The most common reaction pattern seen in our study population was maculopapular eruptions. Antibiotics, anticonvulsants and NSAIDs were the most frequently implicated drug groups. Carbamazepine and allopurinol were the two main causative drugs of severe ADRs in our population.
Of children with idiopathic nephrotic syndrome, 10%-20% fail to respond to steroids or develop secondary steroid resistance (termed initial steroid sensitivity) and the majority progress to transplantation. Although 30%-50% of these patients suffer disease recurrence after transplantation, with poor long-term outcome, no reliable indicator of recurrence has yet been identified. Notably, the incidence of recurrence after transplantation appears reduced in patients with steroid-resistant nephrotic syndrome (SRNS) due to monogenic disorders. We reviewed 150 transplanted patients with SRNS to identify biomarkers that consistently predict outcome of SRNS after transplantation. In all, 25 children had genetic or familial SRNS and did not experience post-transplant recurrence. We reviewed phenotypic factors, including initial steroid sensitivity, donor type, age, ethnicity, time to ESRD, and time on dialysis, in the remaining 125 children. Of these patients, 57 (45.6%) developed post-transplant recurrence; 26 of 28 (92.9%) patients with initial steroid sensitivity recurred after transplantation, whereas only 26 of 86 (30.2%) patients resistant from the outset recurred (odds ratio, 30; 95% confidence interval, 6.62 to 135.86; P,0.001). We were unable to determine recurrence in two patients (one with initial steroid sensitivity), and nine patients did not receive initial steroids. Our data show that initial steroid sensitivity is highly predictive of post-transplant disease recurrence in this pediatric patient population. Because a pathogenic circulating permeability factor in nephrotic syndrome remains to be confirmed, we propose initial steroid sensitivity as a surrogate marker for post-transplant recurrence.
Nephrotic syndrome is a disorder of the glomerular filtration barrier, and central to the filtration mechanism of the glomerular filtration barrier is the podocyte. We are starting to better understand how this cell, with its unique architectural features, fulfils its exact filtration properties. The multiprotein complex between adjacent podocyte foot processes, the slit diaphragm, is essential to the control of the actin cytoskeleton and cell morphology. Many of the proteins within the slit diaphragm, including nephrin, podocin, transient receptor potential-6 channel, and α-actinin-4, have been identified via genetic studies of inherited nephrotic syndromes. Signaling from slit diaphragm proteins to the actin cytoskeleton is mediated via the Rho GTPases. These are thought to be involved in the control of podocyte motility, which has been postulated as a focus of proteinuric pathways. Nephrotic syndrome is currently treated with immunosuppressive therapy, with significant adverse effects. These therapies may work in nephrotic syndrome due to specific effects on the podocytes. This review aims to describe our current understanding of the cellular pathways and molecules within the podocyte relevant to nephrotic syndrome and its treatment. With our current knowledge of the cellular biology of the podocyte, there is much hope for targeted therapies for nephrotic syndromes.
Stratified medicine in paediatrics is increasingly becoming a reality, as our understanding of disease pathogenesis improves and novel treatment targets emerge. We have already seen some success in paediatrics in targeted therapies such as cystic fibrosis for specific cystic fibrosis transmembrane conductance regulator variants. With the increased speed and decreased cost of processing and analysing data from rare disease registries, we are increasingly able to use a systems biology approach (including ‘-omics’) to screen across populations for molecules and genes of interest. Improving our understanding of the molecular mechanisms underlying disease, and how to classify patients according to these will lead the way for targeted therapies for individual patients. This review article will summarise how ‘big data’ and the ‘omics’ are being used and developed, and taking examples from paediatric renal medicine and rheumatology, demonstrate progress being made towards stratified medicine for children.
Aims
To describe the aetiologies of paediatric rhabdomyolysis and explore the medium‐term renal consequences.
Methods
Retrospective, single‐centre review of children with rhabdomyolysis.
Results
Two hundred and thirty‐two children met inclusion criteria for the analysis. Mean age at presentation was 8.4 (SD ± 5.5) years. The commonest aetiology was infection (28%), with viral myositis making up the clear majority (75%). Trauma was identified as a cause in 18% of children, seizures in 10% and immune‐mediated mechanisms in 8%. Acute kidney injury (AKI) was present in 32% of the cases overall. Children with AKI tended to be younger, with higher peak creatine kinase (CK) and active urinary sediment on urinalysis at presentation. AKI and the need for renal replacement therapy (RRT) were associated with a prolonged hospital stay (15 (interquartile range, IQR 6.5–33) vs. 2 (IQR 0–7) days). A total of 18 children and young people required RRT, with a mean duration of 7.1 ± 4.3 days. Those who received RRT were more likely to have abnormalities on urinalysis at presentation (46% vs. 5%). Over the period of the study, 9% of children died and 2% met criteria for a diagnosis of chronic kidney disease.
Conclusions
This large paediatric rhabdomyolysis case series provides new and unique insights into the condition. Our results highlight the common aetiologies and provide evidence of good renal recovery overall, even in the most severely affected cases. Abnormalities of urinalysis appear to be important in predicting the development of AKI and the need for RRT.
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