Prevalence and correlates of metabolic acidosis among patients with homozygous sickle cell disease.
OBJECTIVE
Very few studies report acid base disorders in homozygous patients with sickle cell anemia (SCA) and describe incomplete renal acidosis rather than true metabolic acidosis, the prevalence of which is unknown and presumably low. This study aimed to assess the prevalence of metabolic acidosis and to identify its risk factors and mechanisms.


METHODS
This study retrospectively analyzed 411 homozygous patients with SCA with a GFR ≥ 60 ml/min per 1.73 m(2), referred in a single center between 2007 and 2012. Acidosis and nonacidosis groups were compared for clinical and biologic data including SCA complications and hemolytic parameters. A subgroup of 65 patients with SCA, referred for a measured GFR evaluation in the setting of sickle cell-associated nephropathy, was further analyzed in order to better characterize metabolic acidosis.


RESULTS
Metabolic acidosis was encountered in 42% of patients with SCA, with a higher prevalence in women (52% versus 27% in men; P<0.001). Several hemolytic biomarkers, such as lactate dehydrogenase, were different between the acidosis and nonacidosis groups (P=0.02 and P=0.03 in men and women, respectively), suggesting higher hemolytic activity in the former group. To note, fasting urine osmolality was low in the whole study population and was significantly lower in men with SCA in the acidosis group (392 versus 427 mOsm/kg; P=0.01). SCA subgroup analysis confirmed metabolic acidosis with a normal anion gap in 14 patients, characterized by a lower urinary pH (P<0.02) and no increase in urinary ammonium. Serum potassium, plasma renin, and aldosterone were similar between the two groups and thus could not explain impaired urinary ammonium excretion.


CONCLUSIONS
These results suggest that the prevalence of metabolic acidosis in patients with SCA is underestimated and related to impaired ammonium availability possibly due to an altered corticopapillary gradient. Future studies should evaluate whether chronic metabolic acidosis correction may be beneficial in this population, especially in bone remodeling.
Service d'Explorations Fonctionnelles,, †Sickle Cell Centre, and, ‡Internal Medicine Service, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France;, §Institut National de la Santé et de la Recherche Médicale, UMR_S 1155, Paris, France, ‖Sorbonne Universités, UPMC Univ Paris 06, DHUI2B, Paris, France.
Stéphane
S
Maurel
Katia
K
Stankovic Stojanovic
Virginie
V
Avellino
Alexey
A
Girshovich
Emmanuel
E
Letavernier
Gilles
G
Grateau
Laurent
L
Baud
Robert
R
Girot
Francois
F
Lionnet
Jean-Philippe
JP
Haymann
D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology / Q000652:urine; D000293:Adolescent; D000328:Adult; D064751:Ammonium Compounds / Q000652:urine; D000755:Anemia, Sickle Cell / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D015415:Biomarkers / Q000097:blood / Q000652:urine; D005260:Female; D006461:Hemolysis; D006720:Homozygote; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D010297:Paris / Q000453:epidemiology; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
D064751:Ammonium Compounds; D015415:Biomarkers