Worldwide, more than 4 million patients with end-stage kidney disease require hemodialysis through an arteriovenous fistula (AVF). AVFs fail because of venous neointimal hyperplasia (VNH) resulting in venous stenosis formation. A phase 1 randomized trial in patients undergoing upper extremity AVF placement was performed to evaluate the safety and efficacy of autologous adipose-derived mesenchymal stem cells (MSCs) in improving AVF function. The mechanism of action by which MSCs exert their beneficial effects was investigated using AVFs created in mice and pigs treated with allogenic MSCs and xenotransplant using patient MSCs in CD1-Foxn1nu mice. At a median follow-up of 42 months, patients with MSC-treated AVFs had reduced time to maturation with an increase in the vein diameter compared with controls. AVFs treated with allogenic MSCs in mice and pigs had an increase in M2- and M1-like macrophages with a decrease in VNH. Transcriptomic analysis of AVFs treated with allogenic MSCs in mouse and MSC xenotransplants of patients with successful AVFs showed decreased peroxisome proliferator-activated receptor gamma (Pparγ) and leptin receptor (Lepr) and increased latent transforming growth factor-beta-binding protein 2 (Ltbp2). PPARγ was reduced in CD68 (+) cells from successful AVFs and allogenic MSC-treated mouse AVFs. Venous stenosis and VNH formation were mitigated in AVFs of mice with Pparγ ablation in immune cells. Conditioned medium from MSCs of responders versus nonresponders had decreased proinflammatory genes, senescence-associated proteins, and monocyte-to-macrophage differentiation induced by phorbol 12-myristate-13-acetate. Periadventitial delivery of MSCs to AVFs promoted positive vascular remodeling through decreased inflammatory responses.

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.

Cervical adenocarcinoma is the second most common histology of cervical cancer and treatment can involve surgery, radiotherapy, systemic therapy, and any combination of the three. Photon external beam radiation therapy and brachytherapy have been the mainstay of radiation treatment options for cervical cancer. Here, we report a case of a 41-year-old patient who had a prior renal transplant and was diagnosed with early-stage, intermediate-risk adenocarcinoma treated with modified radical hysterectomy plus adjuvant proton-beam therapy and vaginal brachytherapy. Treatment was well tolerated with a disease-free interval of 14-months and preserved renal function.

ObjectiveTo describe the outcomes of kidney transplant (KT) candidates with obesity undergoing sleeve gastrectomy (SG) to meet the criteria for KT.MethodsRetrospective 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.ResultsThe 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.ConclusionIn 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.

Background. The impact of induction type or high-risk viral discordance on older kidney transplant recipients is unclear. Herein, we analyzed the association between induction type, viral discordance, and outcomes for older recipients. Methods. We analyzed the Scientific Registry of Transplant Recipients standard analysis file for all primary kidney transplant recipients older than 55 y who were transplanted between 2005 and 2022. All transplants were crossmatch negative and ABO-compatible. Recipients were discharged on tacrolimus and mycophenolate ± steroids. Recipients were categorized into 3 groups by induction received: rabbit antithymocyte globulin (r-ATG; N = 51 079), interleukin-2 receptor antagonist (IL-2RA; N = 22 752), and alemtuzumab (N = 13 465). Kaplan-Meier curves were generated for recipient and graft survival, and follow-up was censored at 10 y. Mixed-effect Cox proportional hazard models examined the association between induction type, high-risk viral discordance, and outcomes of interest. Models were adjusted for pertinent recipient and donor characteristics. Results. Induction type did not predict recipient survival in the multivariable model, whereas Epstein-Barr virus high-risk discordance predicted 14% higher mortality (1.14 [1.07-1.21], P < 0.01). In the multivariable model for death-censored graft survival, alemtuzumab, but not IL-2RA, was associated with an increased risk of graft loss (1.18 [1.06-1.29], P < 0.01) compared with r-ATG. High-risk cytomegalovirus discordance predicted 10% lower death-censored graft survival (1.10 [1.01-1.19], P < 0.02). Live donor and preemptive transplantation were favorable predictors of survival. Conclusions. In this large cohort of older transplant recipients, alemtuzumab, but not IL-2RA, induction was associated with an increased risk of graft loss compared with r-ATG. Cytomegalovirus and Epstein-Barr virus high-risk viral discordance portended poor graft and recipient survival, respectively.

Pancreas transplantation alone (PTA) is a beta 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 m(2), and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10-year eGFR (mL/min/1.73 m(2)) 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.

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.

BACKGROUND:Recent studies identified underlying genetic causes in a proportion of patients with various forms of kidney disease. In particular, genetic testing reclassified some focal segmental glomerulosclerosis (FSGS) cases into collagen type 4 (COL4)-related nephropathy. This knowledge has major implications for counseling prospective transplant recipients about recurrence risk and screening biologically related donors. We describe our experience incorporating genetic testing in our kidney transplant multidisciplinary practice.METHODS:Patients' DNA was analyzed using whole exome sequencing for a comprehensive kidney gene panel encompassing 344 genes associated with kidney diseases and candidate genes highly expressed in the kidney. Results were correlated with phenotype by a multidisciplinary committee of nephrologists, renal pathologists, geneticists, and genetic counselors. Between October 2018 and July 2020, 30 recipient and 5 donor candidates completed testing.RESULTS:Among recipient candidates, 24 (80%) carried the diagnosis of FSGS, 2 (6.7%) tubulointerstitial nephritis, and 1 (3.3%) nephrolithiasis, and 3 (10%) had an unknown cause of kidney disease. The yield for pathogenic/likely pathogenic variants was 43.3%, with majority being COL4 variants (53.8%). Among those with FSGS diagnosis, the yield was 10 of 24 (41.6%), with 29% reclassified into a COL4-related nephropathy. Family history of kidney disease was the only clinical characteristic difference between recipients with positive and negative results (76.9 versus 29.4%; P = 0.025). One of 5 donors tested positive for a pathogenic/likely pathogenic variant and was excluded from donation.CONCLUSIONS:We conclude that thoughtful use of genetic testing can be valuable for kidney donor selection and transplant recipient management.

BACKGROUND Kidney transplant is the most common transplant operation performed in the United States. Although various approaches to pain management have been described, the optimal analgesic strategy remains undefined. Specifically, the role of intrathecal opioids in this patient population has not been comprehensively evaluated. METHODS Using a retrospective cohort design, data from kidney transplant operations at a single tertiary care medical center between August 1, 2017, and July 31, 2022, were extracted. Inverse probability of treatment weighting (IPTW) was used to assess differences in clinical outcomes based on the presence or absence of intrathecal opioid administration before surgical incision. The primary outcome was total opioid exposure expressed in milligram morphine equivalents (MME) in the first 72 hours postoperatively, with secondary outcomes including total MME (intraoperative plus postoperative MME, postoperative pain scores, and the presence of postoperative nausea/vomiting [PONV], pruritus, or adverse events). RESULTS A total of 1014 kidney transplants in 1012 unique patients were included, with 411 (41%) receiving intrathecal opioids preoperatively. Hydromorphone was the intrathecal opioid used in all cases with median dose of 100 µg (interquartile range [IQR], 100, 100; range 50-200). Subjects receiving intrathecal opioids had significantly lower postoperative opioid requirements at 72 hours (30 [0-68] vs 64 [22, 120] MME), with ratio of geometric means in the IPTW analysis (ratio of geometric means 0.34, 95% confidence interval [CI], 0.26-0.43; P < .001). Similar findings were observed for total opioids (45 [30-75] vs 75 [60-90] MME; ratio of geometric means 0.58, 95% CI, 0.54-0.63; P < .001). Maximum reported pain scores in the intrathecal group were lower at 24 hours (4 [2-7] vs 7 [5, 8]; OR, 0.28; 95% CI, 0.21-0.37 for experiencing a higher pain score with intrathecal opioids, P < .001) and 72 hours (6 [4-7] vs 7 [5-8]; OR, 0.41; 95% CI, 0.31-0.54; P < .001). Patients receiving intrathecal opioids were more likely to experience PONV (225 of 411 [55%] vs 232 of 603 [38%]; OR, 2.16; 95% CI, 1.63-2.86; P < .001). CONCLUSIONS Intrathecal opioid administration was associated with improved pain outcomes in patients undergoing kidney transplantation, including lower opioid requirements and pain scores through 72 hours. However, this was accompanied by an increased risk of PONV.

Background. 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.

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.

Levy, Michael J. MD1; Bendel, Emily C. MD2; Bjarnason, Haraldur MD2; Reisenauer, Christopher J. MD2; Amer, Hatem MD3; Codipilly, Don C. MD1; Dean, Patrick G. MD4; Gleeson, Ferga C. MB BCh1; Heimbach, Julie K. MD4; Kalra, Manju MBBS5; Prieto, Mikel MD4; Stegall, Mark D. MD4; Taner, Timucin MD4; Kamath, Patrick S. MD1 Author Information

Introduction: Poorly controlled Type 1 Diabetes (T1D) is associated with increased HbA1c, increased severe hypoglycemia, decreased hypoglycemia awareness and diabetic ketoacidosis. These comorbidities and decreased quality of life are indications for Pancreas Transplantation (PT). Limited data are available about patient reported outcomes (PROs) related to Hypoglycemia after PT. Therefore, we prospectively studied these PROs over a year after PT in patients with T1D. Methods: Ten PT recipients were enrolled within a month after PT and completed 3 visits (V1, V2 & V3 at 4 weeks, 4 months and 1 year). At each visit, participants completed Hypoglycemia Fear Survey-II (HFS-II) and Clarke hypoglycemia unawareness survey. HFS-II is a 33-item questionnaire to measure behavior and worry subscales related to fear of hypoglycemia in patients with T1D. Behavior subscale (HFS-B) describes behaviors individual would engage in to avoid hypoglycemia or its consequences. Worry subscale (HFS-W) describes concerns related to hypoglycemia. Clarke questionnaire evaluates awareness of hypoglycemia based on responses to 8 questions, identifying awareness (A) or reduced awareness (R). The Clarke R score ranges from 0 to 7 with ≤ 2 indicating normal A, 3 as undetermined A and score ≥4 suggesting impaired awareness of hypoglycemia (IAH). We analyzed insulin independent and partial graft function on insulin separately. Statistical analysis was done using a linear mixed effects model. Results: Patients were 46.3 ± 14.3 years old, 9 F, duration of T1D 27.8 ± 15.8 years with 29.4 ± 18.3 days interval from PT. Laboratory results were HbA1c (%) 6.3, 5.4 and 5.4, fasting plasma glucose (mg/dL) 88.6, 104.8 and 91 and C-peptide (ng/ml) 4.6, 3.1 and 2.4 on V1, 2 & 3 respectively. In insulin independent participants (n=8), HFS-B showed almost every participant reported taking some behavioral measures over last 6 months to avoid hypoglycemia at V1. On V2, five participants took some behavioral measures and on V3 only one to avoid hypoglycemia (Table). HFS-W showed almost every participant had some concerns about low blood sugar at V1, five on V2 and none on V3. Two participants who had partial graft function around V2 engaged in behavior to avoid hypoglycemia on V1, 2 & 3, with a subsequent decreased behavioral engagement (p 0.1197) and concern to avoid hypoglycemia (p 0.1391) compared to V1. Clarke scoring showed indeterminate awareness at V1, improved significantly (p 00.0146) and attained normal hypoglycemia awareness over the year on V2 and V3 respectively (Table). Two participants who had partial graft failure reported IAH on all 3 visits (V1: V2:V3=5.0: 4.0: 4.0, p 0.5000). Conclusion: PT recipients reported reduced Fear of hypoglycemia and improved hypoglycemia awareness over a period of 1 year, even in patients with partial graft function. More studies would enable better assessment of these PROs and improve the field.

Kidney transplantation remains the best modality for renal replacement therapy for patients with end-stage kidney disease. It is well established that kidney transplantation confers to those patients better long-term survival and quality of life than remaining on the waiting list or chronic dialysis.1,2 In the United States and worldwide, there is a significant shortage of organs. For that reason, the donor deceased pool has been expanded to increase the supply of kidneys to account for that high demand for kidney transplantation.

The authors regret that in the above-stated article, the given name and surname one of the authors, Hatem Amer, was presented inaccurately. The given name is Hatem and the surname is Amer. The authors would like to apologize for any inconvenience caused. A study from The Mayo Clinic evaluated long-term outcomes of kidney transplantation in patients with immunoglobulin light chain amyloidosisKidney InternationalVol. 99Issue 3PreviewLonger 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). Full-Text PDF

Introduction: Type 1 Diabetes (T1D) is associated with increased severe hypoglycemia, decreased hypoglycemia awareness and diabetic ketoacidosis. These comorbidities are associated with decrease quality of life and increase diabetes related distress in T1D patients with uncontrolled diabetes. Some of these patients are evaluated for Pancreas Transplantation (PT) but limited data exist about diabetes related distress after PT. Therefore, we prospectively studied diabetes related distress reported by patients with Type 1 Diabetes (T1D) after Pancreas transplantation (PT) over a period of one year. Methods: Eleven PT recipients (6 pancreas transplantation alone, 4 simultaneous pancreas kidney transplantation and 1 Pancreas after kidney), were enrolled within a month of PT and completed 3 visits (V1, V2 & V3 at 4 weeks, 4 months and 1 year). At each visit, participants completed Type 1-Diabetes distress scale (T1-DDS) reporting distress related to diabetes. T1-DDS contains 28 questions, with each item rated on a 6-point scale from “(1) not a problem” to “(6) a very significant problem”. Overall distress score, as well as scores for individual subscales are rated on scale of 1–6 on the average response on all the items. An average score below 2, indicates little or no distress, score between 2.0–2.9, indicates moderate distress and score above 3 indicates high distress. We analyzed insulin independent and insulin dependent (partial graft failure) participants separately. A statistical analysis was done using a linear mixed effects model to obtain a p-value. Results: PT recipients were 45.5 ± 13.8 years old, 10 F, duration of T1D 28.3 ± 15.1 years with 29 ± 17.4 days interval from PT. Laboratory results showed HbA1c (%) of 6.3, 5.4 and 5.4, fasting plasma glucose (mg/dL) of 87.4, 104.8 and 91 and C-peptide (ng/ml) of 4.7, 3.1 and 2.4 on V1, 2 & 3 respectively. Two participants out of 11 had partial graft failure and became insulin dependent. During V1, insulin independent participants (n=9) showed moderate distress related to powerlessness and hypoglycemia distress subscales, which significantly improved by V3 (Table) with little or no distress at all along with improvement in eating distress subscale from V1. There was significant improvement in total diabetes distress score (p 0.0009) in all insulin independent participant over 1 year. Two participants who became insulin dependent due to partial graft failure did not show significant improvement in diabetes distress score from V1 to V3 except for hypoglycemia distress subscale (V1: V2: V3=3.5: 3.4: 2.9, p 0.0372) which improved from high distress to moderate distress. Conclusion: PT recipients reported little or no diabetes related distress over a period of 1 year with good graft function. These results are important for counselling and decision making for T1D patients who are struggling with poor quality of life and are looking for PT as an option in future.