M. Colleen Hastings

Five years' experience with thymoglobulin induction in a pediatric renal transplant population

Abstract:  Antibody induction therapy is used in the majority of pediatric patients undergoing renal transplantation. Our center has previously reported short‐term outcomes with TMG as induction therapy. We now present our experience over the last five yr. Patients received TMG intra‐ and post‐operatively at a dose of 1.5 mg/kg/day. The dose was decreased to 0.75 mg/kg/day or held dependent on the patients WBC and platelet counts. Post‐transplant immunosuppression also included corticosteroids, MMF, and either TAC or CSA. Patient and graft survival, number of acute rejection episodes, creatinine clearance, incidence and type of infections, and trough levels of calcineurin inhibitor drugs were monitored during the follow‐up period. Thirty‐four renal transplants were performed in 33 pediatric patients ranging in age from 1.7 to 17.8 yr. Seventeen rejection episodes occurred during the time of follow‐up with three patients having more than one episode, but only three episodes occurred within the first year after transplantation. Three patients had graft loss in the first week after transplantation from primary non‐function (1) or technical failure/thrombosis (2). Graft losses occurred in seven additional patients during the time of follow‐up with the first loss occurring at 17.7 months. Among patients with functional grafts at one wk after transplant, graft survival at one and three yr was 100% and 73% respectively. There were no patient deaths. There were no cases of post‐transplant lymphoproliferative disease or other malignancy. One patient had symptomatic CMV disease. TMG is safe and effective as induction therapy in pediatric renal transplant patients. Late graft loss remains a challenge in the pediatric patient population, particularly in adolescents.

Renal survival in pediatric patients with IgA nephropathy.

Sirs, We commend the efforts of Ronkainen et al. [1] in obtaining long-term follow-up data on IgA nephropathy in children, particularly since renal survival data for pediatric patients remain limited. We agree with the authors that the difficulties are considerable with respect to locating former pediatric patients who may have transitioned to providers of adult care or who have simply stopped seeking medical care. The authors determined predicted kidney survival for 55 Finnish patients diagnosed with IgA nephropathy prior to age 18 years. Predicted renal survival rates in this cohort from time of onset of symptoms were 93 and 87% at 10 and 20 years, respectively. In 1995, our group described renal survival in a cohort of 103 pediatric patients of Caucasian (88), African-American (12), Asian (2), and Native American (1) race diagnosed in Memphis, Tennessee, and Lexington, Kentucky. [2] The predicted kidney survival rates from the time of biopsy were 85% at 10 years and 73% at 20 years. Since Berger and Hinglais did not describe IgA nephropathy until 1968 [3], and the condition was not routinely diagnosed in U.S. centers prior to 1972, actual 20-year follow-up was possible for only 5 of 103 patients. We would like to take this opportunity to update renal survival data from 67 Caucasian patients from Tennessee to indicate how they compare to the Finnish data. In this group, 69% were male. The mean age at time of biopsy was 10.8±3.3 years (range 2.1–17.4 years) and mean follow-up from time of biopsy was 9.3±8.2 years (range 0.003– 25.47). Six patients (9%) progressed to end-stage renal disease. Tenand 20-year renal survival rates predicted using the Kaplan-Meier method were 91 and 80%, respectively (Fig. 1). Nine (13%) of our patients had more than 20 years of follow-up. Ronkainen et al. reported survival from time of onset, while we report survival from time of biopsy. They also did not include patients with less than 10 years of follow-up, while we included such patients. Nevertheless, the predicted kidney survival rates for the Finnish cohort and Caucasian patients in the Memphis cohort were quite similar. Pediatr Nephrol (2007) 22:317–318 DOI 10.1007/s00467-006-0303-3

Gastroenteritis caused by Edwardsiella tarda in a pediatric renal transplant recipient

Abstract:  Edwardsiella tarda, a member of the family Enterobacteriaceae, is a Gram‐negative bacillus that is most often pathogenic in aquatic environments. Human infections with Edwardsiella are rare, with most occurring in immunocompromised or immunosuppressed hosts. Reported infections include meningitis, cholecystitis, endocarditis, osteomyelitis, soft tissue infections, bacteremia and septicemia, dysentery, and gastroenteritis. This report describes a case of E. tarda gastroenteritis in a renal transplant patient receiving immunosuppressive therapy. The epidemiology, diagnosis, clinical presentation, and treatment options pertaining to E. tarda infections are examined.

Endoscopic Deflux® injection for pediatric transplant reflux: A feasible alternative to open ureteral reimplant

OBJECTIVE Pediatric renal transplantation is frequently performed using a freely refluxing vesicoureteral anastomosis. The resulting vesicoureteral reflux (VUR) may increase the morbidity of urinary tract infections (UTIs) that commonly occur in this setting, yet open surgical correction of the refluxing anastomosis can prove difficult. We report our experience using endoscopic injection of dextranomer/hyaluronic acid (Deflux) to correct transplant VUR. MATERIALS AND METHODS We retrospectively reviewed the charts of patients treated with endoscopic injection of Deflux (Q-Med, Uppsala, Sweden) for VUR into their renal allograft. Indications for inclusion in the study were renal allograft transplantation for primary end-stage renal disease, radiographically proven VUR into the allograft, normal voiding history, and at least one documented febrile UTI. Preoperative and postoperative images, including voiding cystourethrogram and allograft ultrasound, were compared. Location of the transplant orifice and volume of Deflux were recorded. Clinical outcomes, including documented UTI and changes in serum creatinine following treatment, were also assessed. RESULTS Eight patients were identified who were treated for transplant VUR, with a total of nine transplant ureters injected. Mean patient age at time of injection was 11.6 years (range: 7-19 years). Post-injection voiding cystourethrograms and allograft ultrasound were available for all patients. Following treatment, four ureters demonstrated resolution of VUR and one ureter demonstrated improvement to grade 1 VUR. The remaining four ureters demonstrated no change in VUR grade. No patients showed any change in their serum creatinine, and no episodes of transplant pyelonephritis have occurred during the follow-up period. Mean post-injection follow-up has been 17.3 months (range 9-26 months). CONCLUSION Initial results demonstrate that endoscopic treatment with Deflux is feasible and may provide a less invasive alternative for treatment of transplant VUR. Further investigation with a larger group of patients and longer follow-up is needed.

Serum galactose-deficient IgA1 level is not associated with proteinuria in children with IgA nephropathy.

Introduction. Percentage of galactose-deficient IgA1 (Gd-IgA1) relative to total IgA in serum was recently reported to correlate with proteinuria at time of sampling and during follow-up for pediatric and adult patients with IgA nephropathy. We sought to determine whether this association exists in another cohort of pediatric patients with IgA nephropathy. Methods. Subjects were younger than 18 years at entry. Blood samples were collected on one or more occasions for determination of serum total IgA and Gd-IgA1. Gd-IgA1 was expressed as serum level and percent of total IgA. Urinary protein/creatinine ratio was calculated for random specimens. Spearmans correlation coefficients assessed the relationship between study variables. Results. The cohort had 29 Caucasians and 11 African-Americans with a male : female ratio of 1.9 : 1. Mean age at diagnosis was 11.7 ± 3.7 years. No statistically significant correlation was identified between serum total IgA, Gd-IgA1, or percent Gd-IgA1 versus urinary protein/creatinine ratio determined contemporaneously with biopsy or between average serum Gd-IgA1 or average percent Gd-IgA1 and time-average urinary protein/creatinine ratio. Conclusion. The magnitude of proteinuria in this cohort of pediatric patients with IgA nephropathy was influenced by factors other than Gd-IgA1 level, consistent with the proposed multi-hit pathogenetic pathways for this renal disease.

Association of IgG co-deposition with serum levels of galactose-deficient IgA1 in pediatric IgA nephropathy

Objective: To determine whether the absence of mesangial IgG deposits is associated with the absence of elevated blood levels of galactose-deficient IgA1 (Gd-IgA1) in pediatric patients with IgA nephropathy (IgAN). Design and methods: Serum Gd-IgA1 levels were determined by ELISA using an N-acetylgalactosamine-specific lectin from Helix aspersa. Levels of Gd-IgA1 above the 90th percentile for healthy pediatric controls were considered to be elevated. Renal biopsy samples were examined by immunofluorescence for presence and intensity of staining for IgA, IgG, IgM, C3 and C1q and by light microscopy for histological changes. Findings were graded by a single pathologist (L. Gaber) at UTHSC until 2007 and by NephropathTM (Little Rock, AR, USA) thereafter. Staining for the mesangial deposits was considered negative when intensity was trace or less, and positive at greater intensity. Fisher’s exact-test was used to determine significance of 2 × 2 tables. Results: Serum samples were obtained from 30 patients with IgAN diagnosed before age 18 years. Male : female ratio was 2.3 : 1. Twenty were Caucasian and 10 were African-American. Blood was obtained within 3 months of biopsy (incident cases) for 12, while 18 provided blood > 3 months after biopsy (prevalent cases). Serum Gd-IgA1 level was elevated in 23 (77%) of cases and 20 (67%) had a biopsy positive for IgG. Of those 20 patients, 18 (90%) had an elevated serum Gd-IgA1 level, whereas 5 (50%) of patients with biopsies without IgG had a normal serum Gd-IgA1 level (p = 0.026). Summary: In this small study we found a weak association between the absence of IgG in the biopsy and normal serum Gd-IgA1 level.

Diagnosis of de novo localized thrombotic microangiopathy by surveillance biopsy

Thrombotic microangiopathy has been reported in association with calcineurin inhibitors and less frequently with sirolimus in renal transplant patients. The diagnosis of thrombotic microangiopathy is typically made by diagnostic biopsy in the setting of allograft dysfunction. The finding of thrombotic microangiopathy on surveillance biopsy without a significant elevation of baseline serum creatinine is unusual. The optimal treatment of this disorder remains controversial. Treatment strategies have included dose adjustment, drug substitution, plasmapheresis, and intravenous immunoglobulin G. We report a case of de novo thrombotic microangiopathy diagnosed by surveillance biopsy in a patient without hematologic abnormalities or elevated serum creatinine. This patient had resolution of the renal lesion following conversion from tacrolimus to sirolimus-based immunosuppression.

Heterogeneity of Aberrant O-Glycosylation of IgA1 in IgA Nephropathy

IgA nephropathy (IgAN), a frequent cause of end-stage renal disease, is an autoimmune disease wherein immune complexes consisting of IgA1 with galactose-deficient O-glycans (Gd-IgA1; autoantigen) and anti-glycan autoantibodies deposit in the glomeruli and induce renal injury. Serum IgA1 has three to six clustered O-glycans, some of which may be deficient in galactose and thus expose terminal or sialylated N-acetylgalactosamine. Patients with IgAN usually have elevated serum levels of Gd-IgA1. The mechanisms involved in production of Gd-IgA1 are not fully understood.

Serial Galactose-Deficient IgA1 Levels in Children with IgA Nephropathy and Healthy Controls

Galactose-deficient IgA1 (Gd-IgA1) is a key pathogenic factor for IgA nephropathy (IgAN) and a potential biomarker for the disease. This study examined serial serum Gd-IgA1 levels over 1 year in 13 children with IgAN and 40 healthy children, to determine whether or not serum Gd-IgA1 levels changed over time. Subjects were younger than 18 years of age. Follow-up measurements were scheduled 6 and/or 12 months later. Analysis of variance and regression models for repeated measures were used to estimate group and time effects. Serum Gd-IgA1 level was higher in initial samples for IgAN patients compared to those of healthy children (P < 0.0001). Serum Gd-IgA1 levels did not change over time for healthy controls but increased for IgAN patients (P = 0.001). Serum Gd-IgA1 level was elevated for 9 children with IgAN at study entry and remained elevated. Two of the 4 IgAN patients with initially normal Gd-IgA1 levels had a subsequent elevated level. The persistent elevation of the serum Gd-IgA1 level in children with IgAN enhances its utility as a potential diagnostic test for IgAN.