Alemtuzumab with corticosteroid minimization for pediatric deceased donor renal transplantation: A seven‐yr experience

Alemtuzumab is a monoclonal antibody targeting CD52 receptors on B and T lymphocytes and is an effective induction agent in pediatric renal transplantation. We report a seven‐yr experience using alemtuzumab induction and steroid‐free protocol in the pediatric population as safe and effective. Twenty‐one pediatric deceased donor renal transplants were performed at a single academic institution. All received induction with single‐dose alemtuzumab and were maintained on a steroid‐free protocol using TAC and MMF immunosuppression. There were 15 males and six females in the study whose ages ranged from one to 19 yr. The average follow‐up was 32 months (range from 12 to 78.2 months and median 33.7 ± 23.7 months). All patients had immediate graft function. Graft survival was 95%, and patient survival was 100%. Mean 12 and 36 months eGFR were 63.33 ± 21.01 and 59.90 ± 15.27 mL/min/1.73m², respectively. Three patients developed acute T‐cell‐mediated rejection due to non‐adherence while no recipients developed cytomegalovirus infection, PTLD, or polyoma BK viral nephropathy. Steroid avoidance with single‐dose alemtuzumab induction provides adequate and safe immunosuppression in pediatric deceased donor renal transplant recipients receiving TAC and low‐dose MMF maintenance therapy.     

Long‐term outcomes of living donor kidney transplants in pediatric recipients following laparoscopic vs. open donor nephrectomy

We compared long‐term outcomes of LDKT in pediatric recipients following either laparoscopic (LDN) or ODN. In our retrospective single‐center study, we compared 38 pediatric LDKT recipients of a laparoscopically procured kidney with a historic ODN group comprising 17 pediatric recipients. In our center, the first pure laparoscopic non‐hand‐assisted LDN for a pediatric LDKT recipient was performed in June 2001. Demographic data of donors and recipients were comparable between groups. Mean follow‐up was 64 months in the LDN group and 137 months in the ODN group. Patient survival was comparable between groups. Graft survival at one and five yr was 97% (LDN) vs. 94% (ODN) and 91% (LDN) vs. 88% (ODN; p = n.s.), respectively. Serum creatinine at one and five yr was 1.16 ± 0.47 mg/dL (LDN) vs. 1.02 ± 0.38 mg/dL (ODN) and 1.38 ± 0.5 mg/dL (LDN) vs. 1.20 ± 0.41 mg/dL (ODN), respectively. The type and frequency of surgical complications did not differ between groups. DGF and acute rejection rates were similar between groups. In the ODN group, a higher proportion of right donor kidneys was used. In the ODN group, all kidneys had singular arteries, whereas in the LDN group five kidneys had multiple arteries. Arterial multiplicity was associated with a higher incidence of DGF. In our experience, LDN does not compromise long‐term graft outcomes in pediatric LDKT recipients. Arterial multiplicity of the donor kidney may be a risk factor for impaired early graft function in the pediatric population.     

Tacrolimus therapeutic drug monitoring and pediatric renal transplant graft outcomes

Predose monitoring of tacrolimus levels is standard practice in the care of pediatric renal transplant patients. This is despite a paucity of data investigating the ideal target range in children, and controversy as to whether tacrolimus levels correlate with renal transplant outcomes. We performed a retrospective cohort analysis of 48 renal transplant patients at a single Canadian pediatric transplant center following the initiation of a tacrolimus–mycophenolate–prednisone‐based IS protocol. We analyzed the relationship of graft function, as defined by GFR up to five yr post‐transplant, to the preceding mean tacrolimus level. There was no significant correlation between absolute GFR and mean tacrolimus levels (r = 0.206, p = 0.38). However, a higher mean tacrolimus level, particularly ≥10 ng/mL in the first three months after transplantation, was associated with a slower rate of decline in GFR with time (r = 0.608, p = 0.004) and with a less likelihood of developing CKD five yr after transplant. We suggest that the optimal target range for tacrolimus levels may be at the upper end of what is currently practiced and that further research to validate these findings would be useful.     

Anorexia nervosa in a pediatric renal transplant recipient and its reversal with cyclosporine

We report a 16‐yr‐old female who developed AN within a month after renal transplantation and its resolution after switching from tacrolimus to cyclosporine. Her initial maintenance immunosuppressive regimen after renal transplantation consisted of tacrolimus, mycophenolate, and steroid. She had 7 kg weight loss within the first month of transplant with subsequent 10, 12, 17, and 19 kg loss after three, five, seven, and nine months of transplant, respectively. Besides weight loss and disturbances in body image, the patient developed alopecia, bradycardia, and persistent secondary amenorrhea. Upon switching to cyclosporine from tacrolimus nine months after transplant, she started regaining weight with 5 kg gain within two months and 10 kg after four months. She restarted her menstrual cycle, alopecia and bradycardia resolved, and her body image disturbance improved. Here, we describe a very unusual neuropsychiatric side effect of tacrolimus and its resolution with another calcineurin inhibitor, cyclosporine, in an adolescent renal transplant recipient.     

Treatment of BK virus‐associated nephropathy with CMX001 after kidney transplantation in a young child

NC, with renal failure secondary to bilateral dysplastic kidneys, received an LRD renal transplant (tx) at 17 months of age. Her early post‐tx course was complicated by persistently elevated blood polyoma BK virus DNA loads. A protocol biopsy at six months post‐transplant revealed BKVAN. Blood viral loads did not respond to decreased immunosuppression or treatment with ciprofloxacin and leflunomide. Six months post‐tx, her serum creatinine began to rise and we sought experimental therapy to prevent the loss of her graft. At seven months post‐tx, with FDA approval under an eIND, the patient was started on a 36‐wk course of treatment with the investigational drug. The patient is now more than 24 months after stopping treatment with CMX. BKV viral DNA loads remain at low, but still detectable levels. Urine viral loads have declined, but remain elevated. EBV DNA loads become undetectable. The patient's serum creatinine has declined back to a baseline of 0.5–0.7 mg/dL and has been stable for two yr. Renal function was preserved in association with the use of CMX001 to treat BKV nephropathy in a young pediatric kidney transplant recipient. There were no serious adverse events associated with the use of CMX001. This novel medication may be of value in the treatment of BKVAN in pediatric renal transplant recipients.     

Cardiovascular risk factors in children after kidney transplantation – From short‐term to long‐term follow‐up

Cardiovascular‐related mortality is 100‐fold higher in pediatric renal transplant recipients than in the age‐matched general population. Seventy‐seven post‐renal transplant children's charts were reviewed for cardiovascular risk factors at two and six months after transplantation (short term) and at two yr after transplantation and the last follow‐up visit (mean 7.14 ± 3.5 yr) (long term). Significant reduction was seen in cardiovascular risk factors prevalence from two months after transplantation to last follow‐up respectively: Hypertension from 52.1% to 14%, hypercholesterolemia from 48.7% to 33%, hypertriglyceridemia from 50% to 12.5%, anemia from 29.6% to 18.3%, hyperparathyroidism from 32% to 18.3% and hyperglycemia from 11.7% to 10%, and left ventricular hypertrophy from 25.8% at short term to 15%. There was an increase in the prevalence of obesity from 1.5% to 3.9% and of CKD 3–5 from 4.75% to 24%. The need for antihypertensive treatment decreased from 54% to 42%, and the percentage of patients controlled by one medication rose from 26% to 34%, whereas the percentage controlled by 2, 3, and 4 medications decreased from 21.9%, 5.5%, and 1.4% to 6%, 2%, and 0. Children after renal transplantation appear to have high rates of cardiovascular risk factors, mainly on short‐term follow‐up.     

Comparison of outcomes of hand‐assisted laparoscopic to open donor nephrectomy for pediatric recipients

The purpose of this study is to compare the outcome of pediatric recipients of kidneys procured using a hand‐assisted laparoscopic (HALDN group) to an open technique (ODN group). Twenty‐eight patients ≤18 yr old (HALDN group) were compared with 17 patients (ODN group). The serum creatinine for HALDN and ODN groups at discharge were 0.93 ± 0.48 and 0.94 ± 0.54 mg/dL (p = 0.917), respectively. The serum creatinine for HALDN and ODN groups at six and 12 months was 1.01 ± 0.44 and 1.11 ± 0.55, and 1.04 ± 0.52 and 1.14 ± 0.46 mg/dL (p = 0.516, p = 0.554), respectively. The eGFR for HALDN and ODN groups at discharge was 108.66 ± 37.23 and 106.1 ± 50.55 mL/min/1.73 m² (p = 0.845), respectively. The eGFR for HALDN and ODN groups at six and 12 months was 97.77 ± 28.25 and 81.73 ± 27.46, and 94.56 ± 28.3 and 85.74 ± 30.1 mL/min/1.73 m2 (p = 0.085, p = 0.344), respectively. The patient and graft survival for both groups were 100% at 12 months post‐transplant. In conclusion, the short‐term outcome of recipients of kidneys procured via HALDN is comparable to that of kidneys procured via ODN in pediatric patients.     

Converting immunosuppression from an oral suspension to a granule formulation of tacrolimus in pediatric renal transplant recipients

OS of tacrolimus prepared from tacrolimus powder is not licensed for children. A licensed GF for OS allows flexibility for body weight‐based dose adjustments. This study aimed at exploring the efficacy of conversion from OS to the GF of tacrolimus in stable pediatric renal transplant recipients. Records of 25 pediatric renal transplant recipients aged under 18 years who were switched from an unlicensed tacrolimus OS to GF were reviewed. At day 0, 1 week, and 4‐8 weeks post‐conversion, there were no differences regarding daily tacrolimus dose (3.4 ± 3 vs 3.5 ± 2.9 vs 3.5 ± 2.9 mg/day), trough tacrolimus levels (4.5 ± 2.7 vs 4.2 ± 2.7 vs 4.4 ± 3.1 ng/mL), dose‐normalized trough tacrolimus levels (1.7 ± 1.1 vs 1.5 ± 1.0 vs 1.7 ± 1.3 ng/mL/mg), PCr (65.6 ± 29.4 vs 67.9 ± 30.4 vs 69.8 ± 27.9 μmol/L), and eGFR (73 ± 24.9 vs 68.7 ± 20.2 vs 65.5 ± 18.2 mL/min/1.73 m²) (P > .05). GF dose adjustment was required in 52% of participants. Eighty‐eight percent of patients had to return for repeat tacrolimus levels following dose modifications, generating 33 extra visits (≥2 extra visits for 1/3 of subjects). No rejection episodes occurred in the year after conversion. In conclusion, conversion from tacrolimus OS to GF in stable pediatric renal transplant recipients is safe and efficacious. However, close therapeutic drug monitoring in the immediate post‐conversion period is necessary.     

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.     

Reduced ATG‐F dosage for induction in pediatric renal transplantation: A single‐center experience

Rabbit antithymocyte globulin (ATG‐F) is an extensively used induction agent. To our knowledge, no study to date has assessed reduced ATG‐F dosage in children undergoing renal transplantation. This was a retrospective analysis of pediatric renal recipients in the Department of Kidney Transplantation, The First Affiliated Hospital of Zhengzhou University, from May 2007 to February 2013. Thirty‐nine children underwent renal transplantation including 25 living related and 14 cardiac deceased donor transplantation. Each recipient received ATG‐F 1.5 mg/kg/d once daily for 4 days. Of the 39 recipients, five (12.8%) showed delayed graft function, including one of 25 recipients (4%) of living donor and four of 14 recipients (28.6%) of deceased donor transplantation (p < 0.05). Six of the 39 recipients (15.4%) showed acute rejection on renal biopsy. Follow‐up in these children ranged from 6 to 87 months. The one‐, three‐, and five‐yr recipients and grafts survival rates postoperation were each 94.9% and 97.3%, 97.3%, and 94.6%, respectively. The incidence of postoperative infection was 35.9% (14/39), and did not differ significantly in the living related and deceased donor groups (p > 0.05). Low‐dose ATG‐F can be safely used as an immune induction agent in pediatric renal transplantation.     

Post‐renal transplant erythrocytosis: A case report

PTE is defined as hematocrit >51% or hemoglobin >17 g/dL after renal transplantation. Risk factors include native kidneys with adequate erythropoiesis pretransplant, smoking, renal artery stenosis, and cyclosporine treatment. We report the case of a 14‐yr‐old female kidney transplant patient, with triple therapy immunosuppression and stable graft function who developed PTE at 12 months post‐transplant with hemoglobin 17.3 g/dL, hematocrit 54.2%, stable graft function, and normotensive with normal cardiac echocardiogram and erythropoietin levels. The only risk factor found was tobacco use. As she had no spontaneous improvement, enalapril treatment was started at 19 months post‐transplant with a hemoglobin level of 17.5 g/dL and hematocrit 53%; by 23 months post‐transplant, hemoglobin lowered to 15 g/dL and hematocrit to 44.5% and continued to be in normal range thereafter. PTE is a rare condition in childhood and can be successfully treated with enalapril.     

Comparison of generic tacrolimus and Prograf drug levels in a pediatric kidney transplant program: Brief communication

Abdulnour HA, Araya CE, Dharnidharka VR. Comparison of generic tacrolimus and Prograf drug levels in a pediatric kidney transplant program: Brief communication.
Pediatr Transplantation 2010: 14:1007–1011. © 2010 John Wiley & Sons A/S. Abstract: A generic version of tacrolimus was approved for use in the USA in August 2009. These narrow therapeutic index generics are tested for bioequivalence only in adults. No data are available on generic tacrolimus levels in children with allografts. Four patients with stable renal allografts in our pediatric program were inadvertently switched to generic tacrolimus. We retrospectively analyzed pre‐ and post‐switch trough tacrolimus and serum creatinine levels. Twelve‐h trough tacrolimus levels (mean ± s.e.) were (i) patient 1 (12‐yr‐old girl): 7.0 ± 0.69 and 9.7 ± 3.5 (p = NS); (ii) patient 2 (eight‐yr‐old boy): 4.7 ± 0.68 and 3.4 ± 0.84 (p = 0.04); (iii) patient 3 (22‐yr‐old woman): 6.8 ± 0.17 and 6.6 ± 0.4 (p = NS); (iv) patient 4 (20‐yr‐old woman): 5.4 ± 0.25 and 4.9 ± 1.4 (p = NS). Creatinine levels were similar pre‐ and post‐switch (eGFR > 75 mL/min/1.73 m²) in the first three. Patient 4 experienced a biopsy proven acute rejection immediately after switching. Mean creatinine rose from 1.15 ± 0.05 to 2.168 ± 0.07 after switch (p < 0.001). Given our mixed picture with the early data, we suggest careful monitoring of pediatric patients who get switched to generic tacrolimus.     

Induction therapy in pediatric kidney transplant recipients discharged with a triple drug immunosuppressive regimen

Sampaio MS, Poommipanit N, Kuo H‐T, Reddy PN, Cho YW, Shah T, Bunnapradist S. Induction therapy in pediatric kidney transplant recipients discharged with a triple drug immunosuppressive regimen.
Pediatr Transplantation 2010: 14:770–778. © 2010 John Wiley & Sons A/S. Abstract: We evaluated the effectiveness of induction therapy on transplant outcomes during 2004–2007 in the United States. We retrospectively reviewed OPTN/UNOS registry and selected kidney pediatric (<21‐yr) recipients that received no induction (NoIND), IL‐2RA, or rabbit anti‐THY and were discharged with a triple drug immunosuppressive maintenance regimen, including steroids. Of 2932 recipients, 20%, 36%, and 43% were in NoIND, THY, and IL‐2RA groups, respectively. The majority received tacrolimus (88%) and MMF (89%) at discharge. There was no association of induction with the risk of acute rejection even after adjusting for known cofounders. Compared to NoIND, IL2‐RA, but not THY, had a modest decrease (3%) in absolute rate of graft loss and was associated with a risk reduction ratio of 0.51 (95% CI, 0.31–0.84) in one‐yr graft loss. At three yr, no induction agent was associated with decreased graft loss. In conclusion, induction agents were used in 80% of pediatric kidney recipients discharged with a triple drug immunosuppressive maintenance regimen between 2004–2007 in the United States. Neither THY nor IL‐2RA was associated with reduced rejection episodes. The use of induction therapy was not associated with improvement in three‐yr graft survival.     

Long-term outcome of deceased donor renal transplantation in pediatric recipients: A single-center experience from a developing country

Kute VB, Trivedi HL, Vanikar AV, Shah PR, Gumber MR, Patel HV, Munjappa BC, Modi PR, Gera DN. Long‐term outcome of deceased donor renal transplantation in pediatric recipients: A single‐center experience from a developing country Abstract: RTx is best treatment for children with ESRD. Data scarcity on DDRTx outcome in children prompted us to review our experience. This study was undertaken to evaluate patient/graft survival, function vis‐a‐vis SCr, rejection episodes, and mortality in DDRTx performed in 37 children between 1998 and 2011. The most common recipient diseases leading to ESRD were congenital anomalies of kidney and urinary tract (48.6%) and chronic glomerulonephritis (18.9%). Mean recipient age was 13.8 ± 3.1 yr; 67.5% (n = 25) were men. Mean donor age was 38.8 ± 18.6 yr; 48.5% (n = 18) were men. Mean dialysis duration pre‐transplantation was 15.5 ± 3.5 months. All recipients received r‐ATG, and triple immunosuppression. Over a mean follow‐up of 3.93 ± 3.5 yr, patient and graft survival rates were 72.9% (n = 27) and 83.7% (n = 31), respectively, with a mean SCr of 1.1 mg/dL; 21.6% (n = 8) of patients had acute rejection episodes; 24.3% (n = 9) of patients had DGF. A total of 27% (n = 10) patients died, mainly owing to infections (n = 6) and cardiovascular disease (n = 3). DDRTx is a viable option for children and achieves acceptable graft function with patient/graft survival over long‐term follow‐up, encouraging use of this approach.     

BK viremia and nephropathy in pediatric renal transplant recipients

The renal survival rate of pediatric renal transplant recipients (pRTR) has improved with the use of modern immunosuppressive agents; however, the incidence of post‐transplantation viral infection has increased. This study investigated the incidence of BK viremia and BK viral–associated nephropathy (BKVAN) in pRTR. One‐hundred‐and‐thirty‐four pRTR were divided into two groups: group 1 (n = 20, 14.9%) comprised those who were prospectively followed with longitudinal analyses after renal transplantation in the time period from May 2007 to June 2008, while group 2 (n = 114, 85.1%) cross‐sectional study of those who were transplanted from January 1994 to April 2007. The mean ages at transplantation in groups 1 and 2 were 10.6 ± 4.7 years and 7.8 ± 4.5 years, respectively. BK viremia was detected in four (20.0%) patients in group 1, and seven (6.1%) in group 2 (P = 0.04), with increased incidence associated with induction therapy. The median time to detection of BK viremia after transplantation was 44 days in group 1 and 142 days in group 2. BKVAN was diagnosed in three patients (two in group 1 and one in group 2). All three patients diagnosed with BKVAN were receiving tacrolimus, mycophenolate mofetil, and corticosteroids as maintenance immunosuppression. Reducing immunosuppression resulted in reduced BK viremia. Monitoring for BK viremia and BKVAN is important in pRTR being treated with the current immunosuppressive regimen. The first line of treatment for BK viremia remains careful reduction of immunosuppression and close monitoring of renal allograft function.     

Three‐yr safety and efficacy of everolimus and low‐dose cyclosporine in de novo pediatric kidney transplant patients

The three yr results of a multicenter trial in de novo pediatric KT treated with a proliferative signal inhibitor and low dose CNI are presented. Thirty‐seven children (9.1 ± 5 yr old) received basiliximab, cyclosporine A (CyA C2:1400 ng/mL), (MMF C0:1.5–3 μg/mL), and prednisone. Three wk later everolimus was started (C0:5–10 ng/mL), CyA was reduced (C2:600 ng/mL after 90 days 300 ng/mL), and MMF discontinued. During the three‐yr period patient and graft survivals were 96%. One patient died for causes unrelated to the immunosuppression. Cumulative acute rejection rate including protocol and indication biopsies was 21.9%. None of the patients had signs of chronic humoral rejection. Incidence of dnDSA was 5%, 11%, and 22% at one, two, and three yr post‐transplant, respectively. Mean glomerular filtration rate measured at one yr and three yr post‐transplant was 105.5 ± 31 and 110.7 ± 27 mL/min/1.73 m², respectively. A growth velocity of 7.7 ± 6.7 cm/yr was achieved with positive catch‐up growth. No malignancy or post‐transplant lymphoproliferative diseases were diagnosed. In conclusion, the treatment based on basiliximab induction, everolimus, low‐dose cyclosporine, and low‐dose prednisone leads to good long‐term efficacy in de novo pediatric KT recipients.     

Prope tolerance after pediatric liver transplantation

pT, under mono‐ and infratherapeutic calcineurin inhibition, may constitute an optimal condition combining graft acceptance with low IS load and minimal IS‐related toxicity. We reviewed 171 pediatric (<15.0 yr) survivors beyond one yr after LT, transplanted between April 1999 and June 2007 under tacrolimus‐based regimens (median follow‐up post‐LT: 6.0 yr, range: 0.8–9.5 yr). Their current status regarding IS therapy was analyzed and correlated with initial immunoprophylaxis. pT was defined as tacrolimus monotherapy, with mean trough blood levels <4 ng/mL during the preceding year of follow‐up, combined with normal liver function tests. The 66 children transplanted before April 2001 received a standard tacrolimus–steroid regimen. Beyond April 2001, 105 patients received steroid‐free tacrolimus–basiliximab or tacrolimus–daclizumab immunoprophylaxis. In the latter group, 43 (41%) never experienced any acute rejection episode and never received steroids. In the long term, a total of 79 recipients (47%) developed pT (n = 73) or IS‐free operational tolerance (n = 6), 27 of them belonging to the 43 steroid‐free patients (63%). In contrast, only 52/128 (41%) children treated with steroids subsequently developed prope/operational tolerance (p = 0.012). Steroid‐free tacrolimus‐based IS seems to promote long‐term graft acceptance under minimal/no IS. These results constitute the first evidence that minimization of IS, including steroid avoidance, might be tolerogenic in the long term after pediatric LT.     

Single‐center experience in pediatric renal transplantation using thymoglobulin induction and steroid minimization

Our center has offered thymoglobulin induction with steroid minimization to our pediatric renal transplant patients for the last 10 yr. Steroid minimization or avoidance has shown favorable results in survival, kidney function, and growth in previous studies of pediatric patients. We report our experience with this protocol over the past 10 yr with respect to patient/graft survival, acute rejection episodes, renal function, linear growth, bone density, cardiovascular risk factors, and opportunistic infections. A retrospective chart review was performed for pediatric renal transplant patients on the steroid‐minimized protocol between January 2002 and December 2011 on an intention to treat basis. Patient demographics, height, weight, serum creatinine, iGFR, biopsies, and survival data were collected. Height and weight z‐scores were calculated with EpiInfo 7, using the CDC 2000 growth charts. Survival was calculated using Kaplan–Meier analysis. eGFR was calculated using the original and modified Schwartz equations. Forty‐four pediatric patients were identified, aged 13 months to 19 yr. Five‐yr survival was 95.5% for males and 94.4% for females. Only five patients had biopsy‐proven ACR, two of which were at more than 12 months post‐transplantation. Height delta z‐scores from transplant to one, three, and five yr were 0.34, 0.38, and 0.79, respectively. Weight delta z‐scores from transplant to one, three, and five yr were 0.87, 0.79, and 0.84, respectively. Mean original Schwartz eGFR was 84.3 ± 15.8 mL/min/1.73 m², modified Schwartz eGFR was 59.3 ± 11.5 mL/min/1.73 m², and iGFR was 64.2 ± 8.5 mL/min/1.73 m² at three yr. Of 18 subjects who had a bone density exam, none had a z‐score less than ?2 on DEXA exam at one‐yr post‐transplantation. Fifty‐one percent of patients were on antihypertensives at the time of transplant compared with 43% at one‐yr post‐transplantation. Three yr post‐transplantation, the average LDL was <100 mg/dL, and average total cholesterol was <200 mg/dL. There were no clinical episodes of EBV or CMV infection. A steroid‐minimized protocol with thymoglobulin induction is safe and provides favorable improvement in linear growth, stable graft function, stable or improved cardiovascular risk factors, and normal bone density in pediatric renal transplant patients.     

Long‐term outcome of pediatric renal transplantation: A single center study in Japan

Little is known about the risk factors for long‐term poor outcome in pediatric renal transplantation. Between 1973 and 2010, 111 renal transplants (92 living donations) were performed in 104 children (56 males, mean age, 12.5 yr) at the Social Insurance Chukyo Hospital, and followed‐up for a mean period of 13.6 yr. The patient survival at 1, 5, 10, 15, 20 (living‐ and deceased‐donor transplants), and 30 yr (living‐donor transplants only) was 98.1%, 92.8%, 87.8%, 84.9%, 82.6%, and 79.3%. The graft survival at 1, 5, 10, 15, 20, and 30 yr was 92.0%, 77.3%, 58.4%, 50.8%, 38.5%, and 33.3%. The most common cause of graft loss was CAI, AR, death with functioning, recurrent primary disease, ATN, and malignancy. Donor gender, ATN, malignancy/cardiovascular events, and eras affected patient survival. AR and CAI were the risk factors for graft loss. The evolved immunosuppression protocols improved the outcome by reducing AR episodes and ATN but not CAI, suggesting CAI as the major risk factor for graft loss. CAI was correlated with AR episodes, CMV infection, and post‐transplant hypertension. Strategies for preventing the risk factors for malignancy/cardiovascular events and CAI, including hypertension/infection, are crucial for better outcomes.     

Towards minimizing immunosuppression in pediatric liver transplant recipients

Abstract:  Immunosuppression regimens after liver transplantation focus mainly on preventing rejection and subsequent graft loss. However, in children, morbidity and mortality rates from infections exceed those from rejection after transplant, and immunosuppression can hinder growth, renal function, and graft tolerance. We hypothesized that early steroid withdrawal, with a primary aim of TAC monotherapy would yield no penalty in terms of rejection and graft loss, while reducing risks of infection and maximizing growth. We prospectively evaluated 64 consecutive pediatric liver transplant recipients. One yr patient/graft survival was 93/90%, respectively. At one yr post-transplant, 75.4% of patients were on TAC monotherapy. No deaths or graft losses were caused by infection. Sixty-one percent of patients had at least one episode of rejection, most within three months following transplant and 3.8% were treated for chronic rejection. One non-compliant adolescent died from chronic rejection. CMV, EBV, and lymphoproliferative disease rates were 3.1%, 5.3%, 1.8%, respectively. Pretransplant and one yr post-transplant glomerular filtration rates were unchanged. One yr improved catch-up growth was observed. We conclude that immunosuppression minimization after pediatric liver transplant yields no serious complications from rejection, and might confer advantages with respect to infection, renal function, growth, and is deserving of wider application and study.