Conference Coverage

Dapagliflozin Shows Promise for Sickle Cell Nephropathy Management in UK Multicenter Review

Edited by:
Kate Young

Key Highlights

  • Dapagliflozin use was associated with a significant reduction in albuminuria.
  • A small but expected decline in eGFR occurred shortly after therapy initiation.
  • Treatment was generally well tolerated, with few urinary tract infections reported.
  • Most patients were also receiving ACEi/ARB or disease-modifying sickle cell therapies.

A retrospective audit presented at the 67th ASH Annual Meeting and Exposition in Orlando, FL, examined the real-world use of dapagliflozin, an SGLT2 inhibitor, in patients with sickle cell disease and chronic kidney disease (CKD), which remains a major complication in sickle cell disease.

While SGLT2 inhibitors have become first-line therapy in adult CKD, evidence supporting their use in sickle cell nephropathy has been limited. The investigators sought to characterize clinical effects and tolerability of dapagliflozin in this high-risk group.

Researchers reviewed records from two UK hospitals with large cohorts of patients with sickle cell disease. Eligible participants included all adults with sickle cell disease who attended joint renal–haemoglobinopathy clinics and were prescribed dapagliflozin for routine clinical indications. Baseline characteristics, treatment indications, comorbidities, and adverse events were abstracted. Microbiology and primary care records were examined for confirmed urinary tract infections. Renal outcomes were measured via paired comparisons of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (uACR) using appropriate statistical tests.

Study Findings

The review included 39 patients, most with HbSS or HbSβ⁰ genotypes (90%). The median age was 54 years (range 24–75). Renal-based indications for dapagliflozin were consistent with NICE guidelines: eGFR <45 mL/min/1.73 m² (n = 13) or eGFR 45–90 mL/min/1.73 m² with uACR ≥22.6 mg/mmol (n = 19). Additional indications included cardiac failure (n = 8) and type 2 diabetes (n = 6), with several patients meeting multiple criteria.

Co-prescribing was common: 79% were also receiving ACE inhibitors or ARBs, and 90% were on disease-modifying sickle cell therapy (hydroxyurea or chronic transfusion). Six patients were using antihypertensive agents, and six were on erythropoiesis-stimulating agents.

The mean baseline eGFR was 50 mL/min/1.73 m². A small early decline in kidney function was observed, with a mean eGFR decrease of 5 mL/min/1.73 m² (95% CI, 2–7; P < .001) among 36 patients with follow-up measurements. Median uACR at baseline was 109 mg/mmol; among 25 patients with paired data, uACR decreased by a median of 29 mg/mmol (95% CI, 17–88; P < .001).

Dapagliflozin was generally well tolerated. Two patients developed microbiologically confirmed urinary tract infections requiring antibiotics but continued therapy. Two others had temporary treatment interruption due to reduced eGFR but later restarted therapy. No additional drug-related complications were recorded.

Clinical Implications

The authors note that dapagliflozin is being incorporated into CKD management for sickle cell disease alongside ACEi/ARB therapy and antihypertensives. The significant reduction in albuminuria and manageable safety profile provides early real-world support for its use in this population. The observed transient decline in eGFR aligns with known SGLT2 inhibitor hemodynamic effects rather than signaling progressive kidney injury, according to the authors’ interpretation.

Expert Commentary

“Dapagliflozin appeared generally well tolerated, with a few patients experiencing a recognized complication of urinary tract infections,” the researchers concluded. “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.”

Reference
Cornish N, Fernandes S, Stuart-Smith S, et al. Dapagliflozin for treatment of sickle cell nephropathy: A multi-centre experience. Presented at: American Society of Hematology annual meeting; Dec. 6-9, 2025; Orlando, FL. Presented at: 67th ASH Annual Meeting and Exposition in Orlando, FL. December 6, 2025. https://submit.hematology.org/program/presentation/675715