Long-term effects of in utero exposure to cyclosporin A on renal function in the rabbit.

The number of pregnant women who receive cyclosporin A (CsA) after transplantation or for autoimmune disease has increased. CsA and its metabolites can cross the placental barrier and thus interfere with fetal development. It was shown previously that rabbits that were exposed in utero to 10 mg/kg per d CsA from the 14th to the 18th day of gestation presented a 25% nephron reduction. Thus, this study was conducted to assess the long-term systemic and renal effects of a CsA-induced nephron reduction. Twenty-two pregnant New Zealand white rabbits were randomly divided into two groups: Twelve received 10 mg/kg per d CsA from day 14 to day 18 of gestation, and 10 were used as controls. Rabbits that were born to these animals were evaluated at 4, 11, 18, and 35 wk of life. Pups that were exposed antenatally to CsA presented first a permanent nephron deficit; second, glomerular, tubular, and intrarenal hemodynamics dysfunction; third, enlarged kidneys with numerous tubular and glomerular lesions; and, fourth, an endothelin-dependent systemic hypertension that worsened with age. In utero exposure to CsA induced a nephron reduction that led to systemic hypertension and progressive chronic renal insufficiency in adulthood. A long-term clinical survey is mandatory in infants who are born to mothers who were treated with cyclosporin during pregnancy

Birth weight, malnutrition and kidney-associated outcomes--a global concern

An adverse intrauterine environment is associated with an increased risk of elevated blood pressure and kidney disease in later life. Many studies have focused on low birth weight, prematurity and growth restriction as surrogate markers of an adverse intrauterine environment; however, high birth weight, exposure to maternal diabetes and rapid growth during early childhood are also emerging as developmental risk factors for chronic diseases. Altered programming of nephron number is an important link between exposure to developmental stressors and subsequent risk of hypertension and kidney disease. Maternal, fetal, and childhood nutrition are crucial contributors to these programming effects. Resource-poor countries experience the sequential burdens of fetal and childhood undernutrition and subsequent overnutrition, which synergistically act to augment the effects of developmental programming; this observation might explain in part the disproportionate burden of chronic disease in these regions. Numerous nutritional interventions have been effective in reducing the short-term risk of low birth weight and prematurity. Understanding the potential long-term benefits of such interventions is crucial to inform policy decisions to interrupt the developmental programming cycle and stem the growing epidemics of hypertension and kidney disease worldwide

The Use of Cyclosporine A in Rheumatology: a 2016 Comprehensive Review

Cyclosporine A, an inhibitor of calcineurin, exerts an immunomodulator action interfering with T cell activation. Even though novel therapeutic tools have emerged, CyA still represents a suitable option in several clinical rheumatology settings. This is the case of refractory nephritis and cytopenias associated with systemic lupus erythematosus. Furthermore, CyA is a valued therapeutic tool in the management of uveitis and thrombophlebitis in course of Behçet's disease. Topical CyA has been proven to be beneficial in the dry eye of Sjogren's syndrome, whereas oral treatment with CyA can be considered for the severe complications of adult onset Still's disease. CyA provides a therapeutic option in psoriatic arthritis, being rather effective in skin disease. CyA is currently regarded as a second-line option for patients with inflammatory myopathies refractory to standard regimen. CyA is used even in paediatric rheumatology, in particular in the management of juvenile dermatomyositis and macrophage activation syndrome associated with systemic juvenile idiopathic arthritis. Importantly, CyA has been shown to suppress the replication of HCV, and it can thus be safely prescribed to those patients with chronic hepatitis C. Noteworthy, CyA can be administered throughout the gestation course. Surely, caution should be paid to CyA safety profile, in particular to its nephrotoxicity. Even though most evidence comes from small and uncontrolled studies with few randomised controlled trials, CyA should be still regarded as a valid therapeutic tool in 2016 rheumatology