2023 was a great year and a year with a lot of variety in the topics covered in Top Stories. You have to go back to 2014 to find the last Top Stories in Nephrology without a Flozin story. That is amazing.
2023 brought us has dogma shredding data on hyponatremia and the seeming importance of different diuretics. It has new therapies for old diseases like IgA and hypertension. New drugs for new diseases like inaxaplin for AMKD. And it has new data on old debates like what IVF is best and do thiazides really prevent kidney stones. It is a great list. Dig in!
IgA Nephropathy: Now with new drugs!
It is only fitting that the most widely occurring glomerular disease that’s evaded well-meaning therapy for decades, bags the top spot of top nephrology stories of 2023. While advances occurred in both streams of therapy (conservative care and immunosuppressives) for IgA Nephropathy (IgAN), the big news in 2023 were the new (and only!) regulatory approvals in this field. Firstly, targeted-release formulation of budesonide (Tarpeyo™) received full FDA approval in December 2023, for ‘reducing proteinuria in adults with primary IgAN at risk of rapid progression’, based on results of the two-part, phase-3, NeflgArd study. In part A (Baratt, et al, KI, 2023) budesonide showed a 27% reduction in UPCR at 9 months, along with preservation of eGFR. In Part B, they showed better preservation of eGFR compared to placebo at the end of 2 years (Lafayette, et al, Lancet, 2023). The formulation, which was shown to modify key biomarkers in the phase 2b NEFIGAN study (Wimbury et al, KI, 2023), was well tolerated. What’s waiting to be addressed is a confirmation of how closely its action follows the postulated location and mechanism of action. Similarly, its efficacy needs to be formally compared to traditional budesonide (meant for use in enteric diseases where release in the entire gut is desired), justifying the merits of therapeutic ‘target practice’ in IgA Nephropathy (Barratt, Rovin, KI, 2023) or even good old-fashioned steroids, which we now know are quite effective (Lv et al JAMA 2022).
Second major approval came in form of the Dual Endothelin type A and Angiotensin II Receptor Antagonist (DEARA), Sparsentan (Filspari™), which received accelerated FDA approval early last year, based on an interim analysis of the PROTECT trial, making it the first non-immunosuppressive treatment to be FDA-approved for ‘reduction of proteinuria in adults with IgAN at a high risk of progression’. The pre-specified interim analysis (Heerspink et al, Lancet, 2023) brought out the very noticeable drop in proteinuria (49.8% compared to 15.1% for irbesartan) at 36 weeks, and an acceptable drug safety profile. The grand finale (Rovin et al, Lancet, 2023) brought celebratory end-of-the-year news, though it narrowly missed the total GFR slope endpoint. These two-year results from the trial confirmed the continued reduction of proteinuria, and a hearty relative risk of 0.7 (95% CI 0.4-1.2) for composite kidney failure endpoint compared to RASi alone.
The year-end also saw the much-anticipated secondary analysis of outcomes from EMPA-KIDNEY (Lancet Diabetes Endocrinol, 2024). With a hazard ratio 0.67 (95% CI 0.46-0.97) for kidney disease progression in IgAN subgroup (largest sample size of all IgAN trials, n=817), at par with 0.64 in diabetic kidney disease. More interestingly, the relative risk reduction for decline in eGFR based on chronic slope was 43%. Other promising approaches embarked upon this year involved inflammatory pathways and the complement system. Telitacicept, a fusion protein neutralizing BLyS and APRIL, was found to induce clinically meaningful reduction in proteinuria in a phase 2 trial (Lv et al, KIR, 2023) and paved the way for targeting TNF-family ligands in IgAN. Fostamatinib, an oral spleen tyrosine kinase inhibitor, showed a trend towards reduction in proteinuria in high risk patients (Tam et al, KIR, 2023). A notable mention amongst trials re-exploring conventional agents is the MAIN trial (Hou et al, JAMA Netw Open, 2023) conducted in the Asian population. This study showed a 77% reduction in the composite primary outcomes with MMF added on to supportive care (i.e. ARB) versus supportive care alone on a median follow up of 60 months. The zeitgeist of 2023 inspired some excellent thought-provoking reviews. Just in case you’ve missed the party, listing a handful here- Kohan et al, KIR, 2023 (endothelin A receptor), Yeo, Barratt, CKJ, 2023 (TNF family) Tesar et al, KIR, 2023 and Floege, KI, 2024 (complement).
One foot into the new year, IgAN therapeutics score strongly with two new phase-2 trials in the ensemble already- sibeprenlimab (Mathur M, et al, NEJM, 2024) and iptacopan (Zhang et al, Kidney Int, 2024). We also have high hopes from the open label extensions of PROTECT trial- OLE and SPARTACUS, which explore the alluring prospect of combining DEARA with flozins, in the hope of synergistic benefits. Accelerated approval for therapeutic drug use in IgAN using proteinuria as a surrogate marker (Thompson et al, CJASN 2019) is a promising approach that’s just started paying dividends
2. Hyponatremia correction: Speed doesn’t Kill?
By Joel Topf (Relevant COI, Topf was a co-author on the MacMillan paper)
The treatment of hyponatremia felt like settled science. Despite a lack of prospective trials, experts had accepted retrospective case series and felt that rapid correction of hyponatremia was dangerous and there was no harm to slow correction of hyponatremia. In 2023, there were three retrospective studies that tossed a monkey wrench into the established dogma.
In May, MacMillan (MacMillan et al, NEJM Evidence 2023) published a 10-year retrospective analysis of 5 hospitals in Toronto and the clinical experience of 21,182 patients with hyponatremia (Na < 130). This is the largest analysis of hyponatremia ever, and found that despite a high rate of over-correction (Na increase > 8 mEq/L/day), 18% overall, and 49% in patients with sodium below 120, there were only 12 cases of osmotic demyelinating syndrome (ODS). This represented 0.05% of patients with a sodium less than 130, and 2.7% of patients with a sodium less than 110.
One of the tenets of slow correction of chronic, asymptomatic, hyponatremia is that all of the risk is on the side of fast correction. If you correct the sodium too quickly there could be neurologic consequences, but there is no danger in slow correction. In September, another group (Seethapathy et al NEJM Evidence 2023) published a retrospective analysis of hospital survival in hyponatremia at two Boston hospitals. They reported that slow correction was associated with increased mortality, while fast correction had a survival benefit. Take a look at Harish’s tweetorial describing their central thesis and findings. Perfect. Also see the NephJC summary by Milagros Flores. These results were reproduced by Kinoshita (Kinoshita 2023) in October who looked at 208 hospitals and 1024 ICU patients with a sodium < 120.
While none of these studies are perfect, worth reading also is a Helbert Rondon-Berrios and Richard Sterns written well-thought rebuttal in Kidney News (Rondon-Berrios, 2023). These are careful and deliberate assessments that are important additions to a field devoid of prospective data. Hyponatremia is too important to be ruled by expert opinion and ungraded clinical practice guidelines.
3. Renal denervation is FDA approved (finally)
What a rollercoaster ride renal denervation (RDN) has had! From the heydays of 30-40 mm Hg decrease in systolic BP (SBP) claimed initially, to a null effect after SYMPLICITY HTN-3 (Bhatt et al, NEJM 2014 | NephJC summary), to now an acceptance of about 4-7 mm Hg sham-controlled effect after the SPYRAL and RADIANCE trials (NephJC summary). Because of the SYMPLICITY HTN-3 debacle, RDN was not approved by the FDA, though peeps in Europe, Australia, and other parts of the world went ahead, performing RDN and adding to the Global SYMPLICITY registry (Mahfoud et al EHJ 2019). But the seemingly recalcitrant attitude of the FDA allowed us to understand the true effect of RDN over sham control. As NephJC has discussed before, uncontrolled and unblinded studies with an intervention like RDN give an exaggerated effect estimate stemming from information bias, varying adherence, and regression to mean, among other biases. The recently published final analyses of the RDN trials demonstrate a clear reduction of BP, along the magnitude of that achieved by 12.5 mg of chlorthalidone, or 25 mg of spironolactone (Kandzari et al JACC 2023; Azizi et al Circulation 2023). Is that worthwhile, you say? In terms of cost this is a hard sell, though a recent attempt (Sharp et al, EHJ-QCCO 2024) suggests it might be cost-effective, but with significant assumptions and extrapolations. In fact it’s quite possible that in the control arm one would just give more meds - which is what happened in the longer term results with SPYRAL, as a result of which the 24-hour SBP difference was only 2 mm Hg. On the other hand, people will argue that reduced pill burden, less issues with adherence may provide smoother and better long term BP control. Patient surveys (Schmieder et al J Hypertension 2021) do demonstrate a keen appetite to achieve BP lowering without medications. Now that RDN is approved in the USA, we will see the full force of medicine and the market play out. Time will tell if RDN can help reverse the worsening BP control (Muntner et al JAMA 2020) that has become evident in recent years, or turn out to be just another expensive version of 12.5 mg HCTZ.
4. Diuretics: just a class effect after all (DCP and TRANSFORM HF)
Le premier mythbuster, deux parts (mythbuster number deux following, by Jamie Willows) it’s on nephrologist’s beloved diuretics. Do pharmacokinetic properties translate into clinical benefit?
First, chlorthalidone vs hydrochlorothiazide (HCTZ). Most of the trials which support CV benefits, used chlorthalidone or indapamide (MRFIT, SHEP, ALLHAT trial, HYVET, SPRINT), not the more popular HCTZ. Chlorthalidone has a prolonged duration of action (45-60h) due to its ability to accumulating in red blood cells for slow release. It has to be better, right? The Diuretics Comparison Project (DCP) aimed to find out if changing HCTZ to chlorthalidone was better than just continuing HCTZ (Ishani A et al, NEJM 2023). DCP was a pragmatic, randomized, open-label trial, randomizing 13,523 patients from the Veteran Affairs care system. The primary composite outcome occurred in 10.4% of patients in the chlorthalidone group and in 10% of those treated with HCTZ (HR 1.04 95% CI, 0.94–1.16). There were no differences in the incidence of MI, stroke, HF hospitalizations, revascularization for unstable angina, non-cancer-related death, and death from any cause. But the incidence of hypokalemia was higher with chlorthalidone (6.0% vs 4.1%). NephJC summary. No benefit, some harm with chlorthalidone versus HCTZ>
The torsemide vs furosemide showdown was adjudicated in TRANSFORM-HF. Torsemide, with its higher potency and prolonged effect, boasts potential benefits, including lowering myocardial fibrosis and aldosterone production along with possibly reversing ventricular remodeling (Peters AE et al, Expert Rev CV Ther 2022). However the sheer dominance of furosemide in HF treatment makes the narrative more intriguing(Bikdeli B, et al, JACC, 2013). Amidst a sea of meta-analyses, one stands out, signaling lower CV mortality in torsemide treated patients, although it included only 3 studies (Abraham B, et al, Am J Cardiol, 2020). For deeper insights, consult the NephJC summary. TRANSFORM-HF was a pragmatic, open-label, randomized trial, seeking to settle the torsemide vs furosemide debate in HF treatment (Mentz RJ, et al, JAMA, 2023). With 2859 patients, a median follow-up of 17.4 months, TRANSFORM-HF, showed no difference in all cause mortality (approx. 26% in both arms) or all-cause hospitalization. Statistical wizardry (Fine Gray competing risk model, which considered death as a competing event) in post hoc analysis hinted at lower hospitalizations in the torsemide group (HR 0.88 CI 95%, 0.78-0.99).
These two pragmatic trials expose a lot of what we teach about diuretics and are important additions to our clinical knowledge. Some things are just a class effect. Pharmacokinetics does not matter….at least as far as these diuretics are concerned.
5. The rise of Aldosterone synthase inhibitors
This year we started to see data in the form of a few phase 2 trials on a new method of RAAS inhibition. Aldosterone Synthase inhibitors (ASI) which blunts the rise in aldosterone levels and could be useful in hypertension as well as in CKD.
BI 690517 is an ASI with 250:1 selectivity for aldosterone synthase over cortisol synthase. A randomized controlled trial (Tuttle KR, et al, Lancet, 2023) of three different doses of BI 690517 versus placebo in patients of CKD with eGFR 30 - 90 ml/min and proteinuria of 200-5000 mg/g reported that both 10 mg and 20 mg doses of the drug decreased proteinuria by more 30% at 14 weeks with hyperkalemia rates of between 10-24% (comparable to finerenone in the FIDELIO DKD, Bakris et al NEJM 2020 | NephJC summary) in patients already on RASi. Notably, only patients with baseline serum K less than 4.8 were enrolled in the trial. Earlier ASI trials have been marred by high rates of adrenal insufficiency due to off target effects on cortisol synthase (eg Olundrostat which is now used in Cushing’s syndrome). BSI 690517 had low, but not zero, rates of adrenal insufficiency (1-3%), detected because of a robust monitoring protocol. Will that make it more, or less likely, that we would use BI 690517 in place of finerenone, or even spironolactone, once the ongoing phase 3 EASiKIDNEY trial is completed?
This year has been lucky for the ASIs with two other molecules in difficult to control hypertension coming out as well. The BrigHTN trial (Freeman et al, NEJM 2023) showed a significant decrease in BP with baxdrostat, with low rates of hyperkalemia (2-3% at highest doses) in a population with higher baseline eGFRs (<6% had eGFR <60 ml/min). Lorundrostat came out a fee months later, again in patients with uncontrolled hypertension with or without suppressed plasma renin activity, and significantly lowered BP (Lauffin et al, JAMA 2023). Both these molecules are in phase 3 development as well. Apart from the advantage of lacking the anti-androgenic side effects seen with spironolactone, ASIs also block the non-genomic effects of aldosterone, blunt the aldosterone breakthrough phenomenon seen with chronic RASi, and may be especially helpful in some cases of bilateral adrenal hyperplasia when even supramaximal MRA doses are insufficient.
6. Endothelin antagonists advance
Endothelin receptor antagonists (ETAs) have been around for a long time, mainly for the treatment of pulmonary hypertension. But in 2023 they have, finally, broken in nephrology in a big way. Let’s take a look at what the year brought.
How do they work? The activation of the ET1 (via ETa) receptor mediates kidney vasoconstriction, subsequently causing podocyte damage, endothelial dysfunction, inflammation and ultimately glomerulosclerosis and interstitial fibrosis. ETAs antagonize this action. The ET1 (via ETb) receptor also mediates diuresis and natriuresis and ETA receptor blockade lends itself to fluid overload and heart failure as an adverse effect. Additionally, hepatotoxicity has been another important finding.
Resistant hypertension: The PRECISION trial (Schlaich et al, Lancet 2022, discussed here) was a randomized, blinded, parallel-group phase 3 study examining the effect of aprocicentan, a dual ETA-1 (a and b) versus placebo added to a three drug regimen for hypertension. There was consistent but modest improvement in systolic blood pressures (-3.7 to -5.9 mmHg) over a 4 week period. Fluid retention was the most common adverse event (9.1% with 12.5 mg, 18.4% with 25 mg, and 2.1% with placebo) and 10 out of 488 patients on aprocicentan developed heart failure compared to 1 out of 242 on placebo. It will be interesting to see how aprocicentan find a role in resistant hypertension given the adverse events and modest effect on blood pressure.
IgA nephropathy: Sparsentan, a dual endothelin A/ renin-angiotensin antagonist (DEARA) has shown promising results in IgA nephropathy. The PROTECT trial (Heerspink et al, Lancet 2023, discussed here) compared sparsentan (dosed at 400 mg) to irbesartan (300 mg) in a randomized, double-blind, phase 3 trial in participants with an eGFR >30 ml/min. The interim analysis of PROTECT at 36 weeks showed early (at 4 weeks) and sustained reduction in proteinuria in the sparsentan group as compared to the irbesartan group (↓uPCR -49.8% vs 15.6% respectively, p<0.0001) among patients with IgAN with higher risk of progression (proteinuria > 1g/day despite maximized RASi for 12 weeks). These results have catapulted a fast-track approval status for the drug from the FDA for the management of IgAN. More recently, the two year outcome from this study (Rovin et al, Lancet 2023) reported that participants on sparsentan had sustained reduction of proteinuria and though the decline of total GFR slope results just missed the significance threshold.
Focal and segmental glomerulosclerosis (FSGS): The phase 2 randomized, double-blind trial (DUET, Trachtman et al, JASN 2018) which compared sparsentan to irbesartan in participants with biopsy proven FSGS, eGFR > 30 ml/min and proteinuria showed initial promising results of a significant reduction in proteinuria in the sparsentan group compared to those on irbesartan (47% vs 19%) with no significant increase in AEs (apart from expected hypertension and edema being higher in the former group but not resulting in study withdrawal). Unfortunately though, the large phase 3 follow-on trial of 371 participants (DUPLEX, Rheault et al, NEJM 2023; discussed here) did not show a significant difference in the eGFR slopes between the two groups. The fact that FSGS is a heterogeneous group and that 20% of participants did not receive RASi were major critiques of this otherwise well conducted study. Needless to say, there was no fast-tracked FDA approval for sparsentan in FSGS.
Proteinuric CKD: Learning from the debacle of the SONAR trial, the ZENITH CKD (Tuttle et al, Lancet 2023 | NephJC summary) was designed to minimize ETA adverse effects by adding on an SGLT2i, empagliflozin. The part A demonstrated that they had got the doses all wrong, allowing a much lower dose (0.25 and 1.5 mg) of the ETA, zibotentan, to be tested in the phase 2, part B trial. This resulted in a significant reduction in albuminuria in proteinuric CKD (~ 60% diabetes) over 12 weeks, more than with empagliflozin alone. The addition of a flozin ameliorated some of the adverse effects of the ETA in this carefully chosen population (no heart failure, no BNP > 200 etc) but despite this, more than a quarter needed to discontinue even in this short trial. A phase 3 trial (ZENITH High Proteinuria) with 1500 patients is ongoing.
7. HCTZ doesn’t prevent stones (NOSTONE)
Mythbusters part deux, leaving no stone (and nephrology paradigm) unturned in 2023. Older, low quality studies indicated that thiazide diuretics reduced recurrent kidney stones in patients with hypercalciuria. And this has been recommended by doctors for decades. It is certainly biologically plausible as thiazides decrease urinary calcium excretion. But dogma trembled as the NO-STONE (a high quality, double-blinded, adequately powered) RCT took another look.
NO-STONE tested placebo versus hydrochlorothiazide (HCTZ) at 3 separate doses (12.5 mg, 25 mg, and 50 mg), in adults with recurrent calcium-containing stones. It recruited 416 participants in Switzerland, and followed them for a median follow-up of 2.9 years, including baseline and ‘finish line’ CT imaging. There was no difference in the composite primary outcome of symptomatic or radiological kidney stone recurrence, but as expected the thiazides did cause more hypokalaemia, gout and diabetes than placebo. This study suggests that using thiazides alone for kidney stone prevention, especially at the lower dose, is ineffective.
There are reasonable concerns that we shouldn’t generalize from this trial to everyone – for starters the vast majority of participants were white men with reasonably high sodium intake, which may diminish any positive effect of HCTZ. Another criticism is that the lower radiological recurrence with higher dose HCTZ treatment (~33% with 25/50mg HCTZ versus 49% with placebo) could be more important than sold, so possibly the symptomatic stone rate could have become lower with HCTZ if the trial had been continued longer – you can read a full critique here (Curhan, CJASN 2023). However, no matter how you analyze NO-STONE, it was obviously disappointing for us and our patients that a treatment with such previous widespread acceptance was such a dud within the confines of this well done trial.
8. CONVINCE: Hemodiafiltration is better than hemodialysis (or is it?)
By Cristina Popa, COI: doing convection in chronic and acute settings
Hemodialysis was the shining beacon in the ‘40s when Kolff unveiled the first hemodialysis (HD) machine. Fast forward 80 years, and we’ve decked it out with fancier vascular access, snazzy biocompatible filters, and a broadened dialysis access. However, we realize it’s like putting a band-aid on numbers, while grappling with a mortality rate reminiscent of breast, colorectal or prostate cancer (Naylor KL et al, Am J Kidney Dis, 2019). We tried our best to make hemodialysis cooler (didn’t work, see MY TEMP), searched for more adequately answers in Kt/V (see HEMO study), while playing by the same rules of osmosis and diffusion. Are we naïve to expect better results? What if we add the more physiological convection to the mix? (See tweetorial by Joel Topf). From previous trials comparing HD with high flux hemodiafiltration (HF-HDF), only ESHOL (Maduell et al, JASN 2013) reported a decrease in all-cause mortality. Importantly, ESHOL was also the only RCT where patients achieved convection volumes of 23 L/session. Though the dose of urea removal doesn’t seem to matter, could convection volume matter when it comes to HDF benefit? CONVINCE set out to examine this (Blankenstijn PJ, et al, NEJM, 2023 | NephJC summary). It was a pragmatic RCT, with a median follow up of 30 months, that randomized 1360 patients to HD vs HF-HDF arms. It delivered a lower death from any cause in the HDF group (17.3% vs 21.9%), with a HR of 0.77, 95% CI, 0.65- 0.93. Some nephrologists hovering between realism and pessimism, quickly point out CONVINCE’s shortcomings. Due to COVID, the trial was unable to recruit the 1800 patients demanded by the power analysis. Additionally the cohort was both younger (mean age 62 years) and healthier (only ⅓ patients had diabetes, 40% had CV diseases) than anticipated. This meant that many secondary end point such as CV mortality were not significant. Looking through underpowered trial goggles, a recent analysis reveals an unsettling fragility index- only 3 participants could flip the results from significant to non-significant. (Battaglia Y et al, Nephrol Dial Transplant, 2024)
For now, it seems nephrologists who did HDF will continue doing HDF and change public policies (in Romania, one of the CONVINCE recruiting places, the percentage of reimbursed HDF increased after the trial’s results were published). The counterpart, the unCONVINCEd party will continue wondering if HDF is the better method, while maybe secretly wishing to have access to it. While we wait for the results of H4RT, which included a more diverse population, we underline the importance of the still-awaited economic analysis, the perspective of the patients (PROMs analysis also awaited), and the green nephrology angle.
9. Balanced Fluids best Saline in Transplant
By Tom Oates
It’s sometimes tempting to see the world of RCTs as one where increasingly expensive drugs are evaluated in big market chronic diseases by studies paid for by companies, written up by agencies, and badged up for journals by high recognition KOLs. If this temptation strikes you, dilute your cynicism with an infusion of IV fluid RCTs: SMART, SALT-ED, SPLIT, BASICS, PLUS, all published in the last 6 or so years, have randomized in excess of 47,500 patients to try and answer a question we, and maybe all doctors, have wrestled with at some stage - which IV fluid is best?
Whilst that question is too vague to ever be answerable, the BEST-Fluids trial (Collins et al Lancet 2023) joined the list of fluid trials above in 2023. Even better, it was just for *us*, the true IV fluid nuts, in nephrology. It enrolled 808 participants undergoing deceased donor transplantation in Australia/New Zealand, and randomized their initial 48-hour of fluid replacement to either saline or plasmalyte. The primary outcome of delayed graft function was seen in fewer patients given plasmalyte with a relative risk of 0.74. There was clear separation in chloride, bicarb and pH between the two groups, but no difference in potassium. A host of secondary endpoints to do with graft function and mortality, and adverse events, were all similar.
Which IV fluid is best? Well if you want to avoid DGF, it’s probably not normal saline.
10. Inaxaplin phase 1 trial in APOL1 mediated kidney disease
By Tiffany Caza
APOL1-mediated kidney disease (AMKD) is a leading cause of proteinuric chronic kidney disease and end-stage renal disease in patients of African ancestry, and until recently, no targeted therapeutics were on the horizon. AMKD disease affects patients with homozygosity or compound heterozygosity for G1 or G2 genomic risk alleles in the APOL1 gene (Genovese at al, Science 2010) following an environmental trigger that serves as a second hit. The pathogenesis underlying AMKD involves a toxic gain of function by G1 and/or G2 APOL1 expression within podocytes, which induces formation of pores (Olabisi et al, PNAS 2016) in the podocyte cell membrane. This is mediated by ion flux through this pore channel. A small molecule inhibitor against this channel, inaxaplin, specifically blocks these ion currents. In a mouse model (APOL1 G2/G2 transgenic mouse), inaxaplin reduced interferon-gamma induced proteinuria.
Rapidly moving to human studies, a phase 2a open label clinical trial was performed to evaluate the safety and efficacy of inaxaplin (Egbuna et al, NEJM 2023). Sixteen adults with biopsy-proven focal and segmental glomerulosclerosis, a high-risk APOL1 genotype and proteinuria of 0.7 to 10 g/day were treated with the drug for 13 weeks. Thirteen patients completed the study, and 12 had significant proteinuria reduction (average of 47.6%). One-month after stopping the drug, the proteinuria was still reduced by 30%. The study met its primary endpoints and holds promise for a targeted therapy for AMKD.
A phase 2/3 double-blind, placebo-controlled clinical tria, the AMPLITUDE study (clinicaltrials.gov NCT05312879), is currently enrolling patient to further evaluate inaxaplin in adult and pediatric patients. For further discussion, check out the full NephJC summary and Freely Filtered episode.
