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      A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on Kidney and Pregnancy

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          Abstract

          Pregnancy is increasingly undertaken in patients with chronic kidney disease (CKD) and, conversely, CKD is increasingly diagnosed in pregnancy: up to 3 % of pregnancies are estimated to be complicated by CKD. The heterogeneity of CKD (accounting for stage, hypertension and proteinuria) and the rarity of several kidney diseases make risk assessment difficult and therapeutic strategies are often based upon scattered experiences and small series. In this setting, the aim of this position statement of the Kidney and Pregnancy Study Group of the Italian Society of Nephrology is to review the literature, and discuss the experience in the clinical management of CKD in pregnancy. CKD is associated with an increased risk for adverse pregnancy-related outcomes since its early stage, also in the absence of hypertension and proteinuria, thus supporting the need for a multidisciplinary follow-up in all CKD patients. CKD stage, hypertension and proteinuria are interrelated, but they are also independent risk factors for adverse pregnancy-related outcomes. Among the different kidney diseases, patients with glomerulonephritis and immunologic diseases are at higher risk of developing or increasing proteinuria and hypertension, a picture often difficult to differentiate from preeclampsia. The risk is higher in active immunologic diseases, and in those cases that are detected or flare up during pregnancy. Referral to tertiary care centres for multidisciplinary follow-up and tailored approaches are warranted. The risk of maternal death is, almost exclusively, reported in systemic lupus erythematosus and vasculitis, which share with diabetic nephropathy an increased risk for perinatal death of the babies. Conversely, patients with kidney malformation, autosomal-dominant polycystic kidney disease, stone disease, and previous upper urinary tract infections are at higher risk for urinary tract infections, in turn associated with prematurity. No risk for malformations other than those related to familiar urinary tract malformations is reported in CKD patients, with the possible exception of diabetic nephropathy. Risks of worsening of the renal function are differently reported, but are higher in advanced CKD. Strict follow-up is needed, also to identify the best balance between maternal and foetal risks. The need for further multicentre studies is underlined.

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          Circulating angiogenic factors and the risk of preeclampsia.

          The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role. We performed a nested case-control study within the Calcium for Preeclampsia Prevention trial, which involved healthy nulliparous women. Each woman with preeclampsia was matched to one normotensive control. A total of 120 pairs of women were randomly chosen. Serum concentrations of angiogenic factors (total sFlt-1, free PlGF, and free VEGF) were measured throughout pregnancy; there were a total of 655 serum specimens. The data were analyzed cross-sectionally within intervals of gestational age and according to the time before the onset of preeclampsia. During the last two months of pregnancy in the normotensive controls, the level of sFlt-1 increased and the level of PlGF decreased. These changes occurred earlier and were more pronounced in the women in whom preeclampsia later developed. The sFlt-1 level increased beginning approximately five weeks before the onset of preeclampsia. At the onset of clinical disease, the mean serum level in the women with preeclampsia was 4382 pg per milliliter, as compared with 1643 pg per milliliter in controls with fetuses of similar gestational age (P<0.001). The PlGF levels were significantly lower in the women who later had preeclampsia than in the controls beginning at 13 to 16 weeks of gestation (mean, 90 pg per milliliter vs. 142 pg per milliliter, P=0.01), with the greatest difference occurring during the weeks before the onset of preeclampsia, coincident with the increase in the sFlt-1 level. Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeclampsia was associated with a small-for-gestational-age infant. Increased levels of sFlt-1 and reduced levels of PlGF predict the subsequent development of preeclampsia. Copyright 2004 Massachusetts Medical Society
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            KDIGO clinical practice guideline for the care of kidney transplant recipients.

            (2009)
            The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression, graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially on the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.
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              Prevention of rickets and vitamin D deficiency in infants, children, and adolescents.

              Rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continues to be reported in the United States. There are also concerns for vitamin D deficiency in older children and adolescents. Because there are limited natural dietary sources of vitamin D and adequate sunshine exposure for the cutaneous synthesis of vitamin D is not easily determined for a given individual and may increase the risk of skin cancer, the recommendations to ensure adequate vitamin D status have been revised to include all infants, including those who are exclusively breastfed and older children and adolescents. It is now recommended that all infants and children, including adolescents, have a minimum daily intake of 400 IU of vitamin D beginning soon after birth. The current recommendation replaces the previous recommendation of a minimum daily intake of 200 IU/day of vitamin D supplementation beginning in the first 2 months after birth and continuing through adolescence. These revised guidelines for vitamin D intake for healthy infants, children, and adolescents are based on evidence from new clinical trials and the historical precedence of safely giving 400 IU of vitamin D per day in the pediatric and adolescent population. New evidence supports a potential role for vitamin D in maintaining innate immunity and preventing diseases such as diabetes and cancer. The new data may eventually refine what constitutes vitamin D sufficiency or deficiency.
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                Author and article information

                Contributors
                gbpiccoli@yahoo.it
                Journal
                J Nephrol
                J. Nephrol
                Journal of Nephrology
                Springer International Publishing (Cham )
                1121-8428
                1724-6059
                17 March 2016
                17 March 2016
                2016
                : 29
                : 3
                : 277-303
                Affiliations
                [1 ]Nephrology, Azienda Ospedaliera Brotzu, Cagliari, Italy
                [2 ]Nephrology and Dialysis, Taormina Hospital, Taormina, Italy
                [3 ]Nephrology, S. Maria Degli Angeli Hospital, Putignano, Italy
                [4 ]Nephrology and Dialysis, AOU “G. Martino”, Messina, Italy
                [5 ]ISNI 0000 0004 1757 8749, GRID grid.414818.0, Nephrology, , Fondazione Ca’ Granda Ospedale Maggiore, ; Milano, Italy
                [6 ]Dipartimento Nefrodialitico Città di Bari Hospital, Bari, Italy
                [7 ]GRID grid.412725.7, Nephrology, , Spedali Civili di Brescia, ; Brescia, Italy
                [8 ]Nephrology, Ospedale d’Ivrea, Ivrea, Italy
                [9 ]ISNI 0000 0001 2336 6580, GRID grid.7605.4, Obstetrics, Department of Surgery, , University of Torino, ; Torino, Italy
                [10 ]Nephrology, Azienda Ospedaliera della Provincia di Lecco, Lecco, Italy
                [11 ]Nephrology, Ospedale Fracastoro, San Bonifacio, Italy
                [12 ]ISNI 0000 0001 2336 6580, GRID grid.7605.4, Nephrology, ASOU San Luigi, Department of Clinical and Biological Sciences, , University of Torino, ; Torino, Italy
                [13 ]ISNI 0000 0004 1771 4456, GRID grid.418061.a, Nephrologie, , Centre Hospitalier du Mans, ; Le Mans, France
                Article
                285
                10.1007/s40620-016-0285-6
                5487839
                26988973
                f7435d87-a816-429f-817d-f36499f41a77
                © Italian Society of Nephrology 2016
                History
                : 17 December 2015
                : 8 February 2016
                Funding
                Funded by: GdS Rene e Gravidanza, Società Italiana di Nefrologia
                Categories
                Position Papers and Guidelines
                Custom metadata
                © Italian Society of Nephrology 2016

                chronic kidney disease,evidence based medicine,pregnancy,hypertension,proteinuria,preeclampsia,pre-term delivery

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