Objective To characterize nonsteroidal anti-inflammatory drug (NSAID)-associated acute kidney injury (AKI) in children. Study design We conducted a retrospective chart review of children diagnosed ...with AKI through the use of International Classification of Diseases, Ninth Revision diagnosis code 584.5 or 584.9 from January 1999 to June 2010. Medical records were reviewed to confirm the diagnosis of AKI and to quantify NSAID administration. Pediatric RIFLE criteria were used to codify AKI. Patients were not classified as having NSAID-associated AKI if they had a diagnosis explaining AKI or comorbid clinical conditions predisposing to AKI development. Results Patients (N = 1015) were identified through International Classification of Diseases, Ninth Revision screening. Twenty-one children had clinical, laboratory, and radiographic studies suggesting NSAID-associated acute tubular necrosis and 6 had findings suggesting NSAID-associated acute interstitial nephritis, representing 2.7% (27 of 1015) of the total cohort with AKI and 6.6% when excluding complex patients with multifactorial AKI. Children with NSAID-associated AKI had a median (range) age of 14.7 years (0.5-17.7 years); 4 patients (15%) were <5 years old. Fifteen of 20 children (75%) for whom dosing data were available received NSAIDs within recommended dosing limits. Patients <5 years old were more likely to require dialysis (100% vs 0%, P < .001), intensive care unit admission (75% vs 9%, P = .013), and a longer length of stay (median 10 vs 7 days, P = .037). Conclusions NSAID-associated AKI accounted for 2.7% of AKI in this pediatric population. AKI typically occurred after the administration of correctly dosed NSAIDs. Young children with NSAID-associated AKI may have increased disease severity.
Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in childhood and the reason for chronic renal replacement therapy. It leads to significant morbidity and mortality ...during the acute phase. In addition to acute morbidity and mortality, long-term renal and extrarenal complications can occur in a substantial number of children years after the acute episode of HUS. The most common infectious agents causing HUS are enterohemorrhagic
Escherichia coli
(EHEC)-producing Shiga toxin (and belonging to the serotype O157:H7) and several non-O157:H7 serotypes. D
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HUS is an acute disease characterized by prodromal diarrhea followed by acute renal failure. The classic clinical features of HUS include the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS mortality is reported to be between 3% and 5%, and death due to HUS is nearly always associated with severe extrarenal disease, including severe central nervous system (CNS) involvement. Approximately two thirds of children with HUS require dialysis therapy, and about one third have milder renal involvement without the need for dialysis therapy. General management of acute renal failure includes appropriate fluid and electrolyte management, antihypertensive therapy if necessary, and initiation of renal replacement therapy when appropriate. The prognosis of HUS depends on several contributing factors. In general “classic” HUS, induced by EHEC, has an overall better outcome. Totally different is the prognosis in patients with atypical and particularly recurrent HUS. However, patients with severe disease should be screened for genetic disorders of the complement system or other underlying diseases.
Background
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a small- and medium-sized vasculitis classically seen in adult patients, with peak onset near the fifth to seventh ...decade of life. There is little data on ANCA-associated vasculitis in pediatric patients, and most studies have limited follow-up.
Methods
This is a retrospective chart review of 22 patients with ANCA-positive glomerulonephritis in a single institution from 1991 to 2013.
Results
Of the 22 patients, eight (36 %) required renal replacement therapy (RRT) at diagnosis; four of these patients recovered sufficient renal function to initially discontinue dialysis. Five patients (23 %) were treated with plasmapheresis at presentation. The median time from presentation until first clinical or serologic relapse was 1.7 ± 1.2 years. After a median follow-up of 5.8 years, just over half of our patients had chronic kidney disease (CKD) stages 1–3 (55 %). Seven (32 %) patients progressed to end-stage renal disease (ESRD) and eventually required kidney transplant.
Conclusion
ANCA-associated glomerulonephritis is a rare disorder in children. Presentation and outcomes vary significantly among patients. More research is required to follow these patients who are diagnosed in childhood to further characterize the long-term outcome of the disease.
Despite recent advances in the management of chronic kidney disease (CKD), morbidity and mortality rates in these patients remain high. Although pressure-mediated injury is a well-recognized ...mechanism of disease progression in CKD, emerging data indicate that an intermediate phenotype involving chronic inflammation, oxidative stress, hypoxia, senescence, and mitochondrial dysfunction plays a key role in the etiology, progression, and pathophysiology of CKD. A variety of factors promote chronic inflammation in CKD, including oxidative stress and the adoption of a proinflammatory phenotype by resident kidney cells. Regulation of proinflammatory and anti-inflammatory factors through NF-κB– and nuclear factor, erythroid 2 like 2 (Nrf2)–mediated gene transcription, respectively, plays a critical role in the glomerular and tubular cell response to kidney injury. Chronic inflammation contributes to the decline in glomerular filtration rate (GFR) in CKD. Whereas the role of chronic inflammation in diabetic kidney disease (DKD) has been well-elucidated, there is now substantial evidence indicating unresolved inflammatory processes lead to fibrosis and eventual end-stage kidney disease (ESKD) in several other diseases, such as Alport syndrome, autosomal-dominant polycystic kidney disease (ADPKD), IgA nephropathy (IgAN), and focal segmental glomerulosclerosis (FSGS). In this review, we aim to clarify the mechanisms of chronic inflammation in the pathophysiology and disease progression across the spectrum of kidney diseases, with a focus on Nrf2.
Background
Acute kidney injury (AKI) in children has serious short-term and long-term consequences. We sought 1) to prospectively describe NSAID-associated AKI in hospitalized children; 2) to ...determine if NSAID-associated AKI was more severe in younger children < 5 years; and 3) to follow outcomes after hospitalization for NSAID-associated AKI.
Methods
This was a prospective, multi-center study in hospitalized children 1 month to 18 years. Parents/guardians were given a brief questionnaire to determine the dosing, duration, and type of NSAIDs given. Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria were used to stage AKI severity. Patients with other causes of AKI were excluded (e.g., other nephrotoxins, sepsis, malignancy, etc.).
Results
We identified 25 patients with NSAID-associated AKI, accounting for 3.1% of AKI. All 25 had AKI upon hospital presentation. The median age was 15.5 years, and 20/25 (80%) had volume depletion. Median duration of NSAID use was 2 days, and 63% of patients took the normal recommended NSAID dose. Median hospital length of stay was 4 days, and none required dialysis. At the most recent estimated glomerular filtration rate (eGFR) after discharge (available in 17/25 patients), only 4/17 (24%) had eGFR ≥ 90 ml/min/1.73 m
2
, and 13/17 (76%) had eGFR 60 to < 90 ml/min/1.73 m
2
, indicative of abnormal kidney function.
Conclusions
NSAID-associated AKI usually occurs with recommended NSAID dosing in the setting of dehydration. Follow-up after AKI showed a substantial rate of CKD. Therefore, we recommend that NSAIDs should not be used in dehydrated children.
Graphical abstract
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