Renal function in patients with non-dialysis chronic kidney disease receiving intravenous ferric carboxymaltose: an analysis of the randomized FIND-CKD trial

Iain C Macdougall, Andreas H Bock, Fernando Carrera, Kai-Uwe Eckardt, Carlo Gaillard, David Van Wyck, Yvonne Meier, Sylvain Larroque, Simon D Roger, FIND-CKD Study investigators, Simon D Roger, Alastair Gilles, Randall Faull, Nigel D Toussaint, Lawrence McMahon, Michael Suranyi, David Mudge, Brian Hutchison, Ashley Irish, Peter Kerr, Hemant Kulkarni, Grahame Elder, Margaret Jardine, Karl Lhotta, Gert Mayer, Raymond Vanholder, Bart Dirk Maes, Pieter Evenepoel, Frédéric Debelle, Michel Jadoul, Max Dratwa, Igor Macel, Milan Dunaj, Milan Kvapil, Petr Bucek, Jitka Rehorova, Ales Hruby, Václava Honová, Lada Malanova, Martin Lucak, Dalibor Lecian, Martin Jirovec, Jiri Vlasak, Ivan Rychlik, Stanislav Surel, Anne-Lise Kamper, Ove Ostergaard, Gudrun K Steffensen, Leila Chenine, Gabrial Choukroun, Philippe Zaoui, Christoph Wanner, Wolfgang Backs, Uwe Kraatz, Frank Dellanna, Klaus Busch, Tobias Marsen, Wolfgang Seeger, Rainer Woitas, Nicholas Obermueller, Thomas Haak, Stephan Lueders, Frank Pistrosch, Eckhard Mueller, Peter R Mertens, Werner Sutermer, Scott-Oliver Grebe, Syrus Hafezi-Rachti, Silke Roeser, Dimitrios Tsakiris, Dimitrios Memmos, Demetrios Vlachakos, Vassilis Vargemezis, Ioannis Stefanidis, Christos Syrganis, Polichronis Alivanis, Ioannis Papadakis, Nickolaos Papagalanis, Aimilios Andrikos, Dimitrios Goumenos, Kostas Siamopoulos, Charikelia Gouva, Gabriel Papadakis, Ioannis Boletis, Myrsini Tsimnadi-Spanoudaki, Dimitrios Stamatiades, Kyriaki Stamatelou, Spyridon Moutafis, Francesco Locatelli, Antonio Santoro, Francesco Quarello, Giuseppe Remuzzi, Salvatore Coppola, Rosella Ferraro Mortellaro, Andrea Icardi, Giacomo Colussi, Franco Della Grotta, Luigi Lombardi, Maurizio Gallieni, Giuseppe Villa, Giuseppe Grandaliano, Carlo Gaillard, Sebastiaan Huisman, Jos Barendregt, Peter J H Smak Gregoor, Cecilia Oien, Boleslaw Rutkowski, Robert Malecki, Michal Nowicki, Przemyslaw Rutkowski, Kryzsztof Marczewski, Michal Mysliwiec, Antoni Sydor, Jacek Rysz, Andrzej Rydzewski, Marian Klinger, Rafal Wnuk, Piotr Kozminski, Anna Nocon, Kazimierz Ciechanowski, Pedro Correia, Fernando Neves, José Barata, Gabriel Mircescu, Mihai Voiculescu, Gheorghe Gluhovschi, Eugen Mota, Angel Luís Martín De Francisco, Alberto Torre, Alba Herreros, José Luño, E Gruss, Judith Martins, Marti Vallés, Julio Pascual, Peter Bárány, Andreas H Bock, Patrice M Ambuehl, Sehsuvar Erturk, Mustafa Arici, Saime Paydas, Zeki Soypacaci, Taner Camsari, Sedat Ustundag, Iain C Macdougall, Mark E Thomas, Richard J D'Souza, Jo E Taylor, Nicholas R Pritchard, Robin Jeffery, Stephen G Riley, Deepak Bhatnagar, Sunil Bhandari, David Reaich, Paul E Stevens, Mohsen El Kossi, Simon Roe, Brian Camilleri, Aimun Ahmed, Arif Khwaja, Barbara Thompson, Debasish Banerjee, Johann Nicholas, Alistair Hutchison, Richard Borrows, Iain C Macdougall, Andreas H Bock, Fernando Carrera, Kai-Uwe Eckardt, Carlo Gaillard, David Van Wyck, Yvonne Meier, Sylvain Larroque, Simon D Roger, FIND-CKD Study investigators, Simon D Roger, Alastair Gilles, Randall Faull, Nigel D Toussaint, Lawrence McMahon, Michael Suranyi, David Mudge, Brian Hutchison, Ashley Irish, Peter Kerr, Hemant Kulkarni, Grahame Elder, Margaret Jardine, Karl Lhotta, Gert Mayer, Raymond Vanholder, Bart Dirk Maes, Pieter Evenepoel, Frédéric Debelle, Michel Jadoul, Max Dratwa, Igor Macel, Milan Dunaj, Milan Kvapil, Petr Bucek, Jitka Rehorova, Ales Hruby, Václava Honová, Lada Malanova, Martin Lucak, Dalibor Lecian, Martin Jirovec, Jiri Vlasak, Ivan Rychlik, Stanislav Surel, Anne-Lise Kamper, Ove Ostergaard, Gudrun K Steffensen, Leila Chenine, Gabrial Choukroun, Philippe Zaoui, Christoph Wanner, Wolfgang Backs, Uwe Kraatz, Frank Dellanna, Klaus Busch, Tobias Marsen, Wolfgang Seeger, Rainer Woitas, Nicholas Obermueller, Thomas Haak, Stephan Lueders, Frank Pistrosch, Eckhard Mueller, Peter R Mertens, Werner Sutermer, Scott-Oliver Grebe, Syrus Hafezi-Rachti, Silke Roeser, Dimitrios Tsakiris, Dimitrios Memmos, Demetrios Vlachakos, Vassilis Vargemezis, Ioannis Stefanidis, Christos Syrganis, Polichronis Alivanis, Ioannis Papadakis, Nickolaos Papagalanis, Aimilios Andrikos, Dimitrios Goumenos, Kostas Siamopoulos, Charikelia Gouva, Gabriel Papadakis, Ioannis Boletis, Myrsini Tsimnadi-Spanoudaki, Dimitrios Stamatiades, Kyriaki Stamatelou, Spyridon Moutafis, Francesco Locatelli, Antonio Santoro, Francesco Quarello, Giuseppe Remuzzi, Salvatore Coppola, Rosella Ferraro Mortellaro, Andrea Icardi, Giacomo Colussi, Franco Della Grotta, Luigi Lombardi, Maurizio Gallieni, Giuseppe Villa, Giuseppe Grandaliano, Carlo Gaillard, Sebastiaan Huisman, Jos Barendregt, Peter J H Smak Gregoor, Cecilia Oien, Boleslaw Rutkowski, Robert Malecki, Michal Nowicki, Przemyslaw Rutkowski, Kryzsztof Marczewski, Michal Mysliwiec, Antoni Sydor, Jacek Rysz, Andrzej Rydzewski, Marian Klinger, Rafal Wnuk, Piotr Kozminski, Anna Nocon, Kazimierz Ciechanowski, Pedro Correia, Fernando Neves, José Barata, Gabriel Mircescu, Mihai Voiculescu, Gheorghe Gluhovschi, Eugen Mota, Angel Luís Martín De Francisco, Alberto Torre, Alba Herreros, José Luño, E Gruss, Judith Martins, Marti Vallés, Julio Pascual, Peter Bárány, Andreas H Bock, Patrice M Ambuehl, Sehsuvar Erturk, Mustafa Arici, Saime Paydas, Zeki Soypacaci, Taner Camsari, Sedat Ustundag, Iain C Macdougall, Mark E Thomas, Richard J D'Souza, Jo E Taylor, Nicholas R Pritchard, Robin Jeffery, Stephen G Riley, Deepak Bhatnagar, Sunil Bhandari, David Reaich, Paul E Stevens, Mohsen El Kossi, Simon Roe, Brian Camilleri, Aimun Ahmed, Arif Khwaja, Barbara Thompson, Debasish Banerjee, Johann Nicholas, Alistair Hutchison, Richard Borrows

Abstract

Background: Preclinical studies demonstrate renal proximal tubular injury after administration of some intravenous iron preparations but clinical data on renal effects of intravenous iron are sparse.

Methods: FIND-CKD was a 56-week, randomized, open-label, multicenter study in which patients with non-dialysis dependent chronic kidney disease (ND-CKD), anemia and iron deficiency without erythropoiesis-stimulating agent therapy received intravenous ferric carboxymaltose (FCM), targeting either higher (400-600 μg/L) or lower (100-200 μg/L) ferritin values, or oral iron.

Results: Mean (SD) eGFR at baseline was 34.9 (11.3), 32.8 (10.8) and 34.2 (12.3) mL/min/1.73 m2 in the high ferritin FCM (n = 97), low ferritin FCM (n = 89) and oral iron (n = 167) groups, respectively. Corresponding values at month 12 were 35.6 (13.8), 32.1 (12.7) and 33.4 (14.5) mL/min/1.73 m2. The pre-specified endpoint of mean (SE) change in eGFR from baseline to month 12 was +0.7 (0.9) mL/min/1.73 m2 with high ferritin FCM (p = 0.15 versus oral iron), -0.9 (0.9) mL/min/1.73 m2 with low ferritin FCM (p = 0.99 versus oral iron) and -0.9 (0.7) mL/min/1.73 m2 with oral iron. No significant association was detected between quartiles of FCM dose, change in ferritin or change in TSAT versus change in eGFR. Dialysis initiation was similar between groups. Renal adverse events were rare, with no indication of between-group differences.

Conclusion: Intravenous FCM at doses that maintained ferritin levels of 100-200 μg/L or 400-600 μg/L did not negatively impact renal function (eGFR) in patients with ND-CKD over 12 months versus oral iron, and eGFR remained stable. These findings show no evidence of renal toxicity following intravenous FCM over a 1-year period.

Trial registrations: ClinicalTrials.gov NCT00994318 (first registration 12 October 2009).

Keywords: Chronic kidney disease; Ferinject; Ferric carboxymaltose; Intravenous; Renal function; eGFR.

Figures

Fig. 1
Fig. 1
Estimated GFR to month 12 according to treatment group in patients with eGFR values at baseline and month 12. Values are shown as mean (SD). FCM, ferric carboxymaltose; eGFR, estimated GFR
Fig. 2
Fig. 2
Absolute estimated glomerular filtration rate (eGFR) and change in eGFR from baseline to month 12 according to quartiles of (a) total ferric carboxymaltose (FCM) dose to month 12 in patients randomized to high ferritin FCM or low ferritin FCM (b) change in ferritin from baseline to month 12 across all treatment groups and (c) change in transferrin saturation (TSAT) from baseline at month 12 across all treatment groups. Data are shown for patients with eGFR values at baseline and month 12. Change in eGFR is shown as least squares (LS) mean values. MDRD, Modification of Diet in Renal Disease

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