Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell Disease

Abstract

Background: People with sickle cell disease (SCD) have an elevated estimated glomerular filtration rate (eGFR) compared to the general population and this may alter the usual creatinine-based eGFR cutoffs for which physiologic evidence of kidney dysfunction is apparent. This study aimed to identify eGFR thresholds for hyperkalemia and metabolic acidosis in patients with SCD Methods: This was a cross-sectional analysis of 733 patients with severe (hemoglobin SS or Sβ0-thalassemia) SCD genotype, 238 patients with moderate (hemoglobin SC or Sβ+-thalassemia) SCD genotype, and 1,333 age- and sex-matched African Americans from the National Health and Nutrition Examination Survey (NHANES). The prevalence of hyperkalemia and metabolic acidosis were compared by eGFR category. Cutoffs for hyperkalemia and metabolic acidosis were determined using generalized additive models. Results: Hyperkalemia and metabolic acidosis were more common in those with severe SCD genotype (13% and 21%, respectively) compared to in NHANES (0.3% and 5%, respectively); the prevalence rates in the moderate SCD genotype were intermediate for hyperkalemia (3%) and metabolic acidosis (11%). The proportion of patients with hyperkalemia and metabolic acidosis progressively increased with lower eGFR category in both SCD genotype groups. The eGFR thresholds for hyperkalemia and metabolic acidosis were higher in the severe (85 and 91 mL/min/1.73m2, respectively) and moderate (52 and 102 mL/min/1.73m2, respectively) SCD genotypes compared with NHANES (34 and 46 mL/min/1.73m2). Conclusions: We demonstrate that hyperkalemia and metabolic acidosis are more common and occur at higher eGFR values in patients with SCD compared to age- and sex-matched African Americans, including in eGFR ranges considered to be normal. Future studies using redefined creatinine-based eGFR thresholds for abnormal kidney function may identify high-risk patients for earlier intervention strategies and referral for specialized renal care in SCD.

Sickle Cell Disease and CKD: An Update

“…Hyperkalemia is common in SCD due to (1) increased hemolysis, (2) impaired distal tubular function, and (3) management of albuminuria with RAAS inhibitors. Additionally, patients with SCD manifest hyperkalemia at higher eGFR levels than the general population [128]. General KDIGO hyperkalemia guidelines recommend potassium dietary restriction, discontinuation of medications elevating potassium levels, use of potassium-wasting diuretics, use of potassium binders (patiromer, zirconium cyclosilicate), and low potassium dialyzate in dialysis-dependent patients [129].…”

“…Use of diuretics tends to be less frequently used in SCD due to the increased risk for intravascular dehydration that may promote RBC sickling and vaso-occlusion. Metabolic acidosis is also seen at higher eGFR levels in patients with SCD when compared to non-SCD patients [128]. Treatment strategies for acidosis include sodium bicarbonate replacement therapy or initiating dialysis if the kidney function continues to deteriorate.…”