of GSG and ischemia, but at 5 years, only the percentage of ischemic glomeruli added to predictive models adjusted for Banff scores. CONCLUSIONS: Glomerular changes reflect important pathologic processes that predict graft loss. Measuring glomerular changes quantitatively on surveillance biopsies, especially the proportion of ischemic-appearing glomeruli, may enhance the current Banff system and be a useful surrogate end point for clinical intervention trials. PODCAST: This article contains a podcast at.

The Relationship Between Health Literacy and Outcomes Before and After Kidney Transplantation.

Limited health literacy (HL) is associated with decreased kidney function and death in patients with chronic kidney disease. Less is known about the impact of HL on kidney transplant (KT) outcomes. The aim of this study was to examine the relationship between HL and KT outcomes, including rates of waitlisting, healthcare utilization, acute rejection, renal allograft function, renal allograft failure, and death. Methods: We performed a retrospective review of HL data previously collected at our center. HL was assessed in a convenience sample of consecutive, English-speaking patients age ≥18 y who were evaluated for KT at Mayo Clinic in Minnesota between June 2015 and March 2017 as part of a practice improvement feasibility project (n = 690). HL was assessed using the 4-item Brief Health Literacy Screening Tool modified for the outpatient KT evaluation process. The 4 items assess confidence completing forms, reading comprehension, and oral literacy. Results: Overall, 30.4% of patients had limited or marginal HL. Patients with limited or marginal HL were less likely than those with adequate HL to be waitlisted for KT (hazard ratio = 0.62 and 0.69, respectively), even after adjusting for age, marital status, body mass index, Charlson comorbidity index, or dialysis dependency. Patient HL was not associated with post-KT healthcare utilization, acute rejection, or renal allograft function. Patients with limited or marginal HL appeared to experience a higher risk of renal allograft failure and post-KT death, but the number of events was small, and the relationship was statistically significant only for marginal HL. Conclusions: Inadequate HL is common in KT candidates and independently associated with decreased waitlisting for KT. We observed no statistically significant relationship between HL and posttransplant outcomes in our cohort. Further efforts to improve communication in patients with inadequate HL may improve access to KT.