Idiopathic Hypokalemia in Lupus Nephritis: A Newly Recognized Entity

Abstract

Background: Various causes of hypokalemia (HK) from renal potassium wasting, including distal renal tubular acidosis (RTA), have been described in lupus nephritis (LN). We report a phenomenon of otherwise unexplained HK among a population with LN.

Methods: From our population of 403 patients with LN, we identified a cohort of 20 patients with idiopathic HK, defined by serum potassium <3.5 mmol/L without any apparent explanation. This cohort is compared with 90 LN controls (CON) and ten patients with LN with distal RTA from the same population.

Results: The patients with HK had lower median serum potassium compared with CON and RTA subjects (3.26 versus 4.00 versus 3.75 mmol/L, respectively; P<0.001). The median serum bicarbonate was normal in HK and CON, but low in RTA (26.0 versus 25.0 versus 19.4 mmol/L; P<0.001). The median urine pH was abnormally high only in the RTA group (6.00 versus 6.25 versus 6.67; P=0.012). The median serum magnesium was modestly lower in HK compared with the CON and RTA groups (1.73 versus 2.00 versus 1.85 mg/dl; P=0.002). Although both HK and RTA showed a higher rate of seropositivity than CON for anti-Ro/SSA (79% and 80% versus 37%, respectively; P<0.001), only HK revealed a higher rate of seropositivity than CON for anti-RNP (84% versus 42%; P=0.003) and only RTA showed a higher rate of seropositivity than CON for anti-La/SSB (40% versus 12%; P=0.05).

Conclusions: A syndrome of idiopathic HK was revealed in 20 out of 403 (5%) of patients within our LN population, and proved to be distinct from the RTA that occurs in LN. Furthermore, it was associated with a distinct pattern of autoantibodies. We speculate that idiopathic HK is the result of a novel target of autoimmunity in LN, affecting renal tubular potassium transport.

Keywords: acid/base and electrolyte disorders; autoantibody; hypokalemia; lupus nephritis; renal tubular acidosis.

Graphical abstract

Figure 1.

Box-plots of serum potassium, serum bicarbonate, and urine pH among the three patient groups. The boxes span the 25th and 75th percentile of data points. The thick bar within the box indicates the median. The whiskers represent 1.5 times interquartile range, and the circles describe outliers. CON, control group; HCO3, serum bicarbonate; HK, group with idiopathic hypokalemia; K, serum potassium; RTA, group with renal tubular acidosis; UpH, urine pH.

Figure 2.

Box-plot of serum magnesium among the three patient groups. The boxes span the 25th and 75th percentile of data points. The thick bars within the box indicate the median. The whiskers represent 1.5 times interquartile range, and the circles specify outliers. Mg, magnesium.

Figure 3.

Frequency of autoantibodies among the study cohort.