SLC4A1 (Anion Exchanger 1/ AE1) Variants as a Rare Cause of Distal Renal Tubular Acidosis (dRTA) and Recurrent Nephrolithiasis

Introduction: Patients with dRTA variably manifest basic urine pH, CaP nephrolithiasis, hypokalemia, NAGMA, hypercalciuria and bone disease. Causes include autoimmune disease(Sjogren disease), use of carbonic anhydrase inhibitors (especially topiramate) and pathologic genetic variants including ATP6V1B1 and SLC4A1 that mediate distal renal acidification Case Description: We recently completed targeted gene panel testing in 2 patients that presented to the Mayo Nephrology Clinic with a history of Ca-P and meduallry nephrocalcinosis. Key fingings are detailed in Table 1. Both had clinical evidence for dRTA with high 24 hr urine pH and low urinary citrate. However, there were other subtle differences between the 2 including age of onset, degree of nephrocalcinosis, and the presence of concurrent RBC morphologic changes. Discussion: SLC4A1 encodes AE1 which responsible for bicarbonate (HCO3) and chloride (Cl) exchange on the surface of cirulating RBCs and the basolateral surface of alpha-intercalated cells in the kidney. Genetic variation in SLC4A1 is a rare but reported cause of dRTA, and depending on the variant and resulting defect (mislocalization or loss of function) inheritance may be biallelic or monoallelic. Treatment with alkali (including citrate)may reduce hypercalciuria, and improve urine citrate and reduce systemic acoidosis (if present), which maybe particularly important for bone health. However, the net effect on stones and nephrocalcnosis of any increase in urine pH has not been established with some theoretic concern that in overly alkaline urine may promote Ca-P crystallization. Further identification of cases in order to develop cohorts to study the natural history of this disease and understand genotype phenotype correlations is sorely needed.