Progress in individualizing autologous islet isolation techniques for pediatric islet autotransplantation after total pancreatectomy in children for chronic pancreatitis.

Total pancreatectomy with islet autotransplantation is performed to treat chronic pancreatitis in children. Successful islet isolation must address the challenges of severe pancreatic fibrosis and young donor age. We have progressively introduced modifications to optimize enzymatic and mechanical dissociation of the pancreas during islet isolation. We evaluated 2 islet isolation metrics in 138 children-digest islet equivalents per gram pancreas tissue (IEQ/g) and digest IEQ per kilogram body weight (IEQ/kg), using multiple regression to adjust for key disease and patient features. Islet yield at digest had an average 4569 (standard deviation 2949) islet equivalent (IEQ)/g and 4946 (4009) IEQ/kg, with 59.1% embedded in exocrine tissue. Cases with very low yield (<2000 IEQ/g or IEQ/kg) have decreased substantially over time, 6.8% and 9.1%, respectively, in the most recent tertile of time compared to 19.2% and 23.4% in the middle and 34.1% and 36.4% in the oldest tertile. IEQ/g and IEQ/kg adjusted for patient and disease factors improved in consistency and yield in the modern era. Minimal mechanical disruption during digestion, warm enzymatic digestion using enzyme collagenase:NP activity ratio < 10:1, coupled with extended distension and trimming time during islet isolation of younger and fibrotic pediatric pancreases, gave increased islet yield with improved patient outcomes.

Posterior urethral valve treatments and outcomes in children receiving kidney transplants.

PURPOSE: We evaluated the impact of surgical approaches to posterior urethral valves on renal transplant survival and compared transplant survival in children with vs without posterior urethral valves. MATERIALS AND METHODS: We reviewed the records of all children who underwent renal transplantation from January 1984 to March 2008 and performed univariate subgroup analysis in those with posterior urethral valves. We evaluated the ureteroneocystotomy method, immunosuppression and valve treatment. In patients with posterior urethral valves we regarded nocturnal and/or daytime incontinence, severe urgency and the need for intermittent catheterization or double voiding for increased post-void residual urine as signs of bladder dysfunction. RESULTS: The initial renal transplant was received by 418 children at a mean age of 5.6 years. The 59 boys with posterior urethral valves received a total of 69 kidneys. By 8-year followup the kidney had failed in 24 of 59 boys with and 143 of 359 without posterior urethral valves (OR 0.9665, 95% CI 0.5462-1.692, p = 0.9105). Immunosuppression was consistent in the 2 groups. Outcomes were similar across all ureteroneocystotomy techniques. Initial management for posterior urethral valves was valve ablation alone in 12 boys, vesicostomy in 7 and supravesical diversion in 11. There was no difference in transplant survival or bladder dysfunction based on valve intervention. In 18 boys (55%) we noted overlapping signs of bladder dysfunction, of whom 11 performed intermittent catheterization or had increased post-void residual urine, 4 had severe urgency, 4 had daytime incontinence and 7 had nocturnal incontinence. Bladder dysfunction did not predict increased graft loss (OR 3.306, 95% CI 0.7615-16.27, p = 0.1134). CONCLUSIONS: Of children who undergo renal transplantation boys with posterior urethral valves do not have a higher graft failure rate. Treatment for posterior urethral valves did not significantly impact transplant survival or bladder dysfunction.

Improved Outcomes of Kidney Transplantation in Infants (Age < 2 years): A Single-Center Experience.

BACKGROUND: Infants (age, < 2 years) with end-stage renal disease (ESRD) have increased morbidity and mortality. We evaluated our long-term outcomes of kidney transplants (KTx) in infants. METHODS: Between 1984 and 2014, 136 infants underwent KTx. We examined trends in survival rates and complications by era (1984-1993 [era 1], 1994-2003 [era 2], 2004-2014 [era 3]). RESULTS: Patients were 92.6% white and 70.6% males. Posttransplant (Tx) initial length of hospital stay declined 37% over the 30-year period (P <0.01). Ten-year death-censored graft survival improved from 60% (era 1) to 80% (era 2) (P = 0.04). The incidence of acute rejection, graft thrombosis, cytomegalovirus, and urine leaks did not significantly change across eras. Frequency of Epstein-Barr virus diagnosis (era 2 vs era 3, P < 0.01) increased. Post-Tx lymphoproliferative disorder incidence was increased in era 2 compared with eras 1 and 3 (P = 0.03). CONCLUSIONS: Infants deserve earlier consideration for KTx. Length of initial hospital stay and patient and graft survival rates after KTx have improved in infants since 1984.

Thymoglobulin versus ATGAM induction therapy in pediatric kidney transplant recipients: a single-center report.

BACKGROUND: Induction immunosuppressive therapy with the anti-T-cell antibody Thymoglobulin decreases the incidence of acute rejection in adult kidney transplant (KTx) recipients, but limited data are available for pediatric KTx recipients. METHODS: We conducted a historical cohort study to compare rates of survival, rejection, and infection in pediatric (age <19 years) KTx recipients who received induction therapy with polyclonal antibody, ATGAM (n=127) or Thymoglobulin (n=71), from December 1, 1992, to January 31, 2003. Maintenance immunosuppression included cyclosporine, azathioprine or mycophenolate mofetil, and prednisone. Mean follow-up was 90+/-25 months for ATGAM recipients and 32+/-15 months for Thymoglobulin recipients. RESULTS: Overall, the incidence of acute rejection was lower in Thymoglobulin recipients versus ATGAM recipients (33% vs. 50%, P=0.02). Epstein-Barr virus (EBV) infection was higher in Thymoglobulin recipients versus ATGAM recipients (8% vs. 3%, P=0.002). But the two groups did not significantly differ in patient and graft survival rates, incidence of chronic rejection, EBV lymphoma, or other infection. CONCLUSIONS: Thus, Thymoglobulin induction was associated with a decreased incidence of acute rejection and an increased incidence of EBV infection in pediatric KTx recipients. EBV monitoring should be performed in EBV-naive recipients receiving Thymoglobulin.

Urolithiasis after kidney transplantation in pediatric recipients: a single center report.

BACKGROUND: Urolithiasis occurs in approximately 6% of adult kidney transplant (KTx) recipients. Limited data are available on urolithiasis after pediatric KTx. We report the incidence, management of, and risk factors for stone development in children after KTx. METHODS: We reviewed the medical records of 399 children who received KTx at our center between September 1986 and January 2003. Transplant outcomes were compared in stone formers and controls. RESULTS: Twenty (5%) patients, age 9+/-5 (X +/- SD) years, developed stones over the follow-up period (74+/-53 months). Time to stone presentation was 19+/-22 months post-KTx. Presenting features were urinary tract infection (UTI), 8; gross hematuria, 5; microscopic hematuria, 2; dysuria without infection, 6; difficulty voiding, 3; and silent stones, 2. Stones were removed by cystoscopy in 11 (55%) patients. Stone composition was determined in 11 patients: calcium phosphate (55%), calcium oxalate (18%), mixed calcium phosphate and oxalate (9%), and struvite (18%). Factors predisposing to stones in study patients included suture retention (n = 4), elevated urinary calcium excretion (n = 2), recurrent UTI (n = 2), and urinary stasis (n = 2). The incidence of UTI was higher (P = 0.003) and of acute rejection was lower (P = 0.02) in stone patients compared with controls. Patient and graft survival rates and the incidence of chronic rejection did not significantly differ between study patients and controls (P = NS). CONCLUSIONS: Urolithiasis is not uncommon in pediatric KTx patients. Factors associated with post-KTx urolithiasis include retention of suture material, recurrent UTI, hypercalciuria, and urinary stasis. Treatment is associated with excellent outcome and low recurrence rate.