University of Groningen Albuminuria: more than a renal risk marker? van den Belt, Sophie Mariëlle

Albuminuria: more than a renal risk marker?

van den Belt, Sophie Mariëlle

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Publication date: 2018

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van den Belt, S. M. (2018). Albuminuria: more than a renal risk marker? About the prevalence, measurement, and treatment of albuminuria in children. Rijksuniversiteit Groningen.

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518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

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518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

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518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

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518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 113PDF page: 113PDF page: 113PDF page: 113

113 EĞĚĞƌůĂŶĚƐĞƐĂŵĞŶǀĂƫŶŐĞŶƚŽĞŬŽŵƐƚƉĞƌƐƉĞĐƟĞĨ njŝũŶŝŶƉĞƵƚĞƌƐ͕ŵĂĂƌĚĂƚŚĞƚnjĞĞƌůĂƐƟŐŝƐŽŵĂůďƵŵŝŶĞ͗ŬƌĞĂƟŶŝŶĞǁĂĂƌĚĞƐŵĞƚďĞŚƵůƉ ǀĂŶĂŅĂƉǁĂĂƌĚĞƐƚĞƐƚĂŶĚĂĂƌĚŝƐĞƌĞŶƚƵƐƐĞŶƉĞƌƐŽŶĞŶŵĞƚǀĞƌƐĐŚŝůůĞŶĚĞůĞĞŌŝũĚĞŶĞŶ ǀĞƌƐĐŚŝůůĞŶĚĞƐƉŝĞƌŵĂƐƐĂ͛Ɛ͘ŽŶĐůƵĚĞƌĞŶĚůĂƚĞŶĚĞďĞǀŝŶĚĞŶŝŶĚŝƚŚŽŽĨĚƐƚƵŬnjŝĞŶĚĂƚ ǀĞƌŚŽŽŐĚĞĂůďƵŵŝŶƵƌŝĞǁĂĂƌĚĞƐŽƉũŽŶŐĞůĞĞŌŝũĚŝŶĚĞnjĞůĨĚĞŵĂƚĞĂĂŶǁĞnjŝŐnjŝũŶĂůƐŝŶ ũŽŶŐǀŽůǁĂƐƐĞŶĞŶ͘ŝƚƐƵŐŐĞƌĞĞƌƚĚĂƚǀĞƌŚŽŽŐĚĞĂůďƵŵŝŶƵƌŝĞǁĂĂƌĚĞƐŶŝĞƚŚĞƚŐĞǀŽůŐnjŝũŶ ǀĂŶnjŝĞŬƚĞ͕ŵĂĂƌĞĞŶĂĂŶŐĞďŽƌĞŶŬĞŶŵĞƌŬnjŝũŶ͕ĚĂƚŵŽŐĞůŝũŬŚĞƚƌŝƐŝĐŽǀĂŶŚĞƚŝŶĚŝǀŝĚƵ ŽƉůĂƚĞƌĞůĞĞŌŝũĚǀŽŽƌƐƉĞůƚ͘ƌŝƐǀĞƌĚĞƌŽŶĚĞƌnjŽĞŬŶŽĚŝŐŽŵĚĞŽŽƌnjĂŬĞŶǀĂŶǀĞƌŚŽŽŐĚĞ ĂůďƵŵŝŶƵƌŝĞǁĂĂƌĚĞƐŽƉũŽŶŐĞůĞĞŌŝũĚƚĞŽŶƚĚĞŬŬĞŶ͘ ĞƵƌŝŶĞǀĞƌnjĂŵĞůŝŶŐĞŶŝŶĚĞďŽǀĞŶŐĞŶŽĞŵĚĞƐƚƵĚŝĞǁĂƌĞŶůĂƐƟŐǀŽŽƌŬŝŶĚ͕ŽƵĚĞƌƐ ĞŶůĂďŽƌĂƚŽƌŝƵŵ͘ƌǁĞƌĚŚŝĞƌŐĞďƌƵŝŬŐĞŵĂĂŬƚǀĂŶŝŶůĞŐŬƌƵŝƐũĞƐŝŶĚĞůƵŝĞƌƐ͘EŝĞƵǁĞƵƌŝŶĞ ǀĞƌnjĂŵĞůŵĞƚŚŽĚĞƐnjŝũŶŶŽĚŝŐŽŵĚĞŬǁĂůŝƚĞŝƚǀĂŶǀĞƌnjĂŵĞůĚĞĚĂƚĂŝŶƚŽĞŬŽŵƐƟŐĞƐƚƵĚŝĞƐ ƚĞǀĞƌďĞƚĞƌĞŶ͘Hoofdstuk 3ŚĞĞŌĚĞƉƌĞƐƚĂƟĞǀĂŶǀĞƌƐĐŚŝůůĞŶĚĞƵƌŝŶĞǀĞƌnjĂŵĞůŵĞƚŚŽĚĞƐ ŝŶ ũŽŶŐĞ ŬŝŶĚĞƌĞŶ ǀĞƌŐĞůĞŬĞŶ͕ ŵĞƚ ĂůƐ ĚŽĞů ĚĞ ŵĞĞƐƚ ďĞƚƌŽƵǁďĂƌĞ͕ ƉƌĂŬƟƐĐŚĞ ĞŶ ĐŽŵĨŽƌƚĂďĞůĞŵĞƚŚŽĚĞƚĞǀŝŶĚĞŶ͘,ĞƚŐĞďƌƵŝŬǀĂŶŝŶůĞŐŬƌƵŝƐũĞƐ͕ǁĞůŬĞŝŶŚŽŽĨĚƐƚƵŬϮ njŝũŶƚŽĞŐĞƉĂƐƚ͕ĞŶĚĞŶŝĞƵǁŽŶƚǁŝŬŬĞůĚĞWĞĞ^ƉŽƚŵĞƚŚŽĚĞǁĞƌĚĞŶŽŶĚĞƌnjŽĐŚƚ͘ĞŝĚĞ ŵĞƚŚŽĚĞƐ ǁĞƌĚĞŶ ǀĞƌŐĞůĞŬĞŶ ŵĞƚ ĞĞŶ ƌĞĨĞƌĞŶƟĞŵŽŶƐƚĞƌ͖ ĚĞ ƐƚĂŶĚĂĂƌĚ ŵĞƚŚŽĚĞ ;ĞĞŶŽŶďĞǁĞƌŬƚƵƌŝŶĞŵŽŶƐƚĞƌĚĂƚďĞǁĂĂƌĚǁĞƌĚŽƉϰΣͿ͘,ĞƚĚƌĂŐĞŶǀĂŶĚĞůƵŝĞƌ ĞŶǀĞƌnjĞŶĚŝŶŐŶĂĂƌŚĞƚůĂďŽƌĂƚŽƌŝƵŵǁĞƌĚĞŶŐĞƐŝŵƵůĞĞƌĚĚŽŽƌĚĞŝŶůĞŐŬƌƵŝƐũĞƐĞŶ WĞĞ^ƉŽƚƐŽƉǀĞƌƐĐŚŝůůĞŶĚĞƚĞŵƉĞƌĂƚƵƌĞŶƚĞďĞǁĂƌĞŶ͘ĞWĞĞ^ƉŽƚŵĞƚŚŽĚĞƉƌĞƐƚĞĞƌĚĞ njĞĞƌŐŽĞĚ͖ŵĞƚĞĞŶŬůĞŝŶĞĨŽƵƚŵĂƌŐĞ͕ŚŽŐĞƉƌĞĐŝƐŝĞĞŶŚŽŐĞĂĐĐƵƌĂĂƚŚĞŝĚ͘ĞWĞĞ^ƉŽƚ ƉƌĞƐƚĞĞƌĚĞďĞƚĞƌŝŶŚĞƚŵĞƚĞŶǀĂŶĂůďƵŵŝŶƵƌŝĞĚĂŶĚĞŝŶůĞŐŬƌƵŝƐũĞƐŵĞƚŚŽĚĞ͘ŽǀĞŶĚŝĞŶ ŚĂĚĚĞWĞĞ^ƉŽƚǀĞƌŐĞůĞŬĞŶŵĞƚĚĞŝŶůĞŐŬƌƵŝƐũĞƐŵĞƚŚŽĚĞĂŶĚĞƌĞǀŽŽƌĚĞůĞŶǀŽŽƌŚĞƚ ŐĞďƌƵŝŬŝŶĚĞŬůŝŶŝƐĐŚĞƉƌĂŬƟũŬ͗ĚĞǀĞƌǁĞƌŬŝŶŐŝŶŚĞƚůĂďŽƌĂƚŽƌŝƵŵǁĂƐŵĂŬŬĞůŝũŬĞƌ͕Śŝũ ǁĂƐŚLJŐŝģŶŝƐĐŚĞƌŝŶŐĞďƌƵŝŬĞŶŵĞĞƌŐĞƐĐŚŝŬƚŽŵƚĞŐĞďƌƵŝŬĞŶďŝũnjŝŶĚĞůŝũŬĞŬŝŶĚĞƌĞŶ͘ ^ĂŵĞŶŐĞǀĂƚůŝũŬƚĚĞWĞĞ^ƉŽƚĞĞŶnjĞĞƌŐĞƐĐŚŝŬƚĞŵĞƚŚŽĚĞƚĞnjŝũŶǀŽŽƌŚĞƚǀĞƌnjĂŵĞůĞŶ ǀĂŶƵƌŝŶĞŝŶŬŝŶĚĞƌĞŶǀŽŽƌĚĞŵĞƟŶŐǀĂŶĂůďƵŵŝŶƵƌŝĞ͘ /ŶHoofdstuk 4ŝƐĚĞWĞĞ^ƉŽƚŐĞďƌƵŝŬƚŽŵǀĞƌƐĐŚŝůůĞŶĚĞƵƌŝŶĞǀĞƌnjĂŵĞůƐƚƌĂƚĞŐŝĞģŶ ƚĞŽŶĚĞƌnjŽĞŬĞŶŽŵĞĞŶƌŝĐŚƚůŝũŶƚĞŬƵŶŶĞŶŽŶƚǁŝŬŬĞůĞŶǀŽŽƌŚĞƚŵĞƚĞŶǀĂŶĂůďƵŵŝŶƵƌŝĞ ŝŶƉĞƵƚĞƌƐ͘sĞƌƐĐŚĞŝĚĞŶĚĞƐƚƌĂƚĞŐŝĞģŶǁĞƌĚĞŶŐĞƚĞƐƚĞŶǀĞƌŐĞůĞŬĞŶ͗ĞĞŶĞĞŶŵĂůŝŐĞ ǀĞƌnjĂŵĞůŝŶŐǀĞƌƐƵƐŚĞƌŚĂĂůĚĞǀĞƌnjĂŵĞůŝŶŐĞŶĞŶĞĞŶĞĞƌƐƚĞŽĐŚƚĞŶĚƵƌŝŶĞǀĞƌƐƵƐĞĞŶ ƐƉŽƚƵƌŝŶĞ;ǀĞƌnjĂŵĞůĚŽƉĞĞŶǁŝůůĞŬĞƵƌŝŐŵŽŵĞŶƚŽƉĚĞĚĂŐͿ͘ĞďĞƐƚĞŵĞƚŚŽĚĞŵĞƚĚĞ ŬůĞŝŶƐƚĞŝŶƚƌĂͲŝŶĚŝǀŝĚƵĞůĞǀĂƌŝĂďŝůŝƚĞŝƚďůĞĞŬŚĞƚǀĞƌnjĂŵĞůĞŶǀĂŶĞĞŶĞĞƌƐƚĞŽĐŚƚĞŶĚƵƌŝŶĞ ŽƉĚƌŝĞĂĐŚƚĞƌĞĞŶǀŽůŐĞŶĚĞĚĂŐĞŶ͕ǁĂƚǀĞƌǀŽůŐĞŶƐŚĞƌŚĂĂůĚǁĞƌĚŝŶĚĞƟũĚ͘ŝƚŬŽŵƚ ŽǀĞƌĞĞŶ ŵĞƚ ĞĞƌĚĞƌĞ ďĞǀŝŶĚŝŶŐĞŶ ŝŶ ǀŽůǁĂƐƐĞŶĞŶ͘ /ŶƚĞƌĞƐƐĂŶƚ ŐĞŶŽĞŐ ůĞŝĚĚĞ ŚĞƚ ŐĞďƌƵŝŬǀĂŶĚĞĂůďƵŵŝŶĞ͗ŬƌĞĂƟŶŝŶĞƌĂƟŽŝŶƉůĂĂƚƐǀĂŶĚĞĂůďƵŵŝŶĞĐŽŶĐĞŶƚƌĂƟĞƚŽƚ ŵĞĞƌǀĂƌŝĂďŝůŝƚĞŝƚĞŶůŝũŬƚŚĞƚĚĂĂƌĚŽŽƌĞĞŶŵŝŶĚĞƌƉƌĞĐŝĞnjĞŵĞƟŶŐǀŽŽƌĂůďƵŵŝŶƵƌŝĞ ŝŶŬŝŶĚĞƌĞŶ͘ĞnjĞŚŽŐĞƌĞǀĂƌŝĂďŝůŝƚĞŝƚǁĞƌĚŶŝĞƚǀĞƌŬůĂĂƌĚĚŽŽƌĞĞŶŚŽŐĞƌĞǀĂƌŝĂďŝůŝƚĞŝƚ ŝŶƵƌŝŶĞŬƌĞĂƟŶŝŶĞ͕ŶŽĐŚǁĞƌĚĞŶĞƌĂŶĚĞƌĞƌĞĚĞŶĞŶŐĞǀŽŶĚĞŶĚŝĞĚŝƚǀĞƌƐĐŚŝůŬŽŶĚĞŶ ǀĞƌŬůĂƌĞŶ͘ sĞƌĚĞƌĞ ƐƚƵĚŝĞƐ ŶĂĂƌ ĚĞ ƵƌŝŶĞ ŬƌĞĂƟŶŝŶĞ ŵĞƟŶŐ njĞůĨ ĞŶ ĚĞ ŝŶǀůŽĞĚ ǀĂŶ ƐƉŝĞƌŵĂƐƐĂŽƉĚĞĂůďƵŵŝŶĞ͗ŬƌĞĂƟŶŝŶĞƌĂƟŽnjŝũŶŶŽĚŝŐŽŵĚĞĂůďƵŵŝŶƵƌŝĞŵĞƟŶŐĞŶ

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 114PDF page: 114PDF page: 114PDF page: 114

114 ĚĞĮŶŝƟĞĨƚĞƐƚĂŶĚĂĂƌĚŝƐĞƌĞŶƚƵƐƐĞŶŬŝŶĚĞƌĞŶĞŶǀŽůǁĂƐƐĞŶĞŶ͘ĞƌĞƐƵůƚĂƚĞŶǀĂŶĚŝƚ ŚŽŽĨĚƐƚƵŬŝŶĂĐŚƚŶĞŵĞŶĚ͕njŽƵŚĞƚŐĞĂĚǀŝƐĞĞƌĚŵŽĞƚĞŶǁŽƌĚĞŶŽŵǀŽŽƌĚĞŵĞƟŶŐĞŶ ŵŽŶŝƚŽƌŝŶŐǀĂŶĂůďƵŵŝŶƵƌŝĞŝŶƉĞƵƚĞƌƐĚĞĂůďƵŵŝŶƵƌŝĞĐŽŶĐĞŶƚƌĂƟĞŝŶĚƌŝĞŽƉĞĞŶǀŽůŐĞŶĚĞ ĞĞƌƐƚĞŽĐŚƚĞŶĚƵƌŝŶĞƐ͕ŚĞƌŚĂĂůĚŽǀĞƌĚĞƟũĚ͕ƚĞŵĞƚĞŶ͘ ƌŝƐƐůĞĐŚƚƐǁĞŝŶŝŐďĞŬĞŶĚŽǀĞƌŚĞƚĞīĞĐƚǀĂŶĂůďƵŵŝŶƵƌŝĞǀĞƌůĂŐŝŶŐŽƉƉƌŽŐƌĞƐƐŝĞ ǀĂŶŶŝĞƌnjŝĞŬƚĞŝŶŬŝŶĚĞƌĞŶ͕ŚŝĞƌŽƉǁŽƌĚƚǀĞƌĚĞƌŝŶŐĞŐĂĂŶŝŶĚĞĞůƚǁĞĞǀĂŶĚŝƚƉƌŽĞĨƐĐŚƌŝŌ͘ ZĞŵŵĞƌƐ ǀĂŶ ŚĞƚ ƌĞŶŝŶĞͲĂŶŐŝŽƚĞŶƐŝŶĞͲĂůĚŽƐƚĞƌŽŶƐLJƐƚĞĞŵ ;Z^ ƐLJƐƚĞĞŵͿ njŝũŶ ĚĞ ďĞůĂŶŐƌŝũŬƐƚĞ ŵĞĚŝĐŝũŶĞŶ ĚŝĞ ǁŽƌĚĞŶ ŐĞďƌƵŝŬƚ ǀŽŽƌ ŚĞƚ ǀĞƌůĂŐĞŶ ǀĂŶ ĂůďƵŵŝŶƵƌŝĞ͘ ŝŶŶĞŶĚĞnjĞŵĞĚŝĐŝũŶĞŶŐƌŽĞƉǀĂůůĞŶƌĞŵŵĞƌƐǀĂŶŚĞƚĂŶŐŝŽƚĞŶƐŝŶĐŽŶǀĞƌƟŶŐĞŶnjLJŵĞ ;ƌĞŵŵĞƌƐͿĞŶĂŶŐŝŽƚĞŶƐŝŶĞƌĞĐĞƉƚĞƌďůŽŬŬĞƌƐ;ZƐͿ͘/ŶHoofdstuk 5ŝƐĚĞĂƐƐŽĐŝĂƟĞ ƚƵƐƐĞŶŚĞƚĞīĞĐƚǀĂŶƉƌŽƚĞŢŶƵƌŝĞǀĞƌůĂŐŝŶŐĚŽŽƌŵŝĚĚĞůǀĂŶĚĞƌĞŵŵĞƌƌĂŵŝƉƌŝůĞŶ ƉƌŽŐƌĞƐƐŝĞǀĂŶŶŝĞƌnjŝĞŬƚĞŽŶĚĞƌnjŽĐŚƚŝŶϮϴϬŬŝŶĚĞƌĞŶŵĞƚĐŚƌŽŶŝƐĐŚĞŶŝĞƌnjŝĞŬƚĞ͘/ŶĚĞnjĞ ƉŽƐƚͲŚŽĐĂŶĂůLJƐĞǀĂŶĚĞ^WƐƚƵĚŝĞǁĞƌĚĂĂŶŐĞƚŽŽŶĚĚĂƚĚĞďĞŚĂŶĚĞůŝŶŐŵĞƚƌĂŵŝƉƌŝů ŝŶĞĞŶĚŽƐĞƌŝŶŐǀĂŶϲŵŐͬŵ2_{ͬĚĂŐƉƌŽƚĞŢŶƵƌŝĞŵĞƚŐĞŵŝĚĚĞůĚϰϮйǀĞƌůĂĂŐĚĞ͘ƌǁĞƌĚ} ĞĐŚƚĞƌŝŶĚĞŽŶĚĞƌnjŽĞŬƐƉŽƉƵůĂƟĞĞĞŶŐƌŽƚĞǀĂƌŝĂďŝůŝƚĞŝƚŝŶŚĞƚƉƌŽƚĞŢŶƵƌŝĞǀĞƌůĂŐĞŶĚĞ ĞīĞĐƚŐĞnjŝĞŶ͘<ŝŶĚĞƌĞŶŵĞƚŵĞĞƌƉƌŽƚĞŢŶƵƌŝĞǀĞƌůĂŐŝŶŐŶĂƐƚĂƌƚǀĂŶĚĞŵĞĚŝĐĂƟĞŚĂĚĚĞŶ ĞĞŶůĂŐĞƌƌŝƐŝĐŽŽƉƉƌŽŐƌĞƐƐŝĞǀĂŶŶŝĞƌnjŝĞŬƚĞ͕ǁĂƚŽǀĞƌĞĞŶŬŽŵƚŵĞƚĞĞƌĚĞƌĞďĞǀŝŶĚŝŶŐĞŶ ŝŶǀŽůǁĂƐƐĞŶĞŶ͘'ĞnjĂŵĞŶůŝũŬďĞŶĂĚƌƵŬŬĞŶĚĞnjĞƌĞƐƵůƚĂƚĞŶŚĞƚďĞůĂŶŐǀĂŶƉƌŽƚĞŢŶƵƌŝĞĂůƐ ĞĞŶƌŝƐŝĐŽĨĂĐƚŽƌǀŽŽƌƉƌŽŐƌĞƐƐŝĞǀĂŶŶŝĞƌnjŝĞŬƚĞŝŶŬŝŶĚĞƌĞŶŵĞƚĐŚƌŽŶŝƐĐŚĞŶŝĞƌnjŝĞŬƚĞ͘ dĞǀĞŶƐƐƵŐŐĞƌĞƌĞŶnjŝũĚĂƚƉƌŽƚĞŢŶƵƌŝĞǀĞƌůĂŐŝŶŐĞĞŶďĞůĂŶŐƌŝũŬĚŽĞůŝƐŝŶĚĞďĞŚĂŶĚĞůŝŶŐ ǀĂŶŬŝŶĚĞƌĞŶŵĞƚĐŚƌŽŶŝƐĐŚĞŶŝĞƌnjŝĞŬƚĞ͘ Hoofdstuk 6ĞǀĂůƵĞĞƌƚŚĞƚĞīĞĐƚǀĂŶƐƚŽƉƉĞŶǀĂŶZ^ƌĞŵŵĞƌƐŽƉŵĂƌŬĞƌƐǀĂŶ ŶŝĞƌnjŝĞŬƚĞĞŶƉƌŽŐƌĞƐƐŝĞǀĂŶŶŝĞƌnjŝĞŬƚĞŝŶŬŝŶĚĞƌĞŶŵĞƚĐŚƌŽŶŝƐĐŚĞŶŝĞƌnjŝĞŬƚĞ͘/ŶĚĞnjĞ ƐƚƵĚŝĞŝƐŐĞďƌƵŝŬŐĞŵĂĂŬƚǀĂŶŽďƐĞƌǀĂƟŽŶĞůĞĚĂƚĂƵŝƚŚĞƚϰĐŽŚŽƌƚ͕ǁĂĂƌŝŶŬŝŶĚĞƌĞŶ ŵĞƚĐŚƌŽŶŝƐĐŚĞŶŝĞƌnjŝĞŬƚĞŽǀĞƌĚĞƟũĚǁŽƌĚĞŶŐĞǀŽůŐĚ͘<ŽƌƚĞƚĞƌŵŝũŶǀĞƌĂŶĚĞƌŝŶŐĞŶ ŝŶďůŽĞĚĚƌƵŬ͕ĂůďƵŵŝŶƵƌŝĞĞŶŬĂůŝƵŵŝŶŚĞƚďůŽĞĚĞŶĚĞǀĞƌĂŶĚĞƌŝŶŐŝŶŶŝĞƌĨƵŶĐƟĞŽƉ ůĂŶŐĞƚĞƌŵŝũŶǁĞƌĚĞŶŽŶĚĞƌnjŽĐŚƚŝŶϲϵŬŝŶĚĞƌĞŶĚŝĞƐƚŽƉƚĞŶŵĞƚŚĞƚŐĞďƌƵŝŬǀĂŶZ^ ƌĞŵŵĞƌƐ͘KƉŬŽƌƚĞƚĞƌŵŝũŶǁĞƌĚŚĞƚƐƚĂŬĞŶǀĂŶZ^ƌĞŵŵĞƌƐŐĞǀŽůŐĚĚŽŽƌĞĞŶƐƟũŐŝŶŐ ŝŶĂůďƵŵŝŶƵƌŝĞĞŶĚĂůŝŶŐǀĂŶŬĂůŝƵŵ͘ĐŚƚĞƌ͕ĚĞŶŝĞƌĨƵŶĐƟĞĂĐŚƚĞƌƵŝƚŐĂŶŐǀĞƌƐŶĞůĚĞŶĂ ŚĞƚƐƚŽƉƉĞŶǀĂŶZ^ƌĞŵŵŝŶŐ͘ŝƚƐƵŐŐĞƌĞĞƌƚĚĂƚŚĞƚŐĞďƌƵŝŬǀĂŶZ^ƌĞŵŵĞƌƐ ďĞƐĐŚĞƌŵĞŶĚǁĞƌŬƚĞŶĚĂƚŚĞƚƐƚŽƉƉĞŶǀĂŶZ^ƌĞŵŵĞƌƐĚĞƉƌŽŐƌĞƐƐŝĞǀĂŶŶŝĞƌnjŝĞŬƚĞ ǀĞƌƐŶĞůƚ͘tĞŚĞďďĞŶŽŽŬĚĞŵĞĞƐƚďĞůĂŶŐƌŝũŬĞƌĞĚĞŶĞŶǀŽŽƌŚĞƚƐƚŽƉƉĞŶǀĂŶZ^ ƌĞŵŵĞƌƐŝŶĚĞnjĞŬŝŶĚĞƌĞŶŐĞģǀĂůƵĞĞƌĚ͘ŝƚǁĂƌĞŶĞĞŶƐƟũŐŝŶŐǀĂŶŬƌĞĂƟŶŝŶĞŝŶŚĞƚ ďůŽĞĚ;ǁĂƚĞĞŶĚĂůŝŶŐŝŶŶŝĞƌĨƵŶĐƟĞďĞƚĞŬĞŶƚͿ͕ĞĞŶůĂŐĞďůŽĞĚĚƌƵŬĞŶĞĞŶƚĞŚŽŽŐƐĞƌƵŵ ŬĂůŝƵŵ͘ĞnjĞƐƚƵĚŝĞŚĞĞŌĞĞŶƵŶŝĞŬĚĞƐŝŐŶĚŽŽƌŐĞŐĞǀĞŶƐǀĂŶnjŽǁĞůǀŽŽƌĂůƐŶĂƐƚŽƉƉĞŶ ǀĂŶZ^ƌĞŵŵŝŶŐďŝŶŶĞŶŚĞƚnjĞůĨĚĞŬŝŶĚƚĞŐĞďƌƵŝŬĞŶ͘ĞnjĞƌĞƐƵůƚĂƚĞŶƚŽŶĞŶĂĂŶĚĂƚĞƌ ďĞůĂŶŐƌŝũŬĞŬůŝŶŝƐĐŚĞƌĞĚĞŶĞŶŬƵŶŶĞŶnjŝũŶŽŵŚĞƚŐĞďƌƵŝŬǀĂŶZ^ƌĞŵŵŝŶŐŝŶŬŝŶĚĞƌĞŶ ŵĞƚĐŚƌŽŶŝƐĐŚĞŶŝĞƌnjŝĞŬƚĞƚĞƐƚŽƉƉĞŶ͕ŵĂĂƌĚĂƚŚĞƚƐƚŽƉƉĞŶǁĞůƚŽƚŐĞǀŽůŐŚĞĞŌĚĂƚ ĞƌĞĞŶƐŶĞůůĞƌĞĂĐŚƚĞƌƵŝƚŐĂŶŐǀĂŶĚĞŶŝĞƌĨƵŶĐƟĞŽƉƚƌĞĞĚƚ͘ŝũŚĞƚƐƚŽƉƉĞŶǀĂŶĚĞnjĞ

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 115PDF page: 115PDF page: 115PDF page: 115

115 EĞĚĞƌůĂŶĚƐĞƐĂŵĞŶǀĂƫŶŐĞŶƚŽĞŬŽŵƐƚƉĞƌƐƉĞĐƟĞĨ ďĞŚĂŶĚĞůŝŶŐŵŽĞƚĞŶĚĞƌĞĚĞŶĞŶǀŽŽƌŚĞƚƐƚŽƉƉĞŶĚĂĂƌŽŵŐŽĞĚǁŽƌĚĞŶĂĨŐĞǁŽŐĞŶ ƚĞŐĞŶŚĞƚŵŽŐĞůŝũŬĞĞīĞĐƚŽƉĂĐŚƚĞƌƵŝƚŐĂŶŐǀĂŶŶŝĞƌĨƵŶĐƟĞ͘

7RHNRPVWSHUVSHFWLHI

,ŽĞǁĞů Ěŝƚ ƉƌŽĞĨƐĐŚƌŝŌ ǀĞƌƐĐŚŝůůĞŶĚĞ ĂƐƉĞĐƚĞŶ ǀĂŶ ĂůďƵŵŝŶƵƌŝĞ ŝŶ ŬŝŶĚĞƌĞŶ ŚĞĞŌ ŽŶĚĞƌnjŽĐŚƚ͕ njĂů Ğƌ ŵĞĞƌ ŽŶĚĞƌnjŽĞŬ ŐĞĚĂĂŶ ŵŽĞƚĞŶ ǁŽƌĚĞŶ Žŵ ŚĞƚ ďĞůĂŶŐ ǀĂŶ ĂůďƵŵŝŶƵƌŝĞĂůƐĞĞŶƌŝƐŝĐŽŵĂƌŬĞƌǀŽŽƌŶŝĞƌͲ͕ŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞŶƚĞǀĞƌŚĞůĚĞƌĞŶĞŶŽŵ ĚĞďĞŚĂŶĚĞůŝŶŐǀĂŶĂůďƵŵŝŶƵƌŝĞŝŶŬŝŶĚĞƌĞŶƚĞŽƉƟŵĂůŝƐĞƌĞŶ͘ ĞďĞƐƚĞŵĂŶŝĞƌŽŵƚĞŽŶĚĞƌnjŽĞŬĞŶŽĨĂůďƵŵŝŶƵƌŝĞĞĞŶĂĂŶŐĞďŽƌĞŶŬĞŶŵĞƌŬŝƐĚĂƚ ƐĂŵĞŶŚĂŶŐƚŵĞƚĞĞŶǀĞƌŚŽŽŐĚƌŝƐŝĐŽŽƉŶŝĞƌͲ͕ŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞŶ͕ŝƐŚĞƚƵŝƚǀŽĞƌĞŶǀĂŶ ĞĞŶƐƚƵĚŝĞĚŝĞŝŶĚŝǀŝĚƵĞŶǀŽůŐƚǀĂŶĂĨŚƵŶŐĞƌƚĞƚŽƚŚĞƚĞŝŶĚǀĂŶŚƵŶůĞǀĞŶ͘ĞnjĞ ƐƚƵĚŝĞnjŽƵƌĞŐĞůŵĂƟŐĂůďƵŵŝŶƵƌŝĞŵŽĞƚĞŶŵĞƚĞŶ͕ŽŵƚĞďĞƉĂůĞŶŽĨĞƌĞĞŶƌĞůĂƟĞŝƐ ƚƵƐƐĞŶŚŽŐĞƌĞĂůďƵŵŝŶƵƌŝĞǁĂĂƌĚĞƐŽƉũŽŶŐĞůĞĞŌŝũĚĞŶŚĞƚƌŝƐŝĐŽŽƉŚĂƌƚͲĞŶǀĂĂƚnjŝĞŬƚĞ͕ ŶŝĞƌnjŝĞŬƚĞŽĨĚĞĚŽŽĚŽƉůĂƚĞƌĞůĞĞŌŝũĚ͘ĞƵŝƚǀŽĞƌŝŶŐǀĂŶĞĞŶĚĞƌŐĞůŝũŬĞƐƚƵĚŝĞŝƐŝŶĚĞ ƉƌĂŬƟũŬĞĐŚƚĞƌnjĞĞƌůĂƐƟŐ͘ůƐĂůƚĞƌŶĂƟĞĨnjŽƵĚĞŶĂĨnjŽŶĚĞƌůŝũŬĞƐƚƵĚŝĞƐŬƵŶŶĞŶǁŽƌĚĞŶ ŐĞĚĂĂŶĚŝĞĚŝǀĞƌƐĞĚĞĞůǀƌĂŐĞŶďĞĂŶƚǁŽŽƌĚĞŶ͘ůůĞƌĞĞƌƐƚǁŽƌĚĞŶŽƉĚŝƚŵŽŵĞŶƚĚĞ ĂůďƵŵŝŶƵƌŝĞŵĞƟŶŐĞŶǀĂŶĚĞŬŝŶĚĞƌĞŶŝŶŚĞƚ'<KĐŽŚŽƌƚƵŝƚŚŽŽĨĚƐƚƵŬϭŚĞƌŚĂĂůĚ͕ ŽŵǀĂƐƚƚĞƐƚĞůůĞŶŽĨĚĞĂůďƵŵŝŶƵƌŝĞǁĂĂƌĚĞƐŝŶĚĞnjĞŬŝŶĚĞƌĞŶĐŽŶƐŝƐƚĞŶƚnjŝũŶŽǀĞƌĚĞƟũĚ͘ ŽǀĞŶĚŝĞŶŚĞĞŌĞĞŶůŽŶŐŝƚƵĚŝŶĂůĞĐŽŚŽƌƚƐƚƵĚŝĞŝŶĚĞƌĞŐŝŽƌŝƐƚŽůŝŶŶŐĞůĂŶĚ;ĚĞAvon

Longitudinal Study of Parents and Children;>^WͿͿŵĞĞƌĚĞƌĞŵĂůĞŶďůŽĞĚĞŶƵƌŝŶĞ

ŵŽŶƐƚĞƌǀĞƌnjĂŵĞůĚ;ǀŽŽƌ͕ƟũĚĞŶƐ͕ĞŶŶĂĚĞƉƵďĞƌƚĞŝƚͿ͘ĞnjĞďůŽĞĚĞŶƵƌŝŶĞŵŽŶƐƚĞƌƐ ŬƵŶŶĞŶŚĞůƉĞŶŝŶŚĞƚďĞĂŶƚǁŽŽƌĚĞŶǀĂŶĚĞǀƌĂĂŐŽĨǀĞƌŚŽŽŐĚĞĂůďƵŵŝŶƵƌŝĞǁĂĂƌĚĞƐŽƉ ũŽŶŐĞůĞĞŌŝũĚƐĂŵĞŶŚĂŶŐĞŶŵĞƚĂĐŚƚĞƌƵŝƚŐĂŶŐǀĂŶŶŝĞƌĨƵŶĐƟĞŽƉůĂŶŐĞƚĞƌŵŝũŶ͘ KŵĚĞĮŶŝƟĞĨƚĞŬƵŶŶĞŶďĞǁŝũnjĞŶĚĂƚĂůďƵŵŝŶƵƌŝĞĞĞŶŐĞůĚŝŐďĞŚĂŶĚĞůĚŽĞůŝƐǀŽŽƌ ďĞƐĐŚĞƌŵŝŶŐǀĂŶĚĞŶŝĞƌĞŶ;ĞŶŚĂƌƚĞŶǀĂƚĞŶͿnjŝũŶĞƌŬůŝŶŝƐĐŚĞƐƚƵĚŝĞƐŶŽĚŝŐĚŝĞĂůƐ ƉƌŝŵĂŝƌĚŽĞůŚĞďďĞŶŽŵĂůďƵŵŝŶƵƌŝĞƚĞǀĞƌůĂŐĞŶĞŶƚĞŽŶĚĞƌnjŽĞŬĞŶŽĨĚĞnjĞǀĞƌůĂŐŝŶŐ ƐĂŵĞŶŚĂŶŐƚŵĞƚŚĞƚƌŝƐŝĐŽŽƉůĂŶŐĞƚĞƌŵŝũŶ͘Ğ^ƚƵĚLJŽĨŝĂďĞƟĐEĞƉŚƌŽƉĂƚŚLJǁŝƚŚ Atrasentan;^KEZͿŝƐŽƉĚĞnjĞŵĂŶŝĞƌŽŶƚǁŽƌƉĞŶ͘ĂŶŐĞnjŝĞŶĚĞ^KEZƐƚƵĚŝĞƌĞĐĞŶƚ ŝƐďĞģŝŶĚŝŐĚǁŽƌĚĞŶĚĞƌĞƐƵůƚĂƚĞŶǀĂŶĚĞnjĞƐƚƵĚŝĞŝŶĚĞůŽŽƉǀĂŶϮϬϭϴǀĞƌǁĂĐŚƚ͘ĞŶ ƉŽƐŝƟĞĨƌĞƐƵůƚĂĂƚnjĂůĚĞŚLJƉŽƚŚĞƐĞĚĂƚŚĞƚǀĞƌůĂŐĞŶǀĂŶĂůďƵŵŝŶƵƌŝĞĞĞŶďĞůĂŶŐƌŝũŬĚŽĞů ǀŽŽƌďĞŚĂŶĚĞůŝŶŐŝŶǀŽůǁĂƐƐĞŶĞŶŝƐǀĞƌƐƚĞƌŬĞŶ͘ĂƚĂǀĂŶŬůŝŶŝƐĐŚĞƐƚƵĚŝĞƐŝŶŬŝŶĚĞƌĞŶ ŽǀĞƌĚŝƚŽŶĚĞƌǁĞƌƉnjŝũŶĞĐŚƚĞƌŶŽŐŶŝĞƚďĞƐĐŚŝŬďĂĂƌ͘,ŽĞǁĞůĚĞƌĞƐƵůƚĂƚĞŶŝŶŚŽŽĨĚƐƚƵŬ ϱǀĂŶĚŝƚƉƌŽĞĨƐĐŚƌŝŌŽǀĞƌĞĞŶŬŽŵĞŶŵĞƚĞĞƌĚĞƌĞďĞǀŝŶĚŝŶŐĞŶŝŶǀŽůǁĂƐƐĞŶĞŶ͕njŽƵĞĞŶ ƐƚƵĚŝĞŝŶŬŝŶĚĞƌĞŶ͕ǀĞƌŐĞůŝũŬďĂĂƌŵĞƚĚĞ^KEZƐƚƵĚŝĞ͕njĞĞƌŝŶƚĞƌĞƐƐĂŶƚnjŝũŶ͘ŝƚŝƐǀŽŽƌĂů ďĞůĂŶŐƌŝũŬŽŵĚĂƚĚĞŬĞŶŵĞƌŬĞŶǀĂŶŬŝŶĚĞƌĞŶŵĞƚĐŚƌŽŶŝƐĐŚĞŶŝĞƌnjŝĞŬƚĞnjĞĞƌǀĞƌƐĐŚŝůůĞŶ ǀĂŶĚĞǀŽůǁĂƐƐĞŶƉŽƉƵůĂƟĞŝŶǀĞƌƐĐŚŝůůĞŶĚĞŽƉnjŝĐŚƚĞŶnjŽĂůƐŽŶĚĞƌůŝŐŐĞŶĚĞŶŝĞƌnjŝĞŬƚĞ͕ njŝĞŬƚĞĚƵƵƌĞŶĂĂŶǁĞnjŝŐŚĞŝĚǀĂŶĂŶĚĞƌĞĂĂŶĚŽĞŶŝŶŐĞŶ͘,ĞƚŝƐĚĞǀƌĂĂŐŽĨĚĞŬŝŶĚĞƌĞŶŝŶ ĚĞnjĞƐƚƵĚŝĞnjŽƵĚĞŶŵŽĞƚĞŶǁŽƌĚĞŶďĞŚĂŶĚĞůĚŵĞƚĞĞŶĞŶĚŽƚŚĞůŝŶĞƌĞĐĞƉƚŽƌĂŶƚĂŐŽŶŝƐƚ

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 116PDF page: 116PDF page: 116PDF page: 116

116 njŽĂůƐŝŶĚĞ^KEZƐƚƵĚŝĞ͕ŵĞƚĞĞŶZ^ƌĞŵŵĞƌŽĨnjĞůĨƐĞĞŶŶŝĞƵǁŵŝĚĚĞůĚĂƚƐƉĞĐŝĮĞŬ ĂůďƵŵŝŶƵƌŝĞǀĞƌůĂĂŐƚŝŶŬŝŶĚĞƌĞŶ͘ /ŶŚĞƚĂůŐĞŵĞĞŶŝƐŚĞƚnjĞĞƌďĞůĂŶŐƌŝũŬŽŵǀŽŽƌĚĞǀĞůĞŽŶďĞĂŶƚǁŽŽƌĚĞǀƌĂŐĞŶŝŶ ǁĞƚĞŶƐĐŚĂƉƉĞůŝũŬŽŶĚĞƌnjŽĞŬŵĞĞƌŐĞďƌƵŝŬƚĞŵĂŬĞŶǀĂŶĚĞďĞƐĐŚŝŬďĂƌĞĚĂƚĂĚŝĞnjŝũŶ ǀĞƌnjĂŵĞůĚŝŶĚĂƚĂƌĞŐŝƐƚƌĂƟĞƐ͕ŽďƐĞƌǀĂƟŽŶĞůĞƐƚƵĚŝĞƐĞŶŬůŝŶŝƐĐŚĞƐƚƵĚŝĞƐ͘ĞĚĞĞůŶĂŵĞ ǀĂŶŬǁĞƚƐďĂƌĞƉĞƌƐŽŶĞŶ͕njŽĂůƐŬŝŶĚĞƌĞŶ͕ŝŶŬůŝŶŝƐĐŚŽŶĚĞƌnjŽĞŬŝƐŐĞůŝŵŝƚĞĞƌĚ͘ŝƚŚĞĞŌ ĚĞĞůƐƚĞŵĂŬĞŶŵĞƚĞdžƚƌĂƌĞŐĞůŐĞǀŝŶŐŽŵŚĞŶƚĞďĞƐĐŚĞƌŵĞŶƟũĚĞŶƐĚĞĞůŶĂŵĞŝŶŬůŝŶŝƐĐŚ ŽŶĚĞƌnjŽĞŬ͘dĞŶŐĞǀŽůŐĞǀĂŶĚĞnjĞƐĐŚĂĂƌƐƚĞĂĂŶŽŶĚĞƌnjŽĞŬŝŶŬŝŶĚĞƌĞŶŝƐĞƌĞĐŚƚĞƌŽŽŬĞĞŶ ŐĞďƌĞŬĂĂŶĚĂƚĂĂĂŶŐĂĂŶĚĞĚĞǀĞŝůŝŐŚĞŝĚĞŶĞīĞĐƟǀŝƚĞŝƚǀĂŶďĞŚĂŶĚĞůŝŶŐĞŶŝŶŬŝŶĚĞƌĞŶ͘ ŽŽƌŐĞďƌƵŝŬƚĞŵĂŬĞŶǀĂŶďĞƐƚĂĂŶĚĞĚĂƚĂŝŶĞĞŶƉƌĂŐŵĂƟƐĐŚƐƚƵĚŝĞĚĞƐŝŐŶŬƵŶŶĞŶ ŵŽŐĞůŝũŬŽŶĚĞƌnjŽĞŬƐǀƌĂŐĞŶǁŽƌĚĞŶďĞĂŶƚǁŽŽƌĚǁĂĂƌǀŽŽƌŚĞƚďĞǁŝũƐŝŶŬůŝŶŝƐĐŚĞƐƚƵĚŝĞƐ ďĞƉĞƌŬƚŝƐ͘ĞŚŽŽĨƐƚƵŬŬĞŶŝŶŚĞƚƚǁĞĞĚĞĚĞĞůǀĂŶĚŝƚƉƌŽĞĨƐĐŚƌŝŌnjŝũŶǀŽŽƌďĞĞůĚĞŶǀĂŶ ŚŽĞĞĞŶĚĞƌŐĞůŝũŬƉƌĂŐŵĂƟƐĐŚƐƚƵĚŝĞĚĞƐŝŐŶŬĂŶǁŽƌĚĞŶĂĂŶŐĞƉĂŬƚ͘ ŽŶĐůƵĚĞƌĞŶĚ ŵŽĞƚ Ğƌ ŵĞĞƌ ŽŶĚĞƌnjŽĞŬ ǁŽƌĚĞŶ ŐĞĚĂĂŶ Žŵ ŚĞƚ ďĞůĂŶŐ ǀĂŶ ĂůďƵŵŝŶƵƌŝĞĂůƐĞĞŶƌŝƐŝĐŽĨĂĐƚŽƌŽƉũŽŶŐĞůĞĞŌŝũĚǀĞƌĚĞƌƚĞĂŶĂůLJƐĞƌĞŶ͘'ĞďƌƵŝŬǀĂŶnjŽǁĞů ŽďƐĞƌǀĂƟŽŶĞůĞĚĂƚĂƵŝƚĐŽŚŽƌƚƐƚƵĚŝĞƐĂůƐĞĞŶŐĞƌĂŶĚŽŵŝƐĞĞƌĚĞƉůĂĐĞďŽŐĞĐŽŶƚƌŽůĞĞƌĚĞ ƐƚƵĚŝĞnjŽƵŽŶƐǀĞƌĚĞƌŬƵŶŶĞŶŚĞůƉĞŶŝŶĚĞnjĞnjŽĞŬƚŽĐŚƚ͘

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

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117 EĞĚĞƌůĂŶĚƐĞƐĂŵĞŶǀĂƫŶŐĞŶƚŽĞŬŽŵƐƚƉĞƌƐƉĞĐƟĞĨ

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 119PDF page: 119PDF page: 119PDF page: 119

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 120PDF page: 120PDF page: 120PDF page: 120

120

Dankwoord

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518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 121PDF page: 121PDF page: 121PDF page: 121

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518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 122PDF page: 122PDF page: 122PDF page: 122

122 ŚĞĞůǀĞĞůĚŝŶŐĞŶŐĞŬŽƉƉĞůĚĂĂŶ;ůĞŬŬĞƌͿĞƚĞŶ͕ŵĂĂƌũĞŵŽĞƚƚŽĐŚǁĂƚĂůƐĂĨĚĞůŝŶŐĚŝĞŵĞƚ ŶĂŵĞŽŶĚĞƌnjŽĞŬĚŽĞƚŶĂĂƌĚŝĂďĞƚĞƐ͊ƵƐĚĂŶŬũĞǁĞůĂůůĞŵĂĂů;ǁĂĂƌďŝũŝŬŽŶŐĞƚǁŝũĨĞůĚ ŝĞŵĂŶĚďĞŶǀĞƌŐĞƚĞŶͿ͗ĂƵŬĞ͕ůĂŝƌĞ͕ĞƌďĞǁ͕ůůĞŶ͕'ƌŝŐŽƌLJ͕:ĂĐŽ͕:ĂƐƉĞƌ͕:ĞƌŽĞŶ͕:Žď͕ <ŝŵ͕DĂĂƌƚũĞ͕DĂƌŐũĞ͕DĂƌũŽůĞŝŶ͕DŝĐŚĞůůĞ͕DŝƐŐŚŝŶĂ͕EŝĞŶŬĞ͕WĞƚĞƌ͕WĞƚƌĂ͕ZƵďĞŶ͕^ĞƌŐĞŝ͕ ^ŬĂŶĚĞƌ͕^ƟũŶ͕dĂĐŽ͕dŽďŝĂƐ͘sĞƌĚĞƌǁŝůŝŬŐƌĂĂŐŝŶŚĞƚďŝũnjŽŶĚĞƌƌĚLJ͕ůĞdžĂŶĚƌĂĞŶDĂƌũĂ ďĞĚĂŶŬĞŶǀŽŽƌũƵůůŝĞŚƵůƉďŝũĚĞĐůĂƌĂƟĞƐ͕ŚĞƚŵĂŬĞŶǀĂŶŽŶŵŽŐĞůŝũŬĞĂĨƐƉƌĂŬĞŶ͕ĂŶĚĞƌĞ ĮŶĂŶĐŝģůĞnjĂŬĞŶŵĂĂƌǀŽŽƌĂůǀŽŽƌũƵůůŝĞŝŶƚĞƌĞƐƐĞĞŶĚĞŐĞnjĞůůŝŐĞŬůĞƚƐŵŽŵĞŶƚĞŶ͊Ŷ ŶĂƚƵƵƌůŝũŬůŝĞǀĞ<ŝƌƐƚĞŶ͗ǀĂŶĂĨŚĞƚĞĞƌƐƚĞŵŽŵĞŶƚŚĂĚĚĞŶǁĞĞĞŶŐŽĞĚĞŬůŝŬ͕ǁĂƚŚĞďŝŬ ĞŶŽƌŵŐĞůĂĐŚĞŶŵĞƚũŽƵƟũĚĞŶƐĚĞĂĨŐĞůŽƉĞŶũĂƌĞŶŽƉĚĞĂĨĚĞůŝŶŐ͊:ĂŵŵĞƌŐĞŶŽĞŐǀŽŽƌ ŽŶƐŚĞďũŝũĞĞŶŶŝĞƵǁĞďĂĂŶŐĞǀŽŶĚĞŶŝŶEŝũŵĞŐĞŶ͕ǁĂĂƌũĞĞĞŶŶŝĞƵǁĂǀŽŶƚƵƵƌďĞŶƚ ďĞŐŽŶŶĞŶ͘/ŬǀŽŶĚŚĞƚĞĞŶŽŶƚnjĞƩĞŶĚĞĞĞƌŽŵŽŶůĂŶŐƐũŽƵǁƉĂƌĂŶŝŵĨƚĞnjŝũŶ͕ĞŶũŝũďĞŶƚ ƐƟĞŬĞŵŵŝũŶĚĞƌĚĞ;ŽŶŽĸĐŝģůĞͿƉĂƌĂŶŝŵĨ͊ >ŝĞǀĞsĂůĞŶƟŶĂ͕ǀĂŶĂĨŚĞƚďĞŐŝŶnjŝũŶǁŝũƉĂƌĂůůĞůďĞnjŝŐŐĞǁĞĞƐƚŵĞƚĚŝƚƉƌŽũĞĐƚ͕ǁĂĂƌďŝũŚĞƚ ƐƚĞĞĚƐĚƵŝĚĞůŝũŬĞƌǁĞƌĚŽƉǁĞůŬĞƌŝĐŚƟŶŐǁŝũŽŶƐďĞŝĚĞŶnjŽƵĚĞŶĨŽĐƵƐƐĞŶ͘ZŽŶĚŽŵũŽƵǁ ŽŶƚnjĞƩĞŶĚĚƌƵŬŬĞďĞnjŝŐŚĞĚĞŶŝŶĚĞŬůŝŶŝĞŬǀŽŶĚũŝũƚŽĐŚĚĞƟũĚŽŵŵĞƚĞĞŶWŚƚƌĂũĞĐƚ ĂĂŶĚĞƐůĂŐƚĞŐĂĂŶ͕ǁĂĂƌũĞĚĞŬŽŵĞŶĚĞũĂƌĞŶŚŽƉĞůŝũŬŵĞƚǀĞĞůƉůĞnjŝĞƌŵĞĞǀĞƌĚĞƌŐĂĂƚ͘ ĞƐŵĂĂŶĚĞŶŚĞďŝŬďŝũũŽƵŽƉĚĞĂĨĚĞůŝŶŐĂůƐĂƌƚƐͲĂƐƐŝƐƚĞŶƚŵŽŐĞŶǁĞƌŬĞŶ͕ǁĂĂƌďŝũŝŬ ŚĞĞůǀĞĞůŚĞďŐĞůĞĞƌĚĞŶŚŽƉĞůŝũŬũŽƵŝĞƚƐŽŶƚůĂƐƚŚĞďƚ͘ĞůĨƐƟũĚĞŶƐĚĞnjĞǀƌĞƐĞůŝũŬĚƌƵŬŬĞ ƉĞƌŝŽĚĞǀŽŽƌũŽƵŶĂŵũĞĚĞƟũĚŽŵŵŝũĚŝŶŐĞŶƵŝƚƚĞůĞŐŐĞŶ͕ŚĞĞůŬŶĂƉ͊:ŝũďĞŶƚƚŽĐŚǁĞů ĞĞŶǀĂŶĚĞƌŽĚĞĚƌĂĚĞŶŐĞǁĞĞƐƚƟũĚĞŶƐĚŝƚDͬWŚĂǀŽŶƚƵƵƌ͕ĞŶŝŬďĞŶĚĂŶŽŽŬŚĞĞů ďůŝũĚĂƚũŝũĞĞŶǀĂŶŵŝũŶƉĂƌĂŶŝŵĨĞŶǁŝůĚĞnjŝũŶ͕ŐƌĂnjŝĞŵŝůůĞ͊ >ŝĞǀĞ^ŝĞƚĂ͕ĂůƐĞĞŶǀĂŶĚĞǁĞŝŶŝŐĞŵĞĚĞͲŽŶĚĞƌnjŽĞŬĞƌƐďĞŶũŝũŚŝĞƌŽƉĚĞĂĨĚĞůŝŶŐ ĂĂŶǁĞnjŝŐŐĞǁĞĞƐƚǀĂŶĂĨŚĞƚŵŽŵĞŶƚĚĂƚŝŬĂůƐƐƚƵĚĞŶƚďĞŐŽŶŽƉĚĞĂĨĚĞůŝŶŐ͕ƚŽƚŚĞƚ ŵŽŵĞŶƚĚĂƚŝŬĚĞĂĨĚĞůŝŶŐǁĞĞƌǀĞƌůĂĂƚ͘DĞƚũĞŚĞĞƌůŝũŬ&ƌŝĞƐĞŶƵĐŚƚĞƌŚĞŝĚĞŶŐŽĞĚĞ ĂĚǀŝĞnjĞŶŬŽŶŝŬĂůƟũĚǁĞĞƌĞǀĞŶǀŽŽƌƵŝƚ͕ŚŽƉĞůŝũŬŚĞďŝŬũĞŶŝĞƚƚĞǀĞĞůůĂƐƟŐŐĞǀĂůůĞŶŵĞƚ ŵŝũŶǀƌĂŐĞŶ͘sĞƌĚĞƌŬŽŶĚĞŶǁĞĂůƟũĚŚĞĞůŐĞnjĞůůŝŐŬůĞƚƐĞŶĞŶŚĞďďĞŶǁĞŽŶƚnjĞƩĞŶĚǀĞĞů ŐĞůĂĐŚĞŶ͘ĂƚďŽĞŬŽĨĚŝĞĚŽĐƵŵĞŶƚĂŝƌĞŽǀĞƌŚĞƚŬĂŶƚŽŽƌůĞǀĞŶŬŽŵƚĞƌŚŽƉĞůŝũŬŶŽŐĞĞŶ ŬĞĞƌ͊ůƐƉƌŽĨĞƐƐŝŽŶĞůĞƉĂƌĂŶŝŵĨŬŽŶũŝũŶĂƚƵƵƌůŝũŬŽŽŬŶŝĞƚĂĂŶŵŝũŶnjŝũĚĞŽŶƚďƌĞŬĞŶĂůƐ ƌŽƚƐŝŶĚĞďƌĂŶĚŝŶŐ͕ŵĂĂƌnjŽŶĚĞƌŐĞŬŚĞŝĚďĞŶŝŬŽŶƚnjĞƩĞŶĚďůŝũĚĂƚŽŽŬũŝũŵŝũŶƉĂƌĂŶŝŵĨ ǁŝůĚĞnjŝũŶ͊ ĞĂĨŐĞůŽƉĞŶũĂƌĞŶŚĞďŝŬŵĞƚŚĞĞůǀĞĞůůĞƵŬĞĞŶůŝĞǀĞŵĞŶƐĞŶŚĞĞůǀĞĞůůĞƵŬĞĚŝŶŐĞŶ ŵŽŐĞŶ ďĞůĞǀĞŶ͕ Ěŝƚ njŝũŶ Ğƌ ƚĞǀĞĞů Žŵ ŽƉ ƚĞ ŶŽĞŵĞŶ͊ ƵƐ ůŝĞǀĞ ǀƌŝĞŶĚũĞƐ ǀĂŶ ĚĞ njĞŝůƐĐŚŽŽů͕ůŝĞǀĞǀƌŝĞŶĚŝŶŶĞƚũĞƐǀĂŶ'ŝŽŝĂ͕ǀƌŝĞŶĚŝŶŶĞƚũĞƐǀĂŶǀƌŽĞŐĞƌ͕ƐƚƵĚŝĞŐĞŶŽŽƚũĞƐ ĞŶƚĞĂŵŐĞŶŽŽƚũĞƐǀĂŶŚŽĐŬĞLJ͗ŝŬďĞŶŚĞĞůďůŝũŵĞƚũƵůůŝĞĞŶŚŽŽƉŽƉŶŽŐŚĞĞůǀĞĞůůĞƵŬĞ ĚŝŶŐĞŶŝŶĚĞƚŽĞŬŽŵƐƚ͊

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 123PDF page: 123PDF page: 123PDF page: 123

123 Dankwoord >ŝĞǀĞWĂƉĂ͕DĂŵĂ͕ŚĂƌůŽƩĞĞŶ:ƵůŝĂ͘/ŬďĞŶŚĞĞůďůŝũŵĞƚŽŶƐŐĞnjŝŶ͕ĞŶŚĞďĚĞĂĨŐĞůŽƉĞŶ ũĂƌĞŶŚĞĞůĞƌŐŐĞŶŽƚĞŶǀĂŶŽŶnjĞǀĂŬĂŶƟĞƐ͕ĞƚĞŶƚũĞƐĞŶĂŶĚĞƌĞŐĞnjĞůůŝŐĞĚŝŶŐĞŶ͘WĂƉĂ ĞŶŵĂŵĂ͕ĚĂŶŬũĞǁĞůǀŽŽƌũƵůůŝĞĞŝŶĚĞůŽnjĞǀĞƌƚƌŽƵǁĞŶŝŶŵŝũ͕ŶƵĚŝƚŝƐĂĨŐĞƐůŽƚĞŶŐĂĂŶ ǁĞŽƉŶĂĂƌŚĞƚǀŽůŐĞŶĚĞĂǀŽŶƚƵƵƌ͘ŚĂƌĞŶ:ƵƵů͕ŚĞůĂĂƐǁŽŶĞŶǁĞŶŝĞƚŵĞĞƌĂůůĞĚƌŝĞŝŶ ĚĞnjĞůĨĚĞƐƚĂĚ͕ŵĂĂƌŝŬďĞŶnjŽŽŶƚnjĞƩĞŶĚďůŝũŵĞƚũƵůůŝĞĂůƐŵŝũŶnjƵƐũĞƐ͊KŶnjĞǀĂŬĂŶƟĞŵĞƚ nj͛ŶĚƌŝĞƚũĞƐŝŶdŚĂŝůĂŶĚǁĂƐnjŽŽŶƚnjĞƩĞŶĚůĞƵŬ͕ŝŬŚŽŽƉĚĂƚǁĞŝŶĚĞƚŽĞŬŽŵƐƚĚŝƚƐŽŽƌƚ ůĞƵŬĞĚŝŶŐĞŶƐĂŵĞŶďůŝũǀĞŶĚŽĞŶ͊ ŶĂůƐůĂĂƚƐƚĞŶĂƚƵƵƌůŝũŬĞŶũŝ͘>ŝĞǀĞƐĐŚĂƚ͕ŝŬŚĞďĚĞĂĨŐĞůŽƉĞŶũĂƌĞŶŽŶƚnjĞƩĞŶĚŐĞŶŽƚĞŶ ǀĂŶĂůŽŶnjĞĂǀŽŶƚƵƌĞŶ͊DĂĂƌ͕ŚĞƚŐƌŽŽƚƐƚĞĂǀŽŶƚƵƵƌĚĂƚƐƚĂĂƚŽƉŚĞƚƉƵŶƚŽŵƚĞďĞŐŝŶŶĞŶ͕ ĞŶŚŝĞƌŬĂŶŝŬĂůůĞĞŶŵĂĂƌŵĞƚŽŶƚnjĞƩĞŶĚǀĞĞůŶŝĞƵǁƐŐŝĞƌŝŐŚĞŝĚĞŶƉůĞnjŝĞƌŶĂĂƌƵŝƚŬŝũŬĞŶ͘ ,ĂƌƌLJ͕ŝŬďĞŶďĞŶŝĞƵǁĚǁĂƚũĞĂůůĞŵĂĂůǀŽŽƌŽŶƐŝŶƉĞƩŽŚĞďƚ͊

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 124PDF page: 124PDF page: 124PDF page: 124

518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt 518800-L-sub01-bw-vdBelt Processed on: 17-4-2018 Processed on: 17-4-2018 Processed on: 17-4-2018

Processed on: 17-4-2018 PDF page: 125PDF page: 125PDF page: 125PDF page: 125

125 About the author

About the author

^ŽƉŚŝĞǀĂŶĚĞŶĞůƚǁĂƐďŽƌŶŽŶƵŐƵƐƚϭϱ͕ϭϵϵϬŝŶ'ƌŽŶŝŶŐĞŶ͕ƚŚĞEĞƚŚĞƌůĂŶĚƐ͘ŌĞƌ ĮŶŝƐŚŝŶŐƐĞĐŽŶĚĂƌLJƐĐŚŽŽůĂƚƚŚĞWƌĂĞĚŝŶŝƵƐ'LJŵŶĂƐŝƵŵ'ƌŽŶŝŶŐĞŶŝŶϮϬϬϴ͕ƐŚĞƐƚĂƌƚĞĚ ƐƚƵĚLJŝŶŐDĞĚŝĐŝŶĞĂƚƚŚĞhŶŝǀĞƌƐŝƚLJŽĨ'ƌŽŶŝŶŐĞŶ͘ ƵƌŝŶŐŚĞƌƐƚƵĚŝĞƐ͕ƐŚĞĚĞǀĞůŽƉĞĚĂƐƉĞĐŝĮĐŝŶƚĞƌĞƐƚŝŶƉĞĚŝĂƚƌŝĐƐ͕ŽŶǁŚŝĐŚƐŚĞ ĨŽĐƵƐĞĚĚƵƌŝŶŐƚŚĞĮŶĂůLJĞĂƌŽĨŚĞƌƐƚƵĚŝĞƐ͘^ŚĞĐŚŽƐĞƚŽĐŽŶĚƵĐƚŚĞƌĮŶĂůŝŶƚĞƌŶƐŚŝƉĂƚ ƚŚĞƉĞĚŝĂƚƌŝĐƐĐůŝŶŝĐŝŶƚŚĞDĂƌƟŶŝ,ŽƐƉŝƚĂů;'ƌŽŶŝŶŐĞŶͿĂŶĚƐƚĂƌƚĞĚĂƌĞƐĞĂƌĐŚƉƌŽũĞĐƚŽŶ ĂůďƵŵŝŶƵƌŝĂŝŶLJŽƵŶŐĐŚŝůĚƌĞŶĂƚƚŚĞĚĞƉĂƌƚŵĞŶƚŽĨůŝŶŝĐĂůWŚĂƌŵĂĐLJĂŶĚWŚĂƌŵĂĐŽůŽŐLJ ŽĨƚŚĞhŶŝǀĞƌƐŝƚLJDĞĚŝĐĂůĞŶƚĞƌ'ƌŽŶŝŶŐĞŶ;hD'Ϳ͘ƵƌŝŶŐƚŚŝƐĮŶĂůLJĞĂƌ͕ƐŚĞǁĂƐ ĂĐĐĞƉƚĞĚĨŽƌĂDͬWŚƉŽƐŝƟŽŶŝŶŽƌĚĞƌƚŽĞdžƉĂŶĚƚŚŝƐƌĞƐĞĂƌĐŚƉƌŽũĞĐƚŝŶƚŽĂĨƵůůWŚ ƉƌŽũĞĐƚƚŚĂƚƐŚĞƐƚĂƌƚĞĚĨƌŽŵƚŚĞŵŽŵĞŶƚŽĨĮŶŝƐŚŝŶŐŚĞƌƐƚƵĚŝĞƐ͘ &ƌŽŵEŽǀĞŵďĞƌϮϬϭϱƵŶƟůƉƌŝůϮϬϭϴ͕ƐŚĞǁŽƌŬĞĚĂƚƚŚĞĚĞƉĂƌƚŵĞŶƚŽĨůŝŶŝĐĂů WŚĂƌŵĂĐLJĂŶĚWŚĂƌŵĂĐŽůŽŐLJŽŶŚĞƌWŚƉƌŽũĞĐƚĞŶƟƚůĞĚ͚Albuminuria: more than a

renal risk marker? About the prevalence, measurement and treatment of albuminuria in children’ ƵŶĚĞƌƐƵƉĞƌǀŝƐŝŽŶŽĨƉƌŽĨ͘Ěƌ͘ŝĐŬĚĞĞĞƵǁĂŶĚƉƌŽĨ͘Ěƌ͘,ŝĚĚŽ>ĂŵďĞƌƐ ,ĞĞƌƐƉŝŶŬ͘ƵƌŝŶŐƚŚŝƐƉƌŽũĞĐƚ͕ƐŚĞĐŽŶĚƵĐƚĞĚŵƵůƟƉůĞƐƚƵĚŝĞƐĂŶĚƉƌĞƐĞŶƚĞĚƚŚĞƌĞƐƵůƚƐ ŽĨŚĞƌǁŽƌŬĂƚƚŚĞŵĞƌŝĐĂŶ^ŽĐŝĞƚLJŽĨEĞƉŚƌŽůŽŐLJ<ŝĚŶĞLJtĞĞŬ͕ƚŚĞDĞĞƟŶŐŽĨƚŚĞ ƵƌŽƉĞĂŶ^ŽĐŝĞƚLJŽĨWĞĚŝĂƚƌŝĐEĞƉŚƌŽůŽŐLJ͕ĂŶĚŶĂƟŽŶĂůĐŽŶŐƌĞƐƐĞƐ͘DŽƌĞŽǀĞƌ͕ƐŚĞ ŽďƚĂŝŶĞĚĞdžƉĞƌŝĞŶĐĞŝŶĐůŝŶŝĐĂůƉƌĂĐƟĐĞďLJǁŽƌŬŝŶŐĂƐĂƉŚLJƐŝĐŝĂŶĂƚƚŚĞĚĞƉĂƌƚŵĞŶƚŽĨ WĞĚŝĂƚƌŝĐEĞƉŚƌŽůŽŐLJĂƚƚŚĞhD'ŝŶϮϬϭϲĨŽƌƐŝdžŵŽŶƚŚƐ͘