Investigating the Impact of Finerenone on Retinal Vascular Dysfunction in Patients With Chronic Kidney Disease
Phase: PHASE4
Conditions: Retinal Nerve Fiber Layer Thickness, Chronic Kidney Disease
Sponsor: Alexandria University

 
INVESTIGATING THE IMPACT OF 
FINERENONE ON RETINAL 
VASCULAR DYSFUNCTION IN 
PATIENTS WITH CHRONIC KIDNEY 
DISEASE   
 
 
 
MAY 10, 2025 
ALEXANDRIA UNIVERSITY 
      

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Suggested Proposal  
Student Full Name: Merna Mahmoud Mohamed MohyEldin AbouKhatwa 
Student ID: 060982304  
 
 
Faculty: Pharmacy 
Degree: PhD         Department: Clinical Pharmacy and Pharmacy Practice  
Specialty: Clinical Pharmacy 
Proposed Thesis Title: 
Investigating the impact of finerenone on retinal vascular dysfunction in patients 
with chronic kidney disease   
 
Proposal Supervisor Committee: 
Name 
Position 
Affiliation 
Signature 
Prof. Dr. Labiba Khalil El-
Khordagui 
Professor of 
Pharmaceutics 
 
Faculty of Pharmacy, 
Alexandria University 
 
Prof. Dr. Ahmed Fathi El-keraie 
Professor of Internal 
Medicine 
 
Faculty of Medicine, 
Alexandria University 
 
Prof. Dr. Ahmed Abdelkareem 
El-Masry 
Professor of 
Ophthalmology 
Faculty of Medicine, 
Alexandria University 
 
Prof. Dr. Ahmed Fawzy El-Yazbi 
Professor of 
Pharmacology and 
Toxicology 
Faculty of Pharmacy, 
Alexandria University 
Alamein International 
University 
 
Assoc. Prof. Noha Alaa Eldine 
Hassan Hamdy 
Associate Professor 
of Clinical 
Pharmacy 
Faculty of Pharmacy, 
Alexandria University 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Role of Supervisors: 
Role 
Name 
• Main supervisor 
• Supervise the implementation of the research protocol 
• Assist the researcher in analyzing the results 
• Review of the writing of the thesis 
Prof. Dr. Labiba Khalil 
El-Khordagui 
• Follow up on all matters related to the selection of patients and their 
inclusion in the study and recording their data. 
• Help the researcher in measuring the parameters to be measured as 
proposed in the protocol. 
• Participate in the development and implementation of work plan. 
Prof. Dr. Ahmed Fathi 
El-keraie 
• Follow up on all matters related to the selection of patients and their 
inclusion in the study and recording their data. 
• Help the researcher in measuring the parameters to be measured as 
proposed in the protocol. 
• Participate in the development and implementation of work plan. 
Prof. Dr. Ahmed 
Abdelkareem El-Masry 
• Providing guidance on the pharmacological rationale for using 
finerenone in CKD patients. 
• Offering consultation on interim analyses when needed. 
• Providing mentorship, fostering a robust academic and research 
environment. 
• Assisting in the interpretation of study results and contributing to the 
preparation of manuscripts for peer-reviewed journals or conference 
presentations. 
Prof. Dr. Ahmed Fawzy 
El-Yazbi 
• Follow up with the researcher 
• Help in overcoming the obstacles encountered, analyzing the results 
and performing the appropriate statistical analysis. 
• Help the researcher in arranging the results and writing the thesis. 
Assoc. Prof. Noha Alaa 
Eldine Hassan Hamdy 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Introduction  
It has been observed that kidneys and eyes are significantly interlinked, due to the substantial 
overlaps in  pathways of development, structural anatomy, physiological and pathological characteristics 
(Wong et al., 2014, Elias et al., 2016). For instance, the glomerulus and choroid possess comparable 
vascular circulation, and similar pathological mechanisms are involved in the development of CKD and 
many ocular disorders, such as oxidative stress, inflammation, atherosclerosis, endothelial dysfunction 
and vascular remodeling (Nusinovici et al., 2019). Additionally, both diabetic and non-diabetic kidney 
disease patients have been characterized by lower thickness of peripapillary and parafoveal retinal nerve 
fiber layer (RNFL), peripapillary choroidal, and central macular thickness (Balmforth et al., 2016, Basiony 
et al., 2023, Zeng et al., 2021). The risk of retinal vascular disease (RVD), major eye diseases and impaired 
vision has been shown to be significantly increased in patients with CKD (Grunwald et al., 2010, Jonas et 
al., 2017, Lin et al., 2021).Vision impairment and visual loss can be caused by RNFL defects (RNFLDs) 
,which can be non-invasively detected using fundus photography or optical coherence tomography (OCT), 
and significantly associated with other systemic conditions including CKD (Wan et al., 2024). 
Accordingly, it has been suggested that ocular manifestations have been shown to be the mirror of CKD 
development (Benitez-Aguirre et al., 2012, Wong et al., 2004).  
    Finerenone, a novel orally administered selective non-steroidal MRA demonstrates stronger affinity to 
the mineralocorticoid receptor (MR) in comparison with eplerenone and spironolactone resulting in better 
efficacy in aldosterone's inhibition (Palanisamy et al., 2022). As demonstrated by FIDELIO-DKD 
(NCT02540993; n = 5674) and FIGARO-DKD (NCT02545049; n = 7352) randomized phase 3 trials, 
slower progression of CKD and reduced risk of cardiovascular outcomes were associated with 
administration of finerenone versus placebo in patients with CKD and type 2 diabetes (T2D) (Bakris et al., 
2020, Pitt et al., 2021). Based on these trials, clinical practice guidelines recommended finerenone as part 
of the pharmacological treatment to prevent kidney disease progression and cardiovascular events in CKD 
patients with T2D (de Boer et al., 2022, Blonde et al., 2022). Regarding non-diabetic CKD patients, FIND-
CKD trial, a phase 3 randomized controlled trial of finerenone in patients with CKD of non-diabetic 
etiology, verified the safety and efficacy of finerenone in this population (Heerspink et al., 2024). According 
to a recent comprehensive review, finerenone possesses different or superior multiple mechanisms of action 
to traditional MRAs as indicated by both animal and cell-based studies (Zhai et al., 2024). 
      Regarding vision-threatening complications, it was proven using a mouse model of oxygen-induced 
retinopathy (OIR) that finerenone reduced the retinal levels of IL-1β, ICAM-1 and VEGF, vascular leakage, 
retinal neovascularization as well as the density of retinal microglial cells, while increasing regulatory T 
cells (Tregs) in the retina, spleen and blood (Jerome et al., 2023). Finerenone has demonstrated beneficial 
effects in the retina of rodents with diabetes and ischemic retinopathy, reducing the hallmark features of 
vision-threatening vascular injury including neovascularization, in addition to alleviating retinal 
inflammation (Jerome et al., 2023). Moreover, positive effects were achieved in patients with non-
proliferative diabetic retinopathy according to pooled analysis of two studies from clinical trial participants 
(ReFineDR/DeFineDR) (Rossing et al., 2023). However, definitive conclusions could not be drawn as the 
study was exploratory in nature and based on routine ophthalmological examinations. Data reported so far 
suggest that finerenone might be a potential novel oral treatment for patients suffering from retinal vascular 
dysfunction. This can be further confirmed by more randomized clinical trials with adequate power based 
on more comprehensive and accurate functional and structural assessments of retinopathy. 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AIM OF THE STUDY 
To examine the potential protective effects of finerenone compared to standard treatment (based on patient’s 
symptoms and condition) on retinal vascular dysfunction in CKD patients.  
 
PLAN OF THE STUDY 
Study setting: CKD Patients will be recruited from the outpatients’ clinics and/or inpatients wards in 
Alexandria University hospitals and other private hospitals (if possible). 
Study design: Open labelled, prospective, two-arm, parallel group, non-placebo controlled clinical trial. 
Included patients will be divided into 2 parallel groups randomly. 
Treatment arm: will receive oral finerenone in addition to standard treatment.  
Initial dose of finerenone will be determined according to eGFR: 
eGFR>= 60 mL/min: 20 mg once daily. 
eGFR>25 mL/min, <60 mL/min: 10 mg once daily 
eGFR<15 mL/min: use is contraindicated 
Maintenance dose will be determined by the serum potassium level measured 4 weeks after initiation of therapy 
or dose adjustment according to CKD progression. 
 
Control arm: will receive standard treatment according to patient’s condition and symptoms. 
Type of the trial: Open labelled randomized controlled clinical trial with parallel design. 
Inclusion and exclusion criteria  
Inclusion criteria 
✓ Age: above 18 years 
✓ Diabetic and non-diabetic non-hemodialysis CKD patients (Stage 2 – Stage 4). 
Exclusion criteria 
✓ Patients on hemodialysis (HD). 
✓ Serum potassium level > 5.5 mEq/L 
✓ Prior/planned ocular interventions (retinal laser treatment, intravitreal injection or vitrectomy). 
✓ Pregnant and lactating women 
✓ Malignancy 
 
Target population: CKD patients.    
Sample size: Will be calculated using suitable software to achieve the study objective 
 
 
 
  
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Outcome assessment: 
Primary outcomes 
To elucidate the difference in field vision and optical coherence tomography (OCT) metrics 1 month, 3 months 
and 6 months after treatment initiation compared to baseline findings; OCT metrics include macular thickness 
and retinal nerve fiber layer (RNFL) thickness. 
Secondary outcomes  
• To examine the effect on eGFR slope, defined as the mean rate of change in eGFR from baseline to month 6 
of treatment. 
• Mean change from baseline scores of routine laboratory investigations of CKD patients including serum 
creatinine, urea, uric acid, urinary albumin to creatinine ratio (ACR), complete blood count (CBC), and serum 
albumin. 
• Mean change from baseline values of metabolic parameters including random blood glucose (RBG), glycated 
hemoglobin (HbA1C), lipid profile and liver enzymes (ALT and AST) in addition to mean change in body 
weight. 
• To examine the metabolic regulatory effects exhibited by finerenone by measuring the mean change from 
baseline levels of adipokine leptin. 
• Safety will be assessed at all scheduled visits and includes assessment of vital signs and adverse events. 
Hyperkalemia is an adverse event of special interest in this study. Serum potassium and hyperkalemia will be 
characterized through monitoring the change from baseline in serum potassium and identification of the number 
of patients with serum potassium levels >5.5 mmol/L and >6.0 mmol/L. 
 
Type of sample and method of selection: 
Ocular examinations will be performed by expert ophthalmologists in addition to blood and urine samples that 
will be collected at baseline and after the follow-up duration to conduct laboratory investigations. 
 
Data collection methods and tools: 
Screening of patients according to the inclusion and exclusion criteria. Included patients will be interviewed to 
gather their demographic data, full patient history (medical and medication history) and assessment of their 
baseline characteristics. 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
REFERENCES 
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SCHLOEMER, P. & JOSEPH, A. J. N. E. J. O. M. 2020. Effect of finerenone on chronic kidney disease outcomes in 
type 2 diabetes. New England journal of medicine, 383, 2219-2229 . 
BALMFORTH, C., VAN BRAGT, J. J ,.RUIJS, T., CAMERON, J. R., KIMMITT, R., MOORHOUSE, R., CZOPEK, A., HU, M. 
K., GALLACHER, P. J. & DEAR, J. W. J. J. I. 2016. Chorioretinal thinning in chronic kidney disease links to inflammation 
and endothelial dysfunction. JCI insight, 1 . 
BASIONY, A. I., ATTA, S. N., DEWIDAR, N. M. & ZAKY, A. G. J. B. O. 2023. Association of chorioretinal thickness with 
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& DONAGHUE, K. C. J. D. C. 2012. Retinal vascular geometry predicts incident renal dysfunction in young people 
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DEFRONZO, R. A., EINHORN, D. & GALINDO, R. J. J. E. P. 2022. American Association of Clinical Endocrinology clinical 
practice guideline: developing a diabetes mellitus comprehensive care plan—2022 update. Endocrine Practice, 28, 
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BAKRIS, G. J. D. C. 2022. Diabetes management in chronic kidney disease: a consensus report by the American 
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TOWNSEND, R., GADEGBEKU, C. A. & LASH, J. P. J. C. J. O. T. A. S. O. N. 2010. Prevalence of ocular fundus pathology 
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K. R., WANNER, C. & BRINKER, M. D. J. N. D .T. 2024. Design and baseline characteristics of the Finerenone, in 
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PALANISAMY, S., FUNES HERNANDEZ, M., CHANG, T. I., MAHAFFEY, K. W. J. C. & THERAPY 2022. Cardiovascular 
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C. & SCHLOEMER, P. J. N. E. J. O. M. 2021. Cardiovascular events with finerenone in kidney disease and type 2 
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M., FINIS, D., LEAL, S., SCHMELTER, T. & BAKRIS, G. 2023. Effect of finerenone on the occurrence of vision-
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نموذج د.ع- 
11
- 
 ب 
 
RESEARCH TIME LINE 
 
 
 
 
 
 
Objective 
Activities 
Months 
1-3 
3-6 
6-9 
9-12 
>12 
Ethical 
considerations 
• The researcher will seek the approval of 
the Ethics Committee of Alexandria 
University for conducting the research. 
• The researcher will comply with the 
International Guidelines for Research 
Ethics and declaration of Helsinki. 
• The researcher declares that there is no 
conflict of interest. 
 
√ 
 
 
 
 
Profiling of 
patients 
• Screening of patients and collection of 
demographic data. 
• Recruitment of patients based on 
specific inclusion and exclusion criteria. 
• Patients divided randomly into 2 parallel 
groups (control versus intervention). 
• Samples collection from patients to 
determine baseline levels of selected 
parameters. 
• Follow-up of patients and re-
measurement of selected parameters 
after completion of follow up duration 
√ 
√ 
√ 
 
 
Results  
Statistical analysis will be conducted based on 
the results of the follow-up 
 
 
 
√ 
 
Documentation 
and publication 
of results 
Writing thesis  
Publishing paper in scientific journal 
 
 
 
 
√