The challenges of assessing acute kidney injury in infants

Definitions of pediatric acute kidney injury (AKI) use changes of serum creatinine. There is a paucity of well-designed studies in infants because of creatinine age-dependency. The emerging role of cystatin C as a superior marker of renal dysfunction led to a carefully conducted study on AKI in infants by Zappitelli et al. This Commentary calls for the development of age-independent serum creatinine and estimated glomerular filtration rate z scores. © 2011 International Society of Nephrology

The challenges of assessing acute kidney injury in infants

Definitions of pediatric acute kidney injury (AKI) use changes of serum creatinine. There is a paucity of well-designed studies in infants because of creatinine age-dependency. The emerging role of cystatin C as a superior marker of renal dysfunction led to a carefully conducted study on AKI in infants by Zappitelli et al. This Commentary calls for the development of age-independent serum creatinine and estimated glomerular filtration rate z scores. © 2011 International Society of Nephrology

Trace elements in dialysis

In end-stage chronic kidney disease (CKD), pediatric nephrologists must consider the homeostasis of the multiple water-soluble ions that are influenced by renal replacement therapy (RRT). While certain ions such as potassium and calcium are closely monitored, little is known about the handling of trace elements in pediatric dialysis. RRT may lead to accumulation of toxic trace elements, either due to insufficient elimination or due to contamination, or to excessive removal of essential trace elements. However, trace elements are not routinely monitored in dialysis patients and no mechanism for these deficits or toxicities has been established. This review summarizes the handling of trace elements, with particular attention to pediatric data. The best data describe lead and indicate that there is a higher prevalence of elevated lead (Pb, atomic number 82) levels in children on RRT when compared to adults. Lead is particularly toxic in neurodevelopment and lead levels should therefore be monitored. Monitoring of zinc (Zn, atomic number 30) and selenium (Se, atomic number 34) may be indicated in the monitoring of all pediatric dialysis patients to reduce morbidity from deficiency. Prospective studies evaluating the impact of abnormal trace elements and the possible therapeutic value of intervention are required. © 2013 IPNA

Do we need to worry about mycophenolate overdose?

Introduction: To discuss the significance of the recent observational case series from the Swiss Toxicological Information Centre (STIC). Mycophenolic acid (MPA) and its prodrug mycophenolate mofetil are immunosuppressive agents that are frequently prescribed in renal transplant recipients, and their safety profiles must be established. Areas covered: This case series and systemic literature analysis consists of 15 cases of MPA overdose from the STIC and a systemic analysis of the literature over the past 18 years. This study focuses on acute overdosing, the effects of which are presumably mild. In contrast, the effects of long-term overdosing may be much more severe. Substantial underreporting is likely. The pharmacokinetic monitoring of MPA is rarely performed, which is both striking and does not coincide with findings in academic literature. The scant data on pharmacokinetic monitoring presented demonstrated that MPA has a short terminal half-life, which suggests that decontamination and activated charcoal treatment in acute overdose may not be necessary. Expert opinion: The case series and systematic literature analysis of acute mycophenolate overdose represent an important contribution toward increasing the safety of MPA therapy. © 2014 Informa UK, Ltd

Cystatin C adaptation in the first month of life

Je-Hyan Lee et al. have published a study on cystatin C concentrations in the first 30 days of life in 127 pre-term and 119 term neonates in this edition of Pediatric Nephrology, thereby closing a knowledge gap of detailed cystatin C concentrations beyond 72 h of life by day of life and by post-conceptional age. While the study objective has merit and a large number of measurements were included, there are some methodological limitations that bring the validity of the data into question as pure reference intervals for children up to 1 month of age, mostly because of the inclusion of patients that potentially could have an impaired glomerular filtration rate (GFR), for instance due to exposure to nephrotoxic drugs. We discuss the strengths and weaknesses of the study and outline an approach to definitely close this knowledge gap. We call for a worldwide collaboration to use Box-Cox transformations similar to the methodology used with growth charts to calculate age-independent z-scores and percentiles of neonatal and infant markers of GFR. This could also lead to better definitions of acute kidney injury in infants if GFR markers cross the percentiles based on post-conceptional or chronological age. © 2013 IPNA

Tertiary care centres must do more for patients with unknown conditions: Lessons learned from a child

Postural Orthostatic Tachycardia Syndrome (POTS) is a debilitating disease with a commonly non-uniform and unspecific presentation that makes diagnosis difficult. A twelve-year-old girl, recently diagnosed with Addison’s Disease, was referred to paediatric nephrology for Fludrocortisone-induced nocturnal hypertension. She had fallen off the growth curve for both height and weight from the 50th percentile at birth to below the 5th percentile at presentation. The severity and multitude of her symptoms, including muscle weakness, poor body control, dizziness, light headedness, persistent fatigue, excessive sweating, tachycardia, chronic constipation and recurrent infection hinted at the unusual nature of this case of Addison’s. At the time of referral, she had been seen by more than a dozen specialists and subspecialists as well as undergone a number of tests including neurophysiological testing without sufficient explanation. With the help of tilt-table testing, we established the diagnosis of POTS. There is a lack of tested treatment options for POTS, and we established dosing of pyridostigmine in children, based on the emerging literature in adults. While pyridostigmine therapy substantially improved her quality of life, it took another 6 years and referral outside the country, before a final unifying diagnosis was made. Eventually, the patient was diagnosed with Ehlers Danlos Syndrome with associated autonomic dysfunction, including POTS, as well as primary adrenal insufficiency. The parents and the patient experienced considerable stress due to the lack of willingness of many physicians that the family encountered to search for a diagnosis and a treatment

Chromium: Rise and Shine in Peritoneal Dialysis Patients?

Some trace elements are altered with chronic kidney disease. Selenium, zinc, and manganese tend to be wasted, and there is growing evidence that selenium deficiency is associated with mortality on dialysis. Other trace elements accumulate, such as chromium, cobalt, lead, molybdenum, and vanadium. The highest chromium levels are found in dialysis patients. The dialysis modality may further affect these levels, especially in hemodialysis patients, where even small contaminations in the dialysis feed water may lead to a concentration gradient that increases the concentration of certain trace elements. Chromium levels in peritoneal dialysis (PD) patients have been understudied. A single cross-sectional study found substantially higher chromium levels in PD patients. In that study, the chromium concentration in the spent dialysate decreased substantially, suggesting that PD fluid could be a source of chromium. Chromium-lactate complexes may have been formed, which are easily absorbed. In our center, we observed a decrease in chromium level when using physiological PD fluids. This review discusses the potential mechanisms and raises the question of whether this accumulation of chromium is unlikely to be associated with a beneficial outcome

When CRRT on ECMO Is not Enough for potassium clearance: A case report

Background: Continuous renal replacement therapy (CRRT) is an excellent method used to remove fluid and solutes. It may also reduce the systemic inflammatory response for patients on extracorporeal membrane oxygenation (ECMO) support. Theobjective of this report is to describe a case where CRRT in combination with ECMO was insufficient to control hyperkalemia. Methods: We report the case of an adolescent patient with refractory symptomatic hyperkalemia due to substantial rhabdomyolysis in which CRRT insufficiently cleared the patient\u27s excess potassium. Results: Intermittent hemodialysis (IHD) was added and proved successful. The patient was weaned off ECMO, CRRT, and IHD, and his cardiac and renal function eventually normalized. Conclusions: Two important lessons can be learned from this case report: (1) If CRRT is insufficient in achieving a desirable potassium balance, additional IHD should be considered and (2) separate IHD access should be considered to improve efficacy

Why multidisciplinary clinics should be the standard for treating chronic kidney disease

In adults, strong evidence indicates that slowing progression of chronic kidney disease (CKD) requires an integrated, multidisciplinary approach. In children, however, this approach has not been studied. This editorial commentary to the study by Ajarmeh et al in this volume of Pediatric Nephrology highlights how a dedicated, multidisciplinary team of physicians, nurses, pharmacists, dieticians, social workders and clinic data managers slowed the progression of CKD in children to a remarkable degree. We discuss the strengths and limitations of the study and its cost implications, as well as the issue of determining the optional complement of physicians and allied health care professionals in such clinics. Our calculations indicate that the additional costs of such clinics would be recovered in one year, even if the progession of CKD were to be delayed by 1 year in only 2% of affected children. Here, we call on the international pediatric nephrology community to establihs guidelines for forming multidisciplinary clinics throughout the world. © IPNA 2012