Heart failure (HF) and chronic kidney disease (CKD) are closely interconnected chronic conditions that frequently coexist and substantially increase the risk of morbidity, hospitalization, and mortality [1]. This bidirectional relationship, commonly referred to as the cardiorenal syndrome, results from complex interactions involving hemodynamic alterations, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction [2]. Patients with concomitant HF and CKD experience accelerated disease progression, poorer quality of life, and significantly higher healthcare utilization compared with those affected by either condition alone [3,4]. Consequently, identifying therapeutic strategies that provide simultaneous cardiovascular and renal protection has become a major priority in contemporary clinical practice [5].

Sodium-glucose cotransporter-2 (SGLT2) inhibitors were initially developed as glucose-lowering agents for the management of type 2 diabetes mellitus [6,7]. However, accumulating evidence from large randomized clinical trials has demonstrated that these agents confer substantial cardiovascular and renal benefits independent of their glycemic effects [8]. SGLT2 inhibitors reduce intraglomerular pressure through restoration of tubuloglomerular feedback, promote natriuresis and osmotic diuresis, improve cardiac preload and afterload, and attenuate inflammatory and fibrotic pathways [9]. These pleiotropic mechanisms contribute to improved cardiac function, preservation of renal function, and reduced progression of both heart failure and chronic kidney disease [10].

Landmark trials such as DAPA-HF, EMPEROR-Reduced, DAPA-CKD, EMPEROR-Preserved, DELIVER, and EMPA-KIDNEY have consistently demonstrated reductions in heart failure hospitalization, cardiovascular death, and decline in renal function among patients treated with SGLT2 inhibitors, irrespective of diabetic status [11-15]. These findings have led to the incorporation of SGLT2 inhibitors into international guidelines as foundational therapy for patients with heart failure and CKD [16]. Despite these advances, real-world clinical data evaluating their effectiveness across diverse patient populations remain limited, particularly in routine tertiary care settings where patients often present with multiple comorbidities and varying stages of renal dysfunction.

The present study aimed to evaluate the clinical outcomes of SGLT2 inhibitor therapy in patients with heart failure and chronic kidney disease by assessing changes in functional status, cardiac performance, renal function, metabolic parameters, clinical outcomes, and treatment-related adverse events during follow-up.

This prospective observational study was conducted in the Department of Cardiology and Nephrology at a tertiary care teaching hospital over a period of one year, from June 2024 to June 2025. The study included 120 adult patients diagnosed with heart failure (HF) and chronic kidney disease (CKD) who were initiated on sodium-glucose cotransporter-2 (SGLT2) inhibitor therapy as part of standard guideline-directed medical treatment. The study protocol was approved by the Institutional Ethics Committee, and written informed consent was obtained from all participants before enrollment. Patients aged ≥18 years with clinically diagnosed heart failure (reduced or mildly reduced ejection fraction) and CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m² for ≥3 months) who were prescribed an SGLT2 inhibitor (dapagliflozin or empagliflozin) were included. Patients with type 1 diabetes mellitus, pregnancy, active urinary or genital infections at baseline, end-stage renal disease requiring dialysis, severe hepatic dysfunction, known hypersensitivity to SGLT2 inhibitors, or incomplete follow-up data were excluded. Baseline demographic characteristics, including age, sex, body mass index (BMI), smoking status, and associated comorbidities such as hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation, dyslipidemia, and previous myocardial infarction, were recorded. Clinical evaluation included assessment of New York Heart Association (NYHA) functional class, blood pressure, body weight, and six-minute walk distance (6MWD). Echocardiographic assessment was performed to determine left ventricular ejection fraction (LVEF). Laboratory investigations included serum creatinine, estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI equation, urine albumin-creatinine ratio (UACR), serum potassium, glycated hemoglobin (HbA1c) in diabetic patients, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Baseline measurements were obtained prior to initiation of SGLT2 inhibitor therapy. All patients received SGLT2 inhibitor therapy (dapagliflozin 10 mg or empagliflozin 10 mg once daily) in addition to guideline-directed medical therapy for heart failure and CKD, as determined by the treating physician. Patients were followed prospectively for 6 months, during which clinical assessment, laboratory investigations, echocardiography, and functional evaluation were repeated. Clinical outcomes including improvement in NYHA functional class, changes in LVEF, NT-proBNP, renal function parameters, metabolic parameters, heart failure-related hospitalization, worsening CKD, acute kidney injury, cardiovascular mortality, and all-cause mortality were documented. Adverse events such as genital fungal infection, urinary tract infection, symptomatic hypotension, volume depletion, hypoglycemia, diabetic ketoacidosis, and treatment discontinuation were also recorded throughout the follow-up period. Data were entered into Microsoft Excel and analyzed using IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were presented as frequencies and percentages. Paired Student's t-test was used to compare baseline and follow-up continuous variables, whereas categorical variables were analyzed using the Chi-square test or Fisher's exact test, wherever appropriate. A two-sided p value of <0.05 was considered statistically significant.

A total of 120 patients with heart failure and chronic kidney disease were included in the study. The mean age was 63.8 ± 10.9 years, with males constituting 63.3% of the study population. Hypertension (80.0%) and diabetes mellitus (73.3%) were the most common comorbidities, followed by coronary artery disease (60.0%), dyslipidemia (56.7%), previous myocardial infarction (31.7%), smoking (28.3%), and atrial fibrillation (21.7%). The mean body mass index was 28.1 ± 4.5 kg/m² (Table 1).

Table 1. Baseline Demographic and Clinical Characteristics (N=120)

At baseline, the majority of patients were classified as NYHA Class III (50.8%), followed by Class II (35.0%) and Class IV (14.2%). The mean left ventricular ejection fraction was 35.6 ± 7.8%, while the mean NT-proBNP level was 3450 ± 1260 pg/mL. Renal function assessment showed a mean eGFR of 46.2 ± 14.1 mL/min/1.73 m² and serum creatinine of 1.82 ± 0.54 mg/dL. Most patients had CKD Stage 3 (60.0%), with the remaining classified as Stage 4 (Table 2).

Table 2. Baseline Heart Failure and CKD Characteristics (N=120)

Following six months of SGLT2 inhibitor therapy, significant improvements were observed in heart failure outcomes. The mean NYHA class improved from 2.79 ± 0.67 to 2.01 ± 0.61, while the mean LVEF increased from 35.6 ± 7.8% to 41.8 ± 8.4%. NT-proBNP levels showed a significant reduction, and the six-minute walk distance increased markedly. All changes were statistically significant (p < 0.001) (Table 3).

Table 3. Effect of SGLT2 Inhibitors on Heart Failure Outcomes

Renal function remained stable with modest but significant improvement following treatment. Mean eGFR increased from 46.2 ± 14.1 to 49.8 ± 14.3 mL/min/1.73 m², whereas serum creatinine and urine albumin-creatinine ratio showed significant reductions. Serum potassium levels remained unchanged throughout follow-up, indicating a favorable renal safety profile (Table 4).

Table 4. Effect on Renal Function

Significant improvements were also observed in metabolic parameters after six months of therapy. Among patients with diabetes, HbA1c levels decreased significantly from 8.21 ± 1.14% to 7.32 ± 0.92%. Additionally, reductions were noted in body weight, body mass index, and systolic blood pressure, with all changes reaching statistical significance (p < 0.001) (Table 5).

Table 5. Metabolic Parameters

Clinical outcomes during follow-up were favorable, with 74.2% of patients demonstrating improvement in NYHA functional class. Heart failure-related hospitalization occurred in 11.7% of patients, while worsening CKD and acute kidney injury were observed in 8.3% and 5.0%, respectively. Cardiovascular mortality and all-cause mortality were low, occurring in 2.5% and 4.2% of patients, respectively (Table 6).

Table 6. Hospitalization and Clinical Outcomes

SGLT2 inhibitor therapy was generally well tolerated. Genital fungal infection was the most frequently reported adverse event (8.3%), followed by urinary tract infection (7.5%), symptomatic hypotension (6.7%), and volume depletion (5.8%). Mild hypoglycemia and diabetic ketoacidosis were uncommon, and treatment discontinuation due to adverse events occurred in only 5.0% of patients (Table 7).

Table 7. Adverse Events

The present study demonstrated that SGLT2 inhibitor therapy was associated with significant improvements in both cardiac and renal outcomes among patients with heart failure and chronic kidney disease over a 6-month follow-up period. Significant improvements were observed in NYHA functional class, left ventricular ejection fraction (LVEF), NT-proBNP levels, and six-minute walk distance, indicating better functional capacity and cardiac performance. Additionally, favourable changes in renal function parameters, including improved eGFR and reduced serum creatinine and urine albumin-creatinine ratio (UACR), were observed, along with significant reductions in HbA1c, body weight, BMI, and systolic blood pressure. These findings highlight the dual cardiorenal benefits of SGLT2 inhibitors in routine clinical practice and are consistent with the growing body of evidence supporting their role as foundational therapy in patients with HF and CKD. The improvement in heart failure outcomes observed in our study is consistent with findings from the landmark DAPA-HF and EMPEROR-Reduced trials. In the DAPA-HF trial, dapagliflozin significantly reduced the risk of worsening heart failure or cardiovascular death while improving symptoms and functional status irrespective of diabetes status [12]. Similarly, the EMPEROR-Reduced trial demonstrated that empagliflozin significantly reduced heart failure hospitalizations and improved clinical outcomes in patients with reduced ejection fraction [13]. In the present study, a marked improvement in NYHA class, an increase in LVEF, a substantial reduction in NT-proBNP levels, and a low rate of heart failure hospitalization (11.7%) further support these beneficial effects of SGLT2 inhibitors in real-world patients with HF and CKD. The renoprotective effects observed in our study are also in agreement with previous large-scale clinical trials. The DAPA-CKD trial demonstrated that dapagliflozin significantly reduced the risk of sustained decline in eGFR, progression to end-stage kidney disease, and renal or cardiovascular death irrespective of diabetic status [14]. Likewise, the EMPA-KIDNEY trial reported slower CKD progression and reduced risk of kidney disease progression or cardiovascular death with empagliflozin [15]. Our findings of improved eGFR, reduced serum creatinine, and significant reduction in albuminuria closely mirror these observations, suggesting preservation of renal function in patients receiving SGLT2 inhibitors. Furthermore, improvements in glycemic control, body weight, and blood pressure observed in our study are consistent with the known metabolic and hemodynamic benefits reported across these landmark trials. SGLT2 inhibitors were generally well tolerated in the present study, with genital fungal infections and urinary tract infections being the most commonly reported adverse events, while serious complications such as diabetic ketoacidosis were rare. These findings are comparable to the established safety profile reported in DAPA-HF, DAPA-CKD, and EMPA-KIDNEY, where genital infections were the most frequent adverse events without significant increases in severe renal or cardiovascular complications [12-15]. The relatively low rates of treatment discontinuation and mortality observed in our cohort further reinforce the safety and effectiveness of SGLT2 inhibitors in routine clinical practice. Nevertheless, the study is limited by its single-center observational design, modest sample size, and relatively short follow-up period, which may limit the generalizability of the findings. Larger multicenter studies with longer follow-up are warranted to further validate these outcomes and assess long-term cardiovascular and renal benefits.

SGLT2 inhibitor therapy was associated with significant improvements in cardiac function, renal parameters, functional capacity, and metabolic profile in patients with heart failure and chronic kidney disease. The treatment resulted in improved NYHA functional class, increased left ventricular ejection fraction, reduced NT-proBNP levels, stabilization of renal function, decreased albuminuria, and favorable effects on glycemic control, body weight, and blood pressure, while demonstrating an acceptable safety profile with few serious adverse events. These findings support the use of SGLT2 inhibitors as an effective and well-tolerated therapeutic strategy for the comprehensive management of patients with coexisting heart failure and chronic kidney disease. Further large-scale, multicenter studies with longer follow-up are warranted to confirm these benefits and evaluate long-term cardiovascular and renal outcomes.

Acknowledgement: None

Funding: None

Conflict of Interest: None

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