Significant Reduction of Murine Renal Ischemia-Reperfusion Cell Death Using the Immediate-Acting PrC-210 Reactive Oxygen Species Scavenger Background. Ischemia-reperfusion (IR) injury remains a significant problem for all solid organ transplants; thus, an important unmet need in transplantation is the prevention of IR injury. PrC-210 has demonstrated superior prevention of reactive oxygen species damage in several preclinical studies as a free radical scavenger. Here, we describe its profound efficacy in suppressing IR injury in a murine model of kidney IR injury. Methods. C57/B6 mice underwent laparotomy with the left renal pedicle occluded for 30 minutes to induce IR injury. Right nephrectomy was performed at the time of surgery. Mice received a single systemic dose of the PrC-210, PrC-211, or PrC-252 aminothiols 20 minutes before IR injury. Twenty-four hours following IR injury, blood and kidney tissue were collected for analysis. Kidney caspase-3 level (a marker of cell death), direct histological analysis of kidneys, and serum blood urea nitrogen (BUN) were measured in animals to assess reactive oxygen species scavenger protective efficacies. Results. A single systemic PrC-210 dose 20 minutes before IR injury resulted in significant reductions in (1) IR-induced kidney caspase level (P < 0.0001); caspase was reduced to levels not significantly different than control caspase levels seen in unperturbed kidneys, (2) IR-induced renal tubular injury scores (P < 0.0001); brush border loss and tubular dilation were markedly reduced, and (3) serum BUN compared with control IR injury kidneys (P < 0.0001). The ranked protective efficacies of PrC-210 > PrC-211 >> PrC-252 paralleled previous radioprotection studies of the molecules. Conclusions. A single PrC-210 dose, minutes before the IR insult, profoundly reduced caspase, renal tubular injury, and serum BUN in mice exposed to standard kidney IR injury. These findings support further development of the PrC-210 molecule to suppress or prevent IR injury in organ transplant and other IR injury settings.

Association Between Peripheral Blood CD19-Positive Rate and Antibody-Mediated Rejection Following Rituximab Administration in Kidney Transplant Recipients Background. Rituximab is used widely for desensitization in ABO-incompatible and donor-specific antibody-positive kidney transplantation. However, data about the effects of individual differences in rituximab-induced B-cell suppression on antibody-mediated rejection (AMR) remain unknown. We aimed to assess the association between CD19-positive rate and AMR following rituximab administration after kidney transplantation. Methods. Overall, 42 patients who underwent rituximab therapy for pretransplant desensitization in ABO-incompatible (n = 33) and donor-specific antibody-positive (n = 15) kidney transplantation were observed retrospectively. To predict AMR incidence, the peripheral blood CD19-positive rate was determined and classified into short- and long-acting groups. AMR incidence, allograft function, complications, and rituximab dose were compared. Results. Eight patients (19%) had AMR within 39.2 months after transplantation. The CD19-positive rate cutoff value to predict AMR incidence was 4.4%, 6.4%, and 7.7% at 6, 12, and 18 months after transplantation, respectively. When comparing the short- and long-acting groups stratified according to the CD19-positive rate cutoff value, AMR incidence was significantly higher in the short-acting group than in the long-acting group at 6 (71.4% vs 8.6%), 12 (70.0% vs 3.1%), and 18 (58.3% vs 3.3%) months after transplantation. The CD19-positive rate for all patients with AMR exceeded the cutoff value 6, 12, or 18 months. Conversely, serum creatinine level, tacrolimus trough-level, cytomegalovirus antigenemia-positive rate, neutropenia incidence rate, and total dose of rituximab before transplantation showed no significant differences between the 2 groups. Conclusions. The risk of AMR was higher in patients with short-term B-cell suppression following rituximab administration. Additional rituximab administration after transplantation may prevent AMR in patients with a CD19-positive rate higher than the cutoff value.

Prophylactic Wound Drainage in Renal Transplantation: A Systematic Review Background. Adult kidney transplantation is most commonly into an extraperitoneal potential space, and surgically placed drains are used routinely in many centers. There is limited evidence of clinical benefit for prophylactic drainage in other major abdominal and vascular surgery. Transplantation is, however, a unique setting combining organ dysfunction and immunosuppression, and the risks and benefits of prophylactic drain placement are not known. This study attempts to examine existing literature to determine whether prophylactic intraoperative drains have an impact on the likelihood of perigraft fluid collections and other wound-related complications following kidney transplantation. Methods. A literature search of MEDLINE and EMBASE was conducted to identify published comparative studies, including recipients receiving prophylactic drains to recipients in whom drains were omitted. The main outcomes were the incidence of peritransplant fluid collections and wound-related complications. Meta-analysis was performed on these data. Results. Four retrospective cohort studies were deemed eligible for quantitative analysis and 1 additional conference abstract was included in qualitative discussion. A total of 1640 patients, 1023 with drains and 617 without, were included in the meta-analysis. There was a lower rate of peritransplant collections associated with the drain group (RR 0.62; 95% confidence interval, 0.42-0.90). There was no significant difference in the incidence of wound-related complications between the groups (RR 0.85; 95% confidence interval, 0.34-2.11). Conclusions. These data associate a higher rate of peritransplant fluid collections with omission of prophylactic drainage, without a difference in the incidence of wound-related complications. Further research is required to definitively determine the impact of drains in this patient group.

Effect of Sodium Bicarbonate in Kidney Transplant Recipients With Chronic Metabolic Acidosis Background. Metabolic acidosis (MA) is a common complication after kidney transplantation and regarded to increase mortality, graft failure, and bone fractures. Here, we conducted a retrospective cohort study to analyze the effect of sodium bicarbonate on those events. Methods. All kidney transplant recipients of the German health insurance Allgemeine Ortskrankenkasse (AOK) were selected, who received their transplantation between 2007 and 2015. Three groups were formed: (1) control group (no acidosis, n = 3602), (2) acidosis group (encoded acidosis, n = 370), and (3) treatment group (encoded therapy, n = 769). The study endpoints were mortality, death-censored graft failure, and bone fractures. Results. The prevalence of MA in the first year after transplantation was 46.2%. The 5-year patient and graft survival were 89.8% and 89.3% in the control group, 90% and 90.8% in the acidosis group, and 87.5% and 81.6% in the treatment group, respectively. The rate of bone fractures did not differ between the groups. Neither log-rank tests nor multivariable Cox regression analyses could detect a negative impact of MA on mortality (hazard ratio [HR] 0.94; confidence interval [CI] 0.67–1.30), graft failure (HR1.18; CI 0.82–1.72), or the incidence of bone fractures (HR1.19; CI 0.92–1.55). Treatment with sodium bicarbonate was associated with an increased risk of graft failure (HR1.52; CI 1.03–2.25), whereas mortality (HR0.86; CI 0.59–1.26) and the incidence of bone fractures (HR1.16; CI 0.86–1.56) were not altered. Conclusions. MA is common after kidney transplantation but not associated with an increased frequency of death, graft failure, or bone fractures. Conversely, sodium bicarbonate therapy increased the incidence of graft failure.

Complement Markers in Blood and Urine: No Diagnostic Value in Late Silent Antibody-Mediated Rejection Background. Antibody-mediated rejection (AMR) is a major cause of kidney allograft failure. Its molecular mechanisms are multifaceted and may include a role of complement activation via the classical pathway. Here, we investigated whether noninvasive complement monitoring adds predictive power to the diagnosis of AMR in the setting of donor-specific antibody (DSA) positivity. Methods. In this cross-sectional study, 741 kidney transplant recipients with stable graft function ≥180 days posttransplantation were screened for the presence of human leukocyte antigen (HLA) alloantibodies. Eighty-three of 111 DSA-positive recipients underwent protocol biopsies and were tested for blood and urinary levels of complement proteins (C1q, C4, C3) and activation products (C4d, C3a, C5a, C5b-9). Results. Forty-seven recipients were diagnosed with AMR, and 21 were C4d-positive. While biopsy-confirmed AMR (and C4d) associated with DSA-binding strength (IgG mean fluorescence intensity of the immunodominant DSA versus AMR; area under the receiver operating characteristic curve: 0.76), tested complement markers did not have any predictive value for rejection (area under the receiver operating characteristic curve: 0.49–0.56). There were, however, tight correlations between complement activation products in urine and protein/creatinine ratio (ρ = 0.44–0.64; P < 0.001). Analysis of death-censored graft survival over a median of 60 months revealed no independent associations with levels of complement markers in blood or urine. Conclusions. Complement patterns in blood and urine failed to identify AMR in late biopsies and may have no relevant diagnostic value in this particular context.

Management of Bilateral Ureteral Obstruction After Transplantation of Pediatric En Bloc Kidneys, a Case Report and Review of Available Literature No abstract available

Kidney Donors With Diabetes: Renal Biopsy Findings at Time of Transplantation and Their Significance No abstract available

The Measurement of Donor-Specific Cell-Free DNA Identifies Recipients With Biopsy-Proven Acute Rejection Requiring Treatment After Liver Transplantation Background. Assessment of donor-specific cell-free DNA (dscfDNA) in the recipient is emerging as a noninvasive biomarker of organ rejection after transplantation. We previously developed a digital polymerase chain reaction (PCR)-based approach that readily measures dscfDNA within clinically relevant turnaround times. Using this approach, we characterized the dynamics and evaluated the clinical utility of dscfDNA after liver transplantation (LT). Methods. Deletion/insertion polymorphisms were used to distinguish donor-specific DNA from recipient-specific DNA. Posttransplant dscfDNA was measured in the plasma of the recipients. In the longitudinal cohort, dscfDNA was serially measured at days 3, 7, 14, 28, and 42 in 20 recipients. In the cross-sectional cohort, dscfDNA was measured in 4 clinically stable recipients (>1-y posttransplant) and 16 recipients (>1-mo posttransplant) who were undergoing liver biopsies. Results. Recipients who underwent LT without complications demonstrated an exponential decline in dscfDNA. Median levels at days 3, 7, 14, 28, and 42 were 1936, 1015, 247, 90, and 66 copies/mL, respectively. dscfDNA was higher in recipients with treated biopsy-proven acute rejection (tBPAR) when compared to those without. The area under the receiver operator characteristic curve of dscfDNA was higher than that of routine liver function tests for tBPAR (dscfDNA: 98.8% with 95% confidence interval, 95.8%-100%; alanine aminotransferase: 85.7%; alkaline phosphatase: 66.4%; gamma-glutamyl transferase: 80.1%; and bilirubin: 35.4%). Conclusions. dscfDNA as measured by probe-free droplet digital PCR methodology was reflective of organ health after LT. Our findings demonstrate the potential utility of dscfDNA as a diagnostic tool of tBPAR.

Machine Perfusion of Liver Grafts With Implantable Oxygen Biosensors: Proof of Concept Study in a Rodent Model Background. Normothermic machine perfusion (NMP) is emerging as a novel preservation strategy in liver transplantation, but the optimal methods for assessing liver grafts during this period have not been determined. The aim of this study was to investigate whether implantable oxygen biosensors can be used to monitor tissue oxygen tension in liver grafts undergoing NMP. Methods. Implantable phosphorescence-based oxygen sensors were tested in 3 different experimental groups: (1) in vivo during laparotomy, (2) during NMP of liver grafts with an acellular perfusate (NMP-acellular), and (3) during NMP with perfusate containing red blood cells (NMP-RBC). During in vivo experiments, intrahepatic oxygen tension was measured before and after occlusion of the portal vein (PV). In NMP experiments, intrahepatic oxygen tension was measured as a function of different PV pressure settings (3 vs 5 vs 8 mm Hg) and inflow oxygen concentration (95% O2 vs 6% O2). Results. In vivo, intrahepatic oxygen tension decreased significantly within 2 minutes of clamping the PV (P < 0.05). In NMP experiments, intrahepatic oxygen tension correlated directly with PV pressure when high inflow oxygen concentration (95%) was used. Intrahepatic oxygen tension was significantly higher in the NMP-RBC group compared with the NMP-acellular group for all conditions tested (P < 0.05). Conclusions. Implantable oxygen biosensors have potential utility as a tool for real-time monitoring of intrahepatic oxygen tension during NMP of liver grafts. Further investigation is required to determine how intrahepatic oxygen tension during NMP correlates with posttransplant graft function.

Preliminary Studies of the Impact of CXCL12 on the Foreign Body Reaction to Pancreatic Islets Microencapsulated in Alginate in Nonhuman Primates: Erratum No abstract available