Value of serum cystatin C in estimating renal function in children with non‐renal solid organ transplantation

Children with non‐renal solid organ transplants are surviving longer, but outcome is complicated by CKD. Accurate and frequent renal function monitoring is imperative to recognize and institute measures early to reverse, prevent, or arrest progression. This study of 59 children determined the accuracy (P30), bias, sensitivity and specificity between measured renal function by NM‐GFR, and estimated GFR by three formulas: Filler (serum cystatin C), mSchwartz (serum creatinine), and CKiD (serum cystatin C, creatinine, urea, and height). Mean GFR by all formulas differed significantly from NM‐GFR. Filler and mSchwartz formulas significantly increased the proportion of patients with GFR ≥ 90 mL/min/1.73 m² (CKD stage 1) while decreasing those with GFR 60–89 mL/min/1.73 m² (CKD stage 2). All formulas overestimated GFR. CKiD showed the highest P30 and lowest bias (79.7%; 6.9 mL/min/1.73 m²) followed by Filler (67.7%; 19.9 mL/min/1.73 m²) and Schwartz (57.6%; 26.8 mL/min/1.73 m²) for all GFR values. All formulas performed best with GFR ≥ 90 mL/min/1.73 m², but CKiD was the only formula to achieve 91.1% accuracy. All formulas showed high sensitivities, but low specificities at NM‐GFR cutoff at 90. Thus, GFR estimated by CKiD followed by Filler formula is an adequate method to monitor renal function closely and frequently in these children.     

Two decades of pediatric kidney transplantation in a multi‐ethnic cohort

Muneeruddin S, Chandar J, Abitbol CL, Seeherunvong W, Freundlich M, Ciancio G, Burke GW, Zilleruelo G. Two decades of pediatric kidney transplantation in a multi‐ethnic cohort.
Pediatr Transplantation 2010: 14:667–674. © 2010 John Wiley & Sons A/S. Abstract: This study evaluated a 20‐yr experience in kidney transplantation in children from a predominantly Hispanic community. A retrospective analysis was carried out in children who received kidney transplants from 1985 to 2005. Of 124 kidney transplants, 81 (65%) were from LD. Racial distribution was Hispanic (48%), followed by AA (24%) and Caucasian (26%). First yr allograft survival was similar in LD and DD and significantly better in LD until seven yr post transplant. eGFR <60 mL/min/1.73 m² at one yr post transplant was associated with a median allograft survival of 3.3 yr, compared to 16 yr in those with eGFR ≥ 60 mL/min/1.73 m² (p < 0.0001). Graft loss in the first five yr was from non‐adherence, recurrence of disease, and infections. Those of AA race were more likely to receive a DD and have low socioeconomic status and the poorest median allograft survival compared to Hispanics and Caucasians (6 vs. ≥15 yr; p < 0.001). In conclusion, this predominantly Hispanic cohort emphasizes the disadvantaged profile of AAs compared to other racial groups. Strategies to improve supportive services and living donations in minority populations need to be developed. Long‐term renal allograft survival is achievable if GFR is maintained >60 mL/min/1.73 m².     

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.     

Alemtuzumab induction with tacrolimus monotherapy in 25 pediatric renal transplant recipients

ALA induction in transplantation has been shown to reduce the need for maintenance immunosuppression. We report the outcome of 25 pediatric renal transplants between 2007 and 2010 using ALA induction followed by tacrolimus maintenance monotherapy. Patient ages were 1–19 yr (mean 14 ± 4.1 yr). Time of follow‐up was 7–51 months (mean 26 ± 13 months). Tacrolimus monotherapy was maintained in 48% of patients, and glucocorticoids were avoided in 80% of recipients. Mean plasma creatinine and GFR at one yr post‐transplant were 0.88 ± 0.3 mg/dL and 104.4 ± 25 mL/min/1.73m², respectively. One, two, and three‐yr actuarial patient and graft survival rates were 100%. The incidence of early AR (<12 months after transplantation) was 12%, while the incidence of late AR (after 12 months) was 16%. Forty‐four percent of the recipients recovered normal, baseline renal function after an episode of AR, and 44% had persistent renal dysfunction (plasma creatinine 1.0–1.8 mg/dL). One graft was lost four yr after transplantation due to medication non‐compliance. Four (16%) patients developed BK or CMV infection. In our experience, ALA induction with tacrolimus monotherapy resulted in excellent short‐ and mid‐term patient and graft survival in low‐immunologic risk pediatric renal transplant recipients.     

Donor and recipient ACE I/D genotype are associated with loss of renal function in children following renal transplantation

Genetic polymorphisms of the RAS correlate with allograft function. We therefore analyzed common RAS polymorphisms in kidney donors and in children following RTx to determine the relationship between genotype and decline in GFR, blood pressure, and LVM. A total of 107 children who underwent RTx were included: 70 male, 37 female, mean age 8.8±4.9 yr, mean follow up 5.4 yr. The following RAS polymorphisms were studied in all 107 recipients, 48 donors, and 120 healthy controls: Renin (Renin Mbol 18G/A), ACE I/D; angiotensinogen (AGT M235T), and angiotensin II receptor type-1 (AT1R A1166C). Only patients homozygous for the ACE D allele had a significantly steeper decline in GFR compared with homozygous carriers of the ACE I allele (slope DD: -4.3±0.8 vs. II: -1.3±1.1 mL/min/1.73 m2 per yr; p=0.035). In four cases, a DD recipient received a kidney from a DD donor, and these patients showed a more pronounced decline in GFR (-5.2±0.5 mL/min/1.73 m2 per yr; p=0.002). MABP was not different before vs. after RTx and was independent of ACE I/D genotype. LVMI increased significantly in the majority of patients (36.6±13.9 g/m2.7 six months before RTx vs. 46.4±15.3 g/m2.7 12 months after RTx, p=0.015). However, this difference disappeared after stratification by ACE I/D genotype. The ACE DD genotype is a potential marker for identifying patients at high risk of poor allograft outcome.     

De novo therapy with everolimus and reduced‐exposure cyclosporine following pediatric kidney transplantation: A prospective,multicenter, 12‐month study

Prospective data regarding the de novo use of everolimus following kidney transplantation in children are sparse. In a prospective, 12‐month, single‐arm, open‐label study, pediatric kidney transplant patients received everolimus (target trough concentration ≥3 ng/mL) with reduced‐exposure CsA and corticosteroids, with or without basiliximab induction. Sixteen of the 18 patients completed the study on‐treatment. Age range was 2–16 yr (mean 10.9 yr); eight patients received a living donor graft. Mean (s.d.) everolimus level was 7.4 (3.1) ng/mL during the first 12 months post‐transplant. There were no cases of BPAR, graft loss, or death during the study. Protocol biopsies were performed at month 12 in seven patients, with subclinical (untreated) acute rejection diagnosed in one case. Mean (s.d.) estimated GFR (Schwartz formula) was 98 (34) mL/min/1.73 m² at month 12. Three patients experienced one or more serious adverse events with a suspected relation to study medication. One patient discontinued study medication due to post‐transplant lymphoproliferative disease (5.6%). Everolimus with reduced‐dose CsA and corticosteroids achieved good efficacy and renal function and was well tolerated in this small cohort of pediatric kidney transplant patients. Controlled trials are required to answer remaining questions about the optimal use of everolimus in this setting.     

Tacrolimus vs. cyclosporine A as primary immunosuppression in pediatric renal transplantation: a NAPRTCS study

Using the North American Renal Transplant Cooperative Study (NAPRTCS) database, we performed a retrospective cohort study of 986 pediatric renal transplant recipients (index transplant 1997-2000) who were treated either with Cyclosporine A (CSA), Mycophenolate Mofetil (MMF) and steroids (n = 766) or tacrolimus (TAC), MMF and steroids (n = 220) to examine potential difference in clinical outcomes between these two groups. In the first year post-transplant, time to first rejection (29.1% vs. 29%, p = 0.840), risk for rejection [Adjusted Relative Risk (aRR) 1.01, 95% Confidence Interval (CI) 0.77, 1.323], graft survival (96.8% vs. 97.9%, p = 0.607) and risk for graft failure (aRR 0.988, 95% CI 0.64, 1.928) were not significantly different in TAC and CSA-treated patients. At 2 yr post-transplant, there was also no difference in risk for rejection (aRR 0.918, 95% CI 0.669, 1.259), graft survival (91.4% vs. 95.1%, p = 0.152) and risk for graft failure (aRR 0.702, 95% CI 0.461, 1.762) in the subset of 391 CSA-treated patients and 77 TAC-treated patients on whom 2 yr follow data were available in the database. TAC-treated patients were significantly less likely to require antihypertensive medication at 1 yr [aRR 0.74 (95% CI 0.454, 0.637)] and 2 yr post-transplant [aRR 0.67 (95% CI 0.56, 0.793)]. At 1 yr post-transplant, TAC-treated patients enjoyed a higher mean GFR as estimated by the Schwartz formula [89.1 mL/min/1.73 m(2) (SE 2.64) vs. 78.6 mL/min/1.73 m(2) (SE 1.07), p = 0.0003]. In addition, in the subset of patients with 2 yr of follow-up, TAC patients had a higher mean GFR at both 1 yr [98.6 mL/min/1.73 m(2) (SE 3.83) vs. 78.0 mL/min/1.73 m(2) (SE 1.44), p = 0.0003] and 2 yr post-transplant [96.7 mL/min/1.73 m(2) (SE 3.33) vs. 73.2 mL/min/1.73 m(2) (SE 1.48), p < 0.0001]. In summary, TAC and CSA, in combination with MMF and steroids, produce similar rejection rates and graft survival in pediatric renal transplant recipients. However, TAC is associated with improved graft function at 1 and 2 yr post-transplant. Further analysis as more patient data are obtained will be necessary to determine if this difference in graft function persists and translates into improved graft survival.     

Estimated one-yr glomerular filtration rate is an excellent predictor of long-term graft survival in pediatric first kidney transplants

Acute rejection episodes following pediatric renal transplantation have been progressively reduced by recent immunosuppressive regimens. Nevertheless, grafts continue to fail over time and surrogate parameters for long-term RGS are lacking. We investigated post-transplant renal function within the first yr as an independent predictor of long-term RGS in 104 pediatric first kidney transplant recipients (mean age 11.1 +/- 3.9 yr; mean follow-up 8.3 +/- 3.5 yr) transplanted between January 1989 and December 2000. GFR was assessed by use of the Schwartz formula at 30 days and six and 12 months after transplantation, respectively. Patients were further stratified at all times according to GFR: (i) GFR<45 mL/min/1.73 m(2), (ii) GFR 45-80 mL/min/1.73 m(2), and (iii) GFR>80 mL/min/1.73 m(2). Cox regression analysis including factors potentially influencing long-term RGS, e.g., age, gender, transplant yr, HLA-mismatch, underlying renal disease, clinical acute rejection, absolute GFR as well as the change in GFR within the first yr was performed. Graft failure occurred in 24 out of 104 patients (23%) 6.2 yr (mean) after transplantation corresponding to a cumulative five-yr graft survival of 87.5%. GFRs at 30 days and six and 12 months were significantly associated with long-term RGS in the univariate cox regression analysis (GFR at 30 days, p = 0.045; GFR at six months, p = 0.004; GFR at 12 months, p < 0.001). None of the other variables were significant parameters of correlation. Multivariate cox analysis revealed a GFR below 45 mL/min/1.73 m(2) at 12 months after transplantation as the only independent predictor of long-term RGS (hazard ratio 55.9, 95% CI 5.29-591, p = 0.001). GFR at 12 months post-transplant is an excellent surrogate parameter for long-term RGS in children. This parameter might be useful as a primary end-point in short-term pediatric clinical trials.     

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.     

Renal function assessment in child and adolescent heart transplant recipients during routine cardiac catheterization

CKD identification after pediatric heart transplantation (PHT) is limited by inaccuracies in estimates of GFR. We hypothesized that GFR can be measured by a modified iohexol clearance protocol in PHT recipients and that the CKiD formula provides a better estimate of GFR than other estimating equations. A cross‐sectional study of PHT recipients, ages 2–18 yr, undergoing coronary angiography was undertaken. The angiography dose of iohexol was divided by the area under the curve from three iohexol levels post‐infusion to calculate GFR. Agreement between iGFR and multiple estimating equations (eGFR) was assessed. In 31 subjects, median age was 15.0 yr (IQR 7.6, 16.6). Mean iGFR was 93.8 (s.d. 22.5) mL/min/1.73 m²; 16 (52%) had an iGFR <90 mL/min/1.73 m². The full CKiD formula (mean eGFR 88.9, s.d. 14.9) had low bias (?5.0), narrowest 95% limits of agreement (?42.0, 32.1), highest 30% (94%) and 10% (52%) accuracy, and highest correlation coefficient (0.576) relative to iGFR. We describe a novel modified iohexol clearance method to assess GFR after PHT. Over half of the cohort had an iGFR <90, suggesting CKD. The full CKiD formula performs best with respect to bias, accuracy, and correlation.     

Application of an epitope‐based allocation system in pediatric kidney transplantation

Donor–recipient HLA mismatch remains a leading cause for sensitization and graft loss in kidney transplantation. HLA compatibility at an epitope level is emerging as an improved method of matching compared with current HLA antigen allocation. A novel epitope‐based allocation approach to prospectively exclude donors with high‐level mismatches was implemented for pediatric KTRs on the DD waiting list. Nineteen consecutive transplants were followed for 12 months, including eight DD KTRs listed with eplet exclusions, as well as three DD KTRs and eight LD KTRs without exclusions. KTRs with eplet exclusions had estimated GFR of 78.5 mL/min/1.73 m², no episodes of rejection, and time to transplant 6.55 months. HLA‐A, HLA‐B, HLA‐DR antigen mismatches were similar between all groups. KTRs with exclusions had significantly lower class II eplet mismatches (20.4) than the contemporary DD KTRs without exclusions (63.7) and DD KTRs transplanted in the preceding decade (46.9). dnDSAs were identified in two of eight DD KTRs with exclusions, two of three DD KTRs without exclusions and five of eight LD KTRs. Epitope‐based allocation achieved timely access to transplantation, low class II eplet mismatches, and low rates of dnDSAs in the first year. This strategy requires longer follow‐up and larger numbers, but has the potential to reduce anti‐HLA sensitization and improve both graft survival and opportunities for future retransplantation.     

Outcomes of children receiving en bloc renal transplants from small pediatric donors

The utilization of en bloc renal allografts from small pediatric donors has been adopted as an effective strategy to expand the organ donor pool in adult recipients. Data in children are limited. The aim of our study is to describe the outcomes of en bloc renal transplants in children from our center. Medical records of children receiving pediatric en bloc renal transplants at our institution from January 2007 were abstracted. Data collected included recipient and donor demographics, operative technique and complications, and post‐operative studies. Eight children received en bloc renal transplants at a median age of 17 yr; median follow‐up was 0.9 yr. Donor body weight ranged from 4 to 22 kg. One kidney was lost to intra‐operative thrombosis, while the other kidney from this en bloc graft remained viable. All grafts showed increased renal size at follow‐up ultrasound. Surveillance biopsies showed glomerulomegaly in two patients. At last follow‐up, the median eGFR was 130 mL/min/1.73 m². The urinary protein to creatinine ratio was normal in four of seven patients. Our data suggest that in experienced centers, en bloc renal transplantation from young donors into pediatric recipients is effective. Long‐term follow‐up to monitor for complications, including hyperfiltration injury, is warranted.     

Short-term pediatric renal transplant survival: Blood pressure and allograft function

Hypertension is prevalent after renal transplantation (Tx) and associated with graft failure in children and adults. However, the effect of blood pressure (BP) on short-term renal allograft function is uncertain. We assessed the associations among BP pretransplant, and 3 months and 1 yr post-transplant, and 1-yr post-transplant measured glomerular filtration rate (mGFR) in 61 children with a functioning graft. The GFR was determined using a single intravenous (i.v.) injection of Optiray 350(R). Data were collected between January 1994 and January 2000. The mean mGFR 1 yr after renal transplant was 63.6 +/- 19.9 mL/min/1.73 m2 in 26 live donor recipients and 50.8 +/- 23.3 mL/min/1.73 m2 in 35 cadaveric donors (p = 0.029). Correlation analysis showed significant negative associations of 1-yr mGFR with systolic blood pressure (SBP) and diastolic blood pressure (DBP) 3 months after renal Tx (r = - 0.58, p < 0.0001 and r = - 0.50, p < 0.0001, respectively), and with SBP (r = - 0.37, p = 0.003) and DBP (r = - 0.32, p = 0.01) 1 yr after renal Tx. Multi-variate regression analysis showed that the SBP 3 months after Tx (p < 0.001), number of acute rejections (p = 0.002), donor age (p = 0.02), and cold ischemia time (p = 0.03) were independent predictors for the 1-yr mGFR. These results indicate that a higher SBP in the first few months post-renal Tx is associated with decreased renal allograft function in children 1 yr post-Tx.     

Mycophenolate mofetil introduction stabilizes and subsequent cyclosporine A reduction slightly improves kidney function in pediatric renal transplant patients: a retrospective analysis

Chronic allograft nephropathy (CAN) is the major cause of late graft loss. Among others, chronic calcineurin inhibitor toxicity (CNI) contributes to the development of CAN. Therefore, reduction in CNI dosage may delay the development of CAN, leading to longer graft survival. It was the aim of the present retrospective analysis to investigate the effect of mycophenolate mofetil (MMF) addition with subsequent cyclosporine A (CSA) reduction on renal function in pediatric kidney allograft recipients. Seventeen patients (aged 8.3-17.6 yr) with monotherapy with CSA and progressive loss of renal function at a median of 3.4 yr after kidney transplantation were enrolled. After at least three months of MMF treatment, CSA dosage was stepwise reduced to trough levels of 100, 80, and 60 ng/mL. In all patients, introduction of MMF prevented a further decrease of glomerular filtration rate (GFR). The mean GFR 12 months before study enrollment was 96.1+/-24.5 and 71.0+/-21.0 mL/min/1.73 m2 at start of MMF. After introduction of MMF and unchanged CSA dosage GFR was stabilized to 71.1+/-23.8 mL/min/1.73 m2. After CSA reduction to trough levels of 60 ng/mL, GFR was slightly ameliorated up to 76.3+/-24.1 mL/min/1.73 m2. Within the follow-up period, one borderline rejection occurred in a patient in whom the CSA trough level was 60 ng/mL since seven months. In pediatric kidney allograft recipients with progressive loss of renal function reduction of CSA after introduction of MMF may stabilize and even slightly ameliorate renal function.     

Kidney transplantation from pediatric donors: size-match-based allocation

Abstract:  Use of kidneys from pediatric donors has been associated with worse outcome. We review our 20-yr experience using pediatric kidneys as single grafts in children and adult recipients. Charts review of 29 recipients, transplanted between 1986 and 2005, who received a graft from a donor ≤6 yr was performed. One recipient received "en bloc" graft and the remaining patients received a single kidney. Nine recipients were adults and 21 were children. Creatinine at discharge and at follow-up was recorded and actuarial graft and patient survivals were calculated using life table analysis. All 29 recipients are alive at mean follow-up of 92 months. Five grafts were lost for: primary non-function (1), recurrent FSGS at 14 month (1) and chronic rejection (3). All five recipients who lost their graft received a graft from donors ≤3 yr. Mean calculated GFR (Schwartz formula) at one and five yr were 84.2 mL/m²/1.73 and 98.3 mL/m²/1.73, respectively. Actuarial graft survival was 93.2%, 89.6%, and 81.9% at one, five and at 10 yr after transplant. The use of a single kidney graft from pediatric donors yields good long-term results. Kidneys from small pediatric donors should be allocated first to matched-weight recipients but otherwise can be transplanted in older children or in adults.     

Delayed graft function in pediatric deceased donor kidney transplantation: Donor‐related risk factors and impact on two‐yr graft function and survival: A single‐center analysis

There is mounting evidence that the quality of organs from cadaver donors may be influenced by events occurring around the time of brain death. Aim of this present study was to analyze the correlation of DGF with brain‐dead donor variables in a single‐center pediatric population and to evaluate DGF influence on patients‐ and grafts outcome. End‐points of the study were DGF prevalence, DGF donor‐related risk factors, graft function, patient‐ and graft survival rate, respectively, at six, 12, and 24 months FU. The univariate analysis showed that donor age above 15 yr and vascular cause of donor brain death represented risk factors for DGF. The multivariate analysis confirmed as independent risk factors for DGF donor age >15 yr. At six months FU, DGF showed a negative impact on graft function. In conclusion, among all considered brain‐dead donor resuscitation parameters, just non‐traumatic cause of death turned out to be of impact for DGF. Donor age >15 yr represented the only independent risk factor for prolonged DGF in our series of children. At two‐yr FU, DGF showed a transient negative impact on six‐month graft function.     

A case series of perioperative variables in relation to short‐term outcomes in pediatric renal transplant recipients

Multiple perioperative variables have been shown in existing literature to influence long‐term outcomes of pediatric RTx, such as allograft survival. Their impact on short‐term outcomes is not as well‐documented. This case series aims to investigate the effects of nine perioperative variables on two short‐term outcomes in pRTR: 1‐week post‐operative eGFR and post‐operative LOS. A total of 73 pRTR transplanted over 3 years from 2012 to 2014 at a single center were studied retrospectively and statistical analyses were performed. There was higher 1‐week post‐operative eGFR in pRTR who received living donor transplants compared to those who received deceased donor transplants (P=.01), with mean eGFR of 135 mL/min/1.73 m² and 82 mL/min/1.73 m², respectively. Aorta‐IVC anastomosis was associated with longer LOS compared to iliac vessel anastomosis (P=.03), with median LOS of 19 and 13 days, respectively. There were no significant effects on 1‐week eGFR or LOS of the seven other variables: pRTR age and gender, donor age, preoperative donor SBP, intraoperative mean CVP before graft perfusion, intraoperative median SBP z score after graft perfusion, and intraoperative fluid volume. Living donor transplants were associated with higher 1‐week post‐operative eGFR compared to deceased donor transplants. Aorta‐IVC anastomosis was significantly associated with longer LOS compared to iliac vessel anastomosis.     

Basiliximab with delayed introduction of calcineurin inhibitors as a renal‐sparing protocol following liver transplantation in children with renal impairment

Renal impairment is frequently compromised in patients with end‐stage liver disease and is associated with increased long‐term mortality post‐LT. In contrast to CNI, basiliximab is an immunosuppressive agent with minimal nephrotoxic potential. This study reviews the experience of a single pediatric liver transplant center's renal‐sparing approach with the use of basiliximab and MMF to compensate for delayed entry of CNI in children with renal impairment at the time of organ availability. There were no differences in renal function between pediatric patients with and without pre‐LT renal impairment within the first year (cGFR: 135 mL/min/1.73 m² vs. 144 mL/min/1.73 m²; p = 0.56) or at 5–8 yr following LT, (129 mL/min/1.73 m² vs. 130 mL/min/1.73 m²; p = 0.97). In addition, there was no difference in ACR rates (50% vs. 43%, p = 0.62) between patients in the basiliximab group and those patients receiving standard CNI and steroid strategies. The utilization of a renal‐sparing approach with basiliximab alongside delayed entry and lower early target trough levels of CNI in children with renal impairment at the time of LT is safe and maintains excellent long‐term kidney function.     

Different models of transition to adult care after pediatric kidney transplantation: A comparative study

Transition from pediatric to adult care is a critical and difficult step for young people with transplants and for the multidisciplinary team involved. In our retrospective study, we investigated the clinical course in a two‐yr period of transition. Data from 66 teenagers were collected one yr before and after their transfer to three different adult care settings: (i) a specialized transition clinic, (ii) a general transplantation clinic, and (iii) a nephrologist. Patient survival rate was 100%. Three patients developed graft loss. GFR development was comparable in the three settings (ΔGFR 1.4 ± 8.7 vs. 3.1 ± 10.6 vs. 0.8 ± 4.4 mL/min/1.73 m², p = ns). Immunosuppressive therapy was stable in setting 1, whereas the number of changes increased in setting 2 and even more in setting 3. The percentage of patients with steroids increased from 36% to 38% and 52% in settings 1–3. Patient satisfaction was highest in setting 1 (100% vs. 64% and 78%, p < 0.05). Setting 1 was associated with fewer changes in therapy (13% vs. 91% and 45%, p < 0.05). The use of a specialized transition clinic is associated with fewer changes in medication and care and a higher level of patient satisfaction. This was not associated with a lower increase in GFR one yr after transition. Long‐term results are awaited.     

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.