Finerenone for Cardiorenal Protection in Diabetic CKD: Impact on Renal Function Decline and Heart Failure
Phase: NA
Conditions: Diabetic Kidney Disease (DKD), Heart Failure
Sponsor: College of Physicians and Surgeons Pakistan

Finerenone for Cardiorenal Protection in Diabetic CKD: Impact on Renal 
Function Decline and Heart Failure 
Introduction: 
The parallel rise in chronic kidney disease (CKD) and type 2 diabetes mellitus (T2D) has 
emerged as a major global health challenge, contributing substantially to premature mortality and 
reduced quality of life.1,2 Epidemiological data suggest that the age-standardized mortality rate 
attributable to diabetic CKD more than doubled between 1990 and 2013, while individuals with 
early-stage CKD and T2D may experience a reduction in life expectancy of up to sixteen years.3,4 
Cardiovascular (CV) events remain the predominant cause of death in this population, with 
estimates indicating a sixfold increase in CV mortality compared with the general population. 
Among these, sudden cardiac death frequently accounts for a considerable proportion of overall 
CV fatalities. Declines in estimated glomerular filtration rate (eGFR) and the persistence of 
albuminuria have been independently associated with heightened risks of both all-cause and CV 
mortality, emphasizing the clinical importance of maintaining renal function.5 In addition, 
infections and certain malignancies appear to contribute, albeit to a lesser extent, to the overall 
mortality burden among patients with diabetic kidney disease.6,7 
Pharmacologic interventions targeting the renin–angiotensin–aldosterone system (RAAS), such 
as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), 
have long been established as standard therapy for slowing CKD progression and controlling 
hypertension in individuals with T2D.8 However, despite their renoprotective effects, these 
agents have shown limited capacity to reduce all-cause mortality.9 Mineralocorticoid receptor 
antagonists (MRAs) offer additional cardiorenal benefits, yet the clinical use of traditional 

steroidal MRAs, including spironolactone and eplerenone, is frequently constrained by adverse 
effects such as hyperkalaemia, breast tenderness, and gynaecomastia10. 
Finerenone, a newer nonsteroidal MRA, has been developed to address these limitations. Its 
higher receptor selectivity and favorable safety profile enable effective cardiorenal protection 
with a reduced risk of hyperkalaemia and the absence of hormonal side effects. Evidence from 
the pivotal Phase III trials—FIDELIO-DKD and FIGARO-DKD—demonstrated that finerenone 
significantly reduces the risk of kidney disease progression and CV events when added to 
optimized ACEI or ARB therapy. Subsequent analyses indicated that these clinical benefits are 
largely independent of changes in metabolic or hemodynamic parameters, with only modest 
blood pressure reduction contributing to the observed outcomes. The pooled FIDELITY analysis, 
encompassing more than 13,000 participants across the CKD spectrum, provided comprehensive 
evidence supporting finerenone’s efficacy in reducing both renal and cardiovascular mortality. 
Collectively, these findings underscore finerenone’s emerging role as an evidence-based 
therapeutic option in the integrated management of diabetic CKD.11,12 
This study, therefore, seeks to evaluate the clinical effectiveness and safety of finerenone in 
routine practice, providing context-specific evidence to guide therapeutic decision-making and to 
strengthen the continuum of cardiorenal protection in diabetic kidney disease. 
OBJECTIVE: 
To assess the effect of Finerinone on slowing renal function decline and improving 
cardiovascular outcomes, particularly heart failure risk, in patients with diabetic CKD. 
OPERATIONAL DEFINITIONS: 

●​ Chronic Kidney Disease (CKD):​
 Defined by an estimated glomerular filtration rate (eGFR) of 25–<75 mL/min/1.73 
m² and/or albuminuria, quantified as a urine albumin-to-creatinine ratio (UACR) ≥30 
mg/g. 
●​ Renal Function Decline:​
 Progressive worsening of kidney function is defined as a sustained ≥40% reduction in 
eGFR from baseline, progression to kidney failure (ESKD), or renal death. 
●​ End-Stage Kidney Disease (ESKD):​
 Defined as initiation of chronic dialysis or kidney transplantation, or a sustained 
eGFR <15 mL/min/1.73 m². 
●​ Heart Failure (HF) Event:​
Defined as hospitalization for new or worsening heart failure, confirmed by clinical 
evidence of fluid overload and the requirement for intravenous therapy or hemodynamic 
support. 
●​ Cardiovascular (CV) Event:​
 Includes CV death, non-fatal myocardial infarction, non-fatal stroke, or 
hospitalization for heart failure (HHF) — forming the composite cardiovascular 
outcome measure in the finerenone studies. 
●​ Finerenone Therapy:​
Finerenone is a selective, non-steroidal mineralocorticoid receptor antagonist 
(ns-MRA) administered orally at 10–20 mg once daily. The dose is titrated based on 
serum potassium and eGFR, and therapy is used in addition to a maximally tolerated 
ACE inhibitor or ARB. 

●​ Hyperkalaemia:​
Defined as a serum potassium level >5.5 mmol/L, which served as a safety threshold 
for dose adjustment or discontinuation in the parent trial data. 
●​ Albuminuria:​
Measured as urinary albumin-to-creatinine ratio (UACR), with categories of 
moderately increased (30–300 mg/g) and severely increased (>300 mg/g) albuminuria, 
per KDIGO classification used in the trial protocols. 
●​ eGFR Measurement:​
Estimated glomerular filtration rate calculated using the CKD-EPI formula, 
standardized for body surface area (mL/min/1.73 m²). 
 
MATERIALS AND METHODS: 
Study Design: Single Arm Before/After Trial.  
Study setting: Department of Medicine Unit Nishtar Medical University & Hospital Multan. 
Duration of Study: 06 months after approval of synopsis. 
Sampling technique: Non-probability consecutive sampling. 
Sample Size: 88 
The sample size was calculated using the paired t-test formula for a within-subject continuous 
outcome, taking mean change in estimated glomerular filtration rate (eGFR) as the primary 
variable. Assuming an expected mean paired difference of 3 mL/min/1.73 m² with a standard 
deviation of 10 mL/min/1.73 m², a two-sided significance level (α) of 0.05, and a statistical 
power of 80 %, a minimum of 88 evaluable patients would be required. To compensate for an 
anticipated 20–25 % attrition rate and to improve precision of estimates, the target enrolment will 

be 120 patients. This sample size is considered adequate for detecting a clinically meaningful 
change in eGFR over 12 months in patients with type 2 diabetes and chronic kidney disease 
receiving finerenone in addition to standard renin–angiotensin system inhibition. 
SAMPLE SELECTION: 
Inclusion Criteria: 
●​ Adults aged ≥18 years. 
●​ Diagnosed cases of type 2 diabetes mellitus. 
●​ Chronic kidney disease with eGFR 25–90 mL/min/1.73m² and/or UACR ≥30 mg/g. 
●​ On stable ACE inhibitor or ARB therapy for at least 4 weeks. 
●​ Serum potassium ≤4.8 mmol/L. 
●​ Provided written informed consent. 
Exclusion Criteria: 
●​ Symptomatic heart failure (NYHA class II–IV). 
●​ eGFR <25 mL/min/1.73m² or on maintenance dialysis. 
●​ Known non-diabetic kidney disease. 
●​ Recent major cardiovascular event (within 30 days). 
●​ Serum potassium >4.8 mmol/L or history of severe hyperkalaemia. 
●​ Contraindication or hypersensitivity to finerenone. 
●​ Pregnancy or lactation. 
●​ Any condition limiting compliance or follow-up. 
DATA COLLECTION: 
​
After approval of the synopsis, patients fulfilling the inclusion criteria will be enrolled 
from the nephrology and cardiology departments. Baseline data including demographic details 

(age, gender, BMI), duration of diabetes, blood pressure, comorbid conditions, and current 
medications will be recorded. Laboratory investigations such as serum creatinine, eGFR, urine 
albumin-to-creatinine ratio (UACR), serum potassium, HbA1c, and lipid profile will be obtained 
at baseline and at each follow-up visit. Patients will be followed at 1, 3, and 6 months for 
reassessment of renal function and occurrence of heart failure events. All data will be 
documented on a structured proforma specifically designed for this study. (Annexure-I). 
DATA ANALYSIS PLAN: 
Data will be analyzed using SPSS version 29. Continuous variables including age, systolic and 
diastolic blood pressure, eGFR, urine albumin-to-creatinine ratio (UACR), serum potassium, and 
HbA1c will be expressed as mean ± standard deviation, while categorical variables such as 
gender, presence of hypertension, and occurrence of heart-failure hospitalization will be 
presented as frequency and percentage. The primary outcome will be the mean change in eGFR 
from baseline to 6 months. Paired t-test or repeated-measures ANOVA will be applied for 
within-subject comparisons of continuous variables, and logistic regression will be used to 
explore predictors of renal function decline. Correlation analyses will assess relationships 
between change in eGFR, UACR, and serum potassium. Kaplan–Meier survival analysis and 
Cox proportional hazards regression will be performed for time to first heart-failure 
hospitalization where applicable. A p-value < 0.05 and 95 % confidence intervals will be 
considered statistically significant. 
 
References: 
1.​ Li H, Lu W, Wang A, Jiang H, Lyu J. Changing epidemiology of chronic kidney disease as a 
result of type 2 diabetes mellitus from 1990 to 2017: estimates from Global Burden of Disease 
2017. Journal of diabetes investigation. 2021 Mar;12(3):346-56. 

2.​ Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, de Boer IH. Kidney 
disease and increased mortality risk in type 2 diabetes. Journal of the American Society of 
Nephrology. 2013 Feb 1;24(2):302-8. 
3.​ Collaborators GB. Global, regional, and national age–sex specific all-cause and cause-specific 
mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of 
Disease Study 2013. The Lancet. 2015;385(9963):117-71. 
4.​ Wen CP, Chang CH, Tsai MK, Lee JH, Lu PJ, Tsai SP, Wen C, Chen CH, Kao CW, Tsao CK, Wu 
X. Diabetes with early kidney involvement may shorten life expectancy by 16 years. Kidney 
international. 2017 Aug 1;92(2):388-96. 
5.​ Charytan DM, Fishbane S, Malyszko J, McCullough PA, Goldsmith D. Cardiorenal syndrome 
and the role of the bone-mineral axis and anemia. American Journal of Kidney Diseases. 2015 
Aug 1;66(2):196-205. 
6.​ Cheung CY, Ma MK, Chak WL, Tang SC. Cancer risk in patients with diabetic nephropathy: a 
retrospective cohort study in Hong Kong. Medicine. 2017 Sep 1;96(38):e8077. 
7.​ Charytan DM, Lewis EF, Desai AS, Weinrauch LA, Ivanovich P, Toto RD, Claggett B, Liu J, 
Hartley LH, Finn P, Singh AK. Cause of death in patients with diabetic CKD enrolled in the trial 
to reduce cardiovascular events with aranesp therapy (TREAT). American Journal of Kidney 
Diseases. 2015 Sep 1;66(3):429-40. 
8.​ de Boer IH, Caramori ML, Chan JC, Heerspink HJ, Hurst C, Khunti K, Liew A, Michos ED, 
Navaneethan SD, Olowu WA, Sadusky T. KDIGO 2020 clinical practice guideline for diabetes 
management in chronic kidney disease. Kidney international. 2020 Oct 1;98(4):S1-15. 
9.​ Sarafidis PA, Stafylas PC, Kanaki AI, Lasaridis AN. Effects of renin–angiotensin system blockers 
on renal outcomes and all-cause mortality in patients with diabetic nephropathy: an updated 
meta-analysis. American journal of hypertension. 2008 Aug 1;21(8):922-9. 
10.​Agarwal R, Kolkhof P, Bakris G, Bauersachs J, Haller H, Wada T, Zannad F. Steroidal and 
non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. European heart 
journal. 2021 Jan 7;42(2):152-61. 
11.​ Rossing P, Burgess E, Agarwal R, Anker SD, Filippatos G, Pitt B, Ruilope LM, Gillard P, 
MacIsaac RJ, Wainstein J, Joseph A. Finerenone in patients with chronic kidney disease and type 
2 diabetes according to baseline HbA1c and insulin use: an analysis from the FIDELIO-DKD 
study. Diabetes Care. 2022 Apr 1;45(4):e888-97. 
12.​Ruilope LM, Agarwal R, Anker SD, Filippatos G, Pitt B, Rossing P, Sarafidis P, Schmieder RE, 
Joseph A, Rethemeier N, Nowack C. Blood pressure and cardiorenal outcomes with finerenone in 
chronic kidney disease in type 2 diabetes. Hypertension. 2022 Dec;79(12):2685-95. 

 
Principal Investigator  
Dr. Muhammad Awais Danish 
 
Supervisor  
Prof Dr. Muhammad Zafar Iqbal 
 
 
 
 
 
 
 
 

CONSENT FORM 
Finerenone for Cardiorenal Protection in Diabetic CKD: Impact on Renal 
Function Decline and Heart Failure 
 
I--------------------------------- S/D/W/ of ------------------------------- acknowledge that I have been 
informed in detail about the research titled “Finerenone for Cardiorenal Protection in 
Diabetic CKD: Impact on Renal Function Decline and Heart Failure” I am also informed 
regarding the purpose, nature, aims and objectives of the study. All the information in this study 
will be kept confidential and my name and other data will be utilized only for research purposes. 
I have been informed that I can be asked any type of question related to study. I have also been 
informed that this research is not just for the benefit of a single person but for the humanity at 
large. If after briefing I refuse to participate there will be no obligation on my side.  I shall be 
treated in routine. I may withdraw my name anytime from study and I shall not be forced to 
continue.  I give my consent and willingness to consider myself in this study.  
 
Name of Patient; --------------------------------- 
Signature / thumb impression; -------------------------------- 
Date; ------------------------------------------------------------- 
Counseling Doctor; 
Name;------------------------------------------ 
Designation; - ------------------------------- 
Signature; ------------------------------------- 
 

اجازت نامہ براۓ تحقیق میں شرکت 
Finerenone for Cardiorenal Protection in Diabetic CKD: Impact on Renal 
Function Decline and Heart Failure 
 
 

ANNEXURE-I 
Finerenone for Cardiorenal Protection in Diabetic CKD: Impact on Renal 
Function Decline and Heart Failure 
 
Serial No. 
Serial No. 
Details / 
Units / 
Code 
Baseline 
1 Months 
3 Months 
6 Months 
1 
Study ID / 
Hospital 
No. 
 
 
 
 
 
2 
Age (years) 
 
 
 
 
 
3 
Gender 
☐ Male ☐ 
Female 
 
 
 
 
4 
Body Mass 
Index 
(kg/m²) 
 
 
 
 
 
5 
Duration of 
Diabetes 
(years) 
 
 
 
 
 
6 
Duration of 
CKD (years) 
 
 
 
 
 
7 
Blood 
Pressure 
(mmHg) 
 
 
 
 
 
8 
HbA1c (%) 
 
 
 
 
 
9 
Serum 
Creatinine 
(mg/dL) 
 
 
 
 
 
10 
Estimated 
GFR 
(mL/min/1.
73 m²) 
CKD-EPI 
 
 
 
 
11 
Urine 
Albumin-to-
Creatinine 
Ratio 
 
 
 
 
 

(UACR) 
(mg/g) 
12 
Serum 
Potassium 
(mmol/L) 
 
 
 
 
 
13 
Lipid Profile 
(TC / LDL / 
HDL / TG) 
 
 
 
 
 
14 
Finerenone 
Dose 
(mg/day) 
10 mg ☐ 20 
mg ☐ 
 
 
 
 
15 
Use of 
ACEi/ARB 
☐ Yes ☐ 
No 
 
 
 
 
16 
Use of 
SGLT2 
inhibitor 
☐ Yes ☐ 
No 
 
 
 
 
17 
Presence of 
Hypertensio
n 
☐ Yes ☐ 
No 
 
 
 
 
18 
History of 
Heart 
Failure 
☐ Yes ☐ 
No 
 
 
 
 
19 
Hospitalizat
ion for 
Heart 
Failure 
☐ Yes ☐ 
No Date: 
____ 
 
 
 
 
20 
Occurrence 
of 
Hyperkalae
mia (K⁺ > 
5.5 
mmol/L) 
☐ Yes ☐ 
No 
 
 
 
 
21 
Drug 
Discontinua
tion / 
Adverse 
Events 
Specify: 
__________ 
 
 
 
 
22 
Remarks / 
Investigator 
Notes