Type 4 Renal Tubular Acidosis (RTA) Due to Nonsteroidal Anti-Inflammatory Drug (NSAID) Use

Introduction: A patient with chronic NSAID intake presented with acute kidney injury,proteinuria,hyperproteinemia,non-anion gap metabolic acidosis,hyperkalemia and hyponatremia.Renal biopsy revealed light-chain nephropathy.With chemotherapy his renal function improved,but metabolic acidosis and hyperkalemia did not resolve until treatment with fludrocortisone was initiated Case Description: 46-year-old man with no past medical history presented with back pain due to vertebral fractures,self-treated with Naproxen. Serum creatinine was 7.60 mg/dl,sodium 133 meq/L,bicarbonate 19 meq/L,potassium 5.5 meq/L,albumin 4.0 g/dl,globulin 6.1 g/dl (elevated),anion gap 11. Urine studies showed an albumin/creatine ratio of only 21 mg/g but a protein/creatinine ratio of 3000 mg/g. Serum free kappa light chains 4350 mg/L and lambda light chains 12 mg/L (ratio 378). Kidney biopsy confirmed light-chain nephropathy due to multiple myeloma and chemotherapy was initiated with rapid improvement of renal function (creatinine 3.6 meq/l),but persistent hyperkalemia at 5.5 meq/L,bicarbonate 17 meq/L,anion gap 10.Urine K 16 meq/L,Na 64 meq/L,Cl 39 meq/L,urine creatinine 77.1 mg/dl for a urine anion gap of 41, and spot urine K/creatinine of 21 meq/g.With fludrocortisone serum potassium rapidly improved to 4.8 meq/L,and bicarbonate improved to 19 meq/L Discussion: Hypoaldosteronism causes hyperkalemic metabolic acidosis.Hyperkalemia impairs ammoniagenesis in the proximal tubule and reduces urinary ammonia to buffer urinary hydrogen ions and elimination of hydrogen ions.Use of NSAIDs are known to induce hypoaldosteronism and type 4 RTA.Multiple myeloma is also associated with RTA but classically a proximal RTA type 2 In our case, despite rapid improvement in renal function, hyperkalemia and non-anion gap metabolic acidosis persisted, with a positive urine anion gap and inadequate urinary potassium excretion consistent with RTA type 4. This rapidly improved after empiric treatment with fludrocortisone suggestive of aldosterone deficiency likely due to chronic use of Naproxen Even though renal dysfunction can explain multiple electrolyte abnormalities in patients with light chain nephropathy, clinicians should be aware that chronic NSAID use can be the cause of hyperkalemia and non-anion gap metabolic acidosis, especially when these metabolic disturbances persist despite improvement in renal function