The edition · Nephrology
Aldosterone synthase inhibition lowered blood pressure and albuminuria on top of an SGLT2 inhibitor; a trial commentary advises against somatostatin analogues for ADPKD kidney function
A small crossover trial of lorundrostat leads a nephrology edition that also covers SGLT2 inhibitor surrogate results, a post-hoc look at bicarbonate in ICU acidosis, and response to lumasiran in primary hyperoxaluria.
The edition in brief
In Explore-CKD, a randomised, double-blind, placebo-controlled crossover trial of 59 adults with uncontrolled hypertension, CKD and albuminuria already on an SGLT2 inhibitor and renin-angiotensin blockade, lorundrostat 25 mg a day lowered office systolic pressure by 7.5 mmHg more than placebo (95% CI -12.3 to -2.7) and albuminuria by about 26% (placebo-adjusted); eGFR fell from 42.9 to 40.1 with lorundrostat and 42.9 to 42.1 with placebo, and three participants stopped for adverse events. A meta-analysis of 17 trials (29,192 people) of SGLT2 inhibitors in diabetic CKD found lower HbA1c, weight and systolic pressure but no significant difference in eGFR or albuminuria over short to medium follow-up, and more volume-depletion events (RR 1.36). A post-hoc hierarchical analysis of the SODa-BIC trial (488 patients) found no overall effect of sodium bicarbonate in ICU metabolic acidosis (win ratio 0.97, 95% CI 0.79 to 1.19). The French Daily-Luma cohort (76 patients with primary hyperoxaluria type 1) found 73% met the response criterion at 3 months, with better response in children. A commentary on the LIPS trial says lanreotide did not slow measured GFR decline in ADPKD and supports the existing KDIGO recommendation against prescribing somatostatin analogues solely to preserve kidney function. A pearl on the expected eGFR dip with SGLT2 inhibitors closes the edition.
Explore-CKD: lorundrostat added to an SGLT2 inhibitor lowered blood pressure and albuminuria
An aldosterone synthase inhibitor lowered blood pressure and albuminuria in a 59-person crossover trial; it is investigational and its kidney benefit is unproven.
SGLT2 inhibitors in diabetic CKD: weight, pressure and glucose improved, eGFR and UACR unchanged in pooled trials
In diabetic CKD, SGLT2 inhibitors improved glucose, weight and pressure with more volume-depletion events; the neutral surrogate results should be read alongside the long-term outcome trials.
SODa-BIC re-analysed: hierarchical outcomes did not change the neutral bicarbonate result
The re-analysis confirms no overall effect of bicarbonate in ICU metabolic acidosis; subgroup signals need prospective testing.
Lumasiran in primary hyperoxaluria type 1: 73% responded at 3 months, more often in children
Lumasiran lowered oxalate in most patients, especially children; follow oxalate closely and discuss pyridoxine with a specialist centre.
An early eGFR dip after starting an SGLT2 inhibitor is expected
Expect a small early eGFR dip on starting an SGLT2 inhibitor, recheck, and investigate only if it is large or progressive.
LIPS commentary: lanreotide did not slow measured GFR decline in ADPKD
Do not start a somatostatin analogue solely to protect kidney function in ADPKD; the commentary on LIPS says the current KDIGO advice stands.
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