Management and outcomes of childhood Goodpasture's disease.

BackgroundIn an attempt to improve knowledge about childhood Goodpasture's disease, we performed a retrospective analysis of patients with Goodpasture's disease from several pediatric nephrology centers.MethodsWe analyzed the responses to 27 questions that elicited information about the following: incidence, demographics, patient history and clinical presentation, diagnostics performed, acute and chronic therapy, course of disease, and outcome.ResultsGoodpasture's disease, which is extremely rare in this age group, may manifest in 2-year-old toddlers and does not typically present with pulmonary findings before puberty. Goodpasture's disease has a poor outcome with more than 50% of patients progressing to end-stage renal disease. No deaths were reported in this cohort, and renal improvement was observed in children with severe biopsy findings who required renal replacement therapy during the acute phase.ConclusionThe present investigation gives detailed information about childhood Goodpasture's disease under real-life conditions and reveals that very few pediatric cases have been reported. Nearly 50% of children progressed to end-stage renal disease. However, long-term outcome in children might be better than in adults. Aggressive immunosuppressive therapy might be necessary for all affected children, even in patients who require renal replacement therapy or have severe biopsy findings.

Neonatal hemolytic uremic syndrome after mother-to-child transmission of a low-pathogenic stx2b harboring shiga toxin-producing Escherichia coli.

This case describes evidence for a Shiga toxin-producing Escherichia coli (STEC) O146:H28 infection leading to hemolytic uremic syndrome in a neonate. STEC O146:H28 was linked hitherto with asymptomatic carriage in humans. Based on strain characteristics and genotyping data, the mother is a healthy carrier who transmitted the STEC during delivery. STEC strains belonging to the low-pathogenic STEC group must also be considered in the workup of neonatal hemolytic uremic syndrome.

Primary hypertension in childhood.

There is growing concern about elevated blood pressure in children and adolescents, because of its association with the obesity epidemic. Moreover, cardiovascular function and blood pressure level are determined in childhood and track into adulthood. Primary hypertension in childhood is defined by persistent blood pressure values ≥ the 95th percentile and without a secondary cause. Preventable risk factors for elevated blood pressure in childhood are overweight, dietary habits, salt intake, sedentary lifestyle, poor sleep quality and passive smoking, whereas non-preventable risk factors include race, gender, genetic background, low birth weight, prematurity, and socioeconomic inequalities. Several different pathways are implicated in the development of primary hypertension, including obesity, insulin resistance, activation of the sympathetic nervous system, alterations in sodium homeostasis, renin-angiotensin system and altered vascular function. Prevention of adult cardiovascular disease should begin in childhood by regularly screening for high blood pressure, counseling for healthy lifestyle and avoiding preventable risk factors.

[Childhood's determinants for high blood pressure in adulthood]. / Welche Faktoren in der Kindheit beeinflussenden Blutdruck im Erwachsenenalter?

Hypertension has been estimated to affect 20 - 25% of the adult population and represents an important risk factor for cardiovascular disease like coronary heart disease, stroke and peripheral artery occlusive disease. In addition, hypertension supports the development and progression of chronic kidney insufficiency. The interaction of multiple genetic and environmental factors are felt to influence the level of blood pressure. Epidemiological data in the sixties and seventies demonstrated a correlation between cardiovascular disease and infant mortality in the same population. In the late eighties Barker and coworkers described a strong correlation between low birth weight and increased risk for the development of cardiovascular complications. It has been supposed that factors influencing the intrauterine growth and development can lead to adult cardiovascular diseases, known as the concept of "fetal programming". Beside the effect of fetal programming, multiple (preventable and non-preventable) factors determine the blood pressure level in childhood, which will define adult blood pressure level through the blood pressure tracking from childhood to adulthood. Hence, the prevention of cardiovascular disease in adulthood begins in childhood through identification of preventable risk factors as for example obesity and passive smoking and recognition of risk groups like small for gestational age or preterm children.

Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings.

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy associated with defective regulation of the alternative complement pathway. The prognosis for patients with aHUS is poor, and plasma exchange represents the first-line therapy. Eculizumab is a humanized monoclonal anti-C5 antibody that prevents the activation of the terminal complement pathway. Here, we report the case of a 9-year-old girl with frequent relapsing aHUS due to heterozygous factor H mutation who was initially treated with plasma exchange three times per week with 150% plasma exchange volume. This treatment frequently caused allergic reactions and school absences. Because any reduction in the frequency of plasma exchange immediately induced relapses of the aHUS, treatment with eculizumab, 600 mg every 2 weeks, was started and plasma exchange completely stopped. On this drug regimen the patient showed no evidence of disease activity during a period of more than 24 months. Renal function improved, proteinuria disappeared, the number of antihypertensive medications could be decreased, and the quality of life increased substantially. The inhibition of the terminal complement pathway by eculizumab was also confirmed by renal biopsy, which showed the absence of thrombotic microangiopathy 2 months after the initiation of eculizumab therapy. This case illustrates the long-term favorable outcome of aHUS with eculizumab treatment.

Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists: a systematic review.

The objective was to analyze the outcome following prenatal exposure to angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor antagonists (ARBs). For this purpose, a systematic review of published case reports and case series dealing with intrauterine exposure to ACE-Is or to ARBs using Medline as the source of data was performed. The publications retained for analysis included patients who were described individually, revealing, at minimum, the gestational age, substance used, period of medication intake, and the outcome. In total, 72 reports were included; 37 articles (118 well-documented cases) described the prenatal exposure to ACE-Is; and 35 articles (68 cases) described the prenatal exposure to ARBs. Overall, 52% of the newborns exposed to ACE-Is and 13% of the newborns exposed to ARBs did not exhibit any complications (P<0.0001). Neonatal complications were more frequent following exposure to ARBs and included renal failure, oligohydramnios, death, arterial hypotension, intrauterine growth retardation, respiratory distress syndrome, pulmonary hypoplasia, hypocalvaria, limb defects, persistent patent ductus arteriosus, or cerebral complications. The long-term outcome is described as positive in only 50% of the exposed children. Fetopathy caused by exposure to ACE-Is or ARBs has relevant neonatal and long-term complications. The outcome is poorer following exposure to ARBs. We propose the term "fetal renin-angiotensin system blockade syndrome" to describe the related clinical findings. Thirty years after the first description of ACE-I fetopathy, relevant complications are, at present, regularly described, indicating that the awareness of the deleterious effect of prenatal exposure to drugs inhibiting the renin-angiotensin system should be improved.