Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective.

Donor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx®) gene expression may offer increased precision to histology. This single-center retrospective study monitored kidney transplant recipients for rejection at specified time intervals by utilizing creatinine (SCr), proteinuria, donor-specific antibodies (DSAs), and dd-cfDNA. A clinically indicated biopsy sample was sent for histopathology and MMDx®. Patients were categorized into rejection (Rej) and non-rejection (NRej) groups, and further grouped according to antibody-mediated rejection (ABMR) subtypes. Rej and NRej groups included 52 and 37 biopsies, respectively. Median follow-up duration was 506 days. DSAs were positive in 53% and 22% of patients in both groups, respectively (p = 0.01). Among these groups, pre- and post-intervention median SCr, proteinuria, and dd-cfDNA at 1 month, 2 months, and at the last follow-up revealed significant difference for dd-cfDNA (all p = 0.01), however, no difference was found for SCr and proteinuria (p > 0.05). The AUC was 0.80 (95% CI: 0.69-0.91), with an optimal dd-cfDNA criterion of 2.2%. Compared to histology, MMDx® was more likely to diagnose ABMR (79% vs. 100%) with either C4d positivity or negativity and/or DSA positivity or negativity. Hence, a pre- and post-intervention allograft monitoring protocol in combination with dd-cfDNA, MMDx®, and histology has aided in early diagnosis and timely individualized intervention.

A case series of perioperative anaphylaxis to cefazolin during kidney transplant and review of literature.

BACKGROUND: Intraoperative anaphylaxis is a life threatening and multiorgan system hypersensitivity reaction that frequently leads to cessation of operations. Despite the incidence of Cefazolin allergy being on the rise, the cases of anaphylaxis to Cefazolin during surgeries and its management are seldom reported. CASE PRESENTATION: We present two patients with no known beta-lactam allergy and end stage kidney disease who received perioperative intravenous Cefazolin for planned deceased kidney transplant surgery at our academic medical center. Both patients developed anaphylaxes approximately three minutes following the administration of the antibiotic and experienced severe, refractory hypotension that required the use of vasopressors. The severity of the anaphylactic reactions resulted in the cessation of the transplant operation and multiple days of intensive care unit admission. CONCLUSION: Peri-or intraoperative anaphylaxis to Cefazolin is on the rise and its consequences in transplant candidates are even more dire given the pre-existing end organ failure, financial burden for health care system, potential loss of donor organs, and emotional burden for recipients and their families. These are the first two cases of reported Cefazolin-induced anaphylaxis that actually resulted in aborting the kidney transplant operation. In addition, cases of previously reported Type 1 hypersensitivity to Cefazolin as prophylaxis for operations were reviewed and the allergy workups were discussed.

A National Survey of Practice Patterns for Accepting Living Kidney Donors With Prior COVID-19.

INTRODUCTION: A critical question facing transplant programs is whether, when, and how to safely accept living kidney donors (LKDs) who have recovered from COVID-19 infection. The purpose of the study is to understand current practices related to accepting these LKDs. METHODS: We surveyed US transplant programs from 3 September through 3 November 2020. Center level and participant level responses were analyzed. RESULTS: A total of 174 respondents from 115 unique centers responded, representing 59% of US LKD programs and 72.4% of 2019 and 72.5% of 2020 LKD volume (Organ Procurement and Transplantation Network-OPTN 2021). In all, 48.6% of responding centers had received inquiries from such LKDs, whereas 44.3% were currently evaluating. A total of 98 donors were in the evaluation phase, whereas 27.8% centers had approved 42 such donors to proceed with donation. A total of 50.8% of participants preferred to wait >3 months, and 91% would wait at least 1 month from onset of infection to LD surgery. The most common reason to exclude LDs was evidence of COVID-19-related AKI (59.8%) even if resolved, followed by COVID-19-related pneumonia (28.7%) and hospitalization (21.3%). The most common concern in accepting such donors was kidney health postdonation (59.2%), followed by risk of transmission to the recipient (55.7%), donor perioperative pulmonary risk (41.4%), and donor pulmonary risk in the future (29.9%). CONCLUSION: Practice patterns for acceptance of COVID-19-recovered LKDs showed considerable variability. Ongoing research and consensus building are needed to guide optimal practices to ensure safety of accepting such donors. Long-term close follow-up of such donors is warranted.

Early Fatal Cutaneous Lower Extremity Angiosarcoma Associated with Deep Venous Thrombosis in a Renal Transplant Recipient.

Angiosarcomas are extremely rare malignant tumors of vascular origin. We describe a 63-year-old recipient after a kidney transplant who had an angiosarcoma in the lower extremity that presented after new-onset deep venous thrombosis and was not associated with any fistula. There was rapid progression to metastasis and death. We reviewed the literature of this rare malignant tumor in kidney transplant patients.

Re-transplants compared to primary kidney transplants recipients: a mate kidney paired analysis of the OPTN/UNOS database.

Outcomes of kidney re-transplant recipients (RTR) were compared to primary recipients (FTR) from paired donor kidneys. Organ Procurement and Transplantation Network (OPTN) database was used to identify deceased donors (n = 6266) who donated one kidney to an RTR and the mate kidney to an FTR between January 2000 to December 2010. As compared to FTR, RTR were younger (45 vs. 52 yr, p < 0.001) and had higher proportion of plasma reactive antibody >80 (25% vs 7%, p < 0.001). There were higher 0 mismatches in RTR (19% vs. 16%, p < 0.001). There were more pre-emptive transplants in RTR (24% vs. 21%, p = 0.002). Delayed graft function (28% vs. 25%, p = 0.007) was higher in RTR. Patient survival was similar in FTR and RTR groups at one, three, and five yr (95.7%, 90.2%, and 82.5% vs. 95.2%, 89.8% and 82.7%). Allograft survival rates were higher in FTR group compared to RTR group at one, three, and five yr (91.1%, 82.4%, and 70.9% vs. 87.8%, 77.4%, and 66.1% p < 0.001). Death-censored allograft survival rates were higher in FTR group at one, three, and five yr (91.3%, 82.7% and 71.4% vs. 88%, 77.7% and 66.5% p < 0.001). In today's era of modern immunosuppression, graft survival in RTR has improved but remains inferior to FTR when controlling for donor factors.

Pre-transplant angiotensin receptor II type 1 antibodies and risk of post-transplant focal segmental glomerulosclerosis recurrence.

Post-kidney transplant recurrence of focal segmental glomerulosclerosis (FSGS) is a major problem. AT1R is expressed on podocyte; its expression is elevated in the proteinuric state. Using an ELISA, we tested pre-transplant sera of 28 patients with history of idiopathic FSGS for anti-AT1R levels and serum soluble urokinase-type plasminogen activator receptor (suPAR) as a biomarker for risk of recurrence of FSGS. Sera from 11 patients with polycystic kidney disease (PKD) were used as controls. Twelve patients had biopsy proven post-transplant FSGS recurrence at 1.5 months. No difference was found in the pre-transplant suPAR levels of FSGS patients (5993 ± 2292 pg/mL) vs. PKD (7334 ± 4538 pg/mL) (p = 0.23). Serum suPAR levels in patients with FSGS recurrence (5786 ± 1899 pg/mL) vs. no FSGS recurrence (6149 ± 2598 pg/mL) (p = 0.69) were not different. Anti-AT1R levels in patients with FSGS were 12.66 ± 11.85 U/mL vs. 8.69 ± 6.52 U/mL in PKD (p = 0.32); however, a difference was found in patients with and without FSGS recurrence 20.41 ± 14.36 U/mL 6.84 ± 4.181 U/mL, respectively (p < 0.01). Area under curve for suPAR and anti-AT1R to predict post-transplant FSGS recurrence was 0.51 and 0.84, respectively. Pre-transplant anti-AT1R levels appear to be a helpful biomarker in identifying patients at high risk of post-transplant FSGS recurrence.

Impact of duration of diabetes on outcome following pancreas transplantation.

INTRODUCTION: The impact of duration of T1DM on outcomes following simultaneous pancreas and kidney transplantation (SPK), pancreas after kidney transplantation (PAK), and pancreas transplantation alone (PTA) is currently unknown. MATERIALS AND METHODS: A total of 451 pancreas transplants performed at a single institution between January 2003 and April 2013 (SPK n = 238, PAK, n = 97, and PTA, n = 116) were divided into three groups based on cumulative years of T1DM (0-20 years, 21-30 years, and >30 years). Early (7-day) and late (90-day) pancreas allograft loss, patient and pancreas allograft survivals were analyzed. RESULTS: While, PAK was more common in recipients with >30 years of T1DM (29%, p < 0.0047), PTA was more common in recipients with 0-20 years of T1DM (41%, p < 0.0011). In all transplant types, recipients age was significantly higher the longer the duration of diabetes. Although longer duration of T1DM correlated with a higher rate of major amputations in PAK recipients (p < 0.0032), no difference was observed in SPK or PTA. While early pancreas graft loss was 2-4% in SPK and PAK with shorter or longer T1DM (p = n.s.), it reached to 10% in PTA with T1DM > 30 years (p < 0.0097). Longer duration of T1DM affected late pancreas graft loss in PAK patients (8%, p < 0.0349). Patient and death-censored graft survival rates were similar in all types of pancreas transplantation extracted by accumulation of years of T1DM prior to transplant. CONCLUSIONS: Longstanding T1DM does not seem to negatively impact recipient outcomes following all types of pancreas transplantation.

Late pancreas retransplantation.

Pancreas retransplantation, excluding immediate retransplantation for graft thrombosis, is a technically treacherous operation with the added challenges of adhesions from the prior transplant and difficulties identifying usable recipient vessels. The goal of this study was to review our single-center experience with late pancreas retransplantation. Charts for all pancreas transplant recipients between 01/2003 and 04/2013 were reviewed for demographics, graft and patient survival, length of stay (LOS), readmissions, and technical complications. Of 473 pancreas transplants, there were 20 late pancreas retransplants compared to 441 first transplants. There were no significant differences in donor or recipient demographics. There was no significant difference in graft or patient survival. The mean and median lengths of stay were 22 and nine d, respectively (range 5-175 d), and 11 recipients required readmission within the first three months post-transplant. Five patients were reexplored in the early postoperative period for an enteric leak at the site of the primary allograft (n = 1), complications of percutaneous gastrostomy tube placement (n = 1), hemorrhage (n = 1), and negative laparotomy for hyperglycemia (n = 2). Pancreas retransplantation is technically challenging but can be safely performed with graft and recipient survival comparable to primary transplants.

Pancreas transplantation after bariatric surgery.

Obese transplant candidates are at increased risk for perioperative and postoperative complications. In many transplant programs, morbid obesity is considered to be an exclusion criterion for transplantation. The only potential option that would grant these patients access to transplant is weight loss. Non-operative weight loss strategies such as behavioral modifications, exercise, diet, or medication have only very limited success in achieving long-term weight loss. In contrast, bariatric surgery was shown to achieve not only more excessive weight loss, but more importantly, this weight loss can be sustained for longer periods of time. Therefore, bariatric surgery presents an attractive option for weight loss for morbidly obese transplant candidates. We report our experience with four patients who underwent bariatric surgery prior to successful pancreas transplantation. Even though gastric bypass and laparoscopic adjustable gastric band present as equivalent alternatives for weight reduction, we believe that in the population of morbidly obese diabetic patients who are possible candidates for pancreas transplantation, laparoscopic adjustable gastric band placement is the more suitable procedure.

The strength of donor-specific antibody is a more reliable predictor of antibody-mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients.

The aim of this study was to evaluate the utility of donor-specific antibodies (DSA) and flow cytometry crossmatch (FCCM) as tools for predicting antibody-mediated rejection (AMR) in desensitized kidney recipients. Sera from 44 patients with DSA at the time of transplant were reviewed. Strength of DSA was determined by single antigen Luminex bead assay and expressed as mean fluorescence intensity (MFI). T- and B-cell FCCM results were expressed as mean channel shift (MCS). AMR was diagnosed by C4d deposition on biopsy. Incidence of early AMR was 31%. Significant differences in the number of DSAs (p = 0.0002), cumulative median MFI in DSA class I (p = 0.0004), and total (class I + class II) DSA (p < 0.0001) were found in patients with and without AMR. No significant difference was seen in MCS of T and B FCCM (p = 0.095 and p = 0.307, respectively). The three-yr graft survival in desensitized patients with DSA having total MFI < 9500 was 100% compared to 76% with those having total MFI > 9500 (p = 0.022). Desensitized kidney transplant recipients having higher levels of class I and total DSA MFI are at high risk for AMR and poor graft survival. Recipient DSA MFI appears to be a more reliable predictor of AMR than MCS of FCCM.

Early steroid withdrawal in repeat kidney transplantation.

BACKGROUND AND OBJECTIVES: Kidney re-transplantation (KRT) candidates are considered at high risk for graft failure. Most of these patients are kept on a chronic steroid maintenance (CSM) regimen. The safety of early steroid withdrawal (ESW) remains unanswered in KRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study was aimed at comparing the outcomes of ESW and CSM in KRT. Retrospective analysis of 113 KRT patients (ESW, n=59; CSM, n=54) was performed. All patients received rabbit anti-thymocyte globulin/steroid induction and were maintained on mycophenolate/tacrolimus (±steroids). RESULTS: One- and 5-year patient survival for the ESW and the CSM group were not significantly different (98 versus 96% and 91 versus 88%, respectively; P=0.991). No significant difference was seen in the graft survival for both groups at 1 and 5 years (98 versus 93% and 80 versus 74%, respectively; P=0.779). Mean 1- and 5-year estimated GFR was not statistically different between the groups (P=0.773 and 0.790, respectively). The incidence of acute rejection at 1 year was 17 and 22% in ESW and CSM patients, respectively (P=0.635). Compared with the ESW group, patients in the CSM group were more likely to be hyperlipidemic (P=0.044), osteoporotic (P=0.010), post-transplant diabetics (P=0.051) and required more medications to control BP (P=0.004). CONCLUSIONS: ESW seems to be a reasonable approach in KRT recipients because the short and intermediate patient survival, graft survival, and graft function is comparable to CSM immunosuppression.