Sodium zirconium cyclosilicate (Lokelma) to enable ACEIs/ARBs use in the treatment of patients with diabetic kidney disease.

AIMS: In diabetic kidney disease (DKD), Angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) are key treatments but may cause hyperkalemia. This randomized controlled trial (RCT) firstly evaluates sodium zirconium cyclosilicate (SZC) to optimize renin-angiotensin-aldosterone system inhibitor (RAASi) use in DKD, addressing evidence gaps in this field.

METHODS

This 24-weeks prospective multicenter study enrolled 86 DKD patients at hyperkalemia risk to SZC + ACEIs/ARBs or ACEIs/ARBs alone.

PRIMARY OUTCOME: ACEIs/ARBs dose up-titration at week 12. Exploratory outcomes included urinary albumin-to-creatinine ratio (UACR), serum creatinine, and blood pressure (BP).

RESULTS

At week 12, 55.81 % of patients in the SZC + ACEIs/ARBs arm up-titrated their ACEIs/ARBs dosage (95 % confidence interval [CI]: 39.88 %-70.92 %), compared to 27.91 % in the ACEIs/ARBs arm (95 % CI: 15.33 %-43.67 %, P = 0.009). UACR decreased by 63.46 mg/g in the SZC + ACEIs/ARBs arm at week 24, while increasing by 316.87 mg/g in the ACEIs/ARBs arm (least squares mean difference [LSMD]: -333.63 mg/g [95 % CI: -1148.73 to 481.47]; Per-Protocol Set). BP reductions were greater numerically in the SZC + ACEIs/ARBs arm (systolic: -1.7 mmHg; diastolic: -1.4 mmHg).

CONCLUSIONS

SZC reduced hyperkalemia-related RAASi discontinuation risk, improved proteinuria and BP, supporting its prophylactic use in DKD patients on RAASi.