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.

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.

Early technical pancreas failure in Simultaneous Pancreas-Kidney Recipients does not impact renal allograft outcomes.

Early pancreas loss in simultaneous pancreas-kidney (SPK) transplants has been associated with longer perioperative recovery and reduced kidney allograft function. We assessed the impact of early pancreas allograft failure on transplant outcomes in a contemporary cohort of SPK patients (n = 218). Early pancreas allograft loss occurred in 12.8% (n = 28) of recipients. Delayed graft function (DGF) was more common (21.4% vs. 7.4%, p = 0.03) in the early pancreas loss group, but there were no differences in hospital length of stay (median 6.5 vs. 7.0, p = 0.22), surgical wound complications (p = 0.12), or rejection episodes occurring in the first year (p = 0.87). Despite differences in DGF, both groups had excellent renal function at 1 year post-transplant (eGFR 64.1 ± 20.8 vs. 65.8 ± 22.9, p = 0.75). There were no differences in patient (HR 0.58, 95% CI 0.18-1.87, p = 0.26) or kidney allograft survival (HR 0.84, 95% CI 0.23-3.06, p = 0.77). One- and 2-year protocol kidney biopsies were comparable between the groups and showed minimal chronic changes; the early pancreas loss group showed more cv changes at 2 years (p = 0.04). Current data demonstrate good outcomes and excellent kidney allograft function following early pancreas loss.

Renal transplantation in the setting of aortic atresia: Utilizing hepatic artery inflow with donor vessel jump graft.

Both congenital and acquired recipient anatomy can present a significant challenge to renal transplantation. A patient with congenital aortic atresia and limited dialysis access options presented to our institution for consideration of transplant. Through multidisciplinary planning, a strategy to accommodate the patient's variant anatomy was devised and successfully performed. A deceased donor vessel graft was used as conduit in combination with the recipient hepatic artery for renal graft inflow.

Transplanting kidneys from donation after cardiac death donors with acute kidney injury.

Donation after cardiac death (DCD) and acute kidney injury (AKI) donors have historically been considered independent risk factors for delayed graft function (DGF), allograft failure, and inferior outcomes. With growing experience, updated analyses have shown good outcomes. There continues to be limited data, however, on outcomes specific to DCD donors who have AKI. Primary outcomes for this study were post-kidney transplant patient and allograft survival comparing two donor groups: DCD AKIN stage 2-3 and DBD AKIN stage 2-3. In comparing these groups, there were no short- or long-term differences in patient (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.54-1.93, P = .83) or allograft survival (HR 1.47, 95% CI 0.64-2.97, P = .32). In multivariate models, the DCD/DBD status had no significant impact on the estimated GFR (eGFR) at 1 (P = .38), 2 (P = .60), and 3 years (P = .52). DGF (57.9% vs 67.9%, P = .09), rejection (12.1% vs 13.9%, P = .12), and progression of interstitial fibrosis/tubular atrophy (IFTA) on protocol biopsy (P = .16) were similar between the two groups. With careful selection, good outcomes can be achieved utilizing severe AKI DCD kidneys. Historic concerns regarding primary nonfunction, DGF resulting in interstitial fibrosis and rejection, and inferior outcomes were not observed. Given the ongoing organ shortage, increased effort should be undertaken to further utilize these donors.

Long-term Outcomes Following Kidney Transplantation From Donors With Acute Kidney Injury.

BACKGROUND: Kidneys from deceased donors with acute kidney injury (AKI) are more likely to be discarded because of concerns for poor outcomes after transplantation. The aim of this study was to determine the long-term outcomes of a large cohort of patients transplanted utilizing kidneys from deceased donors with AKI. METHODS: All patients receiving a deceased donor kidney transplant during a recent 10-year period were included. Acute Kidney Injury Network (AKIN) criteria were used to classify the donors. Donor kidneys with >10% cortical necrosis or more than mild chronic changes were discarded. The primary outcome is the combined endpoint of death or graft loss. RESULTS: The cohort included 1313 kidneys from 974 donors, AKIN stage 0 (no AKI) in 319 (24.3%), stage 1 in 370 (28.2%), stage 2 in 177 (13.5), and stage 3 in 447 (34.0%). Estimated 5-year graft survival (95% confidence interval) was 78.5% (72.5-84.5), 77.8% (72.8-82.1), 83.8% (76.8-88.9), and 84.6% (79.5-88.7) for AKIN donor stage 0 to 3, respectively (log-rank P = 0.10). After adjusting for baseline differences, the hazard ratio (95% confidence interval) for the combined endpoint for the AKIN stage 3 group (relative to AKIN 0 group) was 0.70 (0.45-1.10). Delayed graft function occurred in 44.6% and 75.4% of AKIN 2 and 3 groups, as compared to 33.9% and 33.5% in AKIN 0 and 1 (P < 0.001). CONCLUSION: We conclude that transplanting selected kidneys from deceased donors with AKI with preimplantation biopsy showing <10% cortical necrosis and no more than mild chronic changes have excellent long-term graft survival.

De novo coccidioidomycosis among solid organ transplant recipients 1 or more years after transplant.

Solid organ transplant recipients who contract coccidioidomycosis are at risk for complicated, protracted, disseminated, and severe disease. To date, no studies have described outcomes for patients who develop coccidioidomycosis only after the first posttransplant year. This study was a joint project of Mayo Clinic Hospital, Phoenix, Arizona, and the University of Arizona/Banner University Medical Center, Tucson, Arizona. We retrospectively reviewed electronic health records for patients with a history of solid organ transplant between January 1, 1998, and October 11, 2014, who developed coccidioidomycosis after the first transplant year. We identified 91 patients. Of those, 37/91 (40.7%) had pulmonary coccidioidomycosis (29/37 [78.4%] were symptomatic); and 5/91 (5.5%) had extrapulmonary disease (all were symptomatic). One patient (1.1%) died. Coccidioidomycosis was evident in 2/91 (2.2%) patients within 3 months of antirejection treatment. Many of the patients (51/91 [56.0%]) had asymptomatic coccidioidomycosis, 27 (27.9%) of whom were followed up closely but did not receive antifungal medication and had no sequelae. Although solid organ recipients taking low-level immunosuppression after the first posttransplant year appeared to have less symptomatic, disseminated, or fatal coccidioidal infection than historical cohorts, this remains an important infection with morbidity and mortality even after the first posttransplant year.

Kidney Transplant in the Era of Modern Therapy for Multiple Myeloma.

Chronic kidney disease is common in patients with multiple myeloma. Historically, individuals with end-stage renal disease and multiple myeloma did poorly with renal transplantation due to higher mortality rates from the malignancy itself or associated comorbidities. However, over the past 2 decades, there have been significant advances in the treatment of multiple myeloma with the advent of new therapeutic agents resulting in an improvement of long-term survival. As a result, more individuals with multiple myeloma are being referred for kidney transplantation, especially those with good functional capacity and minimal comorbidities. Recent literature has suggested that certain patients with multiple myeloma can successfully undergo renal transplantation after stem transplantation with consideration for maintenance therapy, although caution should be used with immunomodulating drugs due to the anecdotally reported risk of acute rejection. Therefore, having a multidisciplinary approach with the transplant team and hematology both before and after transplant is crucial in maximizing the chance of success for these individuals. This review summarizes the literature on renal transplantation in patients with multiple myeloma as well as the therapeutic advancements that have occurred which may allow certain patients to undergo successful transplantation.

Cardiorespiratory Fitness (Peak Oxygen Uptake): Safe and Effective Measure for Cardiovascular Screening Before Kidney Transplant.

BACKGROUND: Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO2peak), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing. METHODS AND RESULTS: We outlined a pre-renal transplant screening algorithm to incorporate VO2peak testing among a population of asymptomatic high-risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all-cause mortality. We report a high (>90%) negative predictive value, indicating that VO2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all-cause mortality. However, lower VO2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant. CONCLUSIONS: We conclude that incorporating an objective measure of cardiorespiratory fitness with VO2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher-risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.

Glucose homeostasis after simultaneous pancreas and kidney transplantation: a comparison of subjects with C-peptide-positive non-type 1 diabetes mellitus and type 1 diabetes mellitus.

BACKGROUND: While simultaneous pancreas kidney transplant (SPKTx) is a therapeutic option for patients with type 1 diabetes (T1DM) and renal failure, few centers offer SPKTx to "select" non-T1DM patients. To address concerns that existing insulin resistance may limit the benefits of the pancreas allograft among non-T1DM, we compared several indices of glucose homeostasis, in "select" non-T1DM and T1DM patients who received SPKTx. METHODS: Criteria for "select" non-T1DM included the following: positive C-peptide, BMI <30 kg/m(2) , treatment with oral agents before insulin initiation, and insulin at <1 unit/kg/d. We compared several indices of glucose homeostasis within 1 yr post-SPKTx among seven "select" patients with non-T1DM and nine patients with T1DM with similar age, BMI, and immunosuppression. Measurements of insulin resistance included the following: homeostatic model, insulin sensitivity index, and insulin-glucose ratio; insulin secretion measures included the following: corrected insulin response. RESULTS: Non-T1DM had similar pre-transplant metabolic (fasting glucose, HbA1c, blood pressure, and lipid) parameters to the T1DM cohort. There were no significant differences in the various measures of insulin resistance and secretion between T1DM and "select" non-T1DM patients. CONCLUSION: Our results suggest SPKTx should be considered in the therapeutic armamentarium among carefully select non-T1DM with features of minimal insulin resistance; however, a larger cohort with longer follow-up is needed to confirm our results.

Kidney Transplant Program at the Mayo Clinic in Arizona.

Since 1999, we have performed 2,302 kidney transplants at the Mayo Clinic in Arizona. Transplant volume has increased by 45% since 2010. Our center performed 269 kidney transplants in 2013. Our growth is related to multiple factors, including an experienced, committed team and strong support from our institution and referring nephrologists. Areas of program innovation at our center include: transplanting deceased donors with acute kidney injury, outcomes in older kidney transplant recipients, alemtuzumab induction with steroid avoidance, living donor paired kidney exchange-3 site experience, and other non-traditional deceased donor kidney transplants. Of the 162 acute kidney injury (AKI) donor transplants done at our program, 71% had severe AKI. The AKI donor kidneys had more delayed graft function; but graft survival, estimated glomerular filtration rate, and biopsy findings at 1 year were not different form the control group. We have transplanted 188 patients ≥ 70 years old at the time of transplantation. Graft survival at 1, 3, and 5 years was similar to that of patients < 70. Since 2008, 778 (37%) patients received alemtuzumab induction, therapy with excellent patient and graft survival. We have used steroid avoidance immunosuppression with excellent outcomes since 2003. Since starting kidney paired donation in 2009, it has resulted in 54 kidney transplants, including 4 compatible pairs. More than half of the deceased donor transplants done at our center are from non-traditional donors such as Public Health Service increased risk, donation after cardiac death, extended criteria donors/high kidney donor profile index, and pediatric en-bloc donors. One- and 3-year graft survival of the non-traditional deceased donor kidney transplants are not different than the traditional deceased donor kidney transplants.