MO1034: Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Alport Syndrome and Fsgs: A Case Series

Abstract

Abstract BACKGROUND AND AIMS Most hereditary diseases of the glomerular filtration barrier still progress to end-stage renal failure (ESRF)—raising the urgent need for add-on therapies. Recent randomized clinical trials (RCTs) demonstrated the nephroprotective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in chronic kidney diseases (CKD). SGLT2-mediated afferent arteriole vasoconstriction, additive to efferent arteriole vasodilatation by angiotensin-converting enzyme inhibitors (ACEis), is postulated to correct the haemodynamic overload of the glomerular filtration barrier. For that reason, we investigated the nephroprotective effect of SGLT2i in hereditary glomerular diseases. METHOD In 2020, this monocentric prospective case series was started in six patients with Alport syndrome or FSGS, who consented to off-label therapy with empagliflozin or dapagliflozin. To our knowledge, this is the first case series on the effect of SGLT2i in patients with hereditary causes of CKD. RESULTS We report data on the use of SGLT2i in a case series of patients with Alport syndrome and FSGS in respect of the early effect on the kidney function and safety of initiation of therapy. The follow-up was 3–11 months. The mean age was 40 years (standard deviation, SD ± 17), the mean duration of treatment was 4.5 months (SD ± 2.9). The mean serum creatinine before and after SGLT2i initiation was 1.46 (SD ± 0.42) and 1.58 (SD ± 0.55). The mean urinary albumin-creatinine ratio in mg/g creatinine before SGLT2i was 1827 (SD ± 1560) and decreased to 1127 (SD ± 854) after SGLT2i initiation. The estimated glomerular filtration rate (eGFR) ‘dipped’ after initiation of SGLT2i in most patients. Overall, treatment was well tolerated, however, eGFR initially decreased by more than 30% in one patient with FSGS. The initial eGFR drop raises some safety concerns, which underlines the need to collect and evaluate the course of every patient with AS in which therapy with SGLT2i is started. CONCLUSION In conclusion, therapy with SGLT2i on top of ACEi was well tolerated and effective in terms of lowering albuminuria. As a proof of concept, SGLT2-mediated correction of the haemodynamic overload of the glomerular filtration barrier looks like a very promising therapeutic approach in hereditary diseases such as AS and FSGS. Specific RCTs are needed to confirm our findings in this genetically well-defined population with a tremendous unmet medical need for more effective, early on and safe nephroprotective therapies. Proteinuria is reported as a urinary albumin-creatinine ratio in mg/g creatinine. All male patients received SGLT2i additive to renin-angiotensin-aldosterone system (RAAS)-blockade. In the female patient, ACEi was stopped prior to the start of SGLT2i because of angioedema. In addition to ACEi and SGLT2i, one patient also received tacrolimus because of irritable bowel disease. (A) eGFR (CKD-EPI formula) at baseline and at follow-up. (B) UACr at baseline and at follow up. m, male; f, female; FSGS, focal segmental glomerulosclerosis; XLAS, X-linked Alport syndrome; IBD, irritable bowel disease; aHT, arterial hypertension; sHP, secondary hyperparathyroidism; eGFR, estimated glomerular filtration rate; UACr, urine-albumin-creatinine ratio; Crea, serum-creatinine