Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study.

The use of routine monitoring of donor-derived cell-free DNA (dd-cfDNA) after kidney transplant may allow clinicians to identify subclinical allograft injury and intervene prior to development of clinically evident graft injury. To evaluate this, data from 1092 kidney transplant recipients monitored for dd-cfDNA over a three-year period was analyzed to assess the association of dd-cfDNA with histologic evidence of allograft rejection. Elevation of dd-cfDNA (0.5% or more) was significantly correlated with clinical and subclinical allograft rejection. dd-cfDNA values of 0.5% or more were associated with a nearly three-fold increase in risk development of de novo donor-specific antibodies (hazard ratio 2.71) and were determined to be elevated a median of 91 days (interquartile range of 30-125 days) ahead of donor specific antibody identification. Persistently elevated dd-cfDNA (more than one result above the 0.5% threshold) predicted over a 25% decline in the estimated glomerular filtration rate over three years (hazard ratio 1.97). Therefore, routine monitoring of dd-cfDNA allowed early identification of clinically important graft injury. Biomarker monitoring complemented histology and traditional laboratory surveillance strategies as a prognostic marker and risk-stratification tool post-transplant. Thus, persistently low dd-cfDNA levels may accurately identify allograft quiescence or absence of injury, paving the way for personalization of immunosuppression trials.

Abdominal Wall Grafts: A Viable Addition to Arteriovenous Access Strategies.

BACKGROUND: We seek to present our experience with innovative abdominal wall arteriovenous access grafts for patients who have run out of traditional dialysis access options. METHODS: We retrospectively reviewed our cohort of patients who have undergone creation of abdominal wall grafts. In all patients, an iliac artery was used for inflow and either an iliac vein or the distal inferior vena cava (IVC) was use for the outflow. Ringed polytetrafluorethylene (PTFE), nonringed PTFE, and bovine carotid artery were used as access conduits. RESULTS: Our 12-patient cohort had a mean primary patency of 17.4 months with mean secondary patency of 33 months. There were no operative deaths noted and 4 total graft infections. CONCLUSIONS: Abdominal wall grafts with iliac vessel inflow and/or outflow represent viable alternatives for patients who have exhausted more traditional dialysis access options.

Recurrent Postoperative Toxic Shock Syndrome in a Living Kidney Transplant Recipient.

Recurrent toxic shock syndrome (TSS) is uncommon. A certain level of clinical suspicion is indicated with a complex sepsis presentation in the postoperative kidney transplant patient. We present a case of presumed recurrent postoperative TSS in a living kidney transplant recipient. The patient was a 19-year-old Caucasian female with a 4-year prior single episode of toxin-mediated sepsis and chronic kidney disease (CKD) secondary to autosomal recessive Alport's syndrome (confirmed via renal biopsy and genetic testing). She received a human leukocyte antigen (HLA) 2A 2B 1DR MM, CMV -D/-R kidney from her 21-year-old friend. The patient received Campath and IV steroid induction after total cold ischemic time of 170 minutes with 40 minutes of revascularization. On postoperative day (POD) 5, she required re-exploration with reimplantation and stenting of the transplanted ureter. The patient subsequently spiked a fever of 101.6° with a generalized rash prompting collection of blood cultures which demonstrated no growth. Infectious Disease was consulted due to persistent fevers despite IV antibiotics. On POD 12, the patient returned to the operating room (OR) for evacuation of hematoma after decline in Hgb to 5.8 and CT confirmed perinephric hematomas. Kidney biopsy showed no rejection and donor specific antibodies (DSAs) were unremarkable. The patient underwent 1 treatment of empiric plasmapheresis for possible non-HLA antibodies followed by initiation of clindamycin. The patient's condition improved, and she was discharged home with a normal creatinine. Recurrent TSS is rare but should be added to the differential diagnoses of immuno-compromised patients undergoing kidney transplantation with a history of prior toxin-mediated sepsis.

Operative Versus Nonoperative Management of Hemorrhage in the Postoperative Kidney Transplant Patient.

BACKGROUND: Postoperative hemorrhage has been described at rates of 14% in kidney transplant (KT) literature. The preferred management of postoperative hemorrhage in this population is not well described. We hypothesized a difference in outcomes with operative versus nonoperative management of hemorrhage after kidney transplantation. METHODS: We conducted a retrospective cohort study of consecutive KTs from 2012 to 2019 (living and deceased donors). We defined hemorrhage based on the objective finding of hematoma on either ultrasound or CT scan. Management was defined as operative (surgical intervention with or without transfusion) or nonoperative (with or without transfusion). RESULTS: We performed 1758 KTs of which 135 (8%) demonstrated hematoma on ultrasound or CT scan (66 operative vs 69 nonoperative management). The clinical signs and symptoms of low urine output (P = .044), drop in hemoglobin (P < .001), abdominal pain (P = .005), and MAP < 70 mm Hg (P = .034) were 92.5% predictive of postoperative hemorrhage in our KT patients. There were no differences between groups based on medical history, preop anticoagulation, anastomosis type, cold ischemic time, lowest hemoglobin, delayed graft function, or complications. Patients with nonoperative treatment of postoperative hemorrhage had shorter lengths of stay (P = .003), better graft survival (P = .01), and better patient survival (P = .01). DISCUSSION: We found better outcomes of graft and patient survival with shorter lengths of stay when we utilized nonoperative management of postoperative hemorrhage in KT patients. Our findings suggest a role for conservative nonoperative management in select patients. Ultimately, it is the surgeon's choice on how best to manage postoperative hemorrhage.

HCC Liver Transplantation Wait List Dropout Rates Before and After the Mandated 6-Month Wait Time.

BACKGROUND: Studies have shown significant improvement in hepatocellular carcinoma (HCC) recurrence rates after liver transplantation since the united network of organ sharing (UNOS) implementation of a 6-month wait period prior to accrued exception model for end-stage liver disease (MELD) points enacted on October 8, 2015. However, few have examined the impact on HCC dropout rates for patients awaiting liver transplant. Our objective is to evaluate the outcomes of HCC dropout rates before and after the mandatory 6-month wait policy enacted. METHODS: We conducted a retrospective cohort study on adult patients added to the liver transplant wait list between January 1, 2012, and March 8, 2019 (n = 767). Information was obtained through electronic medical records and organ procurement and transplant network (OPTN) publicly available national data reports. RESULTS: In response to the 2015 UNOS-mandated 6-month wait time, dropout rates in the HCC patient population at our center increased from 12% pre-mandate to 20.8% post-mandate This increase was similarly reflected in the national dropout rate, which also increased from 26.3% pre-mandate to 29.0% post-mandate. DISCUSSION: From these changes, it is evident that the UNOS mandate achieved its goal of increasing equity of liver organ allocation, but HCC patients are nonetheless dropping off of the wait list at an increased rate and are therefore disadvantaged.

Outcome of liver transplantation in a Hispanic population: 100 liver transplants in Puerto Ricans.

BACKGROUND: The residents of Puerto Rico (PR) had limited access to liver transplantation (LTx) prior to 1996. LTx remains locally unavailable and success rates for LTx for patients from PR have never been published. The outcome of the first 100 LTx recipients from PR transplanted at our center is analyzed. METHODS: 100 consecutive patients transplanted between 3/1997 and 1/2005 were evaluated. RESULTS: Hepatitis C was the indication for LTx in 44%. Overall patient survival at 1, 3 and 5 yrs was: 94.0%, 81.4% and 75.7%, respectively, while for hepatitis C, it was 90%, 73% and 73%, respectively. At mean follow up of 44 mo., 80% of patients were alive (66% HCV were alive vs 91% non HCV, p < 0.01). CONCLUSIONS: Access to LTx in Puerto Rico has dramatically improved since 1996. The government-sponsored fund has provided access to indigent patients. Decreased survival in this minority population was not observed at 1, 3 and 5 years. Long-term survival was most affected by recurrence of HCV.

Incisional Hernia Repairs after Abdominal Organ Transplantation.

Incisional hernias occur after abdominal organ transplantation with rates of 1.6 per cent to 18 per cent in kidney transplants (KTs) and 1.7 to 32.4 per cent in liver transplants (LTs). We hypothesized a difference in KT and LT outcomes in patients with and without repair of incisional hernias. We conducted a retrospective cohort study of abdominal transplants from 2012 through 2016. The difference across compared groups for continuous variables was assessed using the independent sample t test, and for binary variables, using the chi-squared test. A total of 1518 transplants were performed, including 1138 KTs and 380 LTs. There were 83 KT incisional hernias (67 repaired) and 59 LT incisional hernias (48 repaired). There was no difference between groups with regard to smoking, diabetes, age, BMI, days on dialysis (KTs), pretransplant Model for End-Stage Liver Disease (MELD) (LTs), cold ischemic time, graft survival, or recurrence rate by repair method. In the LT population, there was a statistically significant difference in days on the waitlist (P = 0.02), drain placement (P = 0.04), and cytomegalovirus (CMV) mismatch (P = 0.02). Patient survival was also statistically significant for KTs (P = 0.04) and LTs (P = 0.01). KT and LT patients who have their incisional hernias repaired have better overall survival, regardless of the repair technique.

Outcomes in Hepatocellular Carcinoma Liver Transplantation before and after the Mandated Six-Month Wait Time.

The United Network for Organ Sharing (UNOS) implemented a policy that requires patients with hepatocellular carcinoma seeking liver transplantation to wait six months before being granted Model for End-Stage Liver Disease exception points. We investigated the difference in resource utilization between patients who underwent liver transplantation before and after the present policy. We conducted a retrospective cohort study of adult liver transplants from 2013 to 2018. Patients were classified into prepolicy or postpolicy groups based on 964 days before or after the wait-time policy. We also retrieved national survival outcome data from United Network for Organ Sharing. Differences across compared groups for continuous variables were assessed using the independent sample t test, and the chi-squared test was used for binary variables. We found statistical differences in recipient age (P = 0.005), days on wait-list (P = 0.001), sustained virological response (P < 0.001), and hepatocellular carcinoma recurrence one year posttransplant (P = 0.04). There were statistically significant differences in the number of treatment days pretransplant and length of transplant admission stay, indicating an increase in resource utilization in the postpolicy group. No statistically significant differences were found between groups in one-year graft or patient survival despite an observed increase in resource utilization by the hepatocellular carcinoma postpolicy group.

The Impact of CPR in High-Risk Donation after Circulatory Death Donors and Extended Criteria Donors for Kidney Transplantation.

The demand for organs for kidney transplantation (KTX) compels the use of high-risk donation after circulatory death donors (DCDs) and extended criteria donors (ECDs). Many deceased donors receive prehospital CPR, but the literature does not address CPR as a benefit to graft survival. We hypothesized that donor prehospital CPR correlates with improved graft survival with high-risk DCD/ECD kidneys. We retrospectively analyzed KTX recipients and their donor data from 2008 to 2013. A total of 646 cadaveric donors (498 SCDs, 55 DCDs, and 93 ECDs) facilitated 910 KTX. There were 223 KTX performed from 148 high-risk DCDs/ECDs (31 with CPR and 117 without CPR). The mean age of high-risk DCDs/ECDs with CPR was 44.94 versus 53.45 years without CPR (P = 0.005). The recipients of high-risk DCDs/ECDs revealed no significant difference in body mass index, length of stay, discharge Cr, CIT, or DGF with and without CPR. Graft survival at three years was significant with 0/50 failures from high-risk DCDs/ECDs with CPR versus 16/173 without CPR (P = 0.026). Our findings are limited as a single-center retrospective study; however, the result of significant three-year graft survival in high-risk DCDs/ECDs with CPR suggests that prehospital donor CPR should be further investigated for its contribution to the relative quality of the donor.

Effective arteriovenous fistula alternative for hemodialysis access.

BACKGROUND: The use of autologous arteriovenous fistulae (AVF) for hemodialysis (HD) is the gold standard; however, for many patients at tertiary referral centers, this is not an option. METHODS: We conducted a four year retrospective cohort study to evaluate HD access outcomes with AVF, bovine carotid artery (BCA), and polytetrafluoroethylene arteriovenous graft (PTFE). RESULTS: The study contained 416 AVF, 175 BCA, and 58 PTFE, N = 649. There was statistical difference between rates of infection (AVF 3.4%, BCA 2.9%, PTFE 11.9%), P = 0.02. Maturation failed in 7.5% of AVF but in none of the BCA or PTFE (P = 0.001). Accesses were abandoned with AVF (1.9%), BCA (1.5%), and PTFE (9.5%), P = 0.01. CONCLUSION: Bovine carotid artery can be an effective alternative form of HD access with lower infection, abandonment, and failure to maturation rates when autologous arteriovenous fistula is not an option.

Sensitization of renal transplant candidates by cryopreserved cadaveric venous or arterial allografts.

BACKGROUND: Cryopreserved cadaveric venous or arterial allografts are used in ESRD patients as an alternative to synthetic grafts for hemodialysis access. We evaluated the effect of these allografts on the PRA against HLA class I and II antigens in 11 ESRD patients awaiting a kidney transplant. METHODS: Flow Cytometry using purified antigen coated beads (Flow PRA Beads) was used to determine PRA against HLA class I and II antigens. RESULTS: Patients with no antibody prior to allograft implantation were all positive for HLA class I and II antibodies after implantation. Patients with anti-HLA class I and II antibodies prior to allografting, developed higher antibody titers. Of the 11 patients that received cryopreserved cadaveric allografts no deaths were reported. Two grafts were removed due to thrombosis consistent with rejection. CONCLUSION: Recipients of cadaveric venous or arterial allografts elicit an HLA antibody response attesting to the antigenicity of cryopreserved cadaveric allografts.

The acceptable reactive crossmatch (ARC), post-transplant monitoring, and their impact on kidney transplantation: a single center experience.

Although the adverse allograft outcomes associated with HLA antibodies are well documented, some controversy exists regarding the importance of low-level donor specific anti-HLA antibodies (DSA). To provide further detail on this controversy, we prospectively looked at low-level DSA in negative T- and B-cell flow cytometric crossmatch (FCXM) or acceptable reactive crossmatch (ARC) patients who each underwent protocol based post-transplant antibody monitoring. HLA Class I and II antibody screening and specificity determination was conducted via a solid phase assay (SPA) and FCXM versus donor and autologous T and B cells. Post-transplant patients were immunosuppressed with quadruple maintained immunosuppressive therapy, rabbit anti-thymocyte globulin induction, and HLA antibody monitoring. Out of 31 ARC patients transplanted, 65% had a PRA > 50% and 26% showed increased DSA at 7-14 days post-transplant. Antibody mediated rejection (AMR) was treated with pharmacological and/or plasmapheresis (PP) therapy. DSA were lowered and remained at low-levels (MFI 1000- 3000) or below FCXM cutoffs. None of the 31 patients transplanted developed de-novo antibodies. Two patients lost their allografts, one to polyoma (BK) virus, and one to antibody mediated rejection (AMR). In conclusion, our experience demonstrates that patients deemed higher risk for an immunological event due to low-level DSA should be transplanted with an ARC and followed post-transplant according to an established alloantibody monitoring protocol. With close monitoring, 5-year outcomes can be expected to approach that of low-immunologic risk transplant patients.

Renal autotransplantation for managing a short upper ureter or after ex vivo complex renovascular reconstruction.

OBJECTIVE: To report our contemporary experience with renal autotransplantation (AT), an established treatment for managing patients with a shortened ureter or renovascular disease, as despite its historical importance, AT remains an underused technique by urologists. PATIENTS AND METHODS: All patients undergoing AT between 1997 and 2002 for a short ureter after ureteric injury and for renovascular disease were assessed by creatinine level and blood pressure before and after surgery, and antihypertensive drug use and complications. RESULTS: Eleven patients had AT for renovascular disease and four for ureteric injury. There was no statistical difference in creatinine levels or blood pressure before and after surgery in either group. Eight patients treated with AT for renovascular disease required less antihypertensive medication after surgery. Minor complications occurred in both groups and included a suture abscess, chronic wound pain, and transient acute tubular necrosis. One patient in the ureteric injury group required a transplant nephrectomy after renal vein thrombosis, and one in the renovascular group died from multi-organ system failure. CONCLUSION: AT remains a treatment option for patients with a short ureter after ureteric injury and in those with renovascular disease. Patients had stable renal function and blood pressure after surgery. Most patients treated for renovascular disease required less medication after AT. The procedure is associated with both minor and major complications, which must be considered before surgery.