Efficacy and safety of finerenone in diabetic kidney disease: Latin American experience from FINDKDLATAM trial

Abstract

BACKGROUND

Patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) face high renal and cardiovascular risks. Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has demonstrated efficacy in reducing these risks in clinical trials. However, its real-world safety and effectiveness remain underexplored in local settings.

AIM

To evaluate the real-world safety and effectiveness of finerenone in patients with T2DM and CKD across seven Latin American countries.

METHODS

We conducted an observational, multicenter, retrospective cohort study based on real-world data in 347 patients with T2DM and CKD [urinary albumin-creatinine ratio (UACR) > 30 mg/g]. Patients received finerenone (10 mg or 20 mg daily), and clinical and laboratory parameters were evaluated at baseline and after six months of treatment.

RESULTS

At baseline, median values (interquartile range) were: Glycated hemoglobin A1c 7.6% (6.8%-8.1%); estimated glomerular filtration rate 39.0 mL/minute/1.73 m² (30.0-50.0); UACR 345 mg/g (189-760); systolic blood pressure 143 mmHg (130-160); diastolic blood pressure 79 mmHg (70-82); and serum potassium 4.4 mmol/L (4.1-4.7). After six months, significant reductions were observed: Glycated hemoglobin A1c to 7.0% (6.5%-7.9%); UACR to 81 mg/g (28-167); systolic blood pressure to 130 mmHg (120-140); and diastolic blood pressure to 73 mmHg (70-80). Serum potassium increased to 4.7 mmol/L (4.3-5.0), while estimated glomerular filtration rate remained stable at 41.6 mL/minute/1.73 m² (27.0-52.0).

CONCLUSION

In our cohort of patients with CKD associated with T2DM, finerenone proved to be an effective short-term therapy for reducing albuminuria, demonstrating very good tolerance and a low risk of hyperkalemia.

Key Words: Finerenone; Chronic kidney disease; Type 2 diabetes; Diabetic nephropathy; Albuminuria; Hyperkalemia

Core Tip: In a real-world observational study of 347 Latin American patients with type 2 diabetes mellitus and chronic kidney disease finerenone demonstrated significant short-term benefits. After six months, treatment led to major reductions in the urinary albumin-creatinine ratio and blood pressure. This efficacy was achieved with very good tolerance; the estimated glomerular filtration rate remained stable, and serum potassium increases were minimal, highlighting a low risk of hyperkalemia. This study provides crucial real-world evidence supporting finerenone’s safety and effectiveness.

INTRODUCTION

Chronic kidney disease (CKD) occurs in approximately 40% of people with type 2 diabetes mellitus (T2DM)[1]. This is defined by the presence of an estimated glomerular filtration rate of less than 60 mL/minute/1.73 m² and/or an albuminuria/creatinuria ratio greater than 30 mg/g, for more than 3 months[2-4]. Most guidelines recommend screening for CKD at least once a year in patients with diabetes mellitus[2]. Globally, diabetic kidney disease (DKD) is the leading cause of CKD and the leading cause of end-stage renal disease[1]. It is estimated that in the year 2021 about 204 million people worldwide aged 20-79 years had CKD due to T2DM[5-7].

Several interrelated factors such as hyperglycemia, dyslipidemia, chronic arterial hypertension, activation of the renin angiotensin system, and inflammation have been implicated in the development of microvascular complications in DKD[8-11]. The active form of the mineralocorticoid receptor is associated with systemic inflammation and CKD progression[12-14]. Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist has emerged as a therapeutic option in the management of DKD[15]. Its development represents a breakthrough in the fight against renal complications associated with T2DM. It has been evaluated in clinical studies such as FIDELIO-DKD and FIGARO-DKD, demonstrating significant reduction in the risk of renal disease progression and cardiovascular events in patients with T2DM and CKD with albuminuria[6,10]. These findings generated an important insight in its role not only in renal protection, but also as a prevention of cardiovascular complications, which is a significant benefit in patients with T2DM[16-18].

In the present study, we analyzed the effects of finerenone on blood pressure, glomerular filtration rate and changes in albuminuria/creatinuria ratio in a population of patients from Latin American countries with a diagnosis of CKD associated with T2DM.

MATERIALS AND METHODS

Type of study

An observational, multicenter study based on real-world data. Patients with a mean age between 55 years and 71 years. The objective of this study is to evaluate the efficacy and safety of the mineralocorticoid receptor antagonist finerenone in seven Latin American countries. All participants were informed in writing about the nature of this study and signed the informed consent form. The study was conducted in accordance with the standards of the Declaration of Helsinki. The Ethics Review Committee was the graduate school of the Faculty of Medical Sciences at the University of San Carlos in Guatemala. During this committee meeting, the ethical components, possible assessments in the use of patient information, and characteristics of the interventions were evaluated; each aspect evaluated was found to be in compliance, and the study was accepted.

Population

Inclusion criteria are adult patients older than 18 years, with a diagnosis of T2DM and CKD with a urinary albumin-creatinine ratio (UACR) > 30 mg/g, relevant history of cardiovascular disease and pharmacological interventions for diabetes-associated CKD.

Intervention

Patients received finerenone in daily doses of 10 mg or 20 mg. Finerenone was prescribed according to standard clinical practice guidelines. The medication costs were covered by the patients’ health insurance providers or national health systems, reflecting a real-world setting rather than a sponsored clinical trial environment. This research received no external funding. Medical care, laboratory tests, and medication were covered by the standard of care/health insurance of the patients. The data collection and analysis were performed by the researchers as part of their academic and clinical duties without additional compensation. No comparison was made with other types of interventions, even though most patients were treated with other pharmacological groups [glucagon-like peptide (GLP)-1, sodium-glucose cotransporter 2, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers].

Statistical analysis

Several CKD-related variables were evaluated, including glycated hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), albuminuria/creatinuria ratio, systolic blood pressure (SBP), diastolic blood pressure (DBP) and serum potassium, at baseline and at six months of treatment. The descriptive analysis of qualitative variables was performed by calculating absolute and relative frequencies. Meanwhile, the analysis of quantitative variables was conducted using the median as the measure of central tendency with its respective interquartile ranges (IQRs) as the measure of dispersion, consistent with the non-parametric distribution of these variables, as estimated by the Kolmogorov-Smirnov test, all quantitative variables exhibited non-parametric behavior. Comparisons of paraclinical parameters between baseline and six months were performed using the Wilcoxon signed-rank test, selected as the non-parametric method for paired samples. To compare qualitative variables, such as clinical outcomes stratified by finerenone dose, the χ² test or Fisher’s exact test was used; the latter was applied when one of the four expected values was less than or equal to 5 in the 2 table × 2 table; a P-value of < 0.05 was considered statistically significant. Finally, heat maps were constructed to show the distribution of patients at baseline and at six months with respect to albuminuria/creatinuria ratio classification and CKD classification.

Ethical considerations

This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki, and it was approved by the local Ethics Committee and teaching reference of the Faculty of Medical Sciences of the University of San Carlos of Guatemala. The consent of the participants was not required for publication.

RESULTS

A total of 347 patients from seven countries in Central and South America were included, all with T2DM, individualized management based on international guidelines and therapy for CKD secondary to T2DM. 55.9% were male, the median age was 65 years (IQR 55-71) and the most frequent age group was under 65 years with 49.9%, followed by those between 65 years and 79 years with 45.2%. Among the relevant personal history, arterial hypertension stood out in 84.7% and cardiovascular diseases in 42.7%; obesity, acute myocardial infarction and smoking were found in less than 50% of the population. Pharmacological treatment included sodium-glucose cotransporter inhibitor (SGLT2i) in 84.4%, renin-angiotensin-system inhibitors (RASSI) 61.1% and GLP-1 21%, while finerenone was used at doses of 10 mg 55.9% and 20 mg 44.1%, Table 1. The combination of drugs firstly showed the use of RASSI + SGLT2i in 43.5%, followed by SGLT2i alone in 21.6%, GLP-1 + SGLT2i in 14.1%, RASSI alone in 11.5% and in proportions lower than 10% the combinations of RASSI + GLP-1 + SGLT2i, finerenone alone, RASSI + GLP-1 and GLP alone were used (Figure 1).

Figure 1 Distribution of prescribed nephroprotective regimens. This bar chart illustrates the frequency of different therapeutic combinations. Dual therapy consisting of renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter inhibitors was the most prevalent regimen (43.5%), highlighting the acceptance of combination therapy over monotherapies or other classes of drugs. RASSi: Renin-angiotensin-system inhibitors; SGLT2i: Sodium-glucose cotransporter inhibitor; GLP-1ra: Glucagon-like peptide-1 receptor agonist.

Table 1 Socio-demographic characteristics and relevant background of study population, median (interquartile rage).

	n	%
Gender
Female	153	44.1
Male	194	55.9
Age	65 (55-71)
< 65 years	173	49.9
65-79 years	157	45.2
≥ 80 years	17	4.9
Relevant background
AHT	294	84.7
Cardiovascular disease1	148	42.7
Obesity	113	32 6
AMI	73	21.0
Smoking	56	16.1
Treatment
SGLT2i	293	84.4
RASSI	212	61.1
GLP-1	73	21.0
Finerenone dosage
10	194	55.9
20	153	44.1

¹Cardiovascular disease: Nonfatal acute myocardial infarction, nonfatal stroke, heart failure, peripheral arterial disease.

AHT: Arterial hypertension; AMI: Acute myocardial infarction; SGLT2i: Sodium-glucose cotransporter inhibitor; RASSI: Renin-angiotensin-system inhibitors; GLP-1: Glucagon-like peptide-1.

When comparing the paraclinical parameters of HbA1c, eGFR, albuminuria/creatinuria ratio, SBP, DBP and potassium at baseline and six months after starting finerenone, we found medians IQRs for HbA1c 7.6 (6.8-8.1), eGFR 39.0 (30.0-50.0), albuminuria/creatinuria ratio 345 (189-760), SBP 143 (130-160), DBP 79 (70-82) and potassium 4.4 (4.1-4.7). The final assessment showed a statistically significant decrease in HbA1c, albuminuria/creatinuria ratio, SBP and DBP with respective medians of 7.0, 81, 130, 73, a significant increase in potassium and with median = 4.7 (IQR 4.3-5.0), while eGFR showed no statistical difference with median = 41.6 (IQR 27.0-52.0; Table 2). Comparative analysis of baseline and final paraclinical stratifying the sample by finerenone dose showed similar behavior in all parameters at both doses except eGFR with finerenone 10 mg where a median baseline of 33 mL/minute/1.73 m² (IQR 28-43) and baseline of 30 (IQR 26-43) were observed, P = 0.0104 (Table 2).

Table 2 Comparison of baseline and final paraclinical parameters in total sample and stratified by finerenone dosage, median (interquartile rage).

	Baseline	Final	P value
General
HbA1c	7.6 (6.8-8.1)	7.0 (6.5-7.9)	0.0000
eGFR	39.0 (30.0-50.0)	41.6 (27.0-52.0)	0.7209
ACR	345 (189-760)	81 (28-167)	0.0000
SBP	143 (130-160)	130 (120-140)	0.0000
DBP	79 (70-82)	73 (70-80)	0.0000
Potassium	4.4 (4.1-4.7)	4.7 (4.3-5.0)	0.0000
Dosage 10
HbA1c	7.8 (7.0-8.1)	7.2 (6.5-8.0)	0.0002
eGFR	33 (28-43)	30 (26-43)	0.0104
ACR	430 (257-898)	90 (24-186)	0.0000
SBP	145 (135-160)	130 (120-133)	0.0000
DBP	80 (70-87)	70 (65-80)	0.0000
Potassium	4.5 (4.2-4.8)	5.0 (4.6-5.2)	0.0000
Dosage 20
HbA1c	7.3 (6.7-8.2)	6.9 (6.5-7.5)	0.0002
eGFR	46 (39-56)	49 (42-58)	0.3321
ACR	267 (153-383)	78 (34-153)	0.0000
SBP	140 (130-156)	134 (122-144)	0.0017
DBP	78 (70-80)	75 (70-80)	0.0048
Potassium	4.4 (4.0-4.6)	4.4 (4.1-4.8)	0.0098

HbA1c: Glycated hemoglobin A1c; eGFR: Estimated glomerular filtration rate; ACR: Albuminuria/creatinuria ratio; SBP: Systolic blood pressure; DBP: Diastolic blood pressure.

Table 3 shows the comparative analysis of the baseline and final paraclinical parameters stratified by age group, which showed similar behavior to that of the general sample in the age groups under 65 years and between 65 years and 79 years, with statistically significant decreases in HbA1c, albuminuria/creatinuria ratio, SBP, DBP, a significant increase in potassium levels and no differences in eGFR values. However, in the age group of 80 years or older, statistical differences were only observed in albuminuria/creatinuria ratio values with median = 297 (IQR 85-430) in the baseline measurement and 6-month median of 27 (IQR 23-125), P = 0.0003. Table 4 shows the baseline behavior of the paraclinical data stratified by the six main drugs used alone or in combination.

Table 3 Comparison of baseline and final paraclinical parameters stratified by age range, median (interquartile rage).

	Baseline	Final	P value
< 65 years
HbA1c	7.8 (6.9-8.3)	7.1 (6.5-7.9)	0.0000
eGFR	42 (30-50)	44 (27-51)	0.3656
ACR	352 (189-750)	90 (29-194)	0.0000
SBP	142 (130-160)	130 (120-140)	0.0000
DBP	78 (70-84)	74 (70-80)	0.0000
Potassium	4.4 (4.0-4.6)	4.6 (4.3-5.0)	0.0000
65-79 years
HbA1c	7.5 (6.7-8.1)	7.0 (6.5-7.9)	0.0027
eGFR	38 (29-49)	40 (29-55)	0.7439
ACR	327 (197-850)	86 (33-150)	0.0000
SBP	145 (134-160)	130 (120-140)	0.0000
DBP	80 (70-82)	72 (70-80)	0.0000
Potassium	4.4 (4.1-4.7)	4.8 (4.4-5.0)	0.0000
≥ 80 years
HbA1c	7.0 (6.4-7.7)	6.9 (6.4-7.0)	0.3292
eGFR	33 (30-50)	32 (27-55)	0.9365
ACR	297 (85-430)	27 (23-125)	0.0003
SBP	130 (124-150)	120 (118-130)	0.0928
DBP	77 (69-80)	70 (64-80)	0.4048
Potassium	4.5 (4.1-4.8)	4.8 (4.5-5.1)	0.0512

HbA1c: Glycated hemoglobin A1c; eGFR: Estimated glomerular filtration rate; ACR: Albuminuria/creatinuria ratio; SBP: Systolic blood pressure; DBP: Diastolic blood pressure.

Table 4 Behavior of baseline paraclinical parameters stratified by drug use, median (interquartile rage).

	Baseline
RASSI + SGLT2i (n = 151)
HbA1c	7.5 (6.8-8.1)
eGFR	44 (35-55)
ACR	288 (156-454)
SBP	142 (130-157)
DBP	79 (70-81)
Potassium	4.4 (4.1-4.6)
SGLT2i alone (n = 75)
HbA1c	7.8 (6.8-8.2)
eGFR	32 (28-40)
ACR	458 (270-900)
SBP	145 (130-150)
DBP	80 (70-86)
Potassium	4.4 (4.1-4.6)
GLP-1 + SGLT2i (n = 49)
HbA1c	7.7 (7.0-8.1)
eGFR	32 (28-44)
ACR	644 (321-950)
SBP	145 (135-160)
DBP	75 (70-86)
Potassium	4.4 (4.0-4.7)
RASSI alone (n = 40)
HbA1c	7.2 (6.6-8.0)
eGFR	46 (34-57)
ACR	266 (161-351)
SBP	145 (131-160)
DBP	79 (72-81)
Potassium	4.4 (4.0-4.8)
RASSI + GLP-1 + SGLT2i (n = 18)
HbA1c	7.1 (6.7-9.0)
eGFR	45 (39-59)
ACR	289 (173-523)
SBP	144 (120-156)
DBP	77 (70-86)
Potassium	4.3 (4.0-4.6)
Finerenone alone (n = 8)
HbA1c	7.5 (5.4-7.7)
eGFR	30 (25-55)
ACR	714 (300-1387)
SBP	133 (127-170)
DBP	78 (73-90)
Potassium	4.8 (4.3-5.0)

RASSI: Renin-angiotensin-system inhibitors; SGLT2i: Sodium-glucose cotransporter inhibitor; GLP-1: Glucagon-like peptide-1; HbA1c: Glycated hemoglobin A1c; eGFR: Estimated glomerular filtration rate; ACR: Albuminuria/creatinuria ratio; SBP: Systolic blood pressure; DBP: Diastolic blood pressure.

The clinical evolution of the patients showed the need for renal replacement therapy in 2.9% of the total sample, while 12.7% had hyperkalemia, 3.8% had to suspend treatment and 1.2% had to do so due to hyperkalemia. When comparing these events between the finerenone dose groups used, the 10 mg group had a higher frequency of hyperkalemia and the need for treatment interruption with 19.6% and 5.7%, respectively, which were higher than those observed in the 20 mg finerenone group, with hyperkalemia frequencies of 3.9%, P = 0.0000, and treatment interruption of 1.3%, P = 0.0335. No differences were observed in the need for renal replacement therapy or in the interruption of treatment due to hyperkalemia (Table 5).

Table 5 Clinical outcome of the overall sample and stratified by finerenone dosage, n (%).

	All (n = 347)	Dosage 10 (n = 194)	Dosage 20 (n = 153)	P value
Required RRT	10 (2.9)	8 (4.1)	2 (1.3)	0.0800
Hyperkalemia	44 (12.7)	38 (19.6)	6 (3.9)	0.0000
Suspended treatment	13 (3.8)	11 (5.7)	2 (1.3)	0.0335
Suspended due to hyperkalemia	4 (1.2)	4 (2.1)	0 (0.0)	0.1333

RRT: Renal replacement therapy.

Tables 6 and 7 show the heat maps of patients’ cardiovascular risk according to eGFR and albuminuria/creatinuria ratio levels at baseline measurement (Table 6) and at six months of treatment (Table 7). Low risk was observed in 0.3% at baseline and 4.1% at six months. High risk was 14.0% in the baseline measurement and 31.2% in the final measurement. Finally, the very high-risk category had a baseline frequency of 93.3% and at six months it was 85.7%, which was statistically significant (P = 0.0004; Figure 2).

Figure 2 Changes in very high-risk stratification: Baseline vs final assessment. Comparison of the proportion of patients classified as very high risk at baseline (blue) vs the final visit (orange). The data demonstrates a statistically significant reduction (93.9% vs 85.7%; P = 0.0004), indicating a favorable shift in risk profile following the intervention period.

Table 6 Heat map for stratifying cardiovascular risk according to glomerular filtration rate and albuminuria/creatinuria ratio in diabetic patients at baseline assessment, n (%).

CKD classification				ACR
				A1 (normal or average increase, < 30 mg/g)	A2 (moderate increase, 30-299 mg/g)	A3 (severe increase, ≥ 300 mg/g)
GFR categories (mL/minute/1.73 m2)	G1	Normal or high	≥ 90	0 (0.0)1	3 (0.9)2	5 (1.5)3
	G2	Average decrease	60-89	1 (0.3)1	15 (4.4)2	18 (5.3)3
	G3	Average to moderate decrease	45-59	2 (0.6)2	43 (12.6)3	44 (12.9)3
	G4	Moderate to severe decrease	30-44	0 (0.0)3	52 (15.2)3	84 (24.6)3
	G5	Severe decrease	15-29	0 (0.0)3	26 (7.6)3	49 (14.3)3
	G6	Kidney failure	< 15	0 (0.0)3	0 (0.0)3	0 (0.0)3

¹Moderate risk.

²High risk.

³Vary high risk.

Severe target organ damage is defined as follows: (1) Estimated glomerular filtration rate < 45 mL/minute/1.73 m² independent of albuminuria; (2) Albuminuria/creatinuria ratio > 300mg/g: (A3) independent of estimated glomerular filtration rate; (3) Estimated glomerular filtration rate 45-59 mL/minute/1.73 m² with albuminuria/creatinuria ratio 30-300 mg/g (A2); and (4) Presence of microangiopathy in at least three locations [e.g., albuminuria (stage A2) retinopathy and neuropathy]. CKD: Chronic kidney disease; GFR: Glomerular filtration rate; ACR: Albuminuria/creatinuria ratio.

Table 7 Heat map for stratifying cardiovascular risk according to glomerular filtration rate and albuminuria/creatinuria ratio in diabetic patients at 6-month assessment, n (%).

CKD classification				ACR
				A1 (normal or average increase, < 30 mg/g)	A2 (moderate increase, 30-299 mg/g)	A3 (severe increase, ≥ 300 mg/g)
GFR categories (mL/minute/1.73 m2)	G1	Normal or high	≥ 90	2 (0.6)1	4 (1.3)2	1 (0.3)3
	G2	Average decrease	60-89	11 (3.5)1	19 (6.1)2	5 (1.6)3
	G3	Average to moderate decrease	45-59	9 (2.9)2	74 (23.6)3	10 (3.2)3
	G4	Moderate to severe decrease	30-44	18 (5.7)3	62 (19.7)3	5 (1.6)3
	G5	Severe decrease	15-29	40 (12.7)3	38 (12.1)3	16 (5.1)3
	G6	Kidney failure	< 15	0 (0.0)3	0 (0.0)3	0 (0.0)3

¹Moderate risk.

²High risk.

³Vary high risk.

Severe target organ damage is defined as follows: (1) Estimated glomerular filtration rate < 45 mL/minute/1.73 m² independent of albuminuria; (2) Albuminuria/creatinuria ratio > 300mg/g: (A3) independent of estimated glomerular filtration rate; (3) Estimated glomerular filtration rate 45-59 mL/minute/1.73 m² with albuminuria/creatinuria ratio 30-300 mg/g (A2); and (4) Presence of microangiopathy in at least three locations [e.g., albuminuria (stage A2) retinopathy and neuropathy]. CKD: Chronic kidney disease; GFR: Glomerular filtration rate; ACR: Albuminuria/creatinuria ratio.

DISCUSSION

CKD and cardio-metabolic conditions often coexist in the same individual, sharing common pathophysiological pathways. This cardiovascular-kidney-metabolic overlap is increasingly recognized, and individual therapies could simultaneously ameliorate multiple related diseases[19-22]. Overactivation of the mineralocorticoid receptor drives inflammation and fibrosis in systemic diseases[23]. Steroid receptor antagonists, such as spironolactone and eplerenone, affect these pathways, but their use is limited, especially in patients with cardiovascular-kidney-metabolic multimorbidity. Gaps in the use of mineralocorticoid receptor antagonists in renal failure are due, in part, to safety concerns such as hyperkalemia and renal impairment[24]. Finerenone is a potent, selective non-steroidal mineralocorticoid receptor antagonist, with lower risks of blood potassium elevation and renal impairment compared to spironolactone. It reduces the risk of cardiovascular events and impairment of renal function in patients with T2DM and CKD with albuminuria[24].

The present study highlights the sample of 347 patients with CKD associated with T2DM, older adults on average, relevant cardiovascular comorbidities where the significant impact of the medicine on the variables studied is evident. Efficacy was initially evaluated at six months, identifying a 76.5% decrease in albuminuria/creatinuria ratio regardless of patient age and with no significant differences in medicine dosage.

This result was twice the magnitude of the decrease in albuminuria reported in other studies[10]. In the study by Bakris et al[10], the average decrease was 31% at 4 months, while in FIGARO-DKD, the average was 32%[6]. Other real-life studies such as that of Hanouneh et al[25], in which a 50% decrease over 8 months in albuminuria was documented in a cohort of 402 patients with CKD.

The mechanisms that could explain the positive effect of finerenone in reducing albuminuria are not fully understood. Blocking of the overactivity of the mineralocorticoid receptor that is expressed in the podocyte, endothelial cells and mesangial cells are reported to have a relevant role. However, the fact that albuminuria decreases in the first months of treatment could imply a possible additional hemodynamic effect that could be contributing. We have proposed two possible hemodynamic mechanisms that could explain this rapid decrease in albuminuria. The first is related to the acute effect observed in the first weeks of treatment with finerenone where an initial drop in glomerular filtration rate was observed, as evidenced in the FIDELIO-DKD and FIGARO-DKD studies, where an initial drop between 2-3 mL/minute was observed, which could attenuate the hyperfiltration state that characterizes patients with DKD, which could limit the amount of albumin that is filtered into the urinary space[23]. The other mechanism that could explain at least in part the early decrease of albuminuria is the effect of finerenone on blood pressure. In the FIDELIO-DKD and FIGARO-DKD studies, only a moderate decrease of 2-3 mmHg in SBP was observed vs placebo, and this could not fully explain the cardiorenal benefits; however, it should be considered that the blood pressure recordings in these studies were only made during medical consultation, which does not allow us to reliably infer the effect of finerenone on blood pressure over a 24-hour period.

The results are comparable with studies such as ARTS DN, a phase 2b study including patients with T2DM and CKD, where continuous ambulatory blood pressure monitoring recording of blood pressure was obtained, and results showed a significant decrease of 8.3-9.9 mmHg at 90 days for doses of 10-20 mg of finerenone, which are related to the decrease in intraglomerular pressure, which explains the filtration of proteins[26,27].

Despite the short half-life of finerenone, there appears to be a sustained effect on blood pressure which does not appear to be explained by pharmacokinetic effects. Therefore, the hypothesis arises that this effect could be related to genomic effects. In our cohort, we found no difference in glomerular filtration rate at baseline and at the end of follow-up, which speaks for the safety of the molecule in the short term, not increasing the risk of acute renal failure or impairment of renal function. Our findings are in line with the results of Agarwal et al[28], who reported an impairment of renal function vs placebo. In comparison to the first- and second-generation mineralocorticoid receptor antagonists, which in their studies (TOPCAT and EMPHASIS-HF) not only did not show benefits in glomerular filtration rate but also remained lower than that of patients assigned to placebo throughout follow-up, in addition to the fact that TOPCAT increased the risk of renal failure by 9% in patients receiving spironolactone[29,30]. Our results show significant decreases in SBP and DBP at six months, confirming these benefits for patients with CKD and AHT, and this would in part be a mediator of the renal efficacy seen in this study.

In the analysis of different subgroups, the trend on efficacy and safety results is consistent, with the exception that the group of patients receiving the 10 mg dose had more episodes of hyperkalemia and suspension of medication due to adverse effects vs those receiving 20 mg. The reason for this is that the patients with lower doses were sicker with lower glomerular filtration rate at baseline, 33 mL/minute vs 46 mL/minute, which were the patients who were receiving 20 mg doses.

Regarding hyperkalemia, in our cohort, the result was 12.7%, with no deaths related to hyperkalemia. The rate of treatment suspension due to episodes of hyperkalemia was also low (only 1.2%), a frequency very similar to that reported in other studies. FIGARO-DKD reported 1.2% vs 0.4% placebo, while FIDELIO-DKD reported 2.3% vs 0.9% placebo.

We also observed a significant improvement in patients’ metabolic control at six months, which could be related to the concomitant use of diabetes medicines, such as SGLT2i (84.4%), GLP-1 receptor agonists (21%), much more significantly than that reported in pivotal studies such as FIDELIO-DKD, where only 4.6% of patients reported using SGLT2i. The higher use of these medicines in our sample has to do with the current trend of prescribing SGLT2i, which are first-line therapy in the management of DKD[2,31].

Similarly, when we compared our study with FINEARTS-HF, which evaluated a sample of 6001 patients with mildly reduced or preserved heart failure, based on their glomerular filtration rate results and the need to start renal replacement therapy or renal transplantation in patients using finerenone vs placebo, we found early and sustained decreases in albuminuria, and above all, a decrease in the occurrence of macroalbuminuria[32]. What is important about the study, compared to ours, is that it was the low-risk population that had adverse renal outcomes.

We cannot fail to mention that in our cohort, cardiovascular risk was also modified at the end of follow-up. At baseline, patients with a very high-risk account for 93.9% of the total sample. At six months that proportion decreased to 85.7% with a statistically significant P-value, a similar finding described in the study by Agarwal et al[28], where a higher odds of improvement in the renal risk category in the Kidney Disease: Improving Global Outcomes heat map of 39% was reported, which allows us to understand that cardiovascular and renal risk is dynamic and bidirectional where a patient can migrate from a lower to a higher risk category and vice versa[33].

Our study has strengths and weaknesses. As a strength we should note that it is the first study to date of publication that has a representative sample of the region that demonstrates the efficacy and safety of finerenone in patients with CKD and diabetes mellitus. Information was obtained from 347 patients, and to date it is one of the real-life studies with the most patients.

The authors recognize several limitations inherent to the retrospective observational design of this study. First, the absence of a randomized control group and the non-randomized selection of participants introduce the potential for selection and information bias. Consequently, causality cannot be established, and we cannot rule out that unmeasured residual confounding influenced the outcomes, although the results are consistent with pivotal studies. Second, the follow-up period was limited to six months; while this duration was sufficient to observe meaningful hemodynamic and short-term metabolic changes (such as albuminuria reduction), it precludes the assessment of long-term hard outcomes, including progression to end-stage renal disease or cardiovascular mortality. Third, reliance on medical records from multiple centers across seven countries may introduce heterogeneity in data collection and laboratory measurement techniques. Finally, while the sample size represents a significant cohort for real-world evidence in Latin America, it is smaller than those of global pivotal trials; therefore, the analysis by subgroup should be considered hypothesis-generating, as the study design may lack sufficient statistical power for such specific stratifications.

CONCLUSION

In our cohort of patients with T2DM and CKD in Latin America, finerenone was shown in a short-term follow-up to be a medicine with low risk of hyperkalemia, demonstrating improvement in blood pressure, decrease in urinary albumin-creatinine ratio and good tolerance. We consider expanding the fields of research in this intervention for the prediction of mortality and improvement of CKD in trials with a larger sample size, studies with a lower risk of bias and comparison of interventions with a good response to the pathology described.