Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

Pediatric En Bloc Kidney Transplants: Clinical and Immediate Postoperative US Factors Associated with Vascular Thrombosis.

Purpose To evaluate clinical and immediate postoperative ultrasonographic (US) risk factors associated with vascular thrombosis of pediatric en bloc kidney grafts. Materials and Methods This institutional review board-approved HIPAA-compliant retrospective study consisted of 195 recipients of pediatric en bloc kidney grafts throughout a 10-year period. The average recipient and donor age was 45 years (range, 7-74 years) and 9 months (range, 0-84 months), respectively. Clinical factors and immediate postoperative US findings were assessed. Categorical variables were evaluated by using the Fisher exact test and linear models with generalized estimating equations. Results Seventeen patients (23 kidneys) experienced thrombotic events. In six patients (eight kidneys), thrombosis occurred intraoperatively. The remaining 11 patients (15 kidneys) received a diagnosis of thrombosis on postoperative days 1-13. Recipients more than 40 years old had a higher incidence of arterial thrombosis than did younger recipients (eight of 62 vs three of 133, respectively; P < .01). Recipients were more likely to develop thrombosis with donor weight less than 5 kg (10 of 52 vs seven of 140 with donor weight of ≥ 5 kg; P < .01), with intraoperative perfusional concern (10 of 21 vs seven of 174 without; P < .01), or with right-sided allograft placement (10 of 64 vs seven of 131 left sided; P = .03). At US of the 15 postoperative thrombotic events, the incidence of thrombosis was greater when donor arterial velocity was less than 100 cm/sec (seven of 56 vs four of 126 with velocity ≥ 100 cm/sec; P = .04). An intrarenal arterial resistive index of less than 0.6 was associated with higher incidence of arterial thrombosis (nine of 123 vs zero of 217, respectively; P = .01). A resistive index greater than 0.8 was associated with a higher incidence of venous thrombosis (four of 13 vs one of 217, respectively; P = .04). Conclusion Clinical factors and immediate US findings can help stratify patients receiving pediatric en bloc kidneys into risk categories for vascular thrombosis that, if proven in prospective studies, could affect immediate postoperative treatment. (©) RSNA, 2015.

Effectiveness of Postoperative Single-shot and Continuous Transverse Abdominis Plane Block Compared to Conventional Analgesia in Hand-assisted Laparoscopic Live-donor Nephrectomy.

Background: Few studies have evaluated the efficacy of transverse abdominis plane (TAP) block in patients undergoing hand-assisted laparoscopic live-donor nephrectomy (HALN). We aimed to evaluate the analgesic effectiveness of TAP block as part of a multimodal pain management regimen in patients undergoing HALN. Methods: We retrospectively reviewed the medical records of living kidney donors at our center between June 2016 and February 2020. HALNs were performed via a transperitoneal approach through a suprapubic incision. Additional laparoscopic ports were used in the upper midabdomen. In consenting donors, TAP block was performed postoperatively under ultrasound guidance with either a single-shot or continuous infusion of long-acting local anesthetic (0.2%-0.5% ropivacaine). All the patients received postoperative around-the-clock ketorolac and acetaminophen. Results: Overall, 72 donors received the block (block group, 38 single-shot, 34 continuous), whereas 86 donors did not receive the block (control group). Baseline characteristics were comparable between the groups except for body weight (control: 71.8 ±â€…13.3 versus block: 77.8 ±â€…17.3 kg; P = 0.01) and intraoperative opioid dose (32.1 ±â€…9.6 versus 26.6 ±â€…10.7 morphine milligram equivalents; P < 0.001). After adjusting for baseline differences, postoperative opioid requirements were similar between the groups. When the baseline pain scale was adjusted for, there was no difference in the overall pain scale scores between the groups (P = 0.242). Subgroup analyses comparing single-shot or continuous TAP versus control did not show any differences. Conclusions: With the caveat of the retrospective nature of the study, the adjunctive effect of TAP block after transabdominal HALN was limited when other multimodal analgesia was used.

Outcomes of children receiving en bloc renal transplants from small pediatric donors.

The utilization of en bloc renal allografts from small pediatric donors has been adopted as an effective strategy to expand the organ donor pool in adult recipients. Data in children are limited. The aim of our study is to describe the outcomes of en bloc renal transplants in children from our center. Medical records of children receiving pediatric en bloc renal transplants at our institution from January 2007 were abstracted. Data collected included recipient and donor demographics, operative technique and complications, and post-operative studies. Eight children received en bloc renal transplants at a median age of 17 yr; median follow-up was 0.9 yr. Donor body weight ranged from 4 to 22 kg. One kidney was lost to intra-operative thrombosis, while the other kidney from this en bloc graft remained viable. All grafts showed increased renal size at follow-up ultrasound. Surveillance biopsies showed glomerulomegaly in two patients. At last follow-up, the median eGFR was 130 mL/min/1.73 m(2). The urinary protein to creatinine ratio was normal in four of seven patients. Our data suggest that in experienced centers, en bloc renal transplantation from young donors into pediatric recipients is effective. Long-term follow-up to monitor for complications, including hyperfiltration injury, is warranted.

Renal transplant wound complications in the modern era of obesity.

BACKGROUND: Obesity is a known risk factor for wound complications following kidney transplantation (KTX), and obese transplant candidates are often encouraged to lose weight. The implications of this weight loss for post-KTX wound healing and morbidity have not been examined. Our aim was to study potential risk factors for post-KTX wound complications, with a specific focus on a history of significant weight loss. METHODS: Single-center retrospective review of all KTX recipients ≥ 18 y performed 04/2004-03/2009. We studied potential donor-, transplant-, and recipient-related risk factors for wound complications by univariate and multivariate analyses. Graft and patient survival comparisons were done by Kaplan-Meier curves and two-sided log-rank test. RESULTS: Overall wound complication incidence among the 487 study recipients was 6.4%. Significant independent risk factors for wound complications were BMI (odds ratio [OR] = 1.14 per 1 kg/m(2) increase), and history of significant weight loss (OR = 13.46), peri-KTX transfusion (OR = 5.42), and desensitization (OR = 60.34). Wound complications had no significant impact on graft and patient survival. CONCLUSIONS: Our study demonstrates for the first time that besides BMI, pre-KTX desensitization, and peri-KTX transfusion, a history of significant pre-KTX weight loss is also an independent risk factor for post-KTX wound complications (potentially at least in part due to body contour changes resulting in an unfavorable abdominal panniculus). Further study of KTX candidates who have lost a significant amount of weight is warranted to (1) identify the exact causes for their increased propensity for complications and (2) devise measures to minimize added cost and morbidity. Finally, our findings suggest that the impact of weight loss on the outcomes of non-transplant operations also warrants further investigation.

Short- and Long-term Outcomes of Kidney Transplants From Very Small (≤15 kg) Pediatric Donors With Acute Kidney Injury.

BACKGROUND: Kidneys from small deceased pediatric donors with acute kidney injury (AKI) are commonly discarded owing to transplant centers' concerns regarding potentially inferior short- and long-term posttransplant outcomes. METHODS: We retrospectively analyzed our center's en bloc kidney transplants performed from November 2007 to January 2015 from donors ≤15 kg into adult recipients (≥18 y). We pair-matched grafts from 27 consecutive donors with AKI versus 27 without AKI for donor weight, donation after circulatory death status, and preservation time. RESULTS: For AKI versus non-AKI donors, median weight was 7.5 versus 7.1 kg; terminal creatinine was 1.7 (range, 1.1-3.3) versus 0.3 mg/dL (0.1-0.9). Early graft loss rate from thrombosis or primary nonfunction was 11% for both groups. Delayed graft function rate was higher for AKI (52%) versus non-AKI (15%) grafts (P = 0.004). Median estimated glomerular filtration rate was lower for AKI recipients only at 1 and 3 months (P < 0.03). Graft survival (death-censored) at 8 years was 78% for AKI versus 77% for non-AKI grafts. Late proteinuria rates for AKI versus non-AKI recipients with >4 years follow-up were not significantly different. CONCLUSIONS: Small pediatric donor AKI impacted early posttransplant kidney graft function, but did not increase risk for early graft loss and decreased long-term function. The presently high nonutilization rates for en bloc kidney grafts from very small pediatric donors with AKI appear therefore unjustified. Based on the outcomes of the present study, we infer that the reluctance to transplant single kidneys from larger pediatric donors with AKI lacks a rational basis as well. Our findings warrant further prospective study and confirmation in larger study cohorts.

Pediatric en bloc kidney transplantation into pediatric recipients.

As a result of the ongoing shortage in organ supply, en bloc renal transplantation from small donors has become more common for adult recipients with ESRD. However, because of concern for higher complication rates and sub-optimal outcomes, it is not being performed in every center, and data describing its use in pediatric recipients are even more limited. We retrospectively studied three patients who have undergone en bloc renal transplantation at our center. Median age at transplantation was 16.7 yr with a median follow-up of 1.2 yr. Donor age ranged from nine to 49 months with weight ranging from 10 to 22 kg. There were no post-operative thrombotic complications. All grafts showed increased renal size at follow-up by ultrasound. There was no clinical or histological rejection at last follow-up. To the best of our knowledge, this is the first report on the outcomes of en bloc kidney transplantation from pediatric donors into pediatric recipients. Based on our experience, albeit very limited, we feel that en bloc renal transplantation from young donors is an acceptable and safe procedure with low complication rates in pediatric recipients and should be given consideration to minimize wait times on the wait list and to improve quality of life.

Extended experience with a steroid minimization immunosuppression protocol in pediatric renal transplant recipients.

PURPOSE: To determine the safety and efficacy of a novel steroid minimization protocol after renal transplantation at a single Northern California center. INTRODUCTION: We have previously reported our experience on the short-term outcomes in eight children using our steroid minimization protocol. Herein, we present our ongoing experience in using this regimen in 20 children. METHODS: Children receiving immunosuppression with a steroid minimization protocol at our center from 1/04-12/08 (Group 2) were retrospectively compared with 20 controls (Group 1). RESULTS: At one-month follow-up, Group 2 was observed to have lower eGFR, hemoglobin, white cell count, and cholesterol. The incidence of adverse events during the first yr was comparable. Three patients in Group 1 displayed histological evidence of acute rejection, one patient in Group 2 developed humoral rejection; another patient in Group 2 had sub-clinical rejection. Surgical complications were observed in 20% of patients in both groups. While 10% of patients in Group 1 developed diabetes mellitus, none was observed in Group 2. Thirty and 40% of patients in Groups 1 and 2, respectively, suffered from infectious complications during the first yr. CONCLUSIONS: Our novel steroid minimization immunosuppression is safe in children and associated with no increased risk of rejection and infection.

Success of a steroid-minimization immunosuppression protocol for renal transplantation in the presence of donor-specific antibodies.

Steroid-minimization regimens have gained tremendous popularity for renal Tx in the recent past since they are associated with lower metabolic complications and other adverse effects related to long-term steroid exposure. Most such protocols have been restricted to low-risk recipients due to the concern for acute rejection with steroid-minimization. Herein, we report our experience in managing a child who received a positive flow cytometry cross-match living donor kidney transplant with low titer DSA and was successfully managed using a steroid-minimization drug regimen. The purpose of our report is to make pediatric transplant care providers aware of the feasibility of using a steroid-minimization immunosuppression regimen even in children who have traditionally been perceived to be at higher risk for immunologic complications, allowing successful avoidance of steroid toxicity.

Donor Characteristics, Recipient Outcomes, and Histologic Findings of Kidney Allografts With Diffuse Donor-derived Glomerular Fibrin Thrombi.

BACKGROUND: Limited data are available on whether donor kidneys with diffuse glomerular fibrin thrombi (GFT) are safe to use. In this study, the clinicopathologic characteristics of allografts with diffuse donor-derived GFT were examined. METHODS: All deceased donor kidney transplant implantation biopsies from our institution between July 2011 and February 2018 with diffuse GFT were included. A control group for comparison consisted of all cases with implantation biopsies obtained during the study period without diffuse GFT. Clinical data were extracted from electronic medical records for all study patients, including donor information. RESULTS: Twenty-four recipients received kidneys with diffuse GFT from 16 deceased donors. All donors died from severe head trauma. On average, 79% of glomeruli contained fibrin thrombi. Nineteen cases had subsequent biopsy; all revealed resolution of GFT. Compared with the control group, kidneys with diffuse GFT had longer cold ischemia time (34 versus 27 h), were more frequently pumped using machine perfusion (100% versus 81%), and recipients experienced a higher frequency of delayed graft function (58% versus 27%). Only 2 grafts with diffuse GFT failed within the first year. Overall graft survival was similar between the diffuse GFT group and control group. CONCLUSIONS: Deceased donor kidneys with diffuse GFT appear to be safe to use given that nearly 92% of recipients in this cohort who received such allografts experienced good clinical outcomes. Histologically, GFT demonstrated rapid resolution following transplantation. Interestingly, diffuse GFT only occurred in donors who suffered severe head trauma in this cohort, which may be a predisposing factor.

Combined Ex Vivo Hypothermic and Normothermic Perfusion for Assessment of High-risk Deceased Donor Human Kidneys for Transplantation.

BACKGROUND: Despite careful clinical examination, procurement biopsy and assessment on hypothermic machine perfusion, a significant number of potentially useable deceased donor kidneys will be discarded because they are deemed unsuitable for transplantation. Ex vivo normothermic perfusion (EVNP) may be useful as a means to further assess high-risk kidneys to determine suitability for transplantation. METHODS: From June 2014 to October 2015, 7 kidneys (mean donor age, 54.3 years and Kidney Donor Profile Index, 79%) that were initially procured with the intention to transplant were discarded based on a combination of clinical findings, suboptimal biopsies, long cold ischemia time (CIT) and/or poor hypothermic perfusion parameters. They were subsequently placed on EVNP using oxygenated packed red blood cells and supplemental nutrition for a period of 3 hours. Continuous hemodynamic and functional parameters were assessed. RESULTS: After a mean CIT of 43.7 hours, all 7 kidneys appeared viable on EVNP with progressively increasing renal blood flow over the 3-hour period of perfusion. Five of the 7 kidneys had excellent macroscopic appearance, rapid increase in blood flow to 200 to 250 mL/min, urine output of 40 to 260 mL/h and increasing creatinine clearance. CONCLUSIONS: Favorable perfusion characteristics and immediate function after a 3-hour course of EVNP suggests that high-risk kidneys subjected to long CIT may have been considered for transplantation. The combined use of ex vivo hypothermic and normothermic perfusion may be a useful strategy to more adequately assess and preserve high-risk kidneys deemed unsuitable for transplantation. A clinical trial will be necessary to validate the usefulness of this approach.

Similar long-term outcomes for laparoscopic versus open live-donor nephrectomy kidney grafts: an OPTN database analysis of 5532 adult recipients.

Prior studies that included both adult and pediatric recipients suggested slower early graft function for laparoscopically (vs. openly) procured live donor kidney grafts (LD-Ktxs). Any potential long-term impact, however, remains unknown. We compared long-term outcomes of 2685 (49%) laparoscopic vs. 2847 (51%) open LD-Ktxs reported to the Organ Procurement and Transplantation Network performed in adult (> or =18 yrs) recipients between November 1999 and December 2000, with follow-up to February 2006. Acute and chronic rejection accounted for 152 laparoscopic (51%) vs. 148 (46%) open graft losses (P=NS). At discharge and at 5 years, graft function was similar for both groups; graft survival at 5 years was 79% (laparoscopic) vs. 80% (open) (P=NS). We conclude that despite prior reports of slower early laparoscopic LD-Ktx function, both laparoscopic and open nephrectomy are equally effective for procurement of kidneys for adult recipients with regard to short- and long-term (>5 years) function and survival. Future studies must investigate whether these findings apply also to pediatric LD-Ktx recipients.

Long-term Survival of Grafts From Small and Very Small Pediatric Donors in Women vs Men With End-stage Kidney Disease.

This cohort study compares graft survival of kidneys from small and very small pediatric donors in women vs men with end-stage kidney disease.

Impact of Willingness to Accept Hepatitis C Seropositive Kidneys Among Hepatitis C RNA-Positive Waitlisted Patients.

BACKGROUND: Kidney transplantation from hepatitis C seropositive (HCV+) donors may benefit hepatitis C RNA-positive (RNA+) candidates, but it is unclear how the willingness to be listed for and accept such kidneys affects waitlist and transplant outcomes. METHODS: In a single-center retrospective analysis, HCV+ transplant candidates (N = 169) listed from March 2004 to February 2015 were evaluated. All RNA+ candidates were offered the option to be listed for HCV+ donors. RNA- candidates were listed only for HCV- donors. RESULTS: Fifty-seven patients (51% of all RNA+ transplant candidates) willing to accept HCV+ donors were listed for both HCV+ and HCV- donor kidneys. During 6-year follow up, 43 (75%) of 57 patients accepting HCV+ versus 19 (35%) of 55 patients not accepting HCV+ received a deceased donor kidney transplant (P < 0.0001). Multivariable analysis demonstrated that willingness to be listed for and accept HCV+ kidneys was associated with receiving deceased donor kidney transplant (P = 0.0016). Fewer patients accepting HCV+ donors (7 [12%] vs 16 [29%]) were removed from the list due to death or deteriorated medical condition (P = 0.0117). Posttransplant patient and graft survival rates were not significantly different. Overall patient survival since the listing (combined waitlist and posttransplant survival) was similar among the groups. CONCLUSIONS: HCV RNA+ candidates had better access to transplantation and similar overall survival before the era of widespread use of direct-acting anti-HCV agents.

Learning Curve for Laparoendoscopic Single-Incision Live Donor Nephrectomy: Implications for Laparoendoscopic Practice and Training.

BACKGROUND: The learning curve for laparoendoscopic single-incision live donor nephrectomy, which is technically more complex than the multiport, conventional laparoendoscopic approach, is unknown. PATIENTS AND METHODS: In a retrospective cohort study, we analyzed the learning curve of the initial 114 consecutive single-incision laparoendoscopic nephrectomies performed in nonselected live kidney donors. RESULTS: Median donor body mass index was 26 kg/m2 (range 20-34). In all, 92% of the nephrectomies were performed on the left side; 18% of the recovered kidneys had multiple renal arteries. Cumulative sum (CUSUM) analysis of operating time (OT) demonstrated that the learning curve was achieved after case 61. For the learning curve phase (Group 1 [cases 1-61]) vs the postlearning phase (Group 2 [cases 62-114]), the difference of the mean OT was 20 minutes (p = 0.05). Mean warm ischemic time in the donors was significantly longer during the learning phase (Group 1, 6 minutes; Group 2, 5 minutes; p = 0.04). Rates of conversions to multiport procedures and of donor complications were not significantly different between Groups 1 and 2. For the recipients, we observed delayed graft function in 2 (2%) cases, no technical graft losses; and 1-year death-censored graft survival was 100% (p = n.s. for all comparisons of Group 1 vs 2). CONCLUSIONS: Single-incision laparoendoscopic donor nephrectomy had a long learning curve (>60 cases), but resulted in excellent donor and recipient outcomes. The long learning curve has significant implications for the programs and surgeons who contemplate transitioning from multiport to single-incision nephrectomy. Furthermore, our observations are highly relevant for informing the development of training requirements for fellows to be trained in single-incision laparoendoscopic nephrectomy.

Impact of panniculectomy on transplant candidacy of obese patients with chronic kidney disease declined for kidney transplantation because of a high-risk abdominal panniculus: A pilot study.

BACKGROUND: Obese patients can develop a large lower abdominal panniculus (worsened by significant weight loss). Patients with advanced chronic kidney disease (CKD) affected by this obesity-related sequela are not infrequently declined for kidney transplantation because of the high risk for serious wound-healing complications. We hypothesized that pretransplant panniculectomy in these patients would (1) render them transplant candidates, and (2) result in low posttransplant wound-complication rates. METHODS: In a pilot study, adult patients with CKD who had a high-risk panniculus as the only absolute contraindication to kidney transplantation subsequently were referred to a plastic surgeon to undergo a panniculectomy in order to become transplant candidates. We analyzed the effect of panniculectomy on (1) transplant candidacy and (2) wait list and transplant outcomes (04/2008-06/2014). RESULTS: Overall, 36 patients had panniculectomy (median prior weight loss, 38 kg); all were wait-listed with these outcomes: (1) 22 (62%) patients were transplanted; (2) 7 (19%) remain listed; and (3) 7 (19%) were removed from the wait list. Survival after panniculectomy was greater for those transplanted versus not transplanted (at 5 years, 95% vs 35%, respectively; P = .002). For the 22 kidney recipients, posttransplant wound-complication rate was 5% (1 minor subcutaneous hematoma). CONCLUSION: For obese CKD patients with a high-risk abdominal panniculus, panniculectomy was highly effective in obtaining access to the transplant wait list and successful kidney transplantation. This approach is particularly pertinent for CKD patients because they are disproportionally affected by the obesity epidemic and because obese CKD patients already face multiple other barriers to transplantation.

The presence of a local lung transplant center increases lung procurement rates.

BACKGROUND: The availability of cadaveric organs is the major problem in transplantation today. METHODS: A retrospective review of donors in a single organ procurement organization (OPO) was performed. Donors were divided into three eras: before, during, and after the presence of a local lung transplant program. Lung procurement rates by OPO in the United States in 1999 and 2000 were also retrospectively reviewed. RESULTS: Lung transplant rates were higher in the presence of a local lung program: 4.9% at baseline, 19.1% with a local program, and 7.1% after closure of the local lung program (P<0.01). In the United States, 12.4% of lungs available in OPOs with local lung programs are transplanted, versus 8.9% in OPOs without a local program (P<.001). CONCLUSIONS: Even if donor management protocols are maintained, closure of a local lung program decreases lung recovery rates. This observation supports the importance of maintaining local programs to maximize organ recovery rates.

Amelioration of tacrolimus-induced nephrotoxicity in rats using juniper oil.

BACKGROUND: Calcineurin-inhibitor nephrotoxicity plays a role in the pathogenesis of chronic allograft nephropathy by causing renal ischemia mediated by vasoconstrictive metabolites of the prostanoid pathway. The purpose of our study was to evaluate whether altering the prostanoid profile using juniper oil (JO) would afford renoprotection in rats treated with tacrolimus. METHODS: Diets supplemented with biologic oils (no supplementation, JO, fish oil [FO], safflower oil [SO], and arachidonic acid [AA]) were fed to five groups of rats for 5 weeks; during the last 2 weeks, tacrolimus was administered to all groups except for a control group of animals. At week 5, urinary prostaglandin (PG)F(2-alpha) and inulin clearances were measured. The rat kidneys were harvested to determine the renal cell membrane composition for arachidonic, eicosatrienoic, and eicosapentaenoic acids. RESULTS: Both JO and FO completely reversed the decrease in inulin clearance seen with tacrolimus, the greatest effect being with JO (inulin clearance 15.1+/-3 vs. 6.0+/-1.1 ml/min in the nonsupplemented group; P<0.001); urinary PGF(2-alpha) excretion was also highest in the JO group (328+/-23 pg/mL, P<0.001 vs. the nonsupplemented group). Fatty acid membrane analysis showed greatest incorporation of eicosapentaenoic and eicosatrienoic acids in the JO- (5.7+/-0.6% and 3.1+/-0.4%, respectively) and FO- (8.1+/-0.7% and 2.8+/-0.6%, respectively) treated animals. CONCLUSIONS: JO supplementation in tacrolimus-treated rats was associated with incorporation of vasodilatory prostanoids in the renal-cell membrane and elevated urinary PGF(2-alpha) excretion, and the precipitous fall in inulin clearance induced by tacrolimus was completely prevented. Whether this benefit will translate into a reduction in chronic allograft nephropathy remains to be determined. However, our preliminary data point towards the need for human trials.