TY - JOUR
T1 - Patiromer to Reduce Albuminuria through Increased Renin Angiotensin Aldosterone System Inhibition in Patients With CKD-A Feasibility Trial
AU - Mårup, Frederik H.
AU - Peters, Christian D.
AU - Nielsen, Steffen F.
AU - Nygaard, Louis
AU - Madsen, Bo
AU - Mose, Frank H.
AU - Birn, Henrik
PY - 2024/8
Y1 - 2024/8
N2 - Introduction: We tested the feasibility of adding a potassium binder to enable increased renin angiotensin aldosterone system inhibition (RAASi) and reduce albuminuria in patients with chronic kidney disease (CKD). In a controlled trial design, a potassium binder was introduced exclusively in patients developing hyperkalemia after intensified RAASi, thereby mirroring clinical decision-making. Methods: We planned to include 140 patients aged 18 to 80 years with estimated glomerular filtration rate (eGFR) 25 to 60 ml/min per 1.73 m2, albuminuria, and a history of hyperkalemia to an open-label, randomized trial comparing treatment with or without patiromer alongside maximally tolerated RAASi. Patients were randomized only if developing a documented P-potassium >5.5 mmol/l during run-in with intensified RAASi (losartan/spironolactone). The primary end point was change in urine albumin-creatinine ratio (UACR). Results: Screening among 800,000 individuals with available laboratory results yielded just 317 candidates meeting major selection criteria during 18⅔ months, with 75 ultimately included. Among them, only 23 developed P-potassium >5.5 mmol/l, qualifying for randomization. Consequently, only 20 participants completed the study, falling short of the planned 98, precluding a significant effect on the primary outcome. Inclusion and randomization challenges stemmed from a limited pool of eligible patients for intensified RAASi at risk of hyperkalemia, along with a lower than expected incidence of hyperkalemia during run-in. Conclusion: Despite extensive screening efforts, few eligible patients were identified, and fewer developed hyperkalemia during run-in. Hence, a trial design limited to CKD patients at high hyperkalemia risk and including a run-in phase appears unlikely to provide evidence for a potential renal benefit from additional use of potassium binders.
AB - Introduction: We tested the feasibility of adding a potassium binder to enable increased renin angiotensin aldosterone system inhibition (RAASi) and reduce albuminuria in patients with chronic kidney disease (CKD). In a controlled trial design, a potassium binder was introduced exclusively in patients developing hyperkalemia after intensified RAASi, thereby mirroring clinical decision-making. Methods: We planned to include 140 patients aged 18 to 80 years with estimated glomerular filtration rate (eGFR) 25 to 60 ml/min per 1.73 m2, albuminuria, and a history of hyperkalemia to an open-label, randomized trial comparing treatment with or without patiromer alongside maximally tolerated RAASi. Patients were randomized only if developing a documented P-potassium >5.5 mmol/l during run-in with intensified RAASi (losartan/spironolactone). The primary end point was change in urine albumin-creatinine ratio (UACR). Results: Screening among 800,000 individuals with available laboratory results yielded just 317 candidates meeting major selection criteria during 18⅔ months, with 75 ultimately included. Among them, only 23 developed P-potassium >5.5 mmol/l, qualifying for randomization. Consequently, only 20 participants completed the study, falling short of the planned 98, precluding a significant effect on the primary outcome. Inclusion and randomization challenges stemmed from a limited pool of eligible patients for intensified RAASi at risk of hyperkalemia, along with a lower than expected incidence of hyperkalemia during run-in. Conclusion: Despite extensive screening efforts, few eligible patients were identified, and fewer developed hyperkalemia during run-in. Hence, a trial design limited to CKD patients at high hyperkalemia risk and including a run-in phase appears unlikely to provide evidence for a potential renal benefit from additional use of potassium binders.
KW - albuminuria
KW - CKD
KW - hyperkalemia
KW - patiromer
KW - RAASi
KW - renin angiotensin aldosterone system
UR - http://www.scopus.com/inward/record.url?scp=85196091481&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2024.05.006
DO - 10.1016/j.ekir.2024.05.006
M3 - Journal article
C2 - 39156169
AN - SCOPUS:85196091481
SN - 2468-0249
VL - 9
SP - 2399
EP - 2409
JO - Kidney International Reports
JF - Kidney International Reports
IS - 8
ER -