Dapagliflozin safe, effective in sickle cell nephropathy

The use of dapagliflozin results in a significant improvement in albuminuria and is well tolerated among patients with sickle cell disease (SCD), reports a study presented at ASH 2025. However, a few of them have experienced a complication of urinary tract infections (UTIs).

Furthermore, “[a] small rise in creatinine is expected during initial treatment due to a reduction in intraglomerular pressure caused by dapagliflozin’s protective mechanism of action,” said lead author Dr Naomi Cornish, University of Bristol, Bristol, UK.

Cornish and her team performed a retrospective audit and case-series review across two hospitals with large sickle cell cohorts in the UK. They examined the clinical effect and tolerability of dapagliflozin among patients with SCD (mean age 54 years) who attended joint renal-haemoglobinopathy clinics and who were prescribed dapagliflozin for routine indications.

Cornish and colleagues then reviewed patient records for baseline characteristics, indication of treatment, comorbidities, and adverse events, as well as assessed laboratory microbiology and primary care records for evidence of confirmed UTIs.

The authors also examined the changes in estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (uACR) after initiating dapagliflozin using paired t-tests for eGFR (normally distributed data) and Wilcoxon signed rank tests for uACR (nonparametric distribution).

Indications

Of the 39 SCD patients prescribed dapagliflozin, 90 percent were HbSS or HbSβ⁰ genotype, while the rest were HbSC or HbSβ⁺ genotype. The indications for using dapagliflozin were eGFR 22.6 mg/mmol (n=19), cardiac failure (n=8), and type 2 diabetes (n=6). Some patients had multiple indications for treatment. [ASH 2025, abstract 298]

Thirty-one patients (79 percent) were also prescribed an ACEi/ARB, but two of them discontinued this treatment due to persistent hyperkalaemia. Thirty-five patients (90 percent) received disease-modifying therapy for SCD: 23 on hydroxyurea and 12 on a regular transfusion program.

Moreover, six patients were taking antihypertensive therapy (amlodipine, doxazosin, or indapamide), and six others were prescribed erythropoietin stimulating agents.

“In our cohort of patients with SCD, dapagliflozin is being used either alone or in combination with ACEi/ARB treatment and/or antihypertensive medications for management of chronic kidney disease (CKD),” Cornish said.

Prior to dapagliflozin initiation, the mean eGFR of the SCD patients was 50 ml/min/1.73 m². A slight reduction in eGFR was observed shortly after starting dapagliflozin therapy (mean decrease, 5 ml/min/1.73 m², 95 percent CI, 2‒7; p<0.001) in 36 patients with eGFR measured at least 1 month (median 4.5 months) after commencing dapagliflozin.

Prior to dapagliflozin use, the median uACR was 109 mg/mmol, which decreased to 29 mg/mmol (95 percent CI, 17‒88; p<0.001) after starting dapagliflozin in 25 patients with paired uACR measurements.

Of note, two patients were treated with antibiotics for a confirmed UTI following dapagliflozin initiation, but they subsequently continued dapagliflozin use. Two others had temporary treatment interruption due to eGFR reduction but restarted therapy later. No other treatment-related complications occurred.