Should children receive a kidney transplant before 2 years of age?

BACKGROUND: The optimal age of kidney transplantation for infants and toddlers with kidney failure is unclear. We aimed to evaluate the patient survival associated with kidney transplantation before 2 years of age versus remaining on the waitlist until ≥2 years. METHOD: We used the Scientific Registry of Transplant Recipients to identify all children added to the deceased-donor waitlist before 2 years of age between 1/1/2000 and 4/30/2020. For each case aged <2 years at transplant, we created a control group comprising all candidates on the waitlist on the case's transplant date. Patient survival was evaluated using sequential Cox regression. Dialysis-free time was defined as graft survival time for cases and the sum of dialysis-free time on the waitlist and graft survival time for controls. RESULTS: We observed similar patient survival for posttransplant periods 0-3 and 4-12 months but higher survival for period >12 months for <2-year decreased-donor recipients (aHR: 0.32; 95% CI: 0.13-0.78; p = .01) compared with controls. Similarly, patient survival was higher for <2-year living-donor recipients for posttransplant period >12 months (aHR: 0.21; 95% CI: 0.06-0.73; p = .01). The 5-year dialysis-free survival was higher for <2-year deceased- (difference: 0.59 years; 95% CI: 0.23-0.93) and living-donor (difference: 1.84 years; 95% CI: 1.31-2.25) recipients. CONCLUSION: Kidney transplantation in children <2 years of age is associated with improved patient survival and reduced dialysis exposure compared with remaining on the waitlist until ≥2 years.

More than four decades of graft survival in pediatric kidney transplant recipients.

BACKGROUND: Early in the history of kidney transplantation, short-term graft survival was low. Yet some have had excellent long-term survival. Herein, we describe characteristics of pediatric recipients with > 40 years of graft survival currently alive with a functioning first graft. METHODS: We reviewed all pediatric (age < 18 years) kidney transplants performed at the University of Minnesota between January 1, 1970, and December 31, 1979 (n = 148), to identify all recipients currently alive with a functioning first graft. Data are presented as medians with interquartile ranges (IQR) and proportions. RESULTS: We identified 10 recipients with > 40-year graft survival (median follow-up: 45.0 years (IQR: 43.1, 48.1)). The median age at transplant was 13.8 years (IQR: 5.1, 16.3). All recipients were white; half were male. Of the 10, 4 had glomerulonephritis, 2 had congenital anomalies of the kidney and the urinary tract, 2 had congenital nephrotic syndrome, 1 had Alport syndrome, and 1 had cystic kidney disease as kidney failure cause. Nine patients received a living-related donor transplant, and 1 patient received a deceased-donor transplant. The median estimated glomerular filtration rate at 20 years post-transplant was 79.9 (IQR: 72.3, 98.4); at 30 years, 67.7 (IQR: 63.2, 91.8); and at 40 years, 80.3 ml/min/1.73 m2 (IQR: 73.7, 86.0). None developed rejection, 5 developed hypertension, 2 developed dyslipidemia, 1 developed diabetes, and 7 patients developed malignancy (4 skin cancer, 2 breast cancer, and 1 post-transplant lymphoproliferative disease). CONCLUSION: Pediatric kidney transplant recipients may achieve > 4 decades of graft survival. Cancer is a common complication warranting vigilant screening.

The John S. Najarian symposium: The past, present, and future of surgery and transplantation, May 20, 2022, Minneapolis, MN.

Dr John S Najarian (1927-2020), chairman of the Department of Surgery at the University of Minnesota from 1967 to 1993, was a pioneer in surgery, clinical immunology and transplantation. A Covid-delayed Festschrift was held in his honor on May 20, 2022. The speakers reflected on his myriad contributions to surgery, transplantation, and resident/fellow training, as well as current areas of ongoing research to improve clinical outcomes. Of note, Dr Najarian was a founder of the journal Clinical Transplantation.

Steroid avoidance/withdrawal and maintenance immunosuppression in pediatric kidney transplantation.

BACKGROUND: Corticosteroids have been an integral part of maintenance immunosuppression for pediatric kidney transplantation. However, prolonged steroid therapy is associated with significant toxicities resulting in several SW/avoidance strategies in recent years. METHOD/OBJECTIVE: This comprehensive review aims to discuss steroid-related toxicities and the safety, efficacy, and benefit of steroid avoidance/withdrawal immunosuppression in pediatric kidney transplant recipients. RESULTS: Initial studies of SW/avoidance conducted in the setting of CSA and AZA showed an increased incidence of AR but no increase in graft loss or mortality with SW/avoidance maintenance immunosuppression. Studies performed under modern immunosuppression (induction therapy, Tac, and MMF) show no significant increase in AR or graft loss with SW/avoidance immunosuppression. Furthermore, SW/avoidance immunosuppression is associated with significant improvement in growth, BMI, BP control, and lipid profile in pediatric kidney transplant recipients. Despite these data, SW/avoidance remains controversial, and only 40% of pediatric kidney transplant recipients in the United States are currently on SW/avoidance maintenance immunosuppression. CONCLUSION: SW/avoidance maintenance immunosuppression is safe and associated with fewer side effects compared with steroid-inclusive maintenance immunosuppression in pediatric kidney transplant recipients.

Racial disparities and trends in kidney transplant outcomes in patients with Alport syndrome.

BACKGROUND: Registry data from Europe has shown an increase in age at end-stage kidney disease for patients with Alport syndrome in recent years. Whether a similar delay in transplant age has occurred in the United States for Alport patients across all racial/ethnic groups is unknown. MATERIALS AND METHODS: We used data from the Scientific Registry of Transplant Recipients (SRTR) to identify 3,794 Alport patients transplanted between 12/1987 and 12/2017. We divided the study period into five equal eras to assess temporal trends in age at transplant, graft survival, and patient survival across racial groups using linear regression and Cox regression models. RESULTS: The mean age at transplant for Blacks (28.3 years; difference (Black vs. White): 8.9 years; p < 0.0001) and Hispanics (28.7 years; difference (Hispanics vs. White): 8.7 years; p < 0.0001) was significantly younger compared with that of Whites. We observed a temporal increase in age at transplant for Whites but not for Blacks and Hispanics (p-value for interaction: 0.001). Black recipients were at a higher risk of graft loss (aHR: 1.78; 95% CI: 1.47, 2.15; p < 0.0001) and death (aHR: 1.73; 95% CI: 1.11, 2.69; p = 0.02) compared with White recipients. We observed significant improvements in graft survival with each successive era (p < 0.01). Temporal trends in graft survival (interaction p = 0.46) were not modified by race. CONCLUSION: We found racial disparities in age at transplant and long-term graft survival for patients with Alport syndrome in the United States. The age at transplant increased over time for Whites but not Black and Hispanic patients.

Use of expanded-criteria donors and > 85 KDPI kidneys for pediatric kidney transplantation in the United States.

Pediatric kidney transplant outcomes associated with expanded-criteria donors (ECD) and high Kidney Donor Profile Index (KDPI) kidneys are unknown. We reviewed the Scientific Registry of Transplant Recipients data from 1987-2017 to identify 96 ECD and 92 > 85 KDPI kidney recipients (<18 years). Using propensity scores, we created comparison groups of 375 non-ECD and 357 ≤ 85 KDPI recipients for comparisons with ECD and > 85 KDPI transplants, respectively. We used Cox regression for patient/graft survival and sequential Cox approach for survival benefit of ECD and > 85 KDPI transplantationvs remaining on the waitlist. After adjustment, ECD recipients were at significantly increased risk of graft failure (adjusted hazard ratio [aHR] = 1.6; P = .001) but not of mortality (aHR = 1.33; P = .15) compared with non-ECD recipients. We observed no survival benefit of ECD transplants vs remaining on the waitlist (aHR = 1.05; P = .83). We found no significant difference in graft failure (aHR = 1.27; P = .12) and mortality (aHR = 1.41; P = .13) risks between > 85 KDPI and ≤ 85 KDPI recipients. However, > 85 KDPI transplants were associated with a survival benefit vs remaining on the waitlist (aHR = 0.41; P = .01). ECD transplantation in children is associated with a high graft loss risk and no survival benefit, whereas > 85 KDPI transplantation is associated with a survival benefit for children vs remaining on the waitlist.

Re-hospitalization after pediatric kidney transplant: A single-center study.

BACKGROUND: Little data exist on re-hospitalization rates in pediatric kidney recipients (KTx) particularly with the evolution of transplant immunosuppression. METHODS: In a single-center, retrospective study of pediatric KTx between 2006 and 2016, we assessed re-hospitalization after KTx admission, stratified by whether the re-admit was early (<30 days post-KTx discharge) or late (>30 days), and compared two different immunosuppression eras (one with and one without steroids). RESULTS: Of 197 KTx, 156 (79%) patients were re-hospitalized in 1st year, 85 (56%) within 30 days of discharge (total 490 1st year re-hospitalizations). Younger age was associated with early and late re-hospitalizations. African American race was associated with early re-hospitalizations. Of the 123 and 74 discharged on steroid-avoidance (maintenance immunosuppression included MMF in 95%; FK in 50%; CSA in 50%) and steroid-inclusive (AZA in 66%; MMF in 34%; FK in 30%; CSA in 70%), re-hospitalization rates, timing post-transplant, length, and number were not significantly different (P .38; .1; .56; .11). Admission diagnoses analysis demonstrated that steroid-avoidance recipients had anemia/leucopenia/thrombocytopenia, significantly more often, as one of their admission diagnoses (16% vs 4%; P < .001) and had a rejection diagnosis significantly less often (6% vs 18%; P < .001). Infection diagnoses were not statistically different between groups. Re-hospitalization, early or late, did not predict worse graft/ patient survival but predicted further hospitalizations. CONCLUSIONS: Re-hospitalization is common after pediatric transplant discharge and predicts further hospitalization regardless of discharge on or off steroids.

Kidney transplant outcomes associated with the use of increased risk donors in children.

Increased risk donors (IRDs) may inadvertently transmit blood-borne viruses to organ recipients through transplant. Rates of IRD kidney transplants in children and the associated outcomes are unknown. We used the Scientific Registry of Transplant Recipients to identify pediatric deceased donor kidney transplants that were performed in the United States between January 1, 2005 and December 31, 2015. We used the Cox regression analysis to compare patient and graft survival between IRD and non-IRD recipients, and a sequential Cox approach to evaluate survival benefit after IRD transplants compared with remaining on the waitlist and never accepting an IRD kidney. We studied 328 recipients with and 4850 without IRD transplants. The annual IRD transplant rates ranged from 3.4% to 13.2%. IRDs were more likely to be male (P = .04), black (P < .001), and die from head trauma (P = .006). IRD recipients had higher mean cPRA (0.085 vs 0.065, P = .02). After multivariate adjustment, patient survival after IRD transplants was significantly higher compared with remaining on the waitlist (adjusted hazard ratio [aHR]: 0.48, 95% CI: 0.26-0.88, P = .018); however, patient (aHR: 0.93, 95% CI: 0.54-1.59, P = .79) and graft survival (aHR: 0.89, 95% CI: 0.70-1.13, P = .32) were similar between IRD and non-IRD recipients. We recommend that IRDs be considered for transplant in children.

Trends in kidney transplant outcomes in children and young adults with cystinosis.

Temporal changes in kidney transplant outcomes for cystinosis are unknown. We used the SRTR to identify all kidney transplants performed for cystinosis in patients younger than 31 years between 1987 and 2017. We divided time into three equal eras (1987-1997, 1998-2007, and 2008-2017) to assess changes in outcomes using Cox proportional and linear regression models. We examined 441 transplants in 362 patients. Age at ESRD progressively increased (12.1 vs 13.3 vs 13.4; P = .046). Eras 2 and 3 had lower risk of acute rejection (aHR 2 vs 1:0.45; P < .001) (aHR 3 vs 1:0.26; P < .001) and higher 5-year mean GFR (difference 2 vs 1:9.2 mL/min/1.73 m2 ; P = .005) (difference 3 vs 1:12.9 mL/min/1.73 m2 ; P = .002) compared with era 1. Five-year graft survival was similar across eras, but 5-year patient survival was higher for era 2 (aHR: 0.25; P = .01). Seventy-nine patients underwent retransplantation. Five-year patient (94.2% vs 92.5%; P = .57) and graft survival (79.1% vs 74.1%; P = .52) were similar between primary and subsequent transplants. Age at ESRD, acute rejection, GFR at 5 years, and patient survival improved over time. Kidney retransplantation is associated with excellent outcomes in children and young adults with cystinosis.

Outcomes of kidney transplants in pediatric patients with the vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities association.

In this single-center retrospective study, we analyzed kidney transplant outcomes in nine pediatric patients with VACTERL [vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities] association-making this the largest study of its kind. Of 743 pediatric kidney transplant recipients at our center (1980-2017), nine had documented diagnoses of VACTERL association. All nine had congenital anorectal malformations and renal anomalies, five had vertebral defects, and one had a bifid thumb and tracheoesophageal fistula. Renal anomalies included dysplasia (n = 6), aplasia (n = 3), and horseshoe kidney (n = 2). Congenital lower urinary tract anomalies included neurogenic bladder (n = 6), obstructive uropathy (n = 4), anovesicular fistula (n = 1), rectourethral fistula (n = 1), and posterior urethral valves (n = 1). Age at transplant ranged from 1.2 to 15 years (mean, 7.3; standard deviation [SD], 5.5); 6 (67%) were male, and 3 (33%) were female; 6 (67%) had a living related donor, and 3 (33%) had a deceased donor. The overall graft survival rate was 78% (range, 1.5 to 25.2 years; mean, 10.5; SD, 8.9). One month post-transplant, one recipient died with a functioning graft. At 3.7 years post-transplant, one graft failed because of recurrent pyelonephritis. Post-transplant urologic complications included pyelonephritis (n = 6), vesicoureteral reflux (n = 5), and graft hydronephrosis (n = 4). We conclude that pediatric patients with VACTERL association can be safely transplanted-careful patient selection with vigilance and intervention for pre- and post-transplant urologic complications is essential.

Incidence and magnitude of post-transplant cardiovascular disease after pediatric kidney transplantation: Risk factor analysis of 1058 pediatric kidney transplants at the university of Minnesota.

BACKGROUND: KT recipients have increased the risk of CVD. The incidence of post-transplant CVEs among pediatric recipients has not been well-characterized. PATIENTS AND METHODS: Between 1963 and 2015, 884 pediatric (age: 0-17 years old) recipients received 1058 KTs at our institution. The cumulative incidence of CVEs was analyzed. Statistical models were used to estimate risk factors for developing post-transplant CVEs. RESULTS: Overall median patient survival was 33 years (IQR: 18.7-47). A total of 362 CVEs occurred in 161 (18.3%) patients at a median age of 20.5 years. Arrhythmias (18%) were most common. Cumulative risk of post-transplant CVEs was 9% at 10 years, 17% at 20 years, 25% at 30 years, and 36% at 40 years. Development of post-transplant CVEs was associated with increased mortality (HR 2.25 [95% CI 1.61-3.14]); of those who developed a CVE and died, 22/51 (43.1%) died of CVD. Multivariable risk factors for post-transplant CVEs included a history of pretransplant CVD (aHR 1.92 [1.18-3.13] and graft failure (4.57 [3.13-6.67]). DISCUSSION: A pretransplant history of CVD and a failed graft are significant risk factors for the development of post-transplant CVE. CVD increases the risk of post-transplant death or graft loss.

Hemoglobin of 12 g/dl and above is not associated with increased cardiovascular morbidity in children on hemodialysis.

In adults on chronic hemodialysis, achieving a hemoglobin concentration of 12g/dl and above with erythropoiesis stimulating agents leads to increased cardiovascular events and mortality, but this may not be true in children. Therefore, we conducted a retrospective cohort study of pediatric patients (under 18) from the Centers for Medicare and Medicaid Services End Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) project (2000 to 2008) merged with the United States Renal Data System. Hemoglobin was determined from the Clinical Performance Measures data, and beginning annually on January 1st of the next year, patients were followed for up to 1 year. We determined the outcomes (mortality, hospitalization, and cardiovascular events) during follow-up by hemoglobin group at baseline. Models were adjusted for demographic and clinical characteristics of 1569 children studied. The hemoglobin 12 g/dl and above group was older, had fewer years of ESRD, and was more often transplanted. Inpatient and outpatient visits for congestive heart failure, cardiomyopathy, and valvular heart disease were most common in the hemoglobin under 10g/dl group and the frequency of these diagnoses decreased with increasing hemoglobin. The hazard ratio of all-cause mortality (0.33, 95% confidence interval 0.14-0.81) and the adjusted relative rate of all-cause hospitalizations (0.81, 0.74-0.89) were significantly lower in the hemoglobin 12 g/dl and above group. Cardiovascular hospitalizations were significantly higher in the hemoglobin under 10g/dl group (1.31, 1.05-1.64). Thus, in children on hemodialysis, hemoglobin 12g/dl and above is not associated with increased cardiovascular visits, mortality, or all-cause and cardiovascular-related hospitalizations.

Infection rates in tacrolimus versus cyclosporine-treated pediatric kidney transplant recipients on a rapid discontinuation of prednisone protocol: 1-year analysis.

AR is lower in pKTx recipients on Tac vs CsA. Data comparing infection outcomes for children treated with these agents are limited. We retrospectively studied infection outcomes in 96 pKTx recipients on a RDP. PS, DCGS, AR, and infection-free survival were assessed using Kaplan-Meier/log-rank tests and proportional hazards models. There were no differences in 1-year PS, DCGS, or AR between Tac and CsA recipients. After adjusting for AR, the hazard of CMV viremia was 4.0 times higher (95%CI: 1.04, 15.5; P = .044) and that of BK viremia was 3.8 times higher (95%CI: 1.5, 10.2; P = .007) in Tac recipients. The incidence of EBV viremia was similar between the groups (P = .56). PostTx lymphoproliferative disease was only observed in Tac recipients (3%). There was no difference in the incidence of pneumonia, urinary tract, or Clostridium difficile infections between Tac and CsA recipients. Among KTx recipients on RDP, the hazards of CMV and BK viremia within 1 year post-KTx were significantly higher in Tac recipients compared to CsA. Regular assessment for infections and lower Tac trough levels may be warranted in Tac recipients.

Acute Kidney Injury and the Risk of Mortality in Children Undergoing Hematopoietic Stem Cell Transplantation.

Acute kidney injury (AKI) is a well-documented complication of pediatric hematopoietic stem cell transplantation (HSCT). Dialysis after HSCT is associated with a lower overall survival (OS); however, the association between less severe AKI and OS is unclear. We retrospectively studied 205 consecutive pediatric HSCT patients to determine the incidence and impact of all stages of AKI on OS in pediatric HSCT recipients. We used the peak pRIFLE grade during the first 100 days to classify AKI (ie, R = risk, I = injury, F = failure, L = loss of function, E = end-stage renal disease) and used the modified Schwartz formula to estimate glomerular filtration rate. AKI was observed in 173 of 205 patients (84%). The 1-year OS rate decreased significantly with an increasing severity of pRIFLE grades (P < .01). There was no difference in the OS between patients without AKI and the R/I group. Regardless of the dialysis status, stages F/L/E had significantly lower rates of OS compared with patients without AKI or R/I (P < .01). There was no difference in OS among patients with dialysis and F/L/E without dialysis (P = .65). Stages F/L/E predicted mortality independent of acute graft-versus-host disease, gender, and malignancy. The OS of children after HSCT decreases significantly with an increasing severity of AKI within the first 100 days post-transplant. Although our data did not show an increased risk of mortality with stages R/I, stages F/L/E predicted mortality regardless of dialysis. Prevention and minimization of AKI may improve survival after pediatric HSCT.

Post-transplant blood transfusions and pediatric renal allograft outcomes.

The association of blood transfusions with GS after pediatric KTx is unclear. We retrospectively analyzed blood transfusions post-KTx and subsequent outcomes. Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our center. Recipient demographics, outcomes and transfusion data were collected. Cox regression with post-KTx blood transfusion as a time-dependent covariate was performed to model the impact of blood transfusion on outcomes. Of the 208 (44%) that were transfused, 39% had transfusion <1 month post-KTx; 48% >12 months. Transfused and non-transfused recipients were not significantly different. In univariate and multivariate analyses, there was no difference between transfused and non-transfused recipient patient survival, antibody-mediated and ACR, and DSA free survival. Transfusions <1 month post-KTx did not impact DCGS (P=NS). Patients transfused >12 months post-KTx had significantly lower 12 month eGFR (compared to non-transfused) and worse subsequent DCGS. Post-KTx blood transfusions have increased in pediatric KTx over time but have no negative association with rejection or DSA production. DCGS is unaffected by transfusion within first month. Transfusions after the first year occur in patients with more advanced chronic kidney disease and are associated with significantly worse DCGS.

One-year mortality rates in US children with end-stage renal disease.

BACKGROUND/AIMS: Few published data describe survival rates for pediatric end-stage renal disease (ESRD) patients. We aimed to describe one-year mortality rates for US pediatric ESRD patients over a 15-year period. METHODS: In this retrospective cohort study, we used the US Renal Data System database to identify period-prevalent cohorts of patients aged younger than 19 for each year during the period 1995-2010. Yearly cohorts averaged approximately 1,200 maintenance dialysis patients (60% hemodialysis, 40% peritoneal dialysis) and 1,100 transplant recipients. Patients were followed for up to 1 year and censored at change in modality, loss to follow-up, or death. We calculated the unadjusted model-based mortality rates per time at risk, within each cohort year, by treatment modality (hemodialysis, peritoneal dialysis, transplant) and patient characteristics; percentage of deaths by cause; and overall adjusted odds of mortality by characteristics and modality. RESULTS: Approximately 50% of patients were in the age group 15-18, 55% were male, and 45% were female. The most common causes of ESRD were congenital/reflux/obstructive causes (55%) and glomerulonephritis (30%). One-year mortality rates showed evidence of a decrease in the number of peritoneal dialysis patients (6.03 per 100 patient-years, 1995; 2.43, 2010; p = 0.0263). Mortality rates for transplant recipients (average 0.68 per 100 patient-years) were consistently lower than the rates for all dialysis patients (average 4.36 per 100 patient-years). CONCLUSIONS: One-year mortality rates differ by treatment modality in pediatric ESRD patients.

Familial LCAT deficiency in a child with nephrotic syndrome.

BACKGROUND: Lecitin cholesterol acyltransferase (LCAT) deficiency comprises a group of rare disorders related to HDL metabolism. These disorders are characterized by ophthalmologic, hematologic, and renal findings. Case diagnosis/treatment: A 15-year-old female who presented with nephrotic syndrome and hypertension was diagnosed with LCAT deficiency by renal biopsy and LCAT enzyme activity. Her edema and hypertension improved with diuretic and antihypertensive therapies. Continued care of her LCAT deficiency is ongoing. CONCLUSION: Although rare, LCAT deficiency should be in the differential diagnosis of nephrotic syndrome in the setting of abnormally low HDL cholesterol levels.

Antihypertensive pharmacotherapy and long-term outcomes in pediatric kidney transplantation.

Hypertension (HTN) is common in pediatric recipients following kidney transplantation (KT). We retrospectively assessed the impact of HTN on long-term (>10-yr) outcomes in pediatric KT recipients (aged < 18 yr) at our center. Two hundred and ninety-three pediatric KT recipients (83% living donor [LD]) with graft survival (GS) for ≥5 yr were studied. HTN was defined by antihypertensive medication use at five yr post-KT. One hundred and sixty (55%) recipients did not have HTN, and 133 (45%) had HTN at five yr post-KT. There were no differences in actuarial patient survival between cohorts. Actuarial GS at 15 and 20 yr was 68% and 53% for recipients without HTN, and 53% and 33% for recipients with HTN (p = 0.006). Among LD recipients using one antihypertensive, GS at 15 yr was 100% for those using an angiotensin-converting enzyme inhibitor (ACEI) and 44% for those not using an ACEI (p = 0.04). Among these recipients, HTN treated with no ACEI was a significant risk factor for graft failure at >5 yr (hazard ratio [HR] = 2.5, p = 0.02), but HTN treated with an ACEI was not (HR = 0.6, p = 0.7). HTN at five yr post-KT is associated with poorer long-term GS in pediatric recipients, but ACEI therapy may enable better outcomes and should be studied further.

A randomized controlled trial of preemptive rituximab to prevent recurrent focal segmental glomerulosclerosis post-kidney transplant (PRI-VENT FSGS): protocol and study design.

Background: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence. Methods: We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation. Discussion: Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643.

Graft loss due to recurrent disease in pediatric kidney transplant recipients on a rapid prednisone discontinuation protocol.

Recurrent disease is the fourth most common cause of graft loss (GL) in pediatric KTx recipients. We studied the incidence of recurrent disease and GL due to recurrent disease in pediatric KTx recipients on a RDP protocol. Between 2002 and 2010, we performed 74 KTxs in patients aged 5-18 yr using an RDP protocol, 25 (34%) were at risk of recurrence of primary disease. Outcomes were compared to 69 historical controls (18 [26%] at risk of recurrence), KTx between 1996 and 2000. Follow-up period was 39 ± 25 months in RDP and 124 ± 38 months in controls. The incidence of recurrent disease at three yr post-KTx was 16% in RDP and 28% in controls (p = NS). Mean time to recurrent disease was 22 ± 26 months in RDP and 46 ± 48 months in controls (p = 0.54). Nine (12%) grafts were lost in the RDP group (1-recurrence) and 32 (46%) in the control group (4-recurrence). Time to GL was 85 months in the RDP recipient and 46 ± 21 months in controls. An RDP protocol in pediatric KTx recipients may not be associated with increased risk of graft loss due to recurrent disease.