Health-related quality of life in intensively treated young patients with type 1 diabetes

Abstract:  This study aimed to analyse the impact of the disease and treatment on health-related quality of life (HRQOL) in intensively treated young patients with diabetes. Our main hypothesis was that metabolic control, gender, age and socio-economic status predict HRQOL. All children and adolescents (n = 400, 191 girls) and parents in a geographic population of two paediatric clinics in Sweden [mean age 13.2 yr, ±SD 3.9, range 2.6–19.6; mean duration of diabetes 5.1 yr, ±SD 3.8, range 0.3–17.6; yr mean haemoglobin A1c (HbA1c) 7.1%, ±SD 1.2, range 4.0–10.7] received the DISABKIDS questionnaire, a validated combined chronic generic and condition-specific HRQOL measure for children, and the EuroQol-5D questionnaire. Parents as proxy perceived HRQOL lower than their children. Adolescents with separated parents reported lower generic HRQOL (GeHRQOL) and diabetes-specific HRQOL (DiHRQOL) than those with parents living together (p = 0.027 and p = 0.043, respectively). Adolescent girls reported lower GeHRQOL (p = 0.041) and DiHRQOL (p = 0.001) than boys did. Parents of girls <8 yr of age reported lower DiHRQOL (p = 0.047) than did parents of boys <8 yr. In addition, a difference was found in HRQOL between centres. Intensive insulin therapy did not seem to lower HRQOL. If anything, along with better metabolic control, it increased HRQOL. A correlation between DiHRQOL and HbA1c was found in adolescents (r = −0.16, p = 0.046) and boys aged 8–12 yr (r = −0.28, p = 0.045). We conclude that the diabetes team can influence the HRQOL of the patients as there was a centre difference and because HRQOL is influenced by glycaemic control and insulin regimen. Girls seem to need extra support.     

Physical activity and health related quality of life in children following kidney transplantation

Abstract:  Participation in PA is often diminished in children with CKD. Limited research exists on exercise tolerance/capacity but no studies to date have investigated lifestyle PA and its determinants in these children. The aim of this study was to investigate level of PA and potential physiological and psychological associations in a group of pediatric KTx recipients compared with CS. Twenty KTx and 33 CS participated. PA was measured by PAQ. HRQOL (PedsQL 4.0) and CY-PSPP were also measured. BMI and WC was recorded in all subjects; GFR, BP and immunosuppressants in KTx. Body measurements indicated the two groups were similar: 25% KTx and 24% CS had BMI >85th percentile. KTx were less physically active than CS in total exercise minutes (p = 0.005). CS reported higher HRQOL than KTx (p = 0.001). Higher perceptions of HRQOL were significantly correlated with higher number of steps/day in both groups (p = 0.034). KTx showed significantly lower perceptions of sports competence (p = 0.007) and physical conditioning (p = 0.001) than CS. Higher PAQ activity scores were significantly correlated with higher perceptions of body attractiveness (p = 0.019), Sport (p = 0.003) and Conditioning (p = 0.001). These results suggest that PA may play a role in overall well-being and HRQOL in KTx.     

Health-related quality of life in pediatric liver transplant recipients compared with other chronic disease groups

Limbers CA, Neighbors K, Martz K, Bucuvalas JC, Webb T, Varni JW, Alonso EM, on behalf of the Studies of Pediatric Liver Transplantation (SPLIT) Functional Outcomes Group (FOG). Health‐related quality of life in pediatric liver transplant recipients compared with other chronic disease groups.
Pediatr Transplantation 2011: 15: 245–253. © 2010 John Wiley & Sons A/S. Abstract: This cross‐sectional, multicenter cohort study compares the level of HRQOL of pediatric LT recipients to children with other chronic health conditions. LT sample included 873 children who survived at least 12 months following LT. Six chronic disease samples were compiled from numerous studies, including over 800 patients with JRA, type 1 diabetes, cancer in remission, cardiac disease, end‐stage renal disease, and inflammatory bowel disease. Generic HRQOL was measured from both the parental and patient perspective using the PedsQL? 4.0 Generic Core Scales. Pediatric LT patients reported better physical health than children with JRA. According to parents, pediatric LT recipients had better HRQOL than children on renal dialysis on all domains except school functioning. Across all domains but emotional functioning, pediatric LT recipients reported significantly lower HRQOL than children with type 1 diabetes. Overall, pediatric LT patients reported HRQOL comparable to that of children who had undergone renal transplantation and patients with cancer in remission. Pediatric LT patients manifested impaired HRQOL similar to that of children with chronic diseases and these data suggest that they face ongoing challenges that warrant monitoring and indicate a need for interventions to improve their HRQOL.     

The evaluation of bone metabolism in children with renal transplantation

This study aims to evaluate BMD and bone biomarkers and to investigate the effects of immunosuppressives on bone disease after RTx. Thirty‐three RTR aged 16.7 ± 3.7 yr and healthy controls (n = 32) were enrolled. There was no difference between pre‐RTx BMD and BMD at the time of study (45.9 ± 30.9 months after RTx), while both values were lower than controls (p < 0.01 and p < 0.05, respectively). Worst BMD scores were obtained at sixth month after RTx (?0.2 ± 0.9) and best at fourth year (1.4 ± 1.3). 25‐hydroxy‐(OH) vitamin D and OPG were higher in RTR (p < 0.001). BMD z scores negatively correlated with OPG and cumulative CS doses at the time of study (r = ?0.344, p < 0.05 and r = ?0.371, p < 0.05, respectively). Regression analysis revealed OPG as the only predictor of BMD (β ?0.78, 95% CI ?0.004 to ?0.013, p < 0.001). The increase in OPG, a significant predictor of BMD, could either be secondary to graft dysfunction or for protection against bone loss. CS doses should be minimized to avoid their untoward effects on bone metabolism.     

Hyponatremia increases mortality in pediatric patients listed for liver transplantation

Carey RG, Bucuvalas JC, Balistreri WF, Nick TG, Ryckman FR, Yazigi N. Hyponatremia increases mortality in pediatric patients listed for liver transplantation.
Pediatr Transplantation 2010: 14: 115–120. © 2009 John Wiley & Sons A/S.
Abstract:  To evaluate hyponatremia as an independent predictor of mortality in pediatric patients with end-stage liver disease listed for transplantation. We performed a single-center retrospective study of children listed for liver transplantation. We defined hyponatremia as a serum sodium concentration <130 mEq/L that persisted for at least seven days. The primary outcome was death on the waiting list. Ninety-four patients were eligible for the study. The prevalence of hyponatremia was 26%. Kaplan–Meier survival analysis demonstrated that patients with hyponatremia had decreased pretransplant survival compared with patients who maintained a serum sodium >130 mEq/L (p < 0.001). Univariable association analyses demonstrated death on the waiting list was also associated with higher median PELD scores at listing (p = 0.01), non-white race (p = 0.02), and age <1 yr (p = 0.001). Logistic regression analysis identified hyponatremia and non-white race as independently associated with pretransplant mortality [OR = 8.0 (95% CI: 1.4–45.7), p = 0.02 and OR = 6.3 (95% CI: 1.25–33.3), p = 0.03]. When hyponatremia was added to the PELD score, it was significantly better in predicting mortality than the PELD score alone ( c -statistic = 0.79, p = 0.03). Hyponatremia identifies a subset of pediatric patients with increased risk of pretransplant mortality and improves the predictive ability of the current PELD score.     

Predicting ideal outcome after pediatric liver transplantation: An exploratory study using machine learning analyses to leverage Studies of Pediatric Liver Transplantation Data

Machine learning analyses allow for the consideration of numerous variables in order to accommodate complex relationships that would not otherwise be apparent in traditional statistical methods to better classify patient risk. The SPLIT registry data were analyzed to determine whether baseline demographic factors and clinical/biochemical factors in the first‐year post–transplant could predict ideal outcome at 3 years (IO‐3) after LT. Participants who received their first, isolated LT between 2002 and 2006 and had follow‐up data 3 years post–LT were included. IO‐3 was defined as alive at 3 years, normal ALT (<50) or GGT (<50), normal GFR, no non‐liver transplants, no cytopenias, and no PTLD. Heat map analysis and RFA were used to characterize the impact of baseline and 1‐year factors on IO‐3. 887/1482 SPLIT participants met inclusion criteria; 334 had IO‐3. Demographic, biochemical, and clinical variables did not elucidate a visual signal on heat map analysis. RFA identified non‐white race (vs white race), increased length of operation, vascular and biliary complications within 30 days, and duct‐to‐duct biliary anastomosis to be negatively associated with IO‐3. UNOS regions 2 and 5 were also identified as important factors. RFA had an accuracy rate of 0.71 (95% CI: 0.68‐0.74), PPV = 0.83, and NPV = 0.70. RFA identified participant variables that predicted IO‐3. These findings may allow for better risk stratification and personalization of care following pediatric liver transplantation.     

Methylenetetrahydrofolate reductase and methionine synthase reductase gene polymorphisms and protection from microvascular complications in adolescents with type 1 diabetes

Abstract:  Folate status has been associated with endothelial dysfunction in adolescents with type 1 diabetes, and elevated total plasma homoocyst(e)ine (tHcy) is a risk for vascular disease in the non-diabetic population. Polymorphisms in genes involved in folate and homocysteine metabolism are implicated in vascular disease. We aimed to determine whether polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes are risk factors for early microvascular disease in a large group of adolescents with type 1 diabetes. Four hundred and eighty adolescents were screened annually for retinopathy and microalbuminuria for a median of 4 yr. Molecular analysis for the polymorphisms 677C→T, 1298A→C in MTHFR, and 66A→G in MTRR was performed. The MTRR 66GG genotype reduced the risk for elevated albumin excretion rate (AER) (OR 0.47, CI 0.25, 0.88, p = 0.018) and showed a trend to reduced risk for microalbuminuria (OR 0.27, CI 0.06–1.21, p = 0.09). Survival without elevated AER was increased with the MTRR 66GG genotype (12.4 vs. 9.7 yr, p = 0.04) and with the MTHFR 1298CC genotype (15.2 vs. 10.2 yr, p = 0.007). Conversely, survival without retinopathy was reduced with the MTHFR 677TT and MTRR 66GG combined genotype (6.2 vs. 10.2 yr, p = 0.015). The MTRR 66GG and MTHFR 1298 CC genotypes may confer protection against early nephropathy, possibly because they are associated with lower tHcy. The MTHFR 677 TT was only related to earlier onset retinopathy in combination with MTRR 66GG.     

Parental functioning improves the developmental quotient of pediatric liver transplant recipients

Psychomotor development in pediatric liver transplant (LT) recipients depends on several factors. Our aim was to evaluate the importance of parental involvement and family dynamics on psychomotor development by assessing (i) children and parents individually, (ii) the parent–child relationship, and (iii) the correlation between parental functioning and patient outcome, all before and after LT. Age‐appropriate scales were used before and after LT. Twenty‐one patients, 19 mothers, and 16 fathers were evaluated. Developmental quotient (DQ): No subjects scored in the “very good” range. The proportion of children with deficits increased from LT to two yr: 17.6% vs. 28.6%. Subjects 0–2 yr were more likely to have normal DQ at transplant (66.7% vs. 50% for older children). Abnormal DQ was more prevalent two yr post‐LT in children older at LT (p = 0.02). The mother–child relationship was normal in 59% of families pre‐LT and in 67% at two yr. The relationship was more favorable when the child received a transplant as an infant (p = 0.014 at 12 months post‐LT). Normal DQ was associated with higher maternal global functioning score pre‐LT (p = 0.03). Paternal performance scores were higher than maternal scores. Children transplanted after two yr of age suffer greater long‐term deficits than those transplanted as infants.     

Health‐related quality of life in parents of pediatric solid organ transplant recipients in Japan

Few studies have examined HRQOL in pediatric Tx recipients’ parents. This study investigated HRQOL in these parents and relationships between HRQOL and perceived burden of nurturing, family functioning, and social support. Self‐report anonymous questionnaires and a survey of medical records were completed between September and December 2013. The SF‐36v2, which evaluates physical, psychological, and social health, was used to measure HRQOL. While values for physical and psychological health were higher than standard values (Cohen's d = 0.34 and 0.17, respectively), social health scores were lower (d = 0.21). “Parental consultation unrelated to donation” (standardized partial regression coefficient: β = ?0.52) was associated with physical health. “Family functioning” and “Commuting time between home and primary follow‐up hospital” (β = 0.57 and ?0.31) were related to psychological health. “Total score for perceived burden of nurturing” (β = ?0.31) was related to social health. Regarding parental HRQOL, while physical and psychological health was favorable, social health was impaired. In clinical practice, interventions targeting parents’ physical conditions and facilitation of community and family understanding and support to share recipients’ nurturing are important in improving parental HRQOL.     

The effect of donor/recipient body surface area ratio on outcomes in pediatric kidney transplantation

Abstract:  In pediatric kidney transplantation, the effect of inadequate nephron dosing on graft survival remains undetermined. The aim of this study was to assess the use of D/R BSA, as a reliable indicator of adequate nephron dosing, and eventually a tool to optimize pediatric graft allocation. Following Institutional Review Board approval, we reviewed deceased donor pediatric kidney transplantation (N = 156). We divided patients into three groups, based on D/R BSA: A ≤0.8; B 0.81–1.19; C ≥1.2. Five-yr graft survival rates in the groups were: A 82.0%; B 94.9%; C 97.1% (p   =   0.01). Group C had the lowest rate of acute rejection, suggesting a protective effect of increased D/R BSA (group A = 35.7%, group B = 38.9%, group C = 18.8%; p   =   0.029). The logistic regression analysis showed that decreased D/R BSA ratio is a risk factor for loss of graft function, at one and five yr [i.e., group A OR 6 (95% CI 1.14–39.30, p   =   0.015) and OR 4.49 (95% CI 1.46–13.79, p = 0.009), respectively]. We conclude that for pediatric recipients, D/R BSA is a valuable adjunct when determining long-term graft survival. Its utility may avoid an alloimmune-independent risk factor, increasing the long-term protective value of a good matching policy.     

Health‐related quality of life in pediatric intestinal transplantation

To determine HRQOL after pediatric intestinal transplantation. Thirty‐four IT survivors from 1999 to 2012 were asked to complete age‐specific HRQOL non‐disease‐specific questionnaires: TAPQOL (0–4 yr), KINDL‐R (5–7 yr; 8–12 yr; 13–17 yr), and SF‐36v2 (>18 yr), all validated with Spanish population. Primary caregiver completed a SF‐36 questionnaire and CBI. Thirty‐one participants were included. Median age was 10.2 yr (1–29) and time after transplant 4.4 yr (0–13). Overall patient scores were 78.2 ± 10.6 (n = 8), 83.3 ± 9.7 (n = 6), 72.2 ± 9.21 (n = 6), 80.5 ± 12.4 (n = 7), and 82.2 ± 12.4 (n = 4) for each age group. Highest scores were obtained for vitality (group I), self‐esteem (group IV), and physical and social functioning and emotions (group V). Lowest scores were obtained in appetite and behavior (I), family and school (III), and chronic disease perception (III, IV). No significant differences were found between caregivers and their children. CBI showed stress in 52%. SF‐36 for caregivers was lower than general population. No significant differences were found depending on relevant clinical and sociodemographic data. HRQOL was acceptable and improved with age and time since transplantation. Parents had a slighter own QOL and worse perception of health than their children. When successful, intestinal transplantation allows a normal life in most patients and can be offered as an attractive option.     

Standard dosing of tacrolimus leads to overexposure in pediatric renal transplantation recipients

Abstract:  Tacrolimus dosage in pediatric RTRs is empirically based on weight. There is evidence that adolescents are at greater risk of toxicity than young children on this dosing regimen. We investigated the rate of tacrolimus overexposure within the first three wk post-transplantation in pediatric RTRs receiving tacrolimus 0.15 mg/kg twice daily. Of 63 RTRs studied, 41 (65.1%) experienced a tacrolimus level above the therapeutic range (supratherapeutic), the majority (48.8%) on days two to four post-transplant. Patients with supratherapeutic levels were older (14.2 vs. 9.9 yr, p = 0.016), taller (146.7 vs. 126.5 cm, p = 0.029), larger (1.36 vs. 1.01 m², p = 0.039) and heavier (44.1 vs. 29.3 kg, p = 0.043) and by day 12 were receiving much lower tacrolimus doses than those without supratherapeutic levels (0.425 vs. 0.198 mg/kg/day, p = 0.0002). Supratherapeutic levels were more common among white (British) children than other ethnic groups (74 vs. 45%, p = 0.02). There were no observed differences in rates of patient or graft survival, or acute rejection during the three-yr study period. Adolescent patients appear to be at greater risk of excessive tacrolimus dosing on a standard regimen. We therefore outline a regimen restricting tacrolimus dosage given to larger/older patients, but emphasize the need for a prospective randomized trial to define optimal dosing.     

B‐type natriuretic peptide trends after pediatric heart transplantation

BNP is increasingly utilized in the management of pediatric HT recipients. Performing a retrospective single‐center chart review, we sought to describe BNP changes during the first year after HT and identify factors that affect its trend. After exclusion for rejection, 316 BNP levels from 50 patients were evaluated. BNP underwent an exponential decline 120 days after HT followed by a plateau. Log₁₀BNP decline strongly correlated with time (r = ?0.70, p < 0.0001). Initial BNP was less in pretransplant VAD (p = 0.0016) and lower post‐HT inotrope use (p = 0.0043). Infant recipients, IT >4 h, and those bridged medically were associated with higher plateau BNP. Multivariable logistic regression demonstrated IT >4 h independently predicted plateau BNP in the upper quartile (OR 7.1, p = 0.02). No significant change in BNP coincided with rejection (N = 6 patients) without severe hemodynamic compromise. BNP correlated modestly with right atrial pressure (r = 0.4652, p < 0.0001) and pulmonary capillary wedge pressure (r = 0.2660, p < 0.001), but poorly with echocardiogram (r = ?0.18, p = 0.003). Trending BNP could help provide insight into how the graft recovers after HT and IT >4 h independently predicted higher plateau BNP and may reflect subtle changes in graft performance.     

Adherence and health-related quality of life in adolescent liver transplant recipients

Abstract:  Adolescence is a particularly high-risk period for non-adherence with post-transplant medical regimens. There remains a lack of research investigating factors related to non-adherence in adolescent LT recipients. The present study empirically assessed the relationship between adherence and HRQOL in adolescent LT recipients. Participants included 25 adolescents (mean = 15.1 yr, range 12–17.9) and their parent/guardian(s). Adherence was assessed using multiple indices including clinician-conducted interviews, rate of clinic attendance, and s.d. of consecutive tacrolimus blood levels. HRQOL was examined using self-report and parent-proxy report on well-validated assessment measures. Results indicated that 76% of participants were non-adherent on at least one measure of adherence, and HRQOL was significantly lower than normative data for healthy children. Tacrolimus s.d. were significant related to poor HRQOL across domains of physical, school, and social functioning. Non-adherent adolescents reported poorer health perceptions, self-esteem, mental health, family cohesion, and more limitations in social and school activities related to physical, emotional, and behavioral problems. These results suggest that empirically based assessment of HRQOL may help identify those at highest risk for behavior, emotional and school difficulties, as well as non-adherence. The examination of tacrolimus s.d. may also help identify patients who may benefit from intervention to promote adherence and HRQOL. Prospective investigations are necessary to further identify the impact of HRQOL on adherence and long-term health outcomes to further guide clinical intervention.     

Quality of life in pediatric liver transplantation in a single‐center in South America

Sanchez C, Eymann A, De Cunto C, D’Agostino D. Quality of life in pediatric liver transplantation in a single‐center in South America.
Pediatr Transplantation 2010: 14: 332–336. © 2009 John Wiley & Sons A/S. Abstract: HRQOL in children after LT has not been systematically measured in transplant recipients from South American countries. The aim of this study was to determine the HRQOL using a validated measure for children. The CHQOL‐PF50 was completed by the parents of 54 patients after the clinical assessment. Subscale mean scores were compared with both a normal population (n = 274) and a group of chronic illness patients with Juvenile Idiopathic Arthritis (n = 23). Compared with the normal population, LT recipients had lower subscales scores for general health perceptions, role/social emotional, mental health, and parental impact on time. Bodily pain was significantly lower in our study group. Both mean physical and psychosocial summary scores were lower compared to the normal population but similar to the JIA group. Within the LT population, gender, original diagnosis, type of immunosuppression, type of transplant and time elapsed since LT did not significantly influence any of the summary scores. Our study showed LT children’s physical and psycho‐social areas were lower compared with those of the general population. LT children had less limitations due to pain. Family functioning appeared normal.     

Risk factors for impaired quality of life and psychosocial adjustment after pediatric heart,kidney, and liver transplantation

Few studies compare HRQOL and PSA in children who have undergone different types of solid organ Tx. In this cross‐sectional study, HRQOL and PSA were assessed in 74 Tx patients (16 heart, 44 kidney, 14 liver) at a mean age of 11.5 (range 6.3–16.7), 7.2 yr post‐Tx (range 1.0–15.0). HRQOL was self‐assessed using standardized health utility questionnaires (15D–17D). The patients' PSA was evaluated using the Child Behavior Checklist for parents, Youth Self‐Report for patients aged 11–16 yr, and Teacher Report Form. Outcomes did not differ significantly between Tx groups. Preadolescents (8–11 yr) reported poorer HRQOL compared with same‐age peers (p = 0.020). In contrast, adolescents reported similar HRQOL and PSA compared to the general population. Proxy‐reports revealed more PSA problems compared with age expectations (p < 0.01), mainly in internalizing behavior (p < 0.01). Lower HRQOL was associated with shorter follow‐up time since Tx, congenital disease, and a psychiatric or neurological diagnosis. PSA problems were associated with family‐related variables, neurological diagnosis, shorter follow‐up time, and in teacher‐reports longer disease duration before Tx. Different pediatric Tx groups have similar outcome. Neurological comorbidity and shorter follow‐up time are important risk factors, but the impact of family‐related variables on PSA indicate the need of family interventions.     

The use of hepatitis B immunoglobulin with or without hepatitis B vaccine to prevent de novo hepatitis B in pediatric recipients of anti‐HBc–positive livers

Prophylactic measures are used to reduce DNHB after HBsAg‐negative patients receive anti‐HBc–positive liver grafts. This study investigated the incidence of DNHB and clinical outcomes in pediatric LT recipients under HBIG prophylaxis, with or without hepatitis B vaccination. Between 1995 and 2013, 51 HBsAg‐negative pediatric recipients underwent living‐donor LT from anti‐HBc–positive donors. The median (range) age was 4 (0.1‐17) years, 23 (45%) were male, and 71% were negative for both anti‐HBc and anti‐HBc. During a median follow‐up of 12.1 (0.06‐19.9) years, 13 (25.4%) developed DNHB; 7 of the 13 achieved HBsAg seroconversion after administration of LAM or ETV. Among studied patients, 20 (39%) received hepatitis B vaccination, and 2 of them (10%) developed DNHB. At last follow‐up, 41% (21/51) discontinued HBIG either after successful HBV vaccination (n = 17) or retransplantation with anti‐HBc–negative grafts (n = 4). In conclusion, pediatric LT recipients of anti‐HBc–positive grafts, most of them were naïve to HBV infection, were at high risk of DNHB, and consistent monitoring for the early detection of DNHB was necessary. A combination use of post‐LT vaccination is promising prophylactic strategy against DNHB.     

FcγRIIIa-V/F 158 polymorphism in Turkish children with asthma bronchiale and allergic rhinitis

Fc receptors (FcR) play an important role in immune regulation. This might be linked to the variability in immune response, therefore relating to the pathogenesis of atopic diseases. The aim of the present study was to evaluate the Fc γ RIIIa gene polymorphism in Turkish children with asthma and allergic rhinitis. The study included 364 atopic children (184 bronchial asthma, 180 allergic rhinitis) and 234 healthy subjects as the control group, aged between 5 to 16 years. Patients were recruited from outpatient clinics of allergy and general pediatric care. Plasma IgE concentrations were measured by immunoassays and skin prick test was done in children with atopic diseases. The Fc γ RIIIa gene polymorphism was determined using the polymerase chain reaction method. Distribution of V158V genotype was significantly different among patient groups compared to controls (for asthmatic children OR: 5.33, 95% CI: 2.80–10.23, p < 0.001; for allergic rhinitis OR: 3.25, 95% CI: 1.75–6.07, p = 0.001). Distribution of 158 V allele was significantly different among asthmatic children (OR: 2.20, 95% CI: 1.65–2.92, p < 0.001) and allergic rhinitis patients (OR: 1.77, 95% CI: 1.32–2.35, p < 0.001) compared to healthy controls. Our study shows that the V158V genotype in Fc γ RIIIa gene polymorphism may be a genetic risk factor for the development of atopic diseases.     

Patient selection critical for calcineurin inhibitor withdrawal in pediatric kidney transplantation

Abstract:  CNI withdrawal may be employed as a "rescue" strategy for patients with established renal allograft injury and/or declining allograft function, with the aim at eliminating CNI-associated nephrotoxic effects. This analysis reviews outcomes in a pediatric population and identifies risk factors for adverse events post-CNI withdrawal. We performed a retrospective analysis of 17 pediatric renal transplants who underwent CNI withdrawal, with conversion to sirolimus and MMF. Mean CrCl decreased from 64.3 ± 22 to 59.38 ± 28.6 mL/min/1.73 m² (p = 0.04) at six months and 57.46 ± 31.1 mL/min/1.73 m² (p = 0.02) at 12 months post-withdrawal. Forty-one percent of patients experienced AR. Increased risk for AR was associated with prior AR history, lower sirolimus trough levels, and lower CNIT biopsy scores. Graft loss (24%) was associated with worse CrCl, proteinuria, and histologic chronicity. Proteinuria (spot protein/creatinine ratio) increased from 0.75 ± 1.0 to 1.71 ± 2.0 (p = 0.03), unrelated to de novo sirolimus use. Four patients returned to CNI-based immunosuppression due to AR (n = 3) and gastrointestinal side effects (n = 1). Careful selection of pediatric candidates for CNI withdrawal is recommended. Worsening graft function and graft loss may be minimized by selecting patients with high CNIT scores and low biopsy chronicity and excluding patients with prior AR history.     

Tacrolimus‐related seizure after pediatric liver transplantation – A single‐center experience

To identify the risk factors for new‐onset seizures after pediatric LT and to assess their clinical implications and long‐term prognosis. The clinical and laboratory data of 27 consecutive children who underwent LT from January 2007 to December 2010 in our center were analyzed retrospectively. Patients were divided into seizures group and a non‐seizures group. Pre‐operative, intra‐operative, and post‐operative data were collected. Seizures occurred in four children, an incidence of 14.8%. All exhibited generalized tonic–clonic seizures within the first two wk after LT. Univariate analysis showed that the risk factors associated with seizures after pediatric LT included gender, pediatric end‐stage liver disease score before surgery, Child–Pugh score before surgery, serum total bilirubin after surgery, and trough TAC level. Multivariate analysis showed that trough TAC level was the only independent risk factor associated with the seizures. All children who experienced seizures survived with good graft function and remained seizure‐free without anti‐epileptic drugs over a mean follow‐up period of 33.7 ± 14.6 months. High trough TAC level was the predominant factor that contributed to seizures in the early post‐operative period after pediatric LT. High PELD and Child‐Pugh scores before LT and high post‐operative serum Tbil may be contributory risk factors for TAC‐related seizures.