Maud Cazenave1, Vincent Audard2, Jean-Philippe Bertocchio3, Anoosha Habibi4, Stéphanie Baron3, Caroline Prot-Bertoye3, Jugurtha Berkenou4, Gérard Maruani5, Thomas Stehlé2, Nicolas Cornière6, Hamza Ayari3, Gérard Friedlander5, Frédéric Galacteros4, Pascal Houillier3, Pablo Bartolucci4, Marie Courbebaisse7. 1. Nephrology and Renal Transplantation Department, Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne University, Paris, France. 2. Nephrology and Renal Transplantation Department, Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Henri Mondor Hospital, AP-HP, Paris Est Créteil University, Créteil, France. 3. Physiology Department, European Georges Pompidou University Hospital, AP-HP, Paris Descartes University, INSERM U1138, Centre National de la Recherche Scientifique (CNRS) ERL8228, Paris, France. 4. Sickle Cell Referral Center, Internal Medicine Unit, IMRB team 2, UPEC, Labex GRex, Henri Mondor Hospital, AP-HP, Créteil, France. 5. Physiology Department, European Georges Pompidou University Hospital, AP-HP, Paris Descartes University, Necker-Enfants Malades Institute, INSERM U1151-CNRS UMR8253, Paris, France; and. 6. Nephrology Department, Felix Guyon Hospital, Saint-Denis, Réunion Island, France. 7. Physiology Department, European Georges Pompidou University Hospital, AP-HP, Paris Descartes University, Necker-Enfants Malades Institute, INSERM U1151-CNRS UMR8253, Paris, France; and marie.courbebaisse@aphp.fr.
Abstract
BACKGROUND AND OBJECTIVES: Metabolic acidosis is a frequent manifestation of sickle cell disease but the mechanisms and determinants of this disorder are unknown. Our aim was to characterize urinary acidification capacity in adults with sickle cell disease and to identify potential factors associated with decreased capacity to acidify urine. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 25 adults with sickle cell disease and an eGFR of ≥60 ml/min per 1.73 m2 from a single center in France, we performed an acute acidification test after simultaneous administration of furosemide and fludrocortisone. A normal response was defined as a decrease in urinary pH <5.3 and an increase in urinary ammonium excretion ≥33 µEq/min at one or more of the six time points after furosemide and fludrocortisone administration. RESULTS: Of the participants (median [interquartile range] age of 36 [24-43] years old, 17 women), 12 had a normal and 13 had an abnormal response to the test. Among these 13 participants, nine had normal baseline plasma bicarbonate concentration. Plasma aldosterone was within the normal range for all 13 participants with an abnormal response, making the diagnosis of type 4 tubular acidosis unlikely. The participants with an abnormal response to the test were significantly older, more frequently treated with oral bicarbonate, had a higher plasma uric acid concentration, higher hemolysis activity, lower eGFR, lower baseline plasma bicarbonate concentration, higher urine pH, lower urine ammonium ion excretion, and lower fasting urine osmolality than those with a normal response. Considering both groups, the maximum urinary ammonium ion excretion was positively correlated with fasting urine osmolality (r 2=0.34, P=0.002), suggesting that participants with sickle cell disease and lower urine concentration capacity have lower urine acidification capacity. CONCLUSIONS: Among adults with sickle cell disease, impaired urinary acidification capacity attributable to distal tubular dysfunction is common and associated with the severity of hyposthenuria. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_12_10_CJN07830719.mp3.
BACKGROUND AND OBJECTIVES:Metabolic acidosis is a frequent manifestation of sickle cell disease but the mechanisms and determinants of this disorder are unknown. Our aim was to characterize urinary acidification capacity in adults with sickle cell disease and to identify potential factors associated with decreased capacity to acidify urine. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 25 adults with sickle cell disease and an eGFR of ≥60 ml/min per 1.73 m2 from a single center in France, we performed an acute acidification test after simultaneous administration of furosemide and fludrocortisone. A normal response was defined as a decrease in urinary pH <5.3 and an increase in urinary ammonium excretion ≥33 µEq/min at one or more of the six time points after furosemide and fludrocortisone administration. RESULTS: Of the participants (median [interquartile range] age of 36 [24-43] years old, 17 women), 12 had a normal and 13 had an abnormal response to the test. Among these 13 participants, nine had normal baseline plasma bicarbonate concentration. Plasma aldosterone was within the normal range for all 13 participants with an abnormal response, making the diagnosis of type 4 tubular acidosis unlikely. The participants with an abnormal response to the test were significantly older, more frequently treated with oral bicarbonate, had a higher plasma uric acid concentration, higher hemolysis activity, lower eGFR, lower baseline plasma bicarbonate concentration, higher urine pH, lower urine ammonium ion excretion, and lower fasting urine osmolality than those with a normal response. Considering both groups, the maximum urinary ammonium ion excretion was positively correlated with fasting urine osmolality (r 2=0.34, P=0.002), suggesting that participants with sickle cell disease and lower urine concentration capacity have lower urine acidification capacity. CONCLUSIONS: Among adults with sickle cell disease, impaired urinary acidification capacity attributable to distal tubular dysfunction is common and associated with the severity of hyposthenuria. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_12_10_CJN07830719.mp3.
Authors: Nicolas S Merle; Anne Grunenwald; Helena Rajaratnam; Viviane Gnemmi; Marie Frimat; Marie-Lucile Figueres; Samantha Knockaert; Sanah Bouzekri; Dominique Charue; Remi Noe; Tania Robe-Rybkine; Marie Le-Hoang; Nathan Brinkman; Thomas Gentinetta; Monika Edler; Sara Petrillo; Emanuela Tolosano; Sylvia Miescher; Sylvain Le Jeune; Pascal Houillier; Sophie Chauvet; Marion Rabant; Jordan D Dimitrov; Veronique Fremeaux-Bacchi; Olivier P Blanc-Brude; Lubka T Roumenina Journal: JCI Insight Date: 2018-06-21
Authors: Pablo Bartolucci; Anoosha Habibi; Thomas Stehlé; Gaetana Di Liberto; Marie Georgine Rakotoson; Justine Gellen-Dautremer; Sylvain Loric; Stéphane Moutereau; Dil Sahali; Orianne Wagner-Ballon; Philippe Remy; Philippe Lang; Philippe Grimbert; Etienne Audureau; Bertrand Godeau; Frédéric Galacteros; Vincent Audard Journal: J Am Soc Nephrol Date: 2015-11-19 Impact factor: 10.121
Authors: Gaetana Di Liberto; Laurent Kiger; Michael C Marden; Laurent Boyer; Florence Canoui Poitrine; Marc Conti; Marie Georgine Rakotoson; Anoosha Habibi; Sanam Khorgami; Benoit Vingert; Bernard Maitre; Frederic Galacteros; France Pirenne; Pablo Bartolucci Journal: Am J Hematol Date: 2016-08-04 Impact factor: 10.047
Authors: Mark T Gladwin; Vandana Sachdev; Maria L Jison; Yukitaka Shizukuda; Jonathan F Plehn; Karin Minter; Bernice Brown; Wynona A Coles; James S Nichols; Inez Ernst; Lori A Hunter; William C Blackwelder; Alan N Schechter; Griffin P Rodgers; Oswaldo Castro; Frederick P Ognibene Journal: N Engl J Med Date: 2004-02-26 Impact factor: 91.245
Authors: Santosh L Saraf; Vimal K Derebail; Xu Zhang; Roberto F Machado; Victor R Gordeuk; James P Lash; Jane Little Journal: Kidney360 Date: 2022-02-03
Authors: Pamela L Brito; Alisson F Dos Santos; Hanan Chweih; Maria E Favero; Erica M F Gotardo; Juliete A F Silva; Flavia C Leonardo; Carla F Franco-Penteado; Mariana G de Oliveira; Wilson A Ferreira; Bruna C Zaidan; Athanase Billis; Giorgio Baldanzi; Denise A Mashima; Edson Antunes; Sara T Olalla Saad; Fernando F Costa; Nicola Conran Journal: PLoS One Date: 2022-02-03 Impact factor: 3.240