Glomerular and tubular function following orthotopic liver transplantation in children treated with tacrolimus

The aim of this study was to analyze the impact of TAC on medium term (three-yr follow-up) renal function in pediatric liver transplant (OLT) recipients. Glomerular and tubular indices were retrospectively analyzed in 24 consecutive OLT pediatric recipients on TAC. CrCl increased significantly each month post-OLT (p = 0.003), with a trend toward significance between pre-OLT and 36 months (p = 0.17). There was no correlation between CrCl and TAC troughs (p = 0.783). Sixteen percent of patients had CrCl <60 mL/min/1.73 m(2) pre-OLT vs. none at 36 months post-OLT. TRP values were normal throughout the study. UPr/Cr decreased insignificantly over time and correlated significantly with TAC trough levels (p = 0.031). UCa/Cr values normalized by the third-month post-OLT, decreasing significantly over the time (p = 0.000) but did not correlate with TAC troughs. At three months post-OLT, 65.2% of patients needed antihypertensive therapy, and no patients needed more than one antihypertensive treatment after one yr. Despite nephrotoxic side effects in the early postoperative phase, this study shows that 65.5% patients had a normal renal function by three yr post-OLT. Tubular indices correlated with TAC trough levels.     

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.     

Indications and efficacy of conversion from tacrolimus‐ to sirolimus‐based immunosuppression in pediatric patients who underwent liver transplantation for unresectable hepatoblastoma

SRL‐based immunosuppressive strategies in pediatric liver transplantation are not clearly defined, especially within the first year after liver transplant. TAC is the more common, traditional immunosuppressant used. However, SRL may modulate TAC‐associated kidney injury and may also have antiproliferative properties that are valuable in the management of patients following liver transplantation for HB. We sought to determine whether early conversion from TAC to SRL was safe, effective, and beneficial in a subset of liver transplant recipients with unresectable HB exposed to CDDP‐based chemotherapy. Between 2008 and 2013, six patients were transplanted for unresectable HB. All patients received at least one cycle of CDDP‐based chemotherapy prior to transplant. All patients were switched from TAC‐ to SRL‐based immunosuppression within 1 year of transplant. Five patients had improvement in their mGFR, while one patient had a slight decline. The improvement in mGFR was statistically significant. No adverse events were identified. Three patients had BPAR that responded to pulsed steroids. Historical controls showed similar rates of BPAR within the first year after transplant. There were no identified HB recurrences in the follow‐up time period. Conversion from TAC to SRL appears to be safe and effective in this selected group of pediatric liver transplant recipients without adverse reaction or HB recurrences.     

Influence of CYP3A5 polymorphism on tacrolimus maintenance doses and serum levels after renal transplantation: age dependency and pharmacological interaction with steroids

TAC, MMF and MP are used in pediatric kidney tx. The cytochrome P450 (CYP)3A5 enzyme appears to play a role in TAC metabolism. The aims of this study were to investigate CYP3A5 polymorphism's effect on TAC dosing and the age dependency of TAC dosing by testing blood concentrations, and the interaction between steroids and TAC during the first year after tx. Genomic DNA was extracted and amplified with specific primers. CYP3A5 alleles were confirmed by direct sequencing of PCR products on an automated AB13100 capillary sequencer. We studied 48 renal transplant patients (age at tx 12±0.5yr, 22 boys) receiving TAC, MMF, MP. Of these, 79% were CYP3A5*3/*3 (non-expressers homozygotes) and 21% were CYP3A5*1/*3 (expressers). TAC trough levels were 7.1±0.4ng/mL in CYP3A5*3/*3 patients and 6.5±0.7ng/mL in CYP3A5*1/*3 group (p=0.03). CYP3A5*1/*3 patients had lower levels of dose-adjusted TAC (36.7±5.8ng/mL/mg/kg/day) to achieve target blood concentration and required higher daily dose per weight (0.21±0.03mg/kg/day) than CYP3A5*3/*3 patients, 72.4±8.0ng/mL/mg/kg/day and 0.13±0.01mg/kg/day (p<0.001). Prepubertal patients with different CYP3A5 polymorphisms required significant higher TAC doses and achieved lower dose-normalized concentration compared with pubertal patients. Both TAC dose and adjusted-dose correlated with daily MP dose in CYP3A5*1*3 (r: 0.4, p<0.03 and r: 0.4, p<0.03) and in CYP3A5*3*3 (r: 0.6, p<0.01 and r: 0.47, p<0.001) patients. CYP3A5 polymorphism performed before tx could contribute to a better individualization of TAC therapy. The higher TAC dose in prepubertal patients and the pharmacological interactions between MP and TAC may not be fully explained by different CYP3A5 polymorphisms.     

Tacrolimus withdrawal and conversion to sirolimus at three months post-pediatric renal transplantation

Nephrotoxicity caused by CNI may adversely affect long-term graft outcomes. For this reason, we have adopted a protocol for withdrawing TAC and converting to SRL at three months post-renal transplantation. All recipients received basiliximab induction and TAC, MMF, and prednisone. Patients without acute rejection by surveillance biopsy at three months were eligible for SRL conversion. Results: From August 2004 to September 2006, TAC was withdrawn and replaced by SRL in 30 first transplant recipients, who were followed for six to 39 months (mean 18 +/- 8). Renal function did not improve significantly after SRL conversion (p = 0.25). Acute rejection occurred in three patients (10%) at five to 12 months after CNI withdrawal. There were no occurrences of wound healing problems, pneumonitis or post-transplant lymphoproliferative disease. Thrombocytopenia and diabetes each occurred in one patient. Four patients received treatment for hypercholesterolemia. CNI withdrawal and replacement with SRL was an effective regimen in children who did not display biopsy evidence of acute rejection at three months post-transplant. While these early results are promising, the ultimate benefit of this protocol to enhance the long-term renal function and graft survival requires ongoing follow-up.     

Recovery of tacrolimus-associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient--case report and review of the literature

TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.     

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.     

Five-year experience using sirolimus-based, calcineurin inhibitor-free immunosuppression in pediatric renal transplantation

From December 2003 to December 2008, we employed a protocol for withdrawing TAC and converting to SRL in a cohort of low-risk renal pediatric transplant recipients. We report our experience in these children with respect to graft survival, AR episodes, renal function, and adverse events. All patients received basiliximab induction and TAC, MMF, and prednisone. Criteria for conversion to SRL included first transplants without histologic evidence for AR on three-month surveillance biopsies. Patient exclusion criteria included AR prior to or before surveillance biopsies, polyoma (BK) virus nephropathy, a history of nephrotic syndrome, or multiple organ transplants. Fifty-one of 137 patients who received transplants from December 2003 to December 2008 met criteria for withdrawal of TAC and were converted to SRL. SRL was discontinued in 11 children because of adverse events within 12 months after conversion. Among the remaining 40 patients, actuarial graft survival was 91% at five yr. AR occurred in 13% of patients within one yr after conversion. Complications from SRL included aphthous ulcers (30%); viremia with BK virus (20%), EBV (13%), and CMV (3%); proteinuria (7%); elevated cholesterol (7%); diabetes mellitus (2%); thrombocytopenia (2%); erectile dysfunction (2%); and lymph edema (2%). SRL was discontinued in 20%, predominantly for aphthous ulcers. Our experience with SRL-based immunosuppression demonstrates that a CNI-free regimen can be successful in lower-risk patients meeting our selection criteria. Aphthous ulcers and BK virus viremia were the most prevalent adverse events.     

Long‐term outcomes in pediatric liver recipients: Comparison between cyclosporin A and tacrolimus

In recent years, tacrolimus (FK506, TAC) has been increasingly utilized in liver transplantation. However, long-term risks and benefits as compared with conventional cyclosporin A (CsA) have not been fully elucidated. This retrospective study examined the potential outcome differences between TAC- and CsA-based immunosuppressive therapy in pediatric liver transplant recipients. From March 1988 to December 1996, 218 children (aged 0.1-17 yr) underwent 238 orthotopic liver transplantations; 58.7% (128/218) were under 2 yr of age at time of transplant. Initially, the maintenance immunosuppressive regimen consisted of CsA and prednisone, with antilymphocytic preparations (MALG, ATGAM, and OKT3) as induction therapy. Subsequently, TAC was used first as rescue therapy for steroid refractory rejection in CsA patients and then as maintenance immunosuppression. Fifty-seven out of the 147 CsA patients were converted to TAC for various reasons while 71 patients were placed on TAC as primary maintenance immunosuppression. 62.6 per cent (92/147) of liver recipients on CsA experienced at least one biopsy-proven acute rejection episode as compared to 50.7% (36/71) for TAC patients (p = 0.09); likewise, 34% (50/147) of CsA patients had more than one episode of rejection vs. 18.3% (13/71) for patients on TAC (p < 0.02). Rejection was the reason for conversion from CsA to TAC in 29 of 57 patients. Conversely, 19.0% (28/147) of CsA patients had to be switched to TAC for reasons not related to rejection (i.e. side-effects). The overall incidence of histologically proven chronic rejection was 7.8% (17/218). 10.9 per cent (16/147) of the children who were on CsA initially developed chronic rejection, which was significantly higher compared with one of 71 TAC recipients (p < 0.02). Of these 16 CsA patients with chronic rejection, 50.0% (8/16) underwent retransplantation for graft failure (mean interval from time of diagnosis of chronic rejection to re-transplant, 4.0 months; range 1-8 months), whereas the TAC patient has remained clinically stable with normal liver function tests after 23 months of follow-up. One year after liver transplantation, 72.8% (107/147) of CsA patients were still on steroids (mean dosage 0.20 mg/kg/d), as compared to 42.3% (30/71) of the TAC patients (mean dosage 0.14 mg/kg/d). The incidence of post-transplant lymphoproliferative disorder (PTLD) in Epstein-Barr virus (EBV)-infected patients was 2.2% (2/90), 7.0% (5/71) and 12.3% (7/57) for CsA, primary and TAC-converted groups, respectively. The overall incidence of PTLD was 6.9% (15/218). In summary, pediatric liver transplant recipients treated with TAC as primary maintenance immunosuppressive medication experienced significantly fewer episodes of rejection; especially chronic rejection, which lead to graft loss. However, the trade-off is a potential increased incidence of EBV-related PTLD in these patients.     

Anti-thymocyte globulin induction with delayed introduction of tacrolimus preserves renal function in pediatric liver transplant recipients

Background

Tacrolimus (TAC)-mediated renal disease occurs in up to 70% of pediatric liver transplant (LT) recipients. The safety and efficacy of renal-sparing immunosuppression using anti-thymocyte globulin (ATG) induction and delayed TAC administration has not been studied in children. We evaluated the safety and efficacy of ATG induction on preserving renal function in children within the first year (Y1) post-LT in a single-center retrospective cohort study.

Methods

Children under age 18 years of who received isolated LT from 2008 to 2020 with a GFR < 70 received renal-sparing (RS) protocol consisting of ATG with methylprednisolone (MP), delayed TAC administration, lower initial TAC trough goals, and mycophenolate mofetil (MMF). The RS group was matched 1:2 by age and LT indication with standard immunosuppression (SI) group. Changes in renal function as well as adverse events within Y1 post-LT were compared.

Results

Forty-four pediatric patients were included in the analysis, of which 13 received RS. As expected, the RS group had significantly lower mean TAC trough levels at 30 days (10.3 vs. 13.2, p = .001) post-LT. Renal function was significantly preserved at 6 (−0.26 vs. 0.21, p = .004) and 12 months (−0.33 vs. 0.11, p = .003) post-LT in the RS versus SI group as measured by mean change in serum creatinine, with similar trends observed in eGFR and cystatin C. ACR, sepsis, viremia, graft loss and mortality occurred at similar rates in both RS and SI groups.

Conclusion

Induction immunosuppression with ATG and delayed TAC administration in children with renal impairment is safe and effectively preserves renal function during Y1 post-LT.     

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.     

Dyslipidemia after pediatric renal transplantation—The impact of immunosuppressive regimens

Dyslipidemia contributes to cardiovascular morbidity and mortality in pediatric transplant recipients. Data on prevalence and risk factors in pediatric cohorts are, however, scarce. We therefore determined the prevalence of dyslipidemia in 386 pediatric renal transplant recipients enrolled in the CERTAIN registry. Data were obtained before and during the first year after RTx to analyze possible non‐modifiable and modifiable risk factors. The prevalence of dyslipidemia was 95% before engraftment and 88% at 1 year post‐transplant. Low estimated glomerular filtration rate at 1 year post‐transplant was associated with elevated serum triglyceride levels. The use of TAC and of MPA was associated with significantly lower concentrations of all lipid parameters compared to regimens containing CsA and mTORi. Immunosuppressive regimens consisting of CsA, MPA, and steroids as well as of CsA, mTORi, and steroids were associated with a three‐ and 25‐fold (P<.001) increased risk of having more than one pathologic lipid parameter as compared to the use of TAC, MPA, and steroids. Thus, amelioration of the cardiovascular risk profile after pediatric RTx may be attained by adaption of the immunosuppressive regimen according to the individual risk profile.     

Early post‐transplant hyperbilirubinemia is a possible predictive factor for developing neurological complications in pediatric living donor liver transplant patients receiving tacrolimus

The cause of post‐transplant CNI‐NCs is multifactorial and not ascribed solely to CNI toxicity. A total of 90 children (aged <20 years) who underwent LDLT were evaluated to investigate the predictive factors associated with CNI‐NCs. Twelve patients (13.3%) developed CNI‐NCs after LDLT (age range, 2‐15 years). The symptoms of CNI‐NCs were seizures, VD, and stupor. The median onset of CNI‐NCs was 10 days (range, 5‐30 days) post‐transplant. In the univariate analysis, higher recipient age at LDLT, donor age and recipient's BW, lower actual GV/SLV and TAC dosage/BW, and higher mean T‐Bil and sodium level for 7 days after transplantation were independently significantly associated with TAC‐NCs. Multivariate analysis showed that the T‐Bil level in the first week after LDLT was the only significant independent predictive factor for TAC‐NCs (HR, 1.588; 95% CI, 1.042‐2.358; P=.031). In conclusion, CNI‐NCs occurred most frequently in children over 5 years and were associated with hyperbilirubinemia for 7 days post‐transplant, regardless of TAC levels. The transplant team should refer to a neurologist to define the diagnosis and to collaborate to resolve the neurological problems.     

Early post‐operative intravenous tacrolimus in pediatric liver transplant recipients is not superior to oral tacrolimus

We aimed to compare the early results of i.v. with p.o. TAC as a primary immunosuppressant in pediatric patients undergoing LT. This retrospective study enrolled 75 children who underwent LT and received TAC‐steroid regimens as a primary immunosuppressant between September 2011 and October 2015 at our institution. Thirty‐five recipients received TAC i.v. and 40 received TAC p.o. Early results were evaluated and compared, including ACR, EBV, or CMV infection; renal adverse effects; and hospital stay. Comparisons of 90‐day post‐transplant results showed that the rates of overall viral (74% vs 40% P < 0.002), EBV (46% vs 17.5% P < 0.008), and CMV (51% vs 30% P = 0.05) infections were significantly higher in the i.v. than in the p.o. group. Neither regimen has any adverse effects on renal function. There were no between‐group differences in ACR incidence and severity, serum creatinine concentration, and hospital stay. Patient and graft survival rates at 3 months and 1 year did not differ significantly between the two groups. Compared with p.o. treatment, i.v. administration of high TAC concentration did not have beneficial post‐transplant effects on ACR incidence and severity, while increasing the incidence of viral infections in pediatric LT.     

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

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

Side effects and efficacy of renal sparing immunosuppression in pediatric liver transplantation—A single center matched cohort study

Immunosuppressive combination therapy with MMF can reduce CNI associated nephrotoxicity. We investigated effectiveness and safety of de novo MMF‐tacrolimus based immunosuppression after pLTx. Patients after pLTx receiving immunosuppression with MMF/tacrolimus (MMF/TAC) were compared to retrospectively selected age‐ and diagnosis‐matched patients with tacrolimus monotherapy (TAC) and cyclosporine/prednisolone therapy (CSA) (19 patients each, n = 57). Effectiveness, renal function and side effects were analyzed for 1 year after pLTx. Tacrolimus reduction in combination therapy (0.7 μg/L over the year) was lower than aspired (2 μg/L). Acute BPAR occurred equally in MMF/TAC and TAC groups (31.6% each), being slightly higher in CSA group (42.1%; OR = 1.5; 95% CI = 0.42‐5.44; P = .5). GFR deteriorated comparably in all 3 groups (P < .01 each) without significant differences between the groups. Septicemia was detected significantly more often in MMF/TAC (73.6%) than in TAC (31.6%) (OR 4.17; 1.07‐16.27; P = .04). EBV reactivation occurred more often in CSA patients (84.2%) than in MMF/TAC (47.4%; OR 5.16; 0.98‐27.19; P = .05) and TAC patients (52.6%; OR 8.16; 1.48‐44.89; P = .02) the same was true for other viral infections (47.4% (CSA) vs 15.8% (TAC); OR 4.21; 0.95‐18.55; P = .05). Our study does not provide additional evidence for a benefit of initial use of MMF/TAC over TAC regarding renal function, but raises concerns regarding a potentially increased risk of serious infections under MMF/TAC compared to TAC monotherapy at equivalent renal outcome; our study is, however, limited by the minor CNI reduction in combination therapy.     

高渗及低渗造影剂对儿童肾脏功能影响的临床研究

目的初步探讨高渗及低渗造影剂对儿童肾脏功能的影响,以及水化对造影剂相关性肾病(CAN)的预防作用。方法将行静脉肾盂造影或增强CT检查的患儿分为高渗造影剂组(HOCM)27例和低渗造影剂组(LOCM)33例,各组患儿随机分为水化组和非水化组。水化组于造影后立即给予1/5张含钠维持液20ml/kg于3h内静脉滴入,非水化组不给予静脉补液。结果(1)HOCM组造影前,非水化组与水化组相比,SCr、Ccr差异均无统计学意义。造影后,HOCM非水化组SCr[(59·71±12·49)μmol/L]较造影前[(49·91±6·09)μmol/L]显著增高(P<0·05),而Ccr造影后[(71·33±7·51)ml/(min·1·73m2)]较造影前[(97·81±15·10)ml/(min·1·73m2)]明显降低(P<0·05);HOCM水化组SCr、Ccr在造影前、后差异无统计学意义(P>0·05)。HOCM非水化组有3例(23·1%,3/13)发生CAN,HOCM水化组无1例发生CAN(P>0·05)。(2)LOCM水化和非水化组造影前、后SCr、Ccr差异均无统计学意义。LOCM非水化组CAN发生率为6·7%(1/15),LOCM水化组11·1%(2/18)(P>0·05)。(3)HOCM非水化组与LOCM非水化组相比,造影后SCr显著升高(Z=-2·42,P<0·05),而Ccr降低(Z=-2·83,P<0·05)。(4)HOCM与LOCM组共计6例CAN在2周内SCr及Ccr恢复至造影前水平。结论(1)肾功能正常的儿童应用高渗或低渗造影剂均可发生可逆的造影剂肾病;(2)高渗造影剂对儿童血肌酐及肌酐清除率的影响大于低渗造影剂;(3)水化可减轻高渗造影剂对儿童肾脏功能的损害;(4)儿童应用低渗造影剂水化后仍可发生CAN。     

Renal function and histology in children after small bowel transplantation

Boyer O, Noto C, Patey‐Mariaud De Serre N, Gubler M‐C, Dechaux M, Goulet O, Niaudet P, Lacaille F. Renal function and histology in children after small bowel transplantation. Abstract: CKD is a frequent long‐term complication after SBTx. CNIs are a well‐known factor, but probably not the only cause. We assessed the incidence, risk factors, and severity of CKD in 27 children with SBTx (15 combined liver/SBTx) and prednisone/TAC‐based maintenance immunosuppression. Median follow‐up was seven yr (3–21). A renal biopsy was performed in 14 patients, 1–18 yr post‐SBTx. A reduced GFR was observed in 17 children (63%) during the follow‐up with none requiring dialysis. CNI toxicity was observed in 11/14 biopsies, as early as two yr post‐transplant, and could occur with a normal mGFR. The dose of TAC was reduced by 50% in 13 patients with CKD and/or significant kidney histological lesions, and six were also given MMF. This led to a significant improvement in renal function: mGFR normalized in eight patients and improved or stabilized in five. No rejection occurred. At last follow‐up, 37% had CKD stage 2 and 15% had CKD stage 3. In conclusion, CKD is frequent in children after SBTx and probably multifactorial. Less nephrotoxic immunosuppressive protocols may improve mGFR and should be further considered. The kidney histology helps in designing personalized immunosuppression strategies for patients.     

Perceived barriers to medication adherence remain stable following solid organ transplantation

Perceived barriers to adherence have previously been investigated in SOT to identify plausible intervention targets to improve adherence and transplant outcomes. Fifteen centers in CTOTC enrolled patients longitudinally. Patients >8 years completed Adolescent Scale(AMBS) at two visits at least 6 months apart in the first 17 months post‐transplant while their guardians completed PMBS. Differences over time for pre‐identified AMBS/PMBS factors were analyzed. Perceived barrier reporting impact on subsequent TAC levels was assessed. A total of 123 patients or their guardians completed PMBS or AMBS. Twenty‐six were 6‐11 years and 97 were ≥12. The final cohort consisted of kidney (66%), lung (19%), liver (8%), and heart (7%) recipients. Unadjusted analysis showed no statistically significant change in reported barriers from visit 1 (median 2.6 months, range 1.2‐3.7 post‐transplant) to visit 2 (median 12, range 8.9‐16.5). Of 102 patients with TAC levels, 74 had a single level reported at both visits. The factor of “Disease frustration” was identified through the PMBS/AMBS questions about fatigue around medication and disease. Each point increase in “disease frustration” at visit 1 on the AMBS/PMBS doubled the odds of a lower‐than‐threshold TAC level at visit 2. No clear change in overall level of perceived barriers to medication adherence in the first year post‐transplant was seen in pediatric SOT. However, disease frustration early post‐transplant was associated with a single subtherapeutic TAC levels at 12 months. A brief screening measure may allow for early self‐identification of risk.     

Mycophenolate mofetil in pediatric renal transplantation: non-induction vs. induction with basiliximab

North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) reports have shown anti-T cell antibody, OKT3, to be deleterious in pediatric renal transplant recipients treated with mycophenolate mofetil (MMF). Unlike OKT3, basiliximab is a chimeric monoclonal antibody to the alpha subunit of the interleukin-2 receptor on activated T-lymphocytes. We sought to examine the outcome of MMF with or without basiliximab induction therapy in pediatric renal transplantation. Between January 1998, and June 2001, 49 pediatric renal transplants were performed at our center and 41 met the criteria for this study. We retrospectively analyzed the records of 25 patients who received MMF, Prednisone, CSA or TAC, alone (group I) and 16 patients who received MMF, CSA or TAC, and Prednisone in combination with basiliximab (group II). The two groups were similar with respect to recipient or donor age, gender, ethnicity, donor source (LD vs. CAD), cold ischemia time, and primary diagnosis. The basiliximab group had a shorter follow up period because of its more recent addition to our pediatric immunosuppression protocol, 12.9 +/- 5.9 months vs. 35.5 +/- 7.2 months for group I (p < 0.0001). At 6 months, the acute rejection rate was 16% (group I) compared with 25% (group II) (p = 0.689). The patient and graft survival at 6 and 12 months were 100% respectively for both groups. Basiliximab was well tolerated without significant adverse events. At 6 months, there was no significant difference between the groups in the incidence of urinary tract infection or cytomegalovirus infection. These data suggest that in the short-term, MMF with or without basiliximab induction therapy appears to yield excellent and statistically similar outcomes. However, further controlled studies are necessary to verify these findings as well as to define the role of basiliximab in MMF-treated pediatric renal transplant recipients.