Investigators have identified idiopathic hypokalemia among patients with lupus nephritis (LN) that is distinct from other hypokalemia causes, including extrarenal potassium elimination, renal tubular acidosis, and renal potassium wasting from diuretics and corticosteroids.
“We speculate that idiopathic hypokalemia is the result of a novel target of autoimmunity in LN affecting renal tubular potassium transport, Emmanuel Adomako, MBChB, of University of Texas Southwestern in Dallas and colleagues wrote in Kidney360.
Among 403 patients with LN from the Parkland Health and Hospital System in Dallas, Dr Adomako and colleagues identified 20 idiopathic hypokalemia cases (serum potassium less than 3.5 mmol/L with no known cause) and compared them with 10 renal tubular acidosis (RTA) cases and 90 control cases without RTA or unexplained hypokalemia. Primary outcomes included median serum potassium and serum bicarbonate levels and urine pH. Secondary outcomes included median serum magnesium level and seropositivity rate for autoantibodies to Ro/SSA, La/SSB, and RNP.
The idiopathic hypokalemia group had a significantly lower median serum potassium level compared with the RTA and control groups: 3.26 vs 3.75 vs 4.00 mmol/L, respectively, Dr Adomako’s team reported. All 20 patients with idiopathic hypokalemia required either potassium supplementation or mineralocorticoid antagonist therapy to maintain normokalemia despite 85% of these patients taking angiotensin converting enzyme inhibitors or angiotensin-receptor blockers.
The median serum bicarbonate was lowest and below normal range in the RTA group: 26.0 hypokalemia vs 19.4 RTA vs 25.0 mmol/L control, respectively. Likewise, the median urine pH was highest in the RTA group: 6.00 vs 6.67 vs 6.25, respectively. The RTA group had a higher occurrence of kidney stones.
The median serum magnesium level was significantly lower in the hypokalemia group: 1.73 vs 1.85 vs 2.00 mg/dL), respectively.
The hypokalemia and RTA groups had a significantly higher seropositivity for anti-Ro/SSA (79% and 80%, respectively) compared with the control group (37%). Only the hypokalemia group had a significantly higher seropositivity rate compared with the control group for anti-RNP: 84% vs 42%. Only the RTA group had a significantly higher seropositivity rate compared with control group for anti-La/SSB: 40% vs 12%.
“The fact that potassium sparing diuretics could ameliorate the hypokalemia was indicative that renal potassium loss was the cause of this phenomenon,” Dr Adomako’s team wrote. “Indeed, inappropriate potassium wasting was revealed in all 9 subjects [with hypokalemia] who had assessments of renal potassium handling.” They hypothesized that an acquired immune-mediated impairment in distal convoluted tubule transport explains this phenotype.
Adomako E, Bilal S, Liu Y, et al. Idiopathic hypokalemia in lupus nephritis – A newly recognized entity. Kidney360. August 2021. doi:10.34067/KID.0004352021