Urologic complications after transplantation of 225 en bloc kidneys from small pediatric donors ≤20 kg: Incidence, management, and impact on graft survival.

Pediatric en bloc kidney transplants (EBKs) from small deceased pediatric donors are associated with increased early graft loss and morbidity. Yet, urologic complications post-EBK and their potential impact on graft survival have not been systematically studied. We retrospectively studied urological complications requiring intervention for 225 EBKs performed at our center January 2005 to September 2017 from donors ≤20 kg into recipients ≥18 years. Overall ureteral complication incidence after EBK was 9.8% (n = 22) (12% vs 2% for EBK donors < 10 vs ≥ 10 kg, respectively [P = .031]). The most common post-EBK urologic complication was a stricture (55%), followed by urine leak (41%). In all, 95% of all urologic complications occurred early within 5 months posttransplant (median, 138 days). Urologic complications could be successfully managed nonoperatively in 50% of all cases and had no impact on graft or patient survival. In summary, urologic complications after EBK were common, associated with lower donor weights, occurred early posttransplant, and were often amenable to nonoperative treatment, without adversely affecting survival. We conclude that the higher urologic complication rate after EBK (1) should not prevent increased utilization of small pediatric donor en bloc kidneys for properly selected recipients, and (2) warrants specific discussion with EBK recipients during the preoperative consent process.

Barriers to live and deceased kidney donation by patients with chronic neurological diseases: Implications for donor selection, donation timing, logistics, and regulatory compliance.

Live and deceased kidney donation by the numerous patients with advanced, progressive systemic neurological diseases, and other chronic neurological conditions (eg, high C-spine injury) remains largely unexplored. In a review of our current clinical practice, we identified multiple regulatory and clinical barriers. For live donation, mandatory reporting of postdonation donor deaths within 2 years constitutes a strong programmatic disincentive. We propose that the United Network for Organ Sharing should provide explicit regulatory guidance and reassurance for programs wishing to offer live donation to patients at higher risk of death during the reporting period. Under the proposal, live donor deaths within 30 days would still be regarded as donation-related, but later deaths would be related to the underlying disease. For deceased donation, donation after circulatory death (DCD) immediately following self-directed withdrawal of life-sustaining treatment ("conscious DCD") is not universally covered by existing DCD agreements with donor hospitals. Organ procurement organizations should thus systematically strive to revise these agreements. Obtaining adequate first-person consent from these communicatively severely impaired patients may be challenging. Optimized preservation and allocation protocols may maximize utilization of these DCD kidneys. Robust public debate and action by all stakeholders is necessary to lower existing barriers and maximize donation opportunities for patients with chronic neurological conditions.

Successful Hemodialysis Arteriovenous Fistula Creation in a Patient With Continuous-Flow Left Ventricular Assist Device Support.

Heart failure necessitating left ventricular assist device (LVAD) support can lead to kidney failure requiring dialysis. Some of these patients may require long-term hemodialysis (HD). Optimal vascular access for a patient on long-term HD therapy with an LVAD remains a complex issue. The majority of LVADs are of the continuous-flow type, and it has been theorized that native arteriovenous fistula maturation may be impaired in a setting of decreased pulsatile arterial flow. We describe a case of successful creation and use of an arteriovenous fistula in an HD-dependent patient with a continuous-flow LVAD.

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.

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.

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.

Pretransplant recipient cytomegalovirus seropositivity and hemodialysis are associated with decreased renal allograft and patient survival.

BACKGROUND: Pretransplant systemic inflammation has been associated with decreased renal allograft survival, and infectious agents such as cytomegalovirus (CMV) may play a role. We hypothesized that pretransplant CMV seropositivity is a risk factor for decreased patient and allograft survival after cadaveric renal transplantation and that other factors believed to modulate systemic inflammation, such as dialysis modality, might act synergistically with CMV to decrease patient and allograft survival. METHODS: The United Network for Organ Sharing database was reviewed to identify all patients undergoing cadaveric renal transplantation in the United States from 1988 to 1997. Outcomes for CMV seropositive and seronegative recipients of organs from CMV seronegative donors were analyzed. Subgroup analysis was performed to identify any synergistic influence on outcome between CMV serostatus and known determinants of risk, including degree of human leukocyte antigen mismatch, pretransplant dialysis, and cold ischemia time. RESULTS: Of 29,875 patients who underwent transplantation, 12,239 were CMV seronegative and 17,636 were CMV seropositive. Patient survival was decreased by pretransplant seropositivity (relative risk [RR] 1.11, P =0.001). In addition, this group demonstrated worse overall allograft survival (RR 1.05, P =0.029), although this adverse effect disappeared when patients who died with a functioning graft were censored. Decreased allograft survival was most pronounced in patients who were on hemodialysis before transplantation (RR 1.62, P =0.004). CONCLUSIONS: Pretransplant CMV seropositivity is associated with decreased patient survival. Pretransplant CMV seropositivity and hemodialysis have a synergistic adverse effect on graft survival, independent of patient mortality. Additional studies are required to define mechanisms by which pretransplant CMV infection and dialysis modality may contribute to decreased allograft survival.

Higher surgical wound complication rates with sirolimus immunosuppression after kidney transplantation: a matched-pair pilot study.

Sirolimus, a potent new immunosuppressant, has been anecdotally associated with surgical wound complications. We studied postoperative surgical wound complications in 15 kidney recipients receiving sirolimus, prednisone, and tacrolimus or cyclosporine (study group) compared with 15 recipients receiving tacrolimus, prednisone, and mycophenolate mofetil who were pair-matched for surgical wound complication risk factors. Surgical wound complications were defined as any complication related to the surgical transplant wound requiring reintervention. Fifty-three percent of the study group and 7% of the control group experienced more than one surgical wound complication (P=0.014), and the relaparotomy incidence was 33% and 7%, respectively. Four graft losses have occurred since the beginning of the study: one chronic rejection and two deaths with function in the study group, and one death with function in the control group. At 1 year, graft survival for study recipients compared with control recipients was 87% and 93%, respectively; patient survival was 93% in both groups. Recipients receiving sirolimus demonstrated a significantly higher surgical wound complication rate, but graft and patient survival were not affected. Peritransplant immunosuppression with sirolimus and steroids warrants careful consideration, particularly in recipients with surgical complication risk factors.

Intra-access blood flow in patients with newly created upper-arm arteriovenous native fistulae for hemodialysis access.

BACKGROUND: The upper-arm native arteriovenous fistula for hemodialysis (HD) vascular access is an important option in the long-term HD population. This single-center cohort study evaluated intra-access blood flow (Q AC) in 3 variants of newly created upper-arm fistulae. METHODS: Fifty-three patients with mature, working, upper-arm fistulae composed of brachial artery to cephalic vein (n = 27), brachial artery to basilic vein (n = 13), and brachial artery to median antecubital vein (n = 13) fistulae were included. Nine of 13 brachio-median antecubital fistulae were of the Gracz type and used the deep perforating vein. Q AC was measured by means of ultrasound velocity dilution during HD. In brachio-median antecubital fistulae, additional flow in the alternate draining vein was measured by means of duplex ultrasound, with 9 of 11 studied patients showing a patent alternate outflow, of whom 7 patients showed substantial flow (median, 0.7 L/min). RESULTS: Q AC in the HD-used primary vein in brachio-median antecubital fistulae (0.85 L/min) was significantly less than those of brachiocephalic and brachiobasilic fistulae (1.4 and 1.7 L/min, respectively). However, when the additional flow provided by the patent alternate vein in brachio-median antecubital fistulae was considered, flow rates provided by all 3 variants of fistulae appeared similar. The inverse correlation between alternate-vein and primary-vein flows (r = -0.70; P = 0.017) suggested there was competitive flow between the 2 venous outlets. There was no instance of access recirculation. CONCLUSION: Upper-arm fistulae, regardless of type, provide excellent blood flows and should be considered routinely if a wrist fistula is not feasible. The patent alternate vein in the brachio-median antecubital or Gracz fistula may continue to drain a substantial amount of blood.

Outcomes of upper arm arteriovenous fistulas for maintenance hemodialysis access.

HYPOTHESIS: Radiocephalic fistulas for maintenance hemodialysis access are not feasible in all patients with end-stage renal disease. Our aim was to review our experience with 3 types of upper arm arteriovenous fistula (AVF) to ascertain whether they are reasonable alternatives to radiocephalic fistulas and which, if any, have superior performance. PATIENTS AND METHODS: Patient medical records were retrospectively reviewed. The main outcomes were maturation rate, time to maturation, assisted maturation rate, complication rates, reintervention rates, primary and assisted primary patency rates, and effects of comorbidities. RESULTS: Eighty-six patients with end-stage renal disease underwent creation of a brachiocephalic, brachiobasilic, or brachial artery-to-median antecubital vein AVF. Overall, 80% matured, with 23% requiring an intervention to achieve maturity. The mean time to maturation was 3.8 months; 47% had a complication (inability to access, thrombosis, and so on), and 43% required additional interventions. The overall primary patency and assisted primary patency rates at 12 months were 50% and 74%, respectively. Brachiobasilic AVFs not superficialized immediately often needed a second operation. There were no significant differences in patency rates among the 3 AVF types. The AVFs in patients with diabetes took 2 months longer to mature than did those in patients without diabetes. CONCLUSIONS: An upper arm AVF is a reasonable alternative for maintenance hemodialysis access when a radiocephalic AVF is not possible. There are 3 valid options from which to choose to best accommodate each patient's antecubital anatomy. Diabetes may adversely affect outcomes. Our data suggest that brachiobasilic AVFs should be superficialized at the initial procedure, if feasible.

Pretransplantation soluble adhesion molecule expression predicts outcome after living donor renal transplantation.

HYPOTHESIS: Occult pretransplantation systemic inflammation will identify patients at risk for poor outcomes after renal transplantation. DESIGN: Retrospective cohort study. Adhesion molecule levels were measured in pretransplantation serum samples from 86 recipients. Univariate and multivariate analyses were conducted to assess a possible correlation between serum adhesion molecule level and outcome. SETTING: University referral center. MAIN OUTCOME MEASURES: Allograft rejection and survival. RESULTS: Patients with low levels of vascular cell adhesion molecule 1 had less graft rejection (P=.007). Low levels of vascular cell adhesion molecule 1 independently predicted decreased rejection (relative risk, 0.17; P=.01), and high levels of vascular cell adhesion molecule 1 independently predicted graft loss (relative risk, 3.83; P=.02). Similar correlations were observed for intercellular adhesion molecule 1. CONCLUSIONS: Decreased pretransplantation adhesion molecule expression correlates with less rejection, and increased levels correlate with graft loss. Assessment of pretransplantation inflammatory status may be useful in optimizing immunosuppression therapy.

Early and late recipient graft function and donor outcome after laparoscopic vs open adult live donor nephrectomy for pediatric renal transplantation.

BACKGROUND: Laparoscopically procured live donor kidney grafts are increasingly transplanted into pediatric recipients. The safety and efficacy of this changed surgical practice are unknown. HYPOTHESIS: Outcomes of laparoscopic vs open donor grafts in recipients 18 years and younger are equivalent. DESIGN AND SETTING: Retrospective review at an academic tertiary care referral center. PATIENTS: Eleven consecutive pediatric recipients of laparoscopically procured kidneys between April 1, 1997, and December 31, 2001, were pair matched for age with 11 recipients of openly procured kidneys between December 1, 1991, and March 31, 1997; the 22 adult donors were also studied. MAIN OUTCOME MEASURES: Recipients: surgical complications, graft function and survival. Donors: perioperative morbidity and length of hospital stay. RESULTS: Twenty (91%) of 22 kidneys were donated by a parent of the recipient. In recipients of laparoscopically procured grafts, we observed significantly lower creatinine clearances and higher creatinine levels on days 1, 4, and 6, but by 1 month, graft function was similar in both groups. No significant differences in surgical complications, delayed function, acute and chronic rejection, and graft survival rates were found. No laparoscopic or open donor required blood transfusion, reoperation, or hospital readmission. One laparoscopic donor (9%) was converted to open nephrectomy. For laparoscopic vs open donors, median operative time was longer (difference, 67 min; P =.08), but median postoperative length of stay was significantly shorter (3 vs 5 days; P =.02). CONCLUSIONS: Laparoscopic live donor nephrectomy has no adverse impact on pediatric recipient outcomes. For donors, the laparoscopic operation is safe and the hospital stay is shortened. These results support the continued use of laparoscopically procured live donor kidneys in pediatric renal transplantation.

The transition from laparoscopic to retroperitoneoscopic live donor nephrectomy: a matched pair pilot study.

BACKGROUND: Retroperitoneoscopic live donor nephrectomy (RetroNeph) offers an intrinsic advantage over conventional transperitoneal laparoscopic nephrectomy (LapNeph) because of the potentially lower risk for early and late intraperitoneal donor complications. RetroNeph, however, is infrequently performed and has not been systematically and directly compared with LapNeph in nonselected donors. METHODS: In November 2007, after 10 years of programmatic experience with transperitoneal LapNeph, we implemented RetroNeph at once for all live donor nephrectomies. Donor selection criteria, laparoscopic port positions, and hand-assistance mode were identical for RetroNeph and preceding LapNeph donors. We compared outcomes of retroperitoneoscopically completed cases with those of previous transperitoneal LapNeph cases that were pair matched for donor sex, body mass index, and donor kidney laterality. RESULTS: Of the first 52 donor nephrectomies (48 left, 4 right) consecutively started with the intent to perform a RetroNeph November 2007 to April 2009, 45 (87%) were completed retroperitoneoscopically, and seven (13%) were switched intraoperatively to transperitoneal LapNeph. We observed no conversions to open nephrectomy, donor blood transfusions, readmissions, or reoperations. Matched-pair analysis of the 45 RetroNeph versus 45 LapNeph cases showed no significant differences for warm ischemia time and other donor outcomes, delayed graft function rates, recipient creatinine at 1 week, and 1-year graft survival. CONCLUSIONS: Implementation of a RetroNeph program had no adverse impact on donor morbidity and quality of early graft function. Our pilot experience suggests that the RetroNeph learning curve is short. Given the potential advantages of an extraperitoneal approach for the donor, RetroNeph is an attractive alternative to LapNeph, particularly for surgeons with previous LapNeph experience.

De novo nonalcoholic fatty liver disease after liver transplantation.

Hepatic steatosis is a recognized problem in patients after orthotopic liver transplant (OLT). However, de novo development of nonalcoholic fatty liver disease (NAFLD) has not been well described. The aim of this study was to determine the prevalence and predictors of de novo NAFLD after OLT. A retrospective analysis was performed on 68 OLT patients with donor liver biopsies and posttransplantation liver biopsies. Individual medical charts were reviewed for demographics, indication for OLT, serial histology reports, genotypes for hepatitis C, comorbid conditions, and medications. Liver biopsies were reviewed blindly and graded according to the Brunt Scoring System. Multivariate logistic regression analysis was used to study the risk factors for developing NAFLD. The interval time from OLT to subsequent follow-up liver biopsy was 28 +/- 18 months. A total of 12 patients (18%) developed de novo NAFLD, and 6 (9%) developed de novo NASH. The regression model indicated that the use of angiotensin-converting enzyme inhibitors (ACE-I) was associated with a reduced risk of developing NAFLD after OLT (odds ratio, 0.09; 95% confidence interval, 0.010-0.92; P = 0.042). Increase in body mass index (BMI) of greater than 10% after OLT was associated with a higher risk of developing NAFLD (odds ratio, 19.38; 95% confidence interval, 3.50-107.40; P = 0.001). In conclusion, de novo NAFLD is common in the post-OLT setting, with a significant association with weight gain after transplant. The use of an ACE-I may reduce the risk of developing post-OLT NAFLD.

Assessment of pretransplant inflammation in pediatric renal allograft recipients.

Pretransplant (Tx) inflammation is linked to adverse outcomes in adult Tx recipients but no such data exist for children. Our study evaluated the predictive value of three pre-Tx inflammatory markers: serum C-reactive protein (CRP), Neopterin (Neo) and interleukin (IL) 12, in determining outcome. Pre-Tx serum on 51 children (mean age 11 years) transplanted between 1985 and 2000 was analyzed. Data on other variables were abstracted from patient records. Primary end-points were graft survival and acute rejection (AR). Kaplan-Meier and log-rank statistics compared endpoints in patients at different quartiles for each marker. Cox regression analysis was used to determine the independent effect of the markers on the end-points. The mean CRP, Neo, and IL-12 were 1.3 mg/l, 1.78 ng/ml, and 123 pg/ml, respectively. The mean CRP, Neo, and IL-12 were not different between the patients with and without AR or graft loss (P > 0.4 for all). Neither rejection-free survival nor graft survival was affected by CRP, Neo, or IL-12 quartiles. Cox-regression analysis demonstrated no predictive value of any marker on outcome. Unlike adults, a single pre-Tx determination of inflammatory markers was not predictive of AR or graft loss in children, indicating that the pathogenesis of AR may be different in children.

Upper arm arteriovenous fistula versus forearm looped arteriovenous graft for hemodialysis access: a comparative analysis.

If an autogenous wrist radiocephalic arteriovenous fistula cannot be created, the next choice for chronic hemodialysis access may be a prosthetic forearm looped arteriovenous graft (FAL-AVG) or a native upper arm arteriovenous fistula (UA-AVF). We reviewed our experience with these two forms of dialysis access to determine which is preferable. Patient medical records were retrospectively reviewed. The main outcomes were time to first use, complications, and reinterventions as well as primary and assisted primary patency. Eighty-six patients underwent creation of UA-AVF, and 60 patients underwent placement of FAL-AVG. Time to first use was 3.8 months for UA-AVFs vs. 1.8 months for FAL-AVGs (p < 0.018). Complication rates were 42% vs. 65% for UA-AVFs vs. FAL-AVGs, respectively (p = 0.006). Thrombosis was more common in FAL-AVGs than UA-AVFs (42% vs. 17%, p = 0.001), as was nonelective reintervention (50% vs. 30%, p = 0.016). Patency rates were similar at 1 and 2 years. Although UA-AVFs and FAL-AVGs share similar early patency rates, UA-AVFs may be a better choice for chronic hemodialysis access because of a lower incidence of complications and nonelective reinterventions. To maximize the benefits of UA-AVFs, however, early surgical referral is required.

Impact of portal venous pancreas graft drainage on kidney graft outcome in simultaneous pancreas-kidney recipients reported to UNOS.

Clinical data on the potential immunologic impact of portal (PD) vs. systemic (SD) venous pancreas graft drainage on outcome remains controversial. We reviewed the UNOS database to study the effect of PD vs. SD on the incidence of kidney graft rejection and survival in first cadaveric simultaneous pancreas-kidney (SPK) recipients transplanted 1994-2001. We studied three groups: all SPK (n=6629, 13% PD) (group I), SPK on tacrolimus (n=3563, 17% PD) (group II), and SPK on tacrolimus performed at centers with significant PD experience (n=948, 46% PD) (group III). The cumulative kidney graft rejection incidence for PD vs. SD was only significantly different in group I (for PD vs. SD, respectively: at 6 months, 31% vs. 36% [p=0.015]; at 1 year, 37% vs. 43% [p=0.006]). Kidney graft survival was similar in all groups for PD vs. SD. Multivariate analysis of group III showed only transplantation during the earlier era (1994-96), but not SD, to be an independent risk factor for kidney graft rejection. Portal venous pancreas graft drainage does not affect kidney graft rejection and survival in SPK recipients on tacrolimus. Our data suggests that the efficacy of current immunosuppressive protocols and increasing center experience are clinically much more relevant than any potential immunologic advantage of portal venous drainage in SPK recipients.