A FINE time to be a nephrologist

Nephrologists are keenly aware of the need for improved management of chronic kidney disease (CKD). It is the ninth leading cause of death worldwide; in the UK, 7.2 million people (more than 10% of the population) are living with CKD at an estimated annual economic burden of £7 billion.¹ The projected burden to patients, NHS and the economy emphasises the urgent need for early detection and optimised management to prevent progression to end-stage kidney disease (ESKD). 

Current guidelines recommend renin–angiotensin–aldosterone system inhibitors (RAASi) and sodium–glucose cotransporter 2 inhibitors (SGLT2is) as first-line drugs to slow progression of CKD in patients with and without type 2 diabetes.² FIDELIO-DKD demonstrated that the non-steroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone was able to ameliorate the residual risk of progression, but the drug has previously only been licensed for patients with type 2 diabetes.³ Whilst diabetes is the dominant cause of CKD in most countries, over 50% of incident ESKD is caused by other diseases. SGLT2is are contraindicated in individuals with type 1 diabetes, leaving a large proportion of the population with an unmet need.⁴ 

However, finerenone’s renoprotective mechanisms of action are not specific to diabetic kidney disease; much like SGLT2is before it, it was therefore hypothesised to be beneficial in non-diabetic CKD.⁵ FIND-CKD sought to address this query.⁶

In the FIND-CKD study, investigators screened 3231 patients across 24 countries. A total of 1584 people living with CKD but without diabetes, already on a stable, maximally tolerated RAASi dose, were randomised to receive either finerenone (10 mg or 20 mg) or placebo in a 1:1 ratio. To be eligible, participants had to have either an eGFR 25–29 mL/min/1.73 m² with a uACR between 200–500 mg/g (approximately 22–56 mg/mmol) or an eGFR 25–89 mL/min/1.73 m² with a uACR 300–3500 mg/g (approximately 34–400 mg/mmol). People with pre-existing diabetes or dysglycaemia were excluded, as were those with uncontrolled hypertension, symptomatic heart failure with reduced ejection fraction, polycystic kidney disease and those with lupus nephritis, ANCA-associated vasculitis or any other kidney disease requiring immunosuppression in the preceding 6 months. 

Participants were randomised with their screening uACR and SGLT2i use as stratification factors. They were commenced on either 10 mg or 20 mg daily according to screening eGFR and, if commenced on the lower dose, were uptitrated after one month, provided their serum potassium was ≤4.8 mmol/L and their eGFR had not fallen >30% from the previous visit. Patients were treated for at least 32 months (median 36.6 months), during which finerenone could be dose-reduced at any point for safety reasons or withheld for 72 hours if the serum potassium rose above 5.5 mmol/L and restarted at a lower dose once potassium had fallen to ≤5 mmol/L. 

The study group populations were well matched for clinical characteristics and concomitant medications at baseline. Overall, the mean age was 54.7 years (standard deviation [SD], 14.3), 66.2% of participants were male and 54.7% were Asian. The most common aetiologies of CKD were hypertension (29.0%), IgA nephropathy (26.3%) and focal segmental glomerulosclerosis (13.6%), with IgA being the dominant cause in Asia and hypertension predominant in the rest of the world. Baseline mean eGFR was 46.7 mL/min/1.73 m² (SD, 16.1), mean serum potassium was 4.5 mmol/L (SD, 0.4) and median uACR was 818.9 mg/g (interquartile range [IQR], 577.4–1244.0). A total of 53.3% of participants had an eGFR <45 mL/min/1.73 m² and 37.4% had a uACR >1000 mg/g (113 mg/mmol).⁷

Treatment with finerenone significantly slowed the mean annual rate of eGFR decline over 32 months (−3.3 mL/min/1.73 m² compared with −4.0 mL/min/1.73 m² in the placebo group). During the 3-month treatment-initiation phase, finerenone was associated with an initial 1.2 mL/min/1.73 m²greater decline in eGFR decline, with a corresponding recovery in the follow-up phase after treatment was discontinued. Those receiving finerenone were 33% less likely to experience a composite kidney or cardiovascular event (i.e. a sustained decrease in eGFR of 57%, kidney failure, hospitalisation for heart failure or cardiovascular death) (hazard ratio [HR], 0.77 [95% CI, 0.60 to 0.99; P=0.04]). The HR for finerenone was 0.78 (95% CI, 0.60 to 1.01) for the composite of two kidney events and 0.60 (95% CI, 0.27 to 1.33) for the composite of two cardiovascular events. A total of 56% of participants receiving finerenone had a reduction in uACR of ≥30%, compared with 24% of those receiving placebo. These positive findings were reiterated in a prespecified exploratory subgroup analysis of patients with glomerular disease, including IgA nephropathy, focal segmental glomerulosclerosis and membranous nephropathy.⁸

Finerenone was generally safe and well tolerated. Similar numbers discontinued treatment in the finerenone and placebo groups (157 and 177), with similar proportions stopping because of participant or physician decisions. After an initial modest increase in serum potassium of 0.12 mmol/L during the first month, levels remained stable thereafter. Although hyperkalaemia events were reported more often in the finerenone group than in the placebo group (17.0% vs 13.3%), the overall incidence of serious hyperkalaemic events was <1%. The composite INFINITY analysis, which pooled data from FIDELIO-DKD, FIGARO-DKD and FIND-CKD, confirmed the reassuring safety profile.⁹

It should be recognised that this multinational study was successfully completed despite the extraordinary challenges of the COVID-19 pandemic. Moreover, only four patients were lost to follow-up, which is a remarkable achievement.

We can now celebrate the addition of finerenone to our arsenal of prognostically beneficial medications for CKD, regardless of aetiology. In a related study, finerenone also showed benefit in patients with type 1 diabetes and CKD, with a 25% greater reduction in uACR in the treatment group.¹⁰

The FIND-CKD subgroup analysis of finerenone in glomerular diseases is particularly meaningful as glomerulonephritides are a leading cause of renal disease, but many have few specific disease-directed therapies available to them, especially focal segmental glomerulosclerosis. However, questions remain as to the efficacy of finerenone in patients with lupus, ANCA vasculitis and those on immunosuppression.

Despite the wide geographical distribution of recruitment, only 37 (2.3%) of participants were Black or African–American. This is particularly disheartening given the  disproportionate burden of CKD in this ethnic group, which has also been historically under-served and under-represented in clinical trials.^11,12

It should also be noted that recruitment began prior to the implementation of guidelines recommending SGLT2is for CKD, so only 17% of participants were prescribed an SGLT2i. However, subgroup analysis suggests that finerenone conferred equally protective benefits in those participants taking both RAASi and SGLT2i and in those taking RAASi alone. 

We should anticipate a study examining the combined benefits of finerenone with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The ACHIEVE-2 study led by Welch et al demonstrated improved glycaemic control with the novel once-daily oral GLP-1 RA orforglipron when compared with dapagliflozin in patients with suboptimal control of their type 2 diabetes despite high-dose metformin (see summary here).¹³ Whilst there were no dedicated renal outcomes in this study, our experience with GLP-1 RAs to date demonstrates consistent renoprotective signals across CKD stages and metabolic phenotypes.¹⁴ 

Of course, we need to be able to implement and deliver these novel therapies to our patients early in their disease to prevent progression. This will require increasing integration with our primary care colleagues, efficient and effective delivery of care, and holistic shared care of the cardio-renal-metabolic patient. Dattani et al suggest a potential model for managing this cohort by describing their experiences with the Harrow Hub project in North West London (see summary here).¹⁵

Whilst the challenges of CKD remain substantial, nephrologists should be encouraged by the addition of finerenone to the expanding arsenal of therapeutic options for our patients, and by the dynamic strategies which we are developing with primary care to ensure timely optimisation for the patients we serve.

References

1. Farrimond B, Agathangelou G, Gofman L et al (2023) Kidney disease: A UK public health emergency. Kidney Research UK, London. Available at: https://www.kidneyresearchuk.org/wp-content/uploads/2023/06/Economics-of-Kidney-Disease-full-report_accessible.pdf (accessed 29.06.26)
2. Levin A, Ahmed SB, Carrero JJ et al (2024) Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int 105: 684–701
3. Bakris GL, Agarwal R, Anker SD et al (2020) Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 383: 2219–29
4. Ortiz A, Kramer A, Ariceta G et al (2025) Inherited kidney disease and CAKUT are common causes of kidney failure requiring kidney replacement therapy: an ERA Registry study. Nephrol Dial Transplant 40: 1020–31
5. Zhai S, Ma B, Chen W, Zhao Q (2024) A comprehensive review of finerenone-a third-generation non-steroidal mineralocorticoid receptor antagonist. Front Cardiovasc Med 11: 1476029
6. Heerspink HJL, Neuen BL, Agarwal R et al; FIND-CKD Investigators (2026) Finerenone in persons with chronic kidney disease without diabetes. N Engl J Med 4 Jun [Epub ahead of print]
7. Heerspink HJL, Agarwal R, Bakris GL et al; FIND-CKD Investigators (2025) Design and baseline characteristics of the Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) randomized trial. Nephrol Dial Transplant 40: 308–19
8. Neuen BL, Perkovic V, Agarwal R et al; FIND-CKD Investigators (2026) Finerenone in patients with chronic kidney disease due to glomerular diseases: a randomized clinical trial. JAMA 5 Jun [Epub ahead of print]
9. Neuen BL, Heerspink HJL, Perkovic V et al; FIND-CKD, FIDELIO-DKD and FIGARO-DKD Investigators (2026) Efficacy and safety of finerenone in patients with chronic kidney disease: an individual participant data pooled analysis (INFINITY). Lancet 407: 2375–86
10. Heerspink HJL, Birkenfeld AL, Cherney DZI et al; FINE-ONE Investigators (2026) Finerenone in type 1 diabetes and chronic kidney disease. N Engl J Med 394: 947–57
11. Grobman B, Turkson-Ocran RA, Zhang M, Juraschek SP (2025) Socioeconomic status and chronic kidney disease among black and white adults: An analysis of 2017–2020 NHANES. Kidney Med 7: 101045
12. Alsan M, Campbell RA, Leister L, Ojo A (2025) Investigator racial diversity and clinical trial participation. J Health Econ 100: 102968
13. Welch M, Forst T, Jia W et al; ACHIEVE-2 Trial Investigators (2026) Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial. Lancet 8 Jun [Epub ahead of print]
14. Rico-Fontalvo J, Daza-Arnedo R, Elbert A et al (2026) Renal outcomes of GLP-1 receptor agonists and tirzepatide across CKD stages and metabolic phenotypes (type 2 diabetes and/or overweight/obesity): A scoping review. Diabetes Ther 17: 499–528
15. Dattani R, Rahman R, Siddik S et al (2026) A real-world preventive primary care model for cardiorenal metabolic disease: clinical impact of a personalised care approach in Harrow, North West London. BMC Nephrol 29 May [Epub ahead of print]