{"id":5189,"date":"2026-03-19T09:15:43","date_gmt":"2026-03-19T09:15:43","guid":{"rendered":"https:\/\/dodo.proefschriftmaken.nl\/portfolio\/anne-els-van-de-logt\/"},"modified":"2026-03-19T11:33:29","modified_gmt":"2026-03-19T11:33:29","slug":"anne-els-van-de-logt","status":"publish","type":"us_portfolio","link":"https:\/\/dodo.proefschriftmaken.nl\/en\/portfolio\/anne-els-van-de-logt\/","title":{"rendered":"Anne Els Van De Logt"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":5190,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-5189","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"main_text":"","naam_van_het_proefschift":"Towards personalized treatment in membranous nephropathy","samenvatting":"Membraneuze nefropathie (MN) is de meest voorkomende oorzaak van het nefrotisch syndroom op volwassen leeftijd. In 2009 werd ontdekt dat 70-80 % van de pati\u00ebnten met primaire membraneuze nefropathie antistoffen heeft tegen de M-type fosfolipase A2 receptor (aPLA2Rab). Het natuurlijk beloop kan vari\u00ebren van spontaan herstel bij 30 \u2013 50 % van de pati\u00ebnten, tot eindstadium nierfalen. Behandeling met cyclofosfamide en prednison gedurende 6-12 maanden is een effectieve behandeling gebleken om eindstadium nierfalen te voorkomen, echter deze behandeling gaat gepaard met bijwerkingen. In dit proefschrift hebben wij ons gefocust op het optimaliseren en individualiseren van de behandeling van pati\u00ebnten met MN, waarbij we met name de rol van aPLA2Rab hebben bestudeerd. We hebben daarbij gekeken naar het ontstaan van de ziekte (eerste deel proefschrift, hoofdstuk 2), het gebruik van aPLA2Rab als biomarker (indicator voor ziektebeloop, hoofdstuk 3 en 4) en naar de behandeling van de ziekte (hoofdstuk 5 tm 8).\n\nHet tweede deel van dit proefschrift gaat over prognostische biomarkers. Wij hebben laten zien dat er een forse overschatting is van de albumine waarde met de BCG methode bij pati\u00ebnten met een nefrotisch syndroom. In dit geval heeft de BCP bepaling of immunologische methode dan ook de voorkeur. Daarnaast hebben we gekeken naar de rol van aPLA2Rab als prognostische biomarker voor het voorspellen van het natuurlijk beloop. Indien aPLA2Rab als enige variabele werd meegenomen, bleek dit een belangrijke voorspeller te zijn voor het natuurlijk beloop. Dit bleek echter niet zo te zijn indien ook meerdere variabelen, zoals, kreatinine en prote\u00efnurie werden meegenomen.\n\nHet laatste deel van dit proefschrift gaat over de behandeling van MN. De laatste jaren is er veel interesse in alternatieven voor cyclofosfamide, zoals calcineurine remmers en rituximab. Alhoewel dit voor een deel van de pati\u00ebnten populatie een goed alternatief kan zijn, zijn er aanwijzingen dat deze behandelingen minder effectief zijn bij pati\u00ebnten met hoge aPLA2Rab titers. In dit proefschrift hebben wij aangetoond dat de behandeling met cyclofosfamide en prednison op een veilige en effectieve manier kan worden ge\u00efndividualiseerd op geleide van de aPLA2Rab titer. In onze studie was er een hoog remissie (herstel) percentage van 94 %, en in een aanzienlijk deel van de pati\u00ebnten kon de behandeling worden verkort (42 % van de pati\u00ebnten had slechts 8 weken behandeling nodig in plaats van 6 maanden). Vrijwel alle pati\u00ebnten met een aPLA2Rab titer < 100 RU\/ml bereikten een klinische remissie binnen 8 weken. Tenslotte gaan we in de discussie van dit proefschrift in op de mogelijkheden om de behandeling in de toekomst verder te individualiseren op geleide van betere risico classificatie en gebruik van aPLA2Rab titer monitoring tijdens behandeling.","summary":"assays, either chromogenic (bromocresol green (BCG), bromocresol purple (BCP)) or immunonephelometric. Differences between these assays have received limited attention thus far. In chapter 3 we evaluated bias and imprecision of BCG and BCP assays in comparison to the immunonephelometric assays using blood samples from patients with pMN and nephrotic syndrome. For BCG, mean bias was high (6.2 g\/l, SD 2.4 g\/l), for BCP mean bias was low (0.3 g\/l, SD 1.5 g\/l). Importantly, we illustrated that these differences are clinically relevant by evaluating the agreement of the decision toward the use of prophylactic anticoagulant therapy. Our study showed that nephrologists may reach different treatment decisions in up to 59% of patients. Unfortunately (and with current knowledge inexcusably) assay methods are often not reported in studies. Until standardization of the albumin assay is achieved, nephrologists\/clinicians should realize that large discrepancies between assays exist and should be informed which assay is used in their hospital. Preferably, in patients with low albumin concentration the immunological method is the method of choice. When not available, the BCP method is more accurate compared to the BCG methods for the measurement of albumin at low concentration in patients with MN. In the new guideline it is recommended to use a 5g\/l higher cut-off for serum albumin when using the BCG assay (3). We have extended the above studies in patients with chronic kidney disease (CKD). Preliminary analysis showed that the uncertainty of the target value when using the BCG assay was dependent on the assay platform\/manufacturer with bias between BCG and Immunonephelometric assay ranging from 0 to 4 g\/l. Most CKD patients had albumin values above 30 g\/l in the BCP assay. In future research we will study the bias of different BCG platforms\/manufacturers in nephrotic syndrome, and we expect that these differences will be even higher. In retrospect, the data obtained in chapter 3 were obtained with BCG assays using Beckton Dickinson. The guideline advise to subtract 5g\/L when using BCG therefore is not correct and should be rephrased e.g. \u201cwhen using BCG assay for serum albumin, cut-off values, used in definitions or treatment decisions, should be adapted taking into account the bias of the assay, which is dependent on the manufacturer, and may range from 0 to at least 7 g\/L \u201c.\n\nAnti-PLA2R antibodies\nWe have studied the use of aPLA2Rab as a prognostic biomarker in pMN in chapter 4. Personalized treatment for pMN patients requires accurate prediction of the disease course at an early stage, before the start of immunosuppressive treatment. The current models (Toronto risk score, measurement of low-molecular-weight proteins) lack sufficient accuracy, with an AUC of 0.75-0.80. Our group previously showed that circulating aPLA2Rab correlated with clinical disease activity (8). However, the studied cohort was small and only univariate analysis was performed. Additional studies suggested the value of aPLA2Rab levels as prognostic marker, since low titers of aPLA2Rab were associated with a higher likelihood of remission (9-12). However, in these studies remission and renal progression were evaluated in mixed cohorts of treated and untreated patients. For the first time, we evaluated the prognostic value of aPLA2Rab titers at baseline in untreated patients. In our cohort of 156 patients, in univariate analysis, high aPLA2Rab levels were specific (>80 %) for predicting progression, with positive predictive values of 77 % for levels of 150-300 RU\/ml and 87 % for antibody levels >300 RU\/ml. However, we demonstrated that aPLA2Rab titer had no added value in a multivariate model over traditional biomarkers (serum creatinine, proteinuria) to predict progression in pMN. Although our data thus question the independent prognostic value of aPLA2Rab levels, measured once within few months after diagnosis, we suggest that future research should evaluate if repeated aPLA2Rab measurements during 6 months follow-up increase prognostic value.\n\nThere is some evidence from clinical trials that aPLA2Rab have predictive value and thus would allow to predict response to immunosuppressive therapy (10, 13). These two studies, both using rituximab therapy, analyzed aPLA2Rab levels at start of therapy and showed that non-response was particularly high in patients in the highest tertile of aPLA2Rab levels.\n\nA Spanish group evaluated the predictive value of changes in the aPLA2Rab levels in patients with pMN treated with other immunosuppressive therapy (two different treatment regimens; CP and steroids according to Ponticelli protocol, and combination therapy of tacrolimus and rituximab). During treatment with both regimens the relative reduction of aPLA2Rab at resp. 3 and 6 months could be used to predict clinical remission after 6 and 12 months (e.g. respectively 44 and 48 % aPLA2Rab reduction at 3 months could predict remission at 6 months with an AUC of respectively 0.91 and 0.90)(14). However, no information is included whether changes in aPLA2Rab titer predict final outcome.\n\nToward individualized treatment of patients with membranous nephropathy\n\nIn chapter 5 of this thesis we discussed the different treatment options (up to 2016).","auteur":"Anne Els Van De Logt","auteur_slug":"anne-els-van-de-logt","publicatiedatum":"19 september 2022","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/anneelsvandelogt?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202603190913","isbn":"978-94-6423-892-1","doi_nummer":"","naam_universiteit":"","afbeeldingen":5191,"video_url":"","podcast_url":"","naam_student:":"","binnenwerk":"","universiteit":"Radboud Universiteit","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/5189","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=5189"}],"version-history":[{"count":1,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/5189\/revisions"}],"predecessor-version":[{"id":5192,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/5189\/revisions\/5192"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/5190"}],"wp:attachment":[{"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=5189"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=5189"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}