Howard Sankary

Impact of non-compliance on outcome after pediatric kidney transplantation: An analysis in racial subgroups

Abstract:  Renal transplantation is the therapy of choice for children with end‐stage renal disease. Despite excellent patient survival, long‐term graft survival is poor, especially in the African‐American (AA) population. This article addresses non‐compliance as a major cause of late‐term graft loss in the pediatric population. Between July 1995 and September 2002, a total of 50 pediatric kidney transplants were performed at our institution. We have analyzed data for 44 of these kidney transplants. Twelve recipients were AA, 14 Caucasian (C) and 18 Hispanic (H). The remaining six patients of different racial origin were not included in this analysis. The mean age of the recipients was 10.9 yr (range 1.7–17.8). Thirty‐one were cadaveric and 13 were living donor transplants. We analyzed creatinine level and graft and patient survival at 1, 3 and 5 yr post‐transplant. Compliance was evaluated based on trends in cyclosporine levels, attendance to clinic visits, individual interviews and unexplained late graft dysfunction. One‐ and 3‐yr patient survival rates were 100% for all racial groups, except the 3‐yr patient survival rate for C, which was 86%. One and 3‐yr graft survival rates for AA, C and H were 92 and 67%, 86 and 79% and 100 and 100%, respectively. However, at 5 yr, we found that AA recipients had a significantly higher rate of graft loss when compared to both H and C recipients (42 vs. 95 vs. 71%, respectively). Non‐compliance was the main factor, accounting for 71% of cases of late graft loss. In conclusion, non‐compliance is a problem of great importance in the pediatric transplant population, particularly in AA recipients, where it plays a major role in late‐term graft loss.

Living donor kidney transplantation across positive crossmatch: The University of Illinois at Chicago Experience

Background. To increase living donation for kidney transplantation, we investigated desensitization of recipients with positive crossmatch against a potential living donor. Methods. Between June 2001 and March 2007, 57 consecutive sensitized candidates for kidney transplantation, with crossmatch positive potential living donors, were treated with various desensitization protocols. All patients received plasmapheresis every other day with intravenous immune globulin 100 mg/kg starting 1 week before the scheduled transplant. Postoperatively, the recipients continued to receive every other day plasmapheresis with intravenous immune globulin for the initial week. Immunosuppression therapy consisted of induction with thymoglobulin and a combination of tacrolimus, mycophenolate, and corticosteroids. Results. Six patients failed to convert with pretransplant immunomodulation and were not transplanted; 51 underwent live donor kidney transplant. Mean follow-up was 23 months and 36 patients have more than 1-year follow-up. One-year patient and graft survivals were 95% and 93%, respectively. There were 25 episodes of biopsy-proven or clinically presumed rejection in 22 patients in the first year. Of the 17 biopsy-proven episodes, 12 were antibody-mediated rejection and five were acute cellular rejection. Of the patients with antibody-mediated rejection (biopsy proven or empiric), two patients (12%) lost their graft by 1 year. The median modification of diet in renal disease at 6 and 12 months was 55 mL/min (range 9–104 mL/min) and 48 mL/min (range 8–99), respectively. Conclusions. Despite increased rejection rates, graft and patient survivals indicate that desensitization of positive crossmatch patients is a reasonable alternative for a sensitized patient who could potentially wait 10 or more years for a suitable cadaveric kidney.

Infectious complications associated with the use of rituximab for ABO-incompatible and positive cross-match renal transplant recipients

Abstract:  Immunosuppressive protocols for ABO‐incompatible (ABOI) and positive cross‐match (PCM) solid organ transplant (SOT) recipients have included the use of rituximab (RTX). Infectious complications (IC) have been reported after the use of RTX for other indications, but have not been well studied in the SOT population. We performed a retrospective review of IC occurring within six months of ABOI and PCM renal transplantation (RT) in recipients receiving RTX. Medical records were reviewed for bloodstream, lung, gastrointestinal tract, allograft, or soft tissue infection. Between July 2001 and December 2004, 34 ABOI or PCM RT were performed at University of Illinois at Chicago, 25 of which received RTX with plasmapheresis and antithymocyte globulin (ATG) (eight ABOI and 17 PCM). Among the RTX recipients, the rate of IC was 48% compared with 11% among historical controls who did not receive RTX (p = 0.107). There were 21 episodes of IC in 13 patients including skin and soft tissue infection (8), bloodstream infection (5), esophagitis (3), peritonitis (3), pneumonia (1), and colitis (1). There was no difference in the rate of rejection, graft survival or patient survival between the two groups. These data suggest that there is a trend toward an increased rate of IC with RTX therapy in ABOI and PCM RT recipients.

Successful rescue of refractory, severe antibody mediated rejection with splenectomy

Antibody-mediated rejection (AMR) commonly occurs after transplantation of ABO-incompatible and sensitized renal transplant. Treatment regimens commonly include a combination of plasmapheresis (PL) and intravenous immunoglobulin (IVIG). However, some cases of AMR remain refractory to treatment. We report a case series of four patients with AMR refractory to standard therapy (ST) who resolved after splenectomy. Four living donor kidney transplant recipients were diagnosed with AMR. Two patients were ABO incompatible, one was cross-match positive and one had no obvious predisposing factors. After failure of therapy with corticosteroids, PL, IVIG, Thymoglobulin, and Rituximab (three patients) or Campath (one patient), AMR was treated with laparoscopic splenectomy. After an average of 11 days of ST, laparoscopic splenectomy was performed for rescue. The urinary output improved immediately in all patients, serum creatinine levels decreased within 48 hr, and ABO titers fell in the ABO-incompatible patient and the cross-match became negative in the two sensitized patients. Splenectomy may play a role in the treatment of AMR refractory to ST.

Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury

Abstract:  Background:  Interventions that minimize hepatic ischemia/reperfusion injury (IRI) can expand the donor organ pool. Thymoglobulin (TG) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients. This controlled randomized trial was designated to assess the ability of TG to protect against IRI in liver transplant recipients.

Early discontinuation of steroids is safe and effective in pediatric kidney transplant recipients.

Abstract:  In pediatric kidney transplantation, steroid induced growth retardation and cushingoid features are of particular concern. In children, gradual steroid withdrawal late after kidney transplantation increases the risk of rejection. In this pilot study, we investigated the outcome of pediatric renal transplantation with an early steroid withdrawal protocol. This is a retrospective case‐control study of pediatric renal transplants with age‐matched historical control. Groups were comparable in terms of HLA matching, donor type and graft ischemia time. In the steroid withdrawal group (SWG, n = 13), induction therapy included mycophenolate mofetil (MMF) and a 5‐day course of steroids with Thymoglobulin in 11 and basiliximab in two other patients. In the steroid group (SG, n = 13), in addition to steroids, four patients were given basiliximab, eight were given Thymoglobulin, and one OKT3. Maintenance therapy included tacrolimus (SWG n = 11, SG n = 3) or cyclosporine (SWG n = 2, SG n = 10). Azathioprine was given to all the patients in the SG, except the last two patients of this series who were prescribed MMF. MMF was given to all in the SWG. Patient and graft survival rates were 100% in both groups. In the SWG, no acute rejection episode was detected. In the steroid group, three patients (25%) presented with an acute rejection episode. All but one patient in either group showed immediate graft function. Patients in the steroid‐withdrawal group exhibited a significantly higher creatinine clearance at 6 and 12 months post‐transplant (95.8 ± 23.3 vs. 71.3 ± 21.9, p = 0.03; and 91.3 ± 21.6 vs. 69.6 ± 28.6, p = 0.04). In the SWG delta BMI was significantly lower and delta height Z score was significantly higher, and we observed significantly less hyperlipidemia, body disfigurement, and need for anti‐hypertensive medication. Early steroid withdrawal in pediatric renal transplant recipients is efficacious and safe and does not increase risk of rejection, preserving optimal growth and renal function, and reducing cardiovascular risk factors.

Living Related Segmental Bowel Transplantation: From Experimental to Standardized Procedure

Introduction:Living donor bowel transplantation has recently emerged as a valuable alternative to cadaver bowel transplant. We herein present our single-center experience with this procedure. Materials and Methods:From April 1998 to October 2004, 12 living donor intestinal transplants were performed in 11 patients (7 males, 4 females; average age, 26 years). Four of the patients were children under 5 years. A segment of distal ileum 150 to 180 cm long in pediatric recipients and 200 cm long in adult was used. The immunosuppressive protocol consisted of induction with thymoglobulin and maintenance with tacrolimus with or without mycophenolate mofetil and steroids. Results:All donors recovered well and did not experience any early or late complications. The overall 1- and 3-year patient survival was 82% with a graft survival of 75%. In the last 8 patients, transplanted after January 2000, the 1-year patient and graft survival has been 100% and 88%, respectively. The median hospital stay was 36 days (range, 13–290 days). During the first year after transplant only, the patient who received a totally mismatched graft experienced one episode of rejection (8%). All the surviving patients are currently supported by enteral diet without fluid requirements. Conclusions:Living donor bowel transplantation is a valuable strategy in the treatment of irreversible intestinal failure. The results have improved over the years thanks to increased experience of the team.

Routine left robotic‐assisted laparoscopic donor nephrectomy is safe and effective regardless of the presence of vascular anomalies

The classic approach to donor nephrectomy consists of preferential procurement of the kidney without vascular anomalies. We studied the effect of routine procurement of the left kidney regardless the presence of multiple arteries on the outcomes of robotic‐assisted laparoscopic living donor nephrectomy (LLDN) with particular reference to the incidence of urological complications. From August 2000 to July 2005, 209 left LLDNs were performed. We analyzed the outcomes of donors and recipients in relation to the presence of multiple vessels versus normal anatomy. We divided the patients into two groups: group A (n = 148) with normal vascular anatomy and group B (n = 61) with vascular anomalies. In the donors, no significant difference in conversion to open surgery rate, blood loss, length of stay, was noted between the two groups; operative time and warm ischemia time were slightly higher in group B. One‐year patient survival was 98% in both groups while the 1‐year graft survival was 96.6% in group A and 96% in group B. Only one urological complication was noted in the group with normal anatomy (0.7%) versus none in the group with multiple arteries. Left kidney procurement using robotic‐assisted laparoscopic technique is safe and effective, even in the presence of vascular anomalies.

Intra‐Ductal Glutamine Administration Reduces Oxidative Injury During Human Pancreatic Islet Isolation

Oxidative stress during islet isolation induces a cascade of events injuring islets and hampering islet engraftment. This study evaluated islet isolation and transplantation outcomes after intra‐ductal glutamine administration. Human pancreata deemed unsuitable for pancreas or islet transplantation were treated with either a 5 mM solution of l‐glutamine (n = 6) or collagenase enzyme alone (n = 6) through the main pancreatic duct. Islet yield, viability, in vitro function; markers of oxidative stress [malondialdehyde (MDA) and Glutathione (GSH)] and apoptosis were assessed. Islet yields were significantly increased in the glutamine group compared to controls (318, 559 ± 25, 800 vs. 165, 582 ± 39, 944 mean ± SEM, p < 0.01). The amount of apoptotic cells per islet was smaller in the glutamine group than the control. The percentage of nude mice rendered normoglycemic with glutamine‐treated islets was higher than the controls (83% n = 10/12 vs. 26% n = 6/23; p < 0.01), and the time to reach normoglycemia was decreased in the glutamine group (1.83 ± 0.4 vs. 7.3 ± 3 days; p < 0.01). Glutamine administration increased GSH levels (7.6 ± 1.7 nmol/mg protein vs. 4.03 ± 0.5 in control, p < 0.05) and reduced lipid‐peroxidation (MDA 2.45 ± 0.7 nmol/mg of protein vs. 6.54 ± 1.7 in control; p < 0.05). We conclude that intra‐ductal administration of glutamine reduces oxidative injury and apoptosis and improves islet yield and islet graft function after transplantation.

Simultaneous pancreas-kidney transplant from living related donor: A single-center experience

Background. Simultaneous pancreas and kidney transplantation (SPK) from cadaveric donors has become a widely accepted therapeutic option for insulin-dependent uremic patients. In 1996 the first SPK from a live donor was performed. This procedure offers the advantage of a better immunologic match, reduced cold ischemia injury, and decreased waiting time. As such, it is an attractive alternative treatment for diabetic patients with end-stage nephropathy with an available living donor. Methods. We performed six SPKs from living-related donors. There were four men and two women among the recipients; median age was 34 (range, 29–39) years. All donors were recipients’ siblings with excellent HLA matching. Donors underwent standardized metabolic workup, anti-insulin and anti-islet antibody assays, and computed tomography of the abdomen. Both donors and recipients were treated with octreotide for 5 days perioperatively. After transplantation, the patients were maintained on tacrolimus-based immunosuppression, with the exception of one recipient of SPK from an identical twin, who received cyclosporine monotherapy. Results. All the donors are doing well and have normal renal function and blood glucose levels. One-year patient, renal, and pancreatic graft survival rates were 100%, 100%, and 83%, respectively. Acute kidney rejection was documented in two patients, and both recovered completely after OKT3 therapy. No rejection of pancreatic graft has been documented. Except for one patient who lost the graft because of hemorrhagic pancreatitis, all recipients maintained serum glucose levels at less than 130 mg/dL without insulin therapy. No major surgical complications such as graft thrombosis, intra-abdominal infection, or abscess were reported. Conclusions. Living donor SPK can represent a successful alternative to cadaveric donor SPK. The procedure can be performed safely in the donor and with low morbidity in the recipient.