A pre-transplantation risk assessment tool for graft survival in Dutch pediatric kidney recipients.

Background: A prediction model for graft survival including donor and recipient characteristics could help clinical decision-making and optimize outcomes. The aim of this study was to develop a risk assessment tool for graft survival based on essential pre-transplantation parameters. Methods: The data originated from the national Dutch registry (NOTR; Nederlandse OrgaanTransplantatie Registratie). A multivariable binary logistic model was used to predict graft survival, corrected for the transplantation era and time after transplantation. Subsequently, a prediction score was calculated from the ß-coefficients. For internal validation, derivation (80%) and validation (20%) cohorts were defined. Model performance was assessed with the area under the curve (AUC) of the receiver operating characteristics curve, Hosmer-Lemeshow test and calibration plots. Results: In total, 1428 transplantations were performed. Ten-year graft survival was 42% for transplantations before 1990, which has improved to the current value of 92%. Over time, significantly more living and pre-emptive transplantations have been performed and overall donor age has increased (P < .05).The prediction model included 71 829 observations of 554 transplantations between 1990 and 2021. Other variables incorporated in the model were recipient age, re-transplantation, number of human leucocyte antigen (HLA) mismatches and cause of kidney failure. The predictive capacity of this model had AUCs of 0.89, 0.79, 0.76 and 0.74 after 1, 5, 10 and 20 years, respectively (P < .01). Calibration plots showed an excellent fit. Conclusions: This pediatric pre-transplantation risk assessment tool exhibits good performance for predicting graft survival within the Dutch pediatric population. This model might support decision-making regarding donor selection to optimize graft outcomes. Trial registration: ClinicalTrials.gov Identifier: NCT05388955.

Assessing causality by means of the Naranjo scale in a paediatric patient with life threatening respiratory failure after alemtuzumab administration: a case report.

BACKGROUND: Alemtuzumab is a T cell depleting antibody agent used as induction immunosuppressant therapy in solid organ transplant recipients. In addition, it is being increasingly used to treat severe or glucocorticoid-resistant graft rejection. Despite the effectiveness of the treatment, severe adverse events have been reported related to alemtuzumab administration. We present a similar event illustrating the severity of this adverse drug reaction (ADR) and we highlight the structure causality assessment provides in approaching such a case. CASE PRESENTATION: We report a case of life-threatening respiratory failure after alemtuzumab administration in a 17 year old paediatric kidney transplant recipient. He developed near fatal severe respiratory and circulatory failure based on acute respiratory distress syndrome (ARDS) with diffuse alveolar oedema and haemoptysis hours after his second alemtuzumab administration. As it was questionable whether alemtuzumab could be regarded as the origin of his reaction and in order to assess the causality of this reaction as well as to structure clinical reasoning, we applied a widely used ADR probability scale to systematically review our case. DISCUSSION AND CONCLUSIONS: Our case shows a severe ADR after alemtuzumab administration. It illustrates the importance of proper causality assessment, the structure it provides and the benefit of a clinical pharmacology consultation when a severe reaction is suspected to be an ADR. By taking our case as an example, we demonstrate the added value of structured causality assessment to clinical reasoning and in generating differential diagnoses.

Prognostic Factors on Graft Function in Pediatric Kidney Recipients.

BACKGROUND: Graft survival in pediatric kidney transplant recipients has increased in the last decades. Determining prognostic factors for graft function over time allows the identification of patients at risk for graft loss and could lead to improvement of current guidelines. METHODS: Data were collected among pediatric kidney transplant recipients in a single center during the first 5 years after transplantation. Mixed model analysis was used to indicate possible prognostic factors for the loss of graft function. RESULTS: A total of 100 pediatric kidney transplant recipients were analyzed. Negative prognostics of graft function are higher donor age and higher recipient age, presence of obstructive uropathology, re-transplant, and occurrence of BK viremia. The negative influence on graft function of both donor age and presence of obstructive uropathology increased over time. In this study, the factors that did not influence graft function over time were the number of HLA mismatches, pre-transplant dialysis, intra-abdominal graft placement, ischemia time, occurrence of acute rejection, presence of lower urinary tract dysfunction, occurrence of urinary tract infections, and infections with cytomegalovirus and Epstein-Barr virus. CONCLUSIONS: This study showed that a higher donor age and higher recipient age, presence of obstructive uropathology, a re-transplant, and the occurrence of BK viremia were negative prognostic factors of graft function over time, in the first 5 years after transplant. Graft function was comparable between steroid-sparing regimens (preferable in low-risk patients) and regimens including steroids (for special reasons).

Preparing for a kidney transplant: Medical nephrectomy in children with nephrotic syndrome.

Nephrotic syndrome is characterized by proteinuria, hypoalbuminemia, and general edema. These symptoms may persist in children who reach ESRD, which is unfavorable for the patient's allograft outcome. In addition, this may hamper early diagnosis of a relapse after transplantation. Surgical bilateral nephrectomy is often considered for that reason, but medical nephrectomy may be a less invasive alternative. In this retrospective single-center case series, we identified all children on dialysis with ESRD due to nephrotic syndrome in which a medical nephrectomy was attempted before kidney transplantation between 2013 and 2018. Outcome was measured by urine output and serum albumin levels. Eight patients with either congenital nephrotic syndrome or focal segmental glomerular sclerosis were included in the study. All patients received an ACE inhibitor as drug of first choice for medical nephrectomy, to which 5 patients responded with oligoanuria and a significant rise in serum albumin, and 3 patients responded insufficiently. In 1 of these 3 patients, diclofenac was added to the ACE inhibitor, with good result. In the other 2 patients, indomethacin was initiated without success, and surgical bilateral nephrectomy was performed. Overall, 6/8 patients had a successful medical nephrectomy and did not need surgical nephrectomy. No recurrence of nephrotic syndrome was found after kidney transplantation in all but one. Medical nephrectomy with ACE inhibitors and/or non-steroidal anti-inflammatory drugs is a safe and non-invasive therapy to minimize proteinuria in children with ESRD due to nephrotic syndrome before kidney transplantation. We suggest that this strategy should be considered as therapy before proceeding with surgical nephrectomy.

The potential impact of hematocrit correction on evaluation of tacrolimus target exposure in pediatric kidney transplant patients.

BACKGROUND: Tacrolimus is an important immunosuppressive agent with high intra- and inter-individual pharmacokinetic variability and a narrow therapeutic index. As tacrolimus extensively accumulates in erythrocytes, hematocrit is a key factor in the interpretation of tacrolimus whole blood concentrations. However, as hematocrit values in pediatric kidney transplant patients are highly variable after kidney transplantation, translating whole blood concentration targets without taking hematocrit into consideration is theoretically incorrect. The aim of this study is to evaluate the potential impact of hematocrit correction on tacrolimus target exposure in pediatric kidney transplant patients. METHODS: Data were obtained from 36 pediatric kidney transplant patients. Two hundred fifty-five tacrolimus whole blood samples were available, together responsible for 36 area under the concentration-time curves (AUCs) and trough concentrations. First, hematocrit corrected concentrations were derived using a formula describing the relationship between whole blood concentrations, hematocrit, and plasma concentrations. Subsequently, target exposure was evaluated using the converted plasma target concentrations. Ultimately, differences in interpretation of target exposure were identified and evaluated. RESULTS: In total, 92% of our patients had lower hematocrit (median 0.29) than the reference value of adult kidney transplant patients. A different evaluation of target exposure for either trough level, AUC, or both was defined in 42% of our patients, when applying hematocrit corrected concentrations. CONCLUSION: A critical role for hematocrit in therapeutic drug monitoring of tacrolimus in pediatric kidney transplant patients is suggested in this study. Therefore, we believe that hematocrit correction could be a step towards improvement of tacrolimus dose individualization.

Oscillometric and intra-arterial blood pressure in children post-kidney transplantation: Is invasive blood pressure measurement always needed?

OBJECTIVE: Blood pressure (BP) monitoring in children immediately after kidney transplantation is ideally performed with an arterial line. Accurate measurement of BP is necessary for optimal management. However, during the first days postoperative, the arterial line is removed and BP measurement is switched to a non-invasive device. The aim of this study was to determine the accuracy and reliability of the automated oscillometric device compared to invasive arterial BP (IBP) monitoring in patients after renal transplantation in pediatric intensive care unit (PICU). METHOD: We analyzed all simultaneously measured BPs in children with a kidney transplant in the Amalia Children's Hospital Radboud University Medical Center between January 1, 2012, and January 1, 2016. BP measurements were performed according to the hospital protocol. Agreement between invasive and non-invasive methods was assessed using Bland-Altman plots. RESULTS: A total of 29 patients were included in this retrospective study. The majority of children were male (59%), and median age was 11 years (range 1-17 years). Totally, 80 BP measurements were recorded during the first days post-kidney transplantation. The correlation coefficients (R) of systolic, diastolic, and MAP of non-invasive (NIBP) and IBP measurements were 0.84, 0.76, and 0.77, respectively (P < 0.01). Overall, the average MAP (7.5 ± 1.2 mm Hg; P < 0.05) NIBP values were lower compared to IBP. In hypertensive patients, MAP (10.4 ± 10.0 mm Hg; P < 0.05) BP values were significantly lower using the NIBP device. Clinically relevant difference of >10 mm Hg was found in 51% (41/80) of measurements and mainly observed in hypertensive measurements. CONCLUSIONS: IBP measurement is considered the golden standard for monitoring BP in patients immediately after kidney transplantation. NIBP values showed a good agreement with invasive reading, but the variability of NIBP mainly in hypertensive patients is high as it is the number of clinically relevant differences to IBP. We conclude that IBP remains the golden standard to monitor BP in children directly postoperatively.