title: Kidney Disease among Patients with Sickle Cell Disease, Hemoglobin SS and SC.
abstract: OBJECTIVE
  Sickle cell disease (SCD) is an inherited anemia that afflicts millions worldwide. Kidney disease is a major contributor to its morbidity and mortality. We examined contemporary and historical SCD populations to understand how renal disease behaved in hemoglobin SS (HbSS) compared with HbSC.
  
  
  METHODS
  Kidney function was examined in the multicentered Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) Trial (HbSS=463; HbSC=127; years 2007-2009) and historical comparator populations from the Cooperative Study of Sickle Cell Disease (CSSCD; HbSS=708) and the Multicenter Study of Hydroxyurea in Sickle Cell Disease (MSH; HbSS=299).
  
  
  RESULTS
  In adults with SCD, eGFR was lower among older individuals: -1.78 ml/min per 1.73 m(2) per year of age (95% confidence interval [95% CI], -2.06 to -1.50; Walk-PHaSST Trial), -1.75 ml/min per 1.73 m(2) per year of age (95% CI, -2.05 to -1.44; MSH), and -1.69 ml/min per 1.73 m(2) per year of age (95% CI, -2.00 to -1.38; CSSCD) in HbSS compared with -1.09 ml/min per 1.73 m(2) per year of age (95% CI, -1.39 to -0.75) in HbSC (Walk-PHaSST Trial). Macroalbuminuria was seen in 20% of participants with SCD (HbSS or HbSC; P=0.45; Walk-PHaSST Trial), but microalbuminuria was more prevalent in HbSS (44% versus 23% in HbSC; P<0.002). In the Walk-PHaSST Trial, albuminuria was associated with hemolysis (higher lactate dehydrogenase, P<0.001; higher absolute reticulocyte count, P<0.02; and lower Hb, P=0.07) and elevated systolic BP (P<0.001) in HbSS. One half of all participants with HbSS (20 of 39) versus one fifth without (41 of 228) elevated tricuspid regurgitant jet velocity (≥3 m/s; adverse prognostic indicator in SCD) had macroalbuminuria (P<0.001). In the CSSCD, overt proteinuria, detected (less sensitively) by urine dipstick, associated with higher 3-year mortality (odds ratio, 2.48; 95% CI, 1.07 to 5.77). Serum bicarbonate was lower in HbSS (23.8 versus 24.8 mEq/dl in HbSC; P<0.05) and associated with reticulocytopenic anemia and decreased renal function.
  
  
  CONCLUSIONS
  In SCD, albuminuria or proteinuria was highly prevalent, in HbSS more than in HbSC. Proteinuria associated with mortality in HbSS. Older individuals had a lower than expected eGFR, and this was more prominent in HbSS. Current management does not routinely address renal complications in SCD, which could plausibly reduce morbidity and mortality.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, Minnesota;
authors.forename: Paul
authors.initials: P
authors.lastname: Drawz
authors.affiliation: Divisions of Hematology and Oncology, and.
authors.forename: Sabarish
authors.initials: S
authors.lastname: Ayyappan
authors.affiliation: Center for Sickle Cell Disease, Howard University, Washington, DC;
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nouraie
authors.affiliation: Division of Hematology/Oncology, University of Illinois, Chicago, Illinois; and.
authors.forename: Santosh
authors.initials: S
authors.lastname: Saraf
authors.affiliation: Comprehensive Sickle Cell Center.
authors.forename: Victor
authors.initials: V
authors.lastname: Gordeuk
authors.affiliation: Nephrology and Hypertension,University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio;
authors.forename: Thomas
authors.initials: T
authors.lastname: Hostetter
authors.affiliation: Vascular Medicine Institute and Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.affiliation: Divisions of Hematology and Oncology, and Jane.Little@uhhospitals.org.
authors.forename: Jane
authors.initials: J
authors.lastname: Little
mesh_terms: D000136:Acid-Base Equilibrium; D000328:Adult; D000419:Albuminuria / Q000453:epidemiology; D000755:Anemia, Sickle Cell / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D002986:Clinical Trials as Topic; D005260:Female; D005919:Glomerular Filtration Rate; D006444:Hemoglobin C / Q000378:metabolism*; D006450:Hemoglobin SC Disease / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D065386:Historically Controlled Study; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009656:North America / Q000453:epidemiology; D064887:Observational Studies as Topic; D010641:Phenotype; D015995:Prevalence; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D006451:Hemoglobin, Sickle; D006444:Hemoglobin C
keywords: acidosis; albuminuria; anemia, sickle cell; blood pressure; chronic kidney disease; glomerular filtration rate; humans; hydroxyurea; hypertension, pulmonary