The edition · Nephrology
An early eGFR dip on spironolactone did not cancel its benefit in HFpEF
A TOPCAT Americas analysis shows the eGFR fall after starting spironolactone is common and prognostic, but benefit persisted either way; SGLT2 inhibitor benefit held at every BMI; and high-dose vitamin C in severe burns increased mortality.
The edition in brief
In 1,648 patients from the Americas cohort of TOPCAT, an eGFR fall of 15% or more within four weeks occurred in 33% on spironolactone and 20% on placebo. A dip was associated with worse subsequent cardiovascular outcomes in both arms, but spironolactone's benefit on cardiovascular death, heart failure hospitalisation or aborted arrest was similar with a dip (HR 0.75) or without (HR 0.80), and at every magnitude of decline. A meta-analysis of eight trials and 57,356 patients with heart failure, CKD or type 2 diabetes found SGLT2 inhibitors reduced cardiovascular death or heart failure hospitalisation by 20% both above and below a BMI of 30. The VICTORY trial of high-dose IV vitamin C in 238 patients with severe burns was stopped early: 28-day death or persistent organ dysfunction, including kidney replacement therapy, was 40.8% versus 29.7%, and 28-day mortality 15.0% versus 7.6%. A randomised crossover trial in 21 children on haemodiafiltration found pre-filter HDF removed more middle-molecule uraemic toxins than post-filter HDF, at the cost of higher diastolic pressure. And a review of childhood nephrotic syndrome finds about a quarter of steroid-sensitive patients relapse in adulthood, with kidney failure concentrated in steroid-resistant and monogenic disease.
SGLT2 inhibitors cut cardiovascular death or HF admission by 20% whatever the BMI
Prescribe SGLT2 inhibitors for eligible cardiorenal patients whether they are lean or obese — the benefit was identical.
High-dose IV vitamin C in severe burns was stopped for harm
Stop using high-dose IV vitamin C in severe burns; it did not help and may increase mortality.
Pre-filter haemodiafiltration cleared more middle molecules in children than post-filter
In children on HDF, pre-filter mode removes more middle-molecule toxins than post-filter, but watch sodium and blood pressure.
Childhood nephrotic syndrome: a quarter of steroid-sensitive patients relapse as adults
Childhood nephrotic syndrome often persists into adulthood; test steroid-resistant cases genetically and plan transition carefully.
How much eGFR fall after starting a RAAS blocker, MRA or SGLT2 inhibitor is acceptable?
An early eGFR fall of up to about 30% after starting a kidney-protective drug is usually acceptable — look for another cause before stopping.
Spironolactone in HFpEF: the early eGFR dip was prognostic, but the drug still helped
An early eGFR fall after starting spironolactone in HFpEF is common and does not erase its benefit — do not stop it reflexively.
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