Clinical and Laboratory Predictors for Renal Damage in Sickle Cell Disease
Authors: Saraf Santosh L , Molokie Robert , Hassan Johara , Gowhari Michel , Lash James , Gordeuk Victor R. 
Published: October 2019

Abstract
Abstract 3252
Renal failure is an independent marker for developing other forms of chronic organ damage and for early mortality in sickle cell disease (SCD). We conducted a retrospective, cross-sectional chart review of 292 adults with SCD (type SS or S-beta thal) treated at the University of Illinois Medical Center to assess the prevalence and factors related to kidney damage. Data was recorded from a clinic visit at least four weeks from a vaso-occlusive pain episode or red blood cell transfusion. The glomerular filtration rate (GFR) was calculated using the modification of diet in renal disease formula. Hemoglobinuria was defined by dipstick urinalysis showing trace, small, or moderate blood and <2 RBC/high power field. Urine albumin to creatinine ratios of 30 to 300 mg/g and >300 mg/g were categorized as microalbuminuria and macroalbuminuria, respectively. The median age was 33 years and 46% of patients were on hydroxyurea. We observed microalbuminuria in 41%, macroalbuminuria in 20%, hemoglobinuria in 41% and GFR <90 mL/min in 20% of adults with SCD. Univariate associations with GFR <90 mL/min are summarized in Table 1. By logistic regression, macroalbuminuria (OR 7.5, 95% CI: 2.5–22.2; p<0.0001) and age (OR 1.11, 95% CI: 1.06–1.16; p <0.0001) were independent predictors of GFR <90 mL/min (r2 = 0.23). Given the strong correlation of macroalbuminuria with GFR <90 mL/min, we explored factors related to degree of albuminuria. Univariate associations with degree of albuminuria are shown in Table 2. Logistic regression showed that independent predictors for macroalbuminuria were the presence of hemoglobinuria (OR 93.7, 95% CI: 15.2–576.5; p<0.0001) and age (OR 1.07, 95% CI: 1.01–1.14; p=0.03) (r2=0.28, p<0.0001). We further explored predictors of hemoglobinuria given its independent association with macroalbuminuria. By logistic regression, the strongest predictor of hemoglobinuria was the natural log LDH (OR 32.4; 95% CI: 8.4–124.9; p<0.0001) (r2=0.22), but other markers of hemolysis including higher absolute reticulocyte count, greater indirect bilirubin concentration and lower hemoglobin concentration were also associated with hemoglobinuria in univariate analyses. In summary, increasing age and macroalbuminuria were independent factors associated with GFR < 90mL/min in this cohort of adults with SCD, and intravascular hemolysis as reflected in hemoglobin-positive urine dipstick with negative microscopy was associated with macroalbuminuria. Further research is needed to determine if measures to decrease intravascular hemolysis and to prevent the development of macroalbuminuria can preserve renal function in patients with SCD. Investigation is also needed to identify genomic and genetic markers that put patients at risk for kidney disease and might serve as targets for preventive and therapeutic interventions.
Table 1: Correlation of GFR to clinical and laboratory variables. Variable N >90 N <90 p-value Age (years) 234 30 (25–39) 58 45 (37–54) <0.0001 Female gender 234 141 (60%) 58 38 (65%) 0.63 MAP 231 86 (90–93) 58 91 (86–98) <0.0001 HU therapy 110 48 (44%) 30 16 (53%) 0.35 Hemoglobin (g/dL) 234 8.9 (7.9–10) 58 8.1 (7.4–8.9) <0.0001 LDH (u/L) 146 309 (235–425) 41 375 (251–481) 0.11 Absolute Reticulocyte Count (×103/μL) 111 332 (234–444) 29 302 (197–368) 0.001 Hgb F (%) 218 5.5 (2.9–9.8) 52 5.5 (2.5–9.8) 0.98 Albuminuria: Microalbuminuria Macroalbuminuria 112 46 (41%) 30 11 (36.7%) 0.001 15 (13%) 13 (43.4%)
Table 2: Correlation of Albuminuria to clinical and laboratory variables. Variable N Normal N Micro-albuminuria N Macro-albuminuria p-value Age (years) 57 32 (26–42) 58 38 (28–48) 28 35 (27–45) 0.20 Female gender 57 43 (75%) 58 34 (59%) 28 18 (64%) 0.16 MAP (mmHg) 56 86 (80–97) 58 88 (84–92) 28 91 (84–98) 0.24 HU therapy 56 24 (42.9%) 57 24 (42.1%) 28 17 (60.7%) 0.22 Hemoglobin (g/dL) 57 8.9 (8.1–10.3) 58 8.1 (7.5–9.4) 28 8.5 (6.9–9.4) 0.008 LDH (u/L) 54 270 (212–358) 49 363 (251–434) 27 377 (355–488) <0.0001 Indirect bilirubin (mg/dL) 56 1.7 (1.2–2.5) 57 2.4 (1.4–3.3) 28 2.0 (1.3–4.3) 0.03 Absolute reticulocyte count (×103/μL) 57 256 (213–399) 56 332 (243–448) 28 369 (276–466) 0.06 Hgb F (%) 52 6.6 (2.7–9.7) 56 5.1 (2.8–11.7) 26 7.8 (3.7–13) 0.54 Hemoglobinuria 53 3 (5.7%) 54 29 (53.7%) 26 22 (84.6%) <0.0001

Disclosures:
No relevant conflicts of interest to declare.