Kidney outcomes and safety of sodium-glucose cotransporter-2 inhibitor therapy in autosomal dominant polycystic kidney disease: systematic review and meta-analysis.

BACKGROUND

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and among the leading causes of kidney failure globally. Sodium-glucose cotransporter (SGLT)2 inhibitor therapy is a novel therapeutic alternative for chronic kidney disease but patients with ADPKD were excluded from pivotal trials. Our aim is to evaluate the efficacy and safety of SGLT2 inhibitor therapy in ADPKD patients in terms of kidney and cardiovascular outcomes.

METHODS

We conducted a systematic review and meta-analysis adhering to PRISMA guidelines and registered with PROSPERO (CRD420261295918). We searched PubMed, Scopus, Web of Science, Cochrane Library, and Ovid MEDLINE.

RESULTS

Our meta-analysis included six clinical studies with 451 ADPKD patients. We have demonstrated that initiation of SGLT2 inhibitor therapy was associated with a statistically significant attenuation in the rate of eGFR decline during the first year compared to placebo, with a mean difference of 0.65 mL/min/1.73 m2 per year (95% CI, 0.05-1.26) compared with the pre-SGLT2i slope. However, no such improvement was illustrated in the first-year eGFR slope change between patients treated with SGLT2 inhibitors and those receiving non-SGLT2 inhibitor therapy, with a mean difference of 2.12 mL/min/1.73 m2 per year (95% CI, -8.13-12.38). Similarly, we failed to demonstrate any statistically significant difference in total kidney volume change with SGLT2 inhibitor therapy (mean difference, -31.31 mL per year; 95% CI, -184.00-121.37).

CONCLUSION

Current evidence is insufficient to establish a beneficial effect of SGLT2 inhibitors on kidney outcomes in patients with ADPKD. Although the available studies did not identify major safety concerns, the evidence is limited by small sample sizes, predominantly observational designs, and substantial clinical and methodological heterogeneity.