SGLT2 Inhibition May Reduce Albuminuria in Young Patients with Alport Syndrome

Oliver Gross, MD

Credit: University of Göttingen

SGLT2 inhibition at early chronic kidney disease (CKD) stages may induce positive outcomes in young patients with Alport syndrome, according to findings from a new study.

Presented at the American Society of Nephrology Kidney Week 2023 by Oliver Gross, MD, of the department of nephrology and rheumatology at the University of Göttingen Medical Center, the trial provides the first data for the effect of SGLT2 inhibition in a younger patient population, highlighting an intermediate response in albuminuria reduction from baseline to the end of the treatment period.¹

An inherited form of kidney inflammation caused by a mutation in the collagen gene, Alport syndrome damages the glomeruli of the kidneys and causes gradual loss of kidney function. It can progress to end-stage renal disease at an early age, in which case dialysis or a kidney transplant is needed. There is no specific treatment for Alport syndrome, although kidney transplantation is considered the best approach when kidney failure is approaching.¹

The noninterventional, observational study enrolled 99 patients, including 10 children and 89 adults, with Alport syndrome from 12 countries following the initiation of SGLT2 inhibitors during early CKD stages.¹

Among pediatric participants, the mean age was 16 (range, 9-17) years, the mean estimated glomerular filtration rate (eGFR) was >90ml/min/1.73m2, and the mean albuminuria was >1.0g/g creatinine, although investigators noted only adults with in-label use of SGLT2i were able to be included in the present study.¹

Among adult participants, the mean age was 37±14 years, mean eGFR was 63±35 ml/min/1.73qm, and mean albuminuria was 1822±1484 mg/g creatinine. Investigators compared patients in the present study to nondiabetic CKD patients in the EMPA-Kidney, a clinical trial assessing the impact of taking a single pill of empagliflozin daily on the worsening of kidney disease or deaths from heart disease in patients with CKD. Of note, patients in the current study were younger (37 vs 64 years of age), had similar BMI and blood pressure, better eGFR (63 vs 39 ml/min/qm), and a 4 times greater albuminuria (1822 vs 461 mg/gCrea) compared to patients in EMPA-Kidney.¹

At visit 1 between months 1 and 3 of treatment, albuminuria decreased by 34% (P < .001) and eGFR decreased by 6% (P = .05). At visit 2, a mean duration of 5.7 months into treatment, albuminuria dropped by 29% (P = .003) and eGFR decreased by 6% (P < .001).¹

Investigators pointed out albuminuria and eGFR continued to decrease at visit 3 (mean, 11.7 months of treatment), dropping by 24% and 15%, respectively (n = 26; P = .001). Additionally, BMI decreased from 27.8±6.3 to 27.2±6 kg/m2, serum albumin increased from 3.8±0.7 to 3.9±0.4 g/dL, and blood pressure decreased from 127/82 to 126/80 mmHg.¹

At the fourth and final visit (mean, 21 months of treatment), albuminuria was reduced by 27% and eGFR was reduced by 10% (n = 12; P = .02). Compared to baseline, eGFR slope changed from -13.6 at visit 1, -8.4 at visit 2, -7.7 at visit 3, to -4.1 ml/min/year at visit 4. Although participants showed an intermediate response in albuminuria reduction, the positive effect on long-term eGFR slope remained inconclusive at months 12 and 21. Adverse drug reactions occurred in 7 (11%) patients at a total of 50 patient-years at risk.¹

Although investigators noted the results of the current study leave unanswered questions surrounding the safety and efficacy of SGLT2 inhibition in this patient population, the effects will be further examined in the upcoming first pediatric randomized controlled trial, DOUBLE PRO-TECT Alport.¹

References:

1.Gross O, Boeckhaus J. SGLT2 Inhibition in Alport Syndrome: First Large-Scale Trial to Plan a Randomized Controlled Trial in Children. Paper Presented at: American Society of Nephrology Kidney Week 2023. November 1-5, 2023.

2. Penn Medicine. What is Alport Syndrome? May 19, 2023. Accessed November 2, 2023. https://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/alport-syndrome