Untethering an unusual cause of kidney injury in a teenager with Down syndrome.

Acute kidney injury (AKI) is characterized by the acute nature and the inability of kidneys to maintain fluid homeostasis as well as adequate electrolyte and acid-base balance, resulting in an accumulation of nitrogenous waste and elevation of serum blood urea nitrogen and creatinine values. Acute kidney injury may be a single isolated event, yet oftentimes, it results from an acute chronic kidney disease. It is critical to seek out the etiology of AKI and to promptly manage the underlying chronic kidney disease to prevent comorbidities and mortality that may ensue. We described a case of a 16-year-old adolescent girl with Down syndrome who presented with AKI and electrolyte aberrance.Abdominal and renal ultrasounds demonstrated a significantly dilated bladder as well as frank hydronephrosis and hydroureter bilaterally. Foley catheter was successful in relieving the obstruction and improving her renal function. However, a magnetic resonance imaging was pursued in light of her chronic constipation and back pain, and it revealed a structural defect (tethered cord) that underlies a chronic process that was highly likely contributory to her AKI. She was managed accordingly with a guarded result and required long-term and close monitoring.

Eculizumab and recurrent C3 glomerulonephritis.

BACKGROUND: Hyperactivity of the alternative complement pathway is the principle defect in C3 glomerulopathies (C3G). Eculizumab, a monoclonal antibody that binds C5 to prevent formation of the membrane attack complex, has been shown to be beneficial in some patients with this disease. METHODS: In this open-label, proof-of-concept efficacy-and-safety study, a patient with the initial diagnosis of dense deposit disease (DDD) and allograft recurrence of C3 glomerulonephritis (C3GN) was treated with eculizumab every other week for 1 year. The patient had pathological evidence of C3GN and proteinuria >1 g/day at enrollment. He underwent graft biopsy before enrollment and repeat biopsy at 6 and 12 months. RESULTS: Although no mutations were identified in complement genes, functional studies were positive for C3 nephritic factors and elevated levels of soluble membrane attack complex (sMAC). On therapy, sMAC levels normalized and although proteinuria initially decreased, it increased reaching pre-treatment levels at 12 months. Although serum creatinine remained stable, repeat allograft biopsies showed progression of disease. CONCLUSIONS: Clinical and histopathologic data suggest a partial response to eculizumab in this patient. While eculizumab blocked activation of the terminal complement cascade, persistent dysregulation of the alternative pathway remained, indicating eculizumab alone cannot control disease in this patient. Additional research is required to identify effective anticomplement therapy for this group of C3G patients.

Pilot study of mycophenolate mofetil for treatment of kidney disease due to congenital urinary tract disorders in children.

BACKGROUND: Congenital uropathies account for nearly half the chronic kidney disease in children. Immune-mediated injury may contribute to progressive loss of kidney function in affected patients. STUDY DESIGN: Open-label uncontrolled pilot study to determine the feasibility of treatment with the immunosuppressive drug mycophenolate mofetil (MMF) to prevent a decrease in kidney function in pediatric patients with congenital uropathies. SETTING & PARTICIPANTS: Children treated in an outpatient tertiary-care center were eligible if they had: (1) age of 3 to 16 years, (2) glomerular filtration rate (GFR) less than 50 mL/min/1.73 m(2), and (3) a congenital genitourinary tract abnormality. INTERVENTION: After a 2-month run-in period, patients were prescribed MMF, 600 mg/m(2)/dose, twice daily for a 24-month treatment period. OUTCOMES: The primary end point was feasibility based on the ability to recruit and retain subjects and lack of unanticipated adverse events. The secondary end point was change in GFR. MEASUREMENTS: Patients were monitored by using standard clinical laboratory tests, and GFR was determined by means of iothalamate clearance. RESULTS: 12 patients aged 8.9 +/- 4.8 years (10 boys, 2 girls) were treated with MMF for 18.6 +/- 8.0 months; 7 patients completed the entire treatment period. MMF dosage at the final study visit was 381 +/- 241 mg/m(2) twice daily. Gastrointestinal symptoms were the most common adverse effect. There was only 1 serious adverse event, an episode of fever and neutropenia requiring parenteral antibiotic therapy after 21 months of MMF therapy. GFR remained stable throughout the treatment period. Nutritional status, blood pressure, and serum calcium, phosphorus, and cholesterol levels were unchanged during this period. LIMITATIONS: Insufficient power to assess the safety or efficacy of MMF therapy for patients with congenital uropathies. CONCLUSION: It is feasible to study MMF as an adjunctive therapy to retard the progression of kidney disease in children with congenital uropathies. A multicenter randomized clinical trial is warranted to determine the efficacy of this novel treatment strategy.

Anemia and health-related quality of life in adolescents with chronic kidney disease.

BACKGROUND: A number of studies of adults with chronic kidney disease (CKD) have shown a negative impact of anemia on several aspects of health-related quality of life (HRQOL). Although similar links have been suggested in adolescent dialysis populations, the relationship between anemia and HRQOL in children not requiring dialysis therapy has yet to be studied extensively in a large sample. METHODS: We examined the association between anemia and HRQOL in baseline data collected on a prospective cohort of adolescents with CKD by using a generic HRQOL questionnaire completed by parents or caregivers (Child Health Questionnaire Parent Form [CHQ-PF50]). Our study population included guardians or caregivers of 105 adolescents (mean age, 14 +/- 2 years) with stages 1 to 5 CKD as defined by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative, including subjects with chronic renal insufficiency, patients with functioning kidney transplants, and dialysis patients. RESULTS: Seventy of 105 patients were classified in the study as anemic according to a hematocrit value of 36% or less. Compared with the group with higher hematocrit values and independent of sex, race, and estimated glomerular filtration rate, anemic patients reported greater limitations in CHQ-PF50 domains relating to (1) physical functioning, (2) limitations in schoolwork or activities with friends as a result of physical health, and (3) parental impact in time and family activities. CONCLUSION: Anemia was associated with lower quality of life in adolescents across the spectrum of stages of CKD. Future studies should address the effect of interventions to improve anemia on HRQOL.

Non-enteropathic hemolytic uremic syndrome: causes and short-term course.

BACKGROUND: Nondiarrheal or Streptococcus pneumoniae-related hemolytic uremic syndrome (HUS) represents a heterogeneous group of disorders. This study was performed to: (1) describe the current incidence, causes, demographic features, hospital courses, and short-term outcomes of non-enteropathic HUS; (2) compare findings in patients with non-enteropathic HUS with those obtained from a contemporaneous cohort of children with enteropathic or diarrhea-associated HUS (D+ HUS) diagnosed and treated at the same clinical sites; and (3) identify clinical or laboratory features that differentiate these 2 groups and predict disease severity and the short-term outcome in patients with non-enteropathic HUS. METHODS: Data were collected from patients screened between 1997 and 2001 for enrollment in a multicenter trial of SYNSORB Pk (SYNSORB Biotech Inc, Calgary, Alberta, Canada) in D+ HUS, but who were ineligible because of lack of a diarrhea prodrome. The following features were recorded: age; sex; ethnicity; prodromal symptoms; cause; nadir values for hemoglobin, hematocrit, and platelet count; use of dialysis; and length of hospitalization. RESULTS: Twenty-seven of 247 children with HUS had non-enteropathic HUS (11%). Twenty-four patients (15 boys, 9 girls), whose medical records were complete and available for review, comprise the study cohort. Mean age at onset was 4.2 +/- 0.9 (SE) years. Infection caused by S pneumoniae was diagnosed in 9 patients (38%). Dialysis was performed in 17 patients (71%) for 40 +/- 27 days. Median length of hospitalization was 22 days (range, 2 to 71 days). Children with S pneumoniae-related HUS had a longer hospital stay than those with other causes of non-enteropathic HUS, but all patients with S pneumoniae-related HUS recovered kidney function. Dialysis therapy was required more often (17 of 24 versus 59 of 145 children; P = 0.025) and hospital stays were longer (median, 22 versus 9 days; P = 0.002) in children with non-enteropathic HUS compared with patients with D+ HUS who were enrolled in the SYNSORB Pk clinical trial. CONCLUSION: (1) The incidence of non-enteropathic HUS is approximately one tenth that of D+ HUS; (2) patients with non-enteropathic HUS require dialysis therapy more often and are hospitalized more than twice as long during the acute episode compared with those with D+ HUS; (3) infection caused by S pneumoniae accounts for nearly 40% of cases of non-enteropathic HUS; and (4) although S pneumoniae-related HUS is associated with a less favorable short-term course than other types of non-enteropathic HUS or D+ HUS, the long-term prognosis for recovery of renal function appears to be good in these patients.