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A Dose of Perspective: A Multinational Survey of Patient and Clinician Views on Combination Therapy in CKD
Nasir Ali Shah1,2,3, Rui Du1,4, Brendon L Neuen1
1The George Institute of Global Health, UNSW Sydney, Sydney, New South Wales, Australia.
Key Points:
Both patients and clinicians were broadly supportive of combination therapy in CKD. Implementation remains the main challenge, especially how to start and sequence drugs.
Background:
CKD affects approximately 15% of adults and remains a major cause of kidney failure and cardiovascular events. Several newer drug classes-sodium-glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, glucagon-like peptide-1 receptor agonists, and endothelin receptor antagonists-provide additional kidney and cardiovascular protection added to standard-of-care renin-angiotensin system inhibition, but the real-world acceptability of using these agents in combination is uncertain. To evaluate the willingness of people with CKD and clinicians to use multidrug combination therapy and to characterize perceived benefits, risks, and barriers to implementation.
Methods:
We conducted a cross-sectional, descriptive, semiquantitative online survey of adults with CKD and clinicians who prescribe CKD therapies. Parallel questionnaires captured demographics, current treatment, prior experience with multidrug regimens, willingness to receive or prescribe combination therapy, and ranked priorities and concerns.
Results:
One hundred forty-two people living with CKD and 317 clinicians completed the survey. Most CKD respondents resided in Australia or the United Kingdom; most surveyed clinicians were hospital-based physicians. Willingness to use multiple agents to reduce CKD progression was high (113/142, 80% "yes"; 27/142, 19% "maybe"). Respondents with CKD prioritized reducing CKD progression and preventing complications, while highlighting side effects, long-term safety, and drug-drug interactions as key concerns; pill burden and cost were less frequently prioritized. Clinicians strongly supported combination therapy in a trial context (300/317, 95%) and reported basing prescribing on guideline recommendations, trial evidence, kidney function, and albuminuria. Principal barriers were risks of hyperkalemia and acute eGFR decline, intensified biochemical monitoring, and cost/limited access. Most clinicians preferred staggered rather than simultaneous initiation, typically starting with a sodium-glucose cotransporter 2 inhibitor as the first add-on to background renin-angiotensin system inhibitor therapy.
Conclusions:
People with CKD and clinicians support multidrug combination therapy, but concerns regarding safety, monitoring burden, and affordability must be addressed to enable routine implementation and large-scale trials.
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