ADPedKD: A Global Online Platform on the Management of Children With ADPKD.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of renal failure. For several decades, ADPKD was regarded as an adult-onset disease. In the past decade, it has become more widely appreciated that the disease course begins in childhood. However, evidence-based guidelines on how to manage and approach children diagnosed with or at risk of ADPKD are lacking. Also, scoring systems to stratify patients into risk categories have been established only for adults. Overall, there are insufficient data on the clinical course during childhood. We therefore initiated the global ADPedKD project to establish a large international pediatric ADPKD cohort for deep characterization. METHODS: Global ADPedKD is an international multicenter observational study focusing on childhood-diagnosed ADPKD. This collaborative project is based on interoperable Web-based databases, comprising 7 regional and independent but uniformly organized chapters, namely Africa, Asia, Australia, Europe, North America, South America, and the United Kingdom. In the database, a detailed basic data questionnaire, including genetics, is used in combination with data entry from follow-up visits, to provide both retrospective and prospective longitudinal data on clinical, radiologic, and laboratory findings, as well as therapeutic interventions. DISCUSSION: The global ADPedKD initiative aims to characterize in detail the most extensive international pediatric ADPKD cohort reported to date, providing evidence for the development of unified diagnostic, follow-up, and treatment recommendations regarding modifiable disease factors. Moreover, this registry will serve as a platform for the development of clinical and/or biochemical markers predicting the risk of early and progressive disease.

The malnutrition and inflammation axis in pediatric patients with chronic kidney disease.

Malnutrition and inflammation are closely linked in adult chronic kidney disease (CKD) patients and are both related to poor outcome, but data on pediatric patients are lacking. To describe the prevalence of inflammation, evaluate nutritional status, their correlation to each other, and their possible determinants in pediatric patients with CKD in predialysis, on hemodialysis (HD), and peritoneal dialysis (PD) who were submitted to demographic, nutritional, and inflammatory evaluations. Patients' nutritional status was evaluated according to anthropometric parameters and body composition assessed by measurements of skinfold thickness and bioelectrical impedance. Inflammation was assessed by measurement of highly sensitive C-reactive protein (CRP), ferritin, and albumin. Patients with CRP > 1 mg/l were considered inflamed. Sixty-four pediatric patients (mean age 9 +/- 4 years-, 40% on HD, 22% on PD, and 38% predialysis) were studied. Mean CRP concentration was 3.4 +/- 6.5 mg/l (median 0.78 mg/l, range 0.78-33.4 mg/l), and 41% presented CRP levels above 1 mg/l. Mean ferritin was 148 +/- 197 mg/dl and was above the normal reference values in 28% of patients. On the other hand, mean albumin was 3.9 +/- 0.5 mg/dl, below reference value in only 13% of patients. A larger proportion of HD patients (52%) were inflamed compared with those on PD (31%; p < 0.05). Malnutrition prevalence varied from 5% to 65% according to the method used. While inflamed patients presented lower serum bicarbonate and were on HD for a longer time, there were no consistent associations between malnutrition and inflammation. Inflammation is highly prevalent in the pediatric CKD population and was not consistently related to malnutrition. Other risk factors linked to high mortality and morbidity (acidosis and longer time on dialysis) were associated with inflammation. Prospective studies will need to analyze the predictive value of inflammation and malnutrition markers in the pediatric CKD population.

Chronic kidney disease and inflammation in pediatric patients: from bench to playground.

Signs of an activated immune system can be observed already in the early stages of chronic kidney disease (CKD). Markers of a chronically activated immune system are closely linked to several complications of CKD, such as accelerated atherosclerosis, vascular calcification, insulin resistance, increased muscle catabolism, loss of appetite, bone remodeling, and increased peritoneal permeability. Interestingly, all the aforementioned pathological states resemble a state of accelerated ageing and are strongly associated with increased morbidity and mortality in CKD patients. In recent studies, signs of inflammation have been shown as predictors for mortality in dialysis patients, and the role of inflammation as a risk factor for complications of CKD in children has emerged. Although preliminary findings suggest that inflammation is highly prevalent in the pediatric population with CKD, information related pathogenic links and to clinical outcomes is lacking. For the future, it is crucial for investigations to address the mechanisms and complications of inflammation that are manifested in pediatric patients with CKD in all stages. Since early identification and intervention may generate the most efficient strategies for prevention and treatment of cardiovascular disease in CKD patients, the pediatric population deserves special attention in future studies. In this review, we discuss the mechanisms involved in the inflammatory activation and the main causes and consequences of the inflammatory state observed in the CKD patient, with special emphasis on the pediatric population.