Preemptive plasmapheresis and recurrence of focal segmental glomerulosclerosis in pediatric renal transplantation

Gonzalez E, Ettenger R, Rianthavorn P, Tsai E, Malekzadeh M. Preemptive plasmapheresis and recurrence of focal segmental glomerulosclerosis in pediatric renal transplantation.
Pediatr Transplantation 2011: 15: 495–501. © 2011 John Wiley & Sons A/S. Abstract: FSGS has a high recurrence rate after renal transplantation. To examine the effects of the use of preemptive and post‐transplant PP on recurrence and graft outcome, we conducted a retrospective study on 34 pediatric patients (mean age 13 ± 5 yr) with biopsy‐proven pretransplant FSGS and who underwent a renal transplantation between 1996 and 2007. Recurrence was defined as a serum albumin level of <3.0 g/L in the presence of nephrotic‐range proteinuria (>40 mg/m²/h). Total response to PP therapy was defined as the resolution of the nephrotic‐range proteinuria and partial response as persistent proteinuria despite PP but not in the nephrotic range. Fifteen patients received a LD renal transplantation and 19 patients received a DD renal transplantation. Nineteen patients received CsA and 14 patients received tacrolimus. Nineteen patients (56%) had FSGS recurrence. There was no difference in the recurrence rate between patients receiving CsA vs. tacrolimus. Among the 15 LD patients, 13 received preemptive PP (1–10 sessions) and seven patients (47%) had subsequent FSGS recurrence. Among the 19 DD patients, four received preemptive PP and 12 (63%) had FSGS recurrence. The number of preemptive PP did not affect the recurrence rate. In a group of patients with a previous graft loss secondary to recurrence, the rate of recurrence was lower than expected (40%) and two of the three patients who did not recur had three or more sessions of preemptive PP. Of the 19 patients with recurrence, 17 were treated with PP therapy and 88% of the patients fully or partially responded. Only five patients had graft loss at three yr post‐transplant: two from FSGS recurrence and three from non‐compliance. These results suggest that preemptive PP does not decrease the rate of recurrence after transplantation but might be beneficial in treating high‐risk patients with documented recurrence. Patients with FSGS recurrence post‐transplant can achieve good graft survival with both LD and DD transplantation.     

Success with plasmapheresis treatment for recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients

FSGS recurs in approximately 30% of transplanted kidneys and may lead to graft loss. We retrospectively examined the efficacy of early and intensive PP without additional IS in pediatric kidney transplant patients with recurrent FSGS at our center. Seven of 24 patients (29%) had nephrotic proteinuria and histologic evidence of FSGS recurrence within 1–5 days post‐transplantation. PP was initiated early after transplantation and initially performed daily until sustained decline in proteinuria. PP frequency was then individually tapered according to proteinuria. Recurrent FSGS in all seven patients responded to a four‐ to 32‐wk course of PP. Two of seven patients had a second recurrence of FSGS, and both recurrences remitted after an additional 3–6 wk of PP. Median observation period was 4.5 yr (0.8–16.3 yr). Complete remission of recurrent FSGS has been sustained in all seven patients, and all patients have stable graft function with recent plasma creatinine <1.5 mg/dL in six of seven patients. Most recent urine protein/creatinine is 0.13–0.61 mg/mg in six of seven patients. One patient has heavy proteinuria secondary to chronic allograft nephropathy 16 yr post‐transplant. Intensive and prolonged PP, when initiated early in the post‐operative period, is effective in treating recurrent FSGS and preventing graft loss without the use of additional immunosuppressants.     

Ofatumumab in post‐transplantation recurrence of focal segmental glomerulosclerosis in a child

FSGS is a potentially devastating form of nephrotic syndrome. Treatment of SRNS can be difficult, especially post‐transplantation. The current therapy of post‐transplant SRNS includes plasmapheresis, ACE‐I, CNI, and monoclonal antibodies (rituximab). Patients who are refractory to these interventions have limited therapeutic alternatives. We present a case of a patient with SRNS secondary to FSGS. He did not respond to immunosuppressive medications prior to transplant, progressed to ESRD, and was started on chronic hemodialysis. He received a DDKT which was complicated by post‐transplant FSGS recurrence. A course of plasmapheresis, rituximab, and CNI were administered with some response. Ofatumumab was then given to the patient. As a result, the patient achieved partial remission. Ofatumumab may be a safe and effective option for post‐transplant recurrence of FSGS.     

Effects of the influenza vaccine on pediatric kidney transplant outcomes

The influenza vaccine is critical for preventing influenza‐related complications in transplant patients. Previous studies demonstrated de novo donor‐specific antibody formation and rejection following the influenza vaccination. This risk has not been adequately assessed in the pediatric population. We performed a single‐center retrospective analysis of 187 unique pediatric kidney transplant recipients, transplanted from January 1, 2006, to December 31, 2015, assessing for an association of the influenza vaccination with various transplant outcomes. The influenza vaccine was received by 125 of 187 patients within the first year post‐transplant. Using log‐rank tests and Kaplan‐Meier curves, vaccinated patients had a significantly lower risk of mortality (P = 0.048). There were no differences in death‐censored graft survival (P = 0.253), graft survival (P = 0.098), or rejection (P = 0.195) between vaccinated and unvaccinated groups. To address the problem of multiple exposures for a yearly vaccine, Cox proportional hazards regression was utilized with post‐transplant vaccination status considered as a time‐dependent covariate; analyses were performed using both a 360‐ and 180‐day vaccination period following any post‐transplant influenza vaccination. In this model, being vaccinated did not result in a significant difference in mortality (HR 0.90 [0.16, 5.15], P = 0.91), death‐censored graft survival (HR 0.70 [0.31, 1.58], P = 0.39), graft survival (HR 0.69 [0.32, 1.49], P = 0.34), or rejection (HR 0.67 [0.37, 1.19], P = 0.17). Eight patients developed de novo donor‐specific antibodies following the first post‐transplant influenza vaccination; three then developed biopsy‐proven rejection. These results suggest influenza vaccination is safe in pediatric kidney transplant recipients, and larger prospective studies are required to conclusively confirm our findings.     

Bortezomib in the treatment of antibody‐mediated rejection in pediatric kidney transplant recipients: A multicenter Midwest Pediatric Nephrology Consortium study

Antibody‐mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody‐mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy‐proven antibody‐mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients. Thirty‐three patients received bortezomib for antibody‐mediated rejection at nine pediatric kidney transplant centers. Ninety percent of patients received intravenous immunoglobulin, 78% received plasmapheresis, and 78% received rituximab. After a median follow‐up of 15 months, 65% of patients had a functioning graft. The estimated glomerular filtration rate improved or stabilized in 61% and 36% of patients at 3 and 12 months post‐bortezomib, respectively. The estimated glomerular filtration rate at diagnosis significantly predicted estimated glomerular filtration rate at 12 months after adjusting for chronic histologic changes (P .001). Fifty‐six percent of patients showed an at least 25% reduction in the mean fluorescence intensity of the immune‐dominant donor‐specific antibody, 1‐3 months after the first dose of bortezomib. Non‐life‐threatening side effects were documented in 21 of 33 patients. Pediatric kidney transplant recipients tolerated bortezomib without life‐threatening side effects. Bortezomib may stabilize estimated glomerular filtration rate for 3‐6 months in pediatric kidney transplant recipients with antibody‐mediated rejection.     

Pretransplantation combined therapy with plasmapheresis and rituximab in a second living-related kidney transplant pediatric recipient with a very high risk for focal segmental glomerulosclerosis recurrence

Chikamoto H, Hattori M, Kuroda N, Kajiho Y, Matsumura H, Fujii H, Ishizuka K, Hisano M, Akioka Y, Nozu K, Kaito H, Shimizu M. Pretransplantation combined therapy with plasmapheresis and rituximab in a second living‐related kidney transplant pediatric recipient with a very high risk for focal segmental glomerulosclerosis recurrence.
Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S. Abstract: Prophylactic PP can provide some protection against post‐transplantation recurrences of FSGS, but it cannot prevent recurrences in all cases. Therefore, new preventive therapies are needed. We report on a 7.9‐yr‐old girl treated with pretransplantation prophylactic combined therapy consisting of four sessions of PP and one dose of rituximab before a second living‐related KTX. The patient had a very high risk of post‐transplantation FSGS recurrence because this had occurred after the first KTX. During the 36 months since the second transplantation, she has had no evidence of proteinuria or significant infectious complications. Although our experience is too preliminary to draw any generalizable conclusions, pretransplantation combined therapy with PP and rituximab might be a possible option for the prevention of FSGS recurrence in very high‐risk recipients undergoing living‐donor KTXs.     

Lymphocele after pediatric kidney transplantation: Incidence and risk factors

Lymphocele is a well‐known postoperative complication after kidney transplantation. The aim of this study was to analyze time trend incidence, risk factors, and outcome of post‐transplant lymphocele in a large pediatric cohort. This is a retrospective single institution review of 241 pediatric kidney transplants performed from 2000 to 2013. Etiology of end‐stage renal disease, recipient age and gender, transplant year, BMI percentile for age, type of dialysis, living/non‐living related donor, acute rejection, and multiple transplantations were analyzed in association with lymphocele formation. Fourteen of 241 (5.81%) children developed a postoperative lymphocele. There has been a reduction in the incidence of lymphocele after 2006 (3.22% vs. 8.55%, p < 0.05). Significant risk factors for lymphocele were older age (≥11 yr), transplant before 2006, male gender, BMI percentile for age ≥95%, and multiple transplantations (p < 0.05). The one‐yr graft survival was significantly reduced in the group with lymphocele compared with control (81.2% vs. 92.51%, p < 0.04). This is the first pediatric report showing the following risk factors associated with post‐transplant lymphocele: age ≥11 yr, male gender, BMI for age ≥95%, and multiple transplantations. A lymphocele can contribute to graft loss in the first‐year post‐transplant.     

Impact of active antibody‐mediated rejection treatment on donor‐specific antibodies in pediatric kidney transplant recipients

AMR is a major cause of graft loss after kidney transplantation. We evaluated a retrospective cohort of 13 pediatric kidney transplant patients diagnosed with active AMR. All 13 patients were treated with plasmapheresis (PP), IVIg, and rituximab. Anti‐HLA DSAs were measured at the time of transplantation, AMR diagnosis, 30 days post‐rejection treatment, 90 days post‐rejection treatment, and 24 ± 12 months post‐AMR. A total of 68 DSAs were identified from 13 patients at the time of active AMR diagnosis. The primary objective of this study was to differentiate treatment response rates between class I and class II anti‐HLA DSA post‐AMR treatment. Overall, DSAs were significantly reduced at 30 days, and the reduction was sustained at 90 days post‐treatment, even for class II anti‐HLA and strongly positive DSAs. A significant difference between class I and class II anti‐HLA DSA was observed at 30 days; however, between class significance was lost at 90‐day follow‐up due to continued class II anti‐HLA DSA treatment response. Low DSA strength was predictive of treatment response. eGFR demonstrated significant improvement 90 days after AMR diagnosis compared to the initial value at the time of AMR, and the effect was sustained for 12 months. These results suggest that the AMR treatment is effective in pediatric kidney transplant recipients with an early diagnosis of active AMR across both class I and class II anti‐HLA DSAs.     

Eight‐year follow‐up in pediatric living donor kidney recipients receiving alemtuzumab induction

Recipient lymphocytes are crucial for direct and indirect pathways of allorecognition. We proposed that the administration of alemtuzumab several weeks pretransplantation could eradicate peripheral lymphatic cells and promote donor‐specific acceptance. This was a single‐center, retrospective review of 101 consecutive living donor kidney transplantations in pediatric patients (age 7 months—18 years), performed between September 2006 and April 2010. IS protocol included two 30 mg doses of alemtuzumab: The first was given 12‐29 days prior to transplantation, and the second at the time of transplantation. Maintenance IS was based on combination of low‐dose CNI and mycophenolate, with steroids tapered over the first 5 days post‐transplantation. Patients were followed for 7.8±1.3 years, and protocol biopsies were taken 1 month, 1, 3, and 5 years post‐transplant. The Kaplan‐Meier 8‐year patient and graft survival rates in the cyclosporine‐treated patients were 82.0±7.3% and 71.6±7.3, and in the tacrolimus‐treated patients were 97.2±5.4 and 83.8±6.0%. Biopsy‐proven acute rejection developed in 35% of cyclosporine‐treated patients and in 8% of tacrolimus‐treated patients. Alemtuzumab pretreatment prior to LRD kidney transplantation, followed by maintenance immunosuppression with tacrolimus and MMF, is associated with reasonable long‐term results in pediatric patients.     

Role of race in kidney transplant outcomes in children with focal segmental glomerulosclerosis

It is well established that racial differences exist in kidney transplant outcomes; however, there are no studies which focus on the role of race in transplant outcomes specifically in children diagnosed with FSGS. Associations between race and transplant outcomes in FSGS children were evaluated using the Organ Procurement and Transplantation Network database from 2000 to 2012. Recipients aged 2–21 years who received a kidney‐only transplant were included. Multivariate regression models were used to evaluate transplant outcomes by race. Five hundred and thirty‐six recipients (59.7% male, 15.6±3.9 years) were black and 1134 (55.7% male, 14.3±5.0 years) were non‐black. Graft survival was significantly shorter in the black group (4.2±3.1 vs 4.6±3.3 years, P=.005). Black race was associated with significantly higher risk of graft failure (HR 1.34, 95% CI=1.21–1.49, P<.0001), acute rejection (OR 1.66 95% CI=1.39–1.97, P<.0001), and delayed graft function (OR 1.51, 95% CI=1.33–1.72, P<.001) compared to non‐black race. There were no significant differences in mortality, prolonged hospitalization, or FSGS recurrence between groups. Race is a significant predictor for worse transplant outcomes in children with FSGS.     

Recurrence of idiopathic focal segmental glomerulosclerosis after kidney transplantation: Experience of a Korean tertiary center

FSGS is the second most common cause of idiopathic NS in children. It often progresses to ESRD and commonly recurs after KT. To investigate the risk factors and the prognosis of recurrence in pediatric idiopathic FSGS in Korea, retrospective review of 43 KT in 38 children with idiopathic FSGS of last two decades was conducted. The patients presented at the median age of 5.1 yr (range 1.1–13.8 yr) and received KT 5.7 yr later (range 1.3–17.6 yr). FSGS recurred in 20 allografts immediately after transplantation, only in those who presented with NS but not in those who presented with AUA. The risk factors for recurrence were age of onset >5 yr and progression to ESRD within six yr but not sooner than 18 months. CR was achieved in 13 patients with FSGS recurrence and sustained in nine without subsequent relapse over a median of six and a half yr (0.6–20.7 yr). Pediatric idiopathic FSGS presenting with NS recurred in more than half of patients after transplantation. Interestingly, more rapid progression within less than 18 months did not predict recurrence. To identify high‐risk patients of recurrence, an international cooperative study would be necessary.     

Non‐invasive staging of chronic kidney allograft damage using urine metabolomic profiling

Chronic kidney allograft damage is characterized by IFTA and GS. We sought to identify urinary metabolite signatures associated with severity of IFTA and GS in pediatric kidney transplant recipients. Urine samples (n = 396) from 60 pediatric transplant recipients were obtained at the time of kidney biopsy and assayed for 133 metabolites by mass spectrometry. Metabolite profiles were quantified via PLS‐DA. We used mixed‐effects regression to identify laboratory and clinical predictors of histopathology. Urine samples (n = 174) without rejection or AKI were divided into training/validation sets (75:25%). Metabolite classifiers trained on IFTA severity and %GS showed strong statistical correlation (r = .73, P < .001 and r = .72; P < .001, respectively) and remained significant on the validation sets. Regression analysis identified additional clinical features that improved prediction: months post‐transplant (GS, IFTA); and proteinuria, GFR, and age (GS only). Addition of clinical variables improved performance of the %GS classifier (AUC = 0.9; 95% CI = 0.85‐0.96) but not for IFTA (AUC = 0.82; 95% CI = 0.71‐0.92). Despite the presence of potentially confounding phenotypes, these findings were further validated in samples withheld for rejection or AKI. We identify urine metabolite classifiers for IFTA and GS, which may prove useful for non‐invasive assessment of histopathological damage.     

The effect of transfer to adult transplant care on kidney function and immunosuppressant drug level variability in pediatric kidney transplant recipients

Adolescent age at time of transplant has been recognized as a risk factor for renal allograft loss. Increased risk for graft failure may persist from adolescence to young adulthood. Transfer of care is hypothesized as a risk factor for non‐adherence and graft loss. We explored whether kidney allograft function declined at an accelerated rate after transfer of care to adult transplant centers and whether coefficient of variation of tacrolimus (CV TAC) trough levels predicted allograft loss. Single‐center, retrospective chart review was performed for pediatric kidney transplant recipients who received transplants between 1999 and 2011. Change in eGFR pre‐ and post‐transfer was performed via a linear mixed‐effects model. CV TAC was calculated in transplant recipients with TAC data pre‐ and post‐transfer. t test was performed to determine the difference between means of CV TAC in subjects with and without allograft loss following transfer of care. Of the 138 subjects who transferred to adult care, 47 subjects with data pre‐ and post‐transfer demonstrated a decrease in the rate of eGFR decline post‐transfer from 8.0 mL/min/1.73 m² per year to 2.1 mL/min/1.73 m² per year, an ~80% decrease in eGFR decline post‐transfer (P = 0.01). Twenty‐four subjects had CV TAC data pre‐ and post‐transfer of care. Pretransfer CV TAC for subjects with allograft loss post‐transfer was significantly higher than in subjects without allograft loss (49% vs 26%, P < 0.05). Transfer of care was not independently associated with acceleration in eGFR decline. CV TAC may aid in identifying patients at risk for allograft loss post‐transfer.     

Pretransplant trends in α‐fetoprotein levels as a predictor of recurrence after living donor liver transplantation for unresectable hepatoblastoma: A single‐institution experience

LT is a practical therapeutic alternative for unresectable hepatoblastoma; however, deciding when to perform LT is difficult. The aim of this study was to optimize the timing of LT for hepatoblastoma using pretransplant trends in AFP levels. Trends in pretransplant AFP levels and their influence on post‐transplant outcomes were retrospectively evaluated. All patients who underwent living donor LT for hepatoblastoma in our institution since 2002 were included. Variables analyzed included history of prior tumor resection, pretransplant AFP responses to chemotherapy, metastatic disease at diagnosis, and post‐transplant chemotherapy. Eight patients (seven boys and one girl; median age, 35 months; range, 15 months‐12 years) were transplanted. The overall post‐transplant recurrence‐free survival rate was 62.5% (5/8) with a mean follow‐up of 77 months. Patients with post‐transplant recurrence showed a 0.573 log increase in AFP levels after the last chemotherapy session before LT. This was significantly higher than the 0.279 log decrease observed in patients without post‐transplant recurrence (P = .024). Because the AFP response cannot be accurately predicted before each cycle of chemotherapy, it may be appropriate to perform LT when AFP levels do not decrease after the last cycle and before they are found to be elevated again.     

Alemtuzumab induction in pediatric kidney transplantation

Recipient parenchymal lymphatic cells are crucial for direct and indirect pathways of allorecognition. We proposed that alemtuzumab, being infused several weeks pretransplant could eradicate peripheral lymphatic cells and promote donor‐specific tolerance. We present here a single center, retrospective review of 101 consecutive living‐donor kidney transplantations to pediatric patients aged from seven month to 18 yr, performed between September 2006 and April 2010. Immunosupression protocol included two 30 mg doses of alemtuzumab: first given 12–29 d prior to transplantation and second at the time of transplantation. Maintenance immunosupression was based on combination of low dose and wide range CNI and mycophenolate. Patients were followed for 3.8 ± 1.4 yr and protocol biopsies were taken one month, one, and three yr post transplant. The Kaplan–Meier graft and patient survival was 96% and 97% for one yr, 89% and 93% for three yr. Biopsy proven acute rejection developed in 26% patients at one yr and in 35% at two yr, no rejections occurred beyond two yr. We conclude that alemtuzumab pretreatment prior to living related donor kidney transplantation allows to reach satisfactory middle‐term results in pediatric patients with wide range and low CNI concentrations.     

Demographics and response to therapeutic plasma exchange in pediatric renal transplantation for focal glomerulosclerosis: a single center experience

Abstract:  Recurrence of FSGS following renal transplantation in pediatric patients is reported as 20–57%. Records of 37 pediatric patients transplanted for FSGS between 1990 and 2005 at a single center were reviewed. Recurrence of disease was assessed by nephrotic range proteinuria and/or FSGS on biopsy. Response to TPE was defined as urine protein to creatinine ratio <0.2. Forty-nine percent of patients were African American, 38% were Caucasian. Fifty-four percent received kidneys from deceased donors and 46% from live donors. Seven patients received preemptive TPE prior to transplantation. Two of these seven patients recurred in the transplanted kidney (28%). Recurrent FSGS occurred in 16 of 37 patients (46%), all of whom received TPE. Recurrence occurred within one month in 12 of 37 patients (32%); eight remitted with TPE (67%). Four of 12 patients failed to respond to TPE. Four of 37 patients (14%) recurred more than one month after transplantation and underwent TPE; three-fourths of patients remitted (75%). Twenty-one of 37 patients (54%) did not recur. One and five yr graft survivals were 84% and 67%, respectively. Median graft survival was 6.7 yr (5.2–10.3). Despite recurrence, FSGS patients can achieve sustained graft function.     

Use of public health service increased risk kidneys in pediatric renal transplant recipients

With the opioid epidemic and expansion of “IR” classification, 25% of deceased donors are categorized PHS‐IR. Studies have assessed utilization of PHS‐IR organs among adults, but little is known about pediatric recipients. This retrospective cohort study from 2004‐2016 (IR period) aimed to: (a) assess IR kidney utilization patterns between adults and children; (b) identify recipient factors associated with transplant from IR donors among pediatric kidney recipients; and (c) determine geography's role in IR kidney utilization for children. The proportion of pediatric recipients receiving IR kidneys was significantly lower than adults (P < 0.001), even when stratified by donor mechanism of death (non‐overdose/overdose) and era. In mixed effects models accounting for clustering within centers and regions, older recipient age, later era (post‐PHS‐IR expansion), and blood type were associated with significantly higher odds of receiving an IR kidney (17 years era 5: OR 5.16 [CI 2.05‐13.1] P < 0.001; 18‐21 years era 5: OR 2.72 [CI 1.05‐7.06] P = 0.04; blood type O: OR 1.32 [CI 1.06‐1.64] P = 0.013). The median odds ratio for center within region was 1.77 indicating that when comparing two patients in a region, the odds of receiving an IR kidney were 77% higher for a patient from a center with higher likelihood of receiving an IR kidney. Utilization of PHS‐IR kidneys is significantly lower among pediatric recipients versus adult counterparts. More work is needed to understand the reasons for these differences in children in order to continue their access to this life‐prolonging therapy.     

The impact of recipient BKV shedding before transplant on BKV viruria,DNAemia, and nephropathy post‐transplant: A prospective study

We previously demonstrated that detectable BKV replication in donor urine pretransplant was significantly associated with post‐transplant recipient BKV viremia. In this 4‐year prospective study, we assessed whether recipient BKV replication pretransplant was associated with post‐transplant viremia/BKV nephropathy. We studied 220 primary adult and pediatric organ transplant recipients for 490 person‐years and 2100 clinical visits. BKV viruria was detectable in 28 (16%), 26 adults and two children; and viremia in none pretransplant. Post‐transplant viruria occurred in all recipients with pretransplant BKV viruria, significantly more than in recipients without pretransplant viruria on univariate (P<.005) and multivariate analysis including type of organ transplanted and immunosuppression type (P .008). Time to post‐transplant viruria was significantly shorter in recipients with pretransplant viruria (P .01). By univariate and multivariate analysis, BKV viruria in recipients pretransplant did not impact post‐transplant BKV viremia (P=.97 and .97, respectively) even when stratified by type of organ transplant (kidney P=.6; liver P=.5). The peak serum and urine BKV PCR post‐transplant were not significantly different in patients with pretransplant BKV viruria and no one developed BK nephropathy. In conclusion, recipient BKV viruria prior to transplant predicts post‐transplant viruria but not viremia or BKV nephropathy.     

Long‐term surveillance biopsy: Is it necessary after pediatric heart transplant?

Due to limited and conflicting data in pediatric patients, long‐term routine surveillance endomyocardial biopsy (RSB) in pediatric heart transplant (HT) remains controversial. We sought to characterize the rate of positive RSB and determine factors associated with RSB‐detected rejection. Records of patients transplanted at a single institution from 1995 to 2015 with >2 year of post‐HT biopsy data were reviewed for RSB‐detected rejections occurring >2 year post‐HT. We illustrated the trajectory of significant rejections (ISHLT Grade ≥3A/2R) among total RSB performed over time and used multivariable logistic regression to model the association between time and risk of rejection. We estimated Kaplan‐Meier freedom from rejection rates by patient characteristics and used the log‐rank test to assess differences in rejection probabilities. We identified the best‐fitting Cox proportional hazards regression model. In 140 patients, 86% did not have any episodes of significant RSB‐detected rejection >2 year post‐HT. The overall empirical rate of RSB‐detected rejection >2 year post‐HT was 2.9/100 patient‐years. The percentage of rejection among 815 RSB was 2.6% and remained stable over time. Years since transplant remained unassociated with rejection risk after adjusting for patient characteristics (OR = 0.98; 95% CI 0.78‐1.23; P = 0.86). Older age at HT was the only factor that remained significantly associated with risk of RSB‐detected rejection under multivariable Cox analysis (P = 0.008). Most pediatric patients did not have RSB‐detected rejection beyond 2 years post‐HT, and the majority of those who did were older at time of HT. Indiscriminate long‐term RSB in pediatric heart transplant should be reconsidered given the low rate of detected rejection.     

Nephrotic syndrome after conversion to alternate day steroids in two children with a history of recurrent FSGS

FSGS is a common indication for kidney transplantation in children. However, transplantation is often complicated by recurrence of FSGS in the transplanted kidney, resulting in nephrotic syndrome and an increased risk of graft loss. Acute treatment strategies for recurrent FSGS include plasmapheresis and increased immunosuppressive therapy. There is little information on the long-term management of immunosuppression in these patients. We describe two children who were successfully treated with plasmapheresis for recurrent FSGS that occurred immediately post-transplant. Nephrotic syndrome reappeared years later when the patients were converted from daily to alternate day prednisone. In children with a history of FSGS, caution is necessary when altering the dosing schedule of prednisone.