#6212 SEVERE HYPERCHLOREMIC METABOLIC ACIDOSIS WITH SGLT-2 INHIBITORS IN PATIENTS WITH URINARY DIVERSION

Abstract

Abstract Background and Aims Urinary diversion after cystectomy using autologous intestinal segments has been the gold standard treatment of benign and malignant diseases of urinary tract. The most frequent metabolic abnormalities is hyperchloremic metabolic acidosis, due to ammonium absorption alongside chloride gain and bicarbonate excretion in the bowel conduit. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a class of antihyperglycemic agents that recently revolutionized the paradigm of chronic kidney disease. It exerts its effect by preventing the reabsorption of filtered glucose from the tubular lumen, acting on the SGLT2 proteins in the renal proximal convoluted tubules, and thus promoting a greater urinary glucose excretion. The authors described 2 patients with bowel conduit and mild hyperchloremic metabolic acidosis, presented with severe metabolic acidosis short after starting SGLT2 inhibitors. Method Consultation of medical records. Results Case 1: 62-year-old male with an orthotopic neobladder since 2005, type 2 diabetes and nonspecific interstitial pneumonia. In 2018 arterial blood gas (ABG) was: pH 7.45, pO2 81, pCO2 28, HCO3- 19.3, Cl 107, AG 7.7 (normal albumin), K+ 3.25. In February 2022 he was sent to the emergency department (ER) from a Pneumology appointment, after an ABG showed an aggravated hyperchloremic metabolic acidosis: pH 7.25, pCO2 27.5, HCO3- 12, Cl 122, Na+ 143, K+ 3.74, AG 9, lactate 0.69, glucose 261, ketone bodies negative); blood workup added acute kidney injury (AKI), urea 81, creatinine 1.6. The patient medical history revealed: administration of 5 cycles of cyclophosphamide (7 months before) and the introduction of empagliflozin 10mg id, 10 months prior to this event, as an addition to Metformin 1000mg id. A progressive metabolic normalization was observed after the SGLT2 inhibitor was withdrawn and intravenous hydration. Case 2: A 63-year-old male with an ileal conduit since 2018 and type 2 diabetes. He had chronic renal disease since 2021 with serum creatinine 1.5-2. He presented with a 3-day history of lethargy and anorexia. He had started dapagliflozina 10mg id 10 months prior to this event. At admission the patient had normal vital signs, glasgow coma scale 15 and no major signs at observation. ABG showed severe hyperchloremic metabolic acidemia (pH 6.98, pCO2 20.5, pO2 124.4, HCO3- 4.7, Na 129, Cl 120, AG 4.3, K+ 3.54, glucose 200, lactate 0.5) alongside AKI, urea 209 and creatinine 2.8 and spot urine without ketone bodies. He was admitted for a short period to the intensive care unit, for intravenous sodium bicarbonate and hydration, on top of SGLT2 inhibitor suspension, with progressive clinical and metabolic resolution. Conclusion Chronic hyperchloremic metabolic acidosis is a frequent and known complication of urinary diversion, due to the reabsorption of solutes by the intestinal mucosa because of the presence of urine (ammonium and chloride absorption and bicarbonate excretion) and diarrhea and volume depletion due to reduced sodium absorption in the gout. Euglycemic Ketoacidosis is a well-known complication of SGLT2 Inhibitor therapy and was not this case as both patients had normal anion gap. Hyperchloremic acidosis as been rarely described but not so severe as we presented. Although both patients had AKI, was not severe. We hypothesize that SGLT2 inhibitors, could exacerbate the chronic hyperchloremic metabolic acidosis by increasing urinary sodium and glucose excretion, that could exacerbate volume depletion, diarrhea and hyperglycemia (and subsequent volume depletion). This are the first 2 cases reported of severe hyperchloremic metabolic acidosis in patients with orthotopic neobladder and SGLT2 inhibitors treatment. The physiopathology of this presentation needs to be studied.