Pediatric Kidney Transplantation in the Netherlands collaborative studies

The first successful kidney transplantation dates back to the year 1954. A healthy adult donated a kidney to his identical twin brother with life-threatening kidney disease. No immunosuppressive medication was used. The recipient lived for nine more years, got married, had children, and had a job to his liking.1 This event raised the hopes of all patients with end stage kidney disease. It took another five years before the first kidney transplantation in a child succeeded, with a kidney donated by his identical twin.2 Transplantation is the ultimate modality of renal replacement therapy for end stage renal failure in children. It replaces most of the lost functions of the native kidneys, in contrast to any form of dialysis. Transplantation may restore kidney function within normal ranges, whereas with dialysis no more than 10% of normal clearance is reached. Moreover, dialysis is associated with high morbidity and even mortality. Chronic dialysis in children is therefore not considered as a permanent solution, but as a bridge to transplantation. In the Netherlands kidney transplantation in children is an accepted and feasible option since 1973. In our country the procedure is thought to be feasible in children with a minimum age of 3 years, or a minimum body weight of 12 kg. Either a pediatric or a vascular surgeon performs the transplantation, in some centers together with a pediatric urologist. The grafted kidney is usually placed in the iliac fossa; in case of a small child receiving an adult kidney, the abdomen may be the graft site. The renal blood vessels are anastomosed with the recipient’s external or commune iliac vessels, or, in case of intra-abdominal placement, with the aorta and inferior caval vein. The donor ureter is implanted in the recipient’s bladder. In most centers a temporary intraureteral splint is placed to enable the urine to drain without resistance from the transplanted kidney

The impact of estimated glomerular filtration rate equations on chronic kidney disease staging in pediatric renal or heart transplant recipients

Background: The aim of this study was to evaluate the performance of selected pediatric estimated glomerular filtration rate (eGFR) equations in relation to the clinical management of children after renal or heart transplantation or post-chemotherapy treatment. Methods: This study was a retrospective cross-sectional analysis of 61 children whose glomerular function (GFR) had been determined using a single-dose inulin clearance (iGFR) method. Eight equations for estimating the GFR were evaluated for bias, agreement, accuracy, and clinical stratification. Results: The outcome of all eight eGFR equations differed from the value determined using the iGFR method, with the mean bias ranging from −3.4 to 20.7 ml/min/1.73 m2 and 90 % accuracy ranging from 16 to 26 %. All eGFR equations overestimated renal function in patients with decreased kidney function as determined by the iGFR method and underestimated renal function in patients with normal kidney function. Consequently, based on the eGFR values, patients with low GFR values according to the iGFR method were staged in a less severe chronic kidney disease (CKD) category, and patients with normal GFR values according to the iGFR method were staged in a more severe CKD category. The percentage of correctly classified patients ranged from 32.6 to 41.6 %. Conclusions: In our cohort we found the CKiDIII equation to be the best alternative to calculating the GFR using the inulin clearance method, closely followed by the Hoste and the revised Grubb equations. The performances of all eight eGFR equations assessed were moderate at best and only slightly better than the easy-to-do bedside Schwartz equation

Bronchiectasis in children after renal or liver transplantation: A report of five cases

More effective immunosuppressive treatment in children following organ transplantation has significantly improved the survival of the grafts. Therefore, quality of life, long-term prognosis and adverse drug reactions have become more important. One of the main complications of immunosuppressive drugs is infections of the respiratory tract, but irreversible damage to the airways has not been described after renal or liver transplantation. Five children following transplantation of kidney or liver were referred to the Paediatric Pulmonology department because of chronic respiratory complaints. Pulmonary function tests and HRCT scan were performed as routine patient care. Four children with a renal transplant and one with a liver transplant showed chronic bronchitis and moderate to severe airways obstruction. HRCT showed bronchiectasis in all of them. We speculate that the immunosuppressive treatment (in) directly contributes to irreversible airway damage. We recommend including follow-up of lung function in the post-transplantation protocol and considering bronchiectasis in case of respiratory symptoms, to try preventing further damage to the lung

Diagnostic value of urinary dysmorphic erythrocytes in clinical practice

Background: In clinical practice, discriminating between glomerular and nonglomerular causes of hematuria is often difficult. Dysmorphic red blood cells (dRBC) in the urinary sediment are claimed to be effective, but the cutoff points in the literature vary. This follow-up study aimed to determine the diagnostic value of dRBC. Methods: We investigated 134 hematuria patients in the departments of nephrology and urology. To diagnose the origin of hematuria, urological and/or nephrological examination was performed and the %dRBC identified by microscopy. Follow-up was performed after 3.5 years. Results: The cause of hematuria was proven in 68 patients (35% glomerular; 65% nonglomerular). Patients with glomerular disease had significantly more albuminuria and dRBC than patients with nonglomerular disease, but the %dRBC ranged from 1 to 50% and no optimal cutoff could be identified. Logistic regression analysis showed that %dRBC had a predicted probability to diagnose glomerular disease of 77.9% (area under the curve, AUC, 0.85). When %dRBC was combined with other risk factors such as serum creatinine, sex, age, dipstick erythrocyte or proteinuria score and number of casts, the predictive probability increased to 90.6% (AUC 0.97). Follow-up of the included patients showed no benefit of dRBC to identify patients at risk for glomerular disease. Conclusions: The diagnostic value of routinely collected urinary dRBC to diagnose glomerular disease in patients presenting with hematuria is modest. However, including dRBC with other variables, such as age and erythrocyte score on dipstick testing may increase the sensitivity, but needs to be confirmed in another, preferably larger, population. Copyrigh

Topotecan distribution in an anephric infant with therapy resistant bilateral Wilms tumor with a novel germline WT1 gene mutation

The therapeutic strategy for bilateral Wilms tumor (WT) remains a challenge. Especially in cases with chemotherapy resistant disease, bilateral nephrectomy is sometimes inevitable. For optimal cure rates stage V WT patients benefit from adjuvant treatment; however, there are limited data available on chemotherapy pharmacokinetics in anephric children. In this report, we describe a 10-month old girl with bilateral Wilms tumor and a novel germline WT1 gene mutation. This patient hardly showed any response on preoperative chemotherapy, and ultimately, underwent sequential bilateral tumor-nephrectomy. Subsequently, during peritoneal dialysis, she received topotecan as adjuvant chemotherapy based on plasma levels, indicating that this is a reasonable option as adjuvant treatment in therapy-resistant Wilms tumor patients after bilateral nephrectomy. This case showed a novel germline WT1 gene mutation of which the correlation with resistant phenotype has to be confirmed in larger cohorts of WT patients

Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission

__Introduction__ Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are novel AKI biomarkers whose performance in pediatric ICU patients is largely unknown. In this study, we aimed to characterize uNGAL and KIM-1 patterns in children following ICU admission and to assess their properties in relation to identifying children at risk for AKI development. __Methods__ From June 2010 until January 2014, we conducted a prospective observational cohort study of term-born children ages 1day to 1year on mechanical ventilation. Blood and urine samples were obtained every 6 to 12hours up to 72hours post-admission. Blood samples were assayed for SCr, and urine samples were assayed for uNGAL and KIM-1. The RIFLE (risk, injury, failure, loss, end-stage renal disease) classification as 150%, 200% or 300% of median SCr reference values was used to define AKI. __Results__ A total of 100 children were included (80 survived). Their median age at admission was 27.7days (interquartile range (IQR), 1.5 to 85.5). The median duration of mechanical ventilation was 5.8days (IQR, 3.1 to 11.4). Thirty-five patients had evidence of AKI within the first 48hours post-admission, of whom 24 (69%) already had AKI when they entered the ICU. uNGAL and KIM-1 concentrations in AKI peaked between 6 to 12hours and between 12 to 24hours post-admission, respectively. The maximal area under the receiver operating characteristic curve (AUC) for uNGAL was 0.815 (95% confidence interval (CI), 0.685 to 0.945, P <0.001) at 0 to 6hours post-admission. The discriminative ability of KIM-1 was moderate, with a largest AUC of 0.737 (95% CI, 0.628 to 0.847; P <0.001) at 12 to 24hours post-admission. At the optimal cutoff point (126ng/ml), uNGAL concentration predicted AKI development correctly in 16 (84%) of 19 children, up to 24hours before a rise in SCr became apparent. __Conclusions__ Levels of uNGAL and KIM-1 increase in patients with AKI following ICU admission and peak at 6 to 12hours and 12 to 24hours post-admission, respectively. uNGAL seems to be a reliable marker for identifying children who will develop AKI 24hours later

Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1-infected children treated with indinavir

BACKGROUND: Prolonged administration of indinavir is associated with the occurrence of a variety of renal complications in adults. These well-documented side effects have restricted the use of this potent protease inhibitor in children. DESIGN: A prospective study to monitor indinavir-related nephrotoxicity in a cohort of 30 human immunodeficiency virus type 1-infected children treated with indinavir. METHODS: Urinary pH, albumin, creatinine, the presence of erythrocytes, leukocytes, bacteria and crystals, and culture were analyzed every 3 months for 96 weeks. Serum creatinine levels were routinely determined at the same time points. Steady-

Childhood Estimates of Glomerular Filtration Rate Based on Creatinine and Cystatin C: Importance of Body Composition

__Background:__ Creatinine and cystatin C concentrations are commonly used to estimate glomerular filtration rate (eGFR) in clinical practice and epidemiological studies. To estimate the influence of different body composition measures on eGFR from creatinine and cystatin C blood concentrations, we compared the associations of different anthropometric and body composition measures with eGFR derived from creatinine (eGFRcreat) and cystatin C (eGFRcystC) blood concentrations. __Methods:__ In a population-based cohort study among 4,305 children aged 6.0 years (95% range 5.7-8.0), we measured weight and height and calculated body mass index (BMI) and body surface area (BSA), and lean and fat mass using dual-energy X-ray absorptiometry. At the same age, we measured creatinine and cystatin C blood concentrations and estimated the GFR. __Results:__ Correlation between eGFR based on creatinine and cystatin C concentrations was r = 0.40 (p value <0.01). Higher BMI was associated with lower eGFRcystC but not with eGFRcreat. Higher BSA was associated with higher eGFRcreat and lower eGFRcystC (p value <0.05). Lean and fat mass percentages were associated with eGFRcreat but not with eGFRcystC. __Conclusion:__ Our findings suggest that both eGFRcreat and eGFRcystC are influenced by BMI and BSA. eGFRcreat is more strongly influenced by body composition than eGFRcystC

Acute kidney injury is a frequent complication in critically ill neonates receiving extracorporeal membrane oxygenation: A 14-year cohort study

Introduction: Newborns in need of extracorporeal membrane oxygenation (ECMO) support are at high risk of developing acute kidney injury (AKI). AKI may occur as part of multiple organ failure and can be aggravated by exposure to components of the extracorporeal circuit. AKI necessitates adjustment of dosage of renally eliminated drugs and avoidance of nephrotoxic drugs. We aimed to define systematically the incidence and clinical course of AKI in critically ill neonates receiving ECMO support. Methods: This study reviewed prospectively collected clinical data (including age, diagnosis, ECMO course, and serum creatinine (SCr)) of all ECMO-treated neonates within our institution spanning a 14-year period. AKI was defined by using the Risk, Injury, Failure, Loss of renal function, and End-stage renal disease (RIFLE) classification. SCr data were reviewed per ECMO day and compared with age-specific SCr reference values. Accordingly, patients were assigned to RIFLE categories (Risk, Injury, or Failure as 150%, 200%, or 300% of median SCr reference values). Data are presented as median and interquartile range (IQR) or number and percentage. Results: Of 242 patients included, 179 (74%) survived. Median age at the start o