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The Role of SGLT-2 Inhibitors in Chronic Kidney Disease: Clinical Applications, Precautions, and Future Directions

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Introduction: A Paradigm Shift in Chronic Kidney Disease Management

Chronic Kidney Disease (CKD) is a progressive condition characterized by the gradual loss of kidney function due to various causes, including diabetes, hypertension, and glomerulonephritis. CKD patients face an elevated risk of cardiovascular diseases, making early diagnosis and appropriate pharmacological intervention essential.

Among the latest advancements in CKD management, SGLT-2 (Sodium-Glucose Cotransporter-2) inhibitors have gained significant attention. Originally developed as glucose-lowering agents for type 2 diabetes, these drugs also exhibit remarkable kidney-protective and cardiovascular benefits.

Major clinical trials such as CREDENCE, DAPA-CKD, and EMPA-KIDNEY have demonstrated that SGLT-2 inhibitors slow eGFR decline, reduce the risk of end-stage kidney disease (ESKD), and lower cardiovascular mortality in CKD patients.

The EMPA-KIDNEY Study (NEJM, 2025)

One of the most comprehensive studies, the EMPA-KIDNEY trial, included patients with eGFR between 20 and 45 mL/min/1.73m² or those with preserved kidney function but significant albuminuria (ACR ≥200mg/g). The study found that empagliflozin significantly reduced CKD progression and cardiovascular mortality compared to placebo. Notably, even after discontinuation of the drug, a residual protective effect was observed for some time, reinforcing the long-term benefits of SGLT-2 inhibitors in CKD management.

Case Study: A 60-Year-Old Male with Type 2 Diabetes and CKD

Patient Profile:

  • Age: 60 years
  • Medical history: Hypertension and Type 2 diabetes for 10 years
  • Current treatment: Metformin, ACE inhibitor, statin
  • Recent findings: Increased albuminuria (ACR 500mg/g), eGFR ~35 mL/min/1.73m²

Despite being on ACE inhibitors, this patient exhibited worsening albuminuria and declining kidney function. Blood sugar control was also slightly above the target range, and cardiovascular risk remained elevated. Given these factors, SGLT-2 inhibitor therapy was considered to slow CKD progression and reduce cardiovascular risk.

Treatment and Outcome:

The patient was started on empagliflozin (10mg/day). After three months, the following improvements were observed:
✅ Significant reduction in albuminuria
✅ Stabilization of eGFR decline
✅ Improved glycemic control (HbA1c reduction)
✅ Modest weight loss (2-3kg), leading to slight antihypertensive medication adjustments

This case exemplifies how SGLT-2 inhibitors can provide simultaneous renal and cardiovascular protection in CKD patients with diabetes.

Clinical Guidelines: When and How to Use SGLT-2 Inhibitors

Indications for Use

✔ eGFR 20–45 mL/min/1.73m²: Strong evidence supports kidney protection in this range (CREDENCE, DAPA-CKD, EMPA-KIDNEY).
✔ eGFR 45–90 mL/min/1.73m² with albuminuria (ACR ≥200mg/g): Recommended for proteinuric CKD patients, even without diabetes.
✔ Non-diabetic CKD: Although initially developed for diabetes, studies show significant renal benefits in non-diabetic CKD patients.

Dosing and Administration

  • Starting dose: Empagliflozin 10mg/day or Dapagliflozin 10mg/day
  • eGFR <20 mL/min/1.73m²: Insufficient data for routine use—further studies needed
  • Monitoring: Blood pressure, volume status, and kidney function should be monitored regularly

Combination Therapy

✅ ACE inhibitors/ARBs: Combining SGLT-2 inhibitors with RAS inhibitors enhances renoprotective effects
✅ Diuretics and beta-blockers: Can be co-administered, but hypotension risk should be considered

Precautions and Management Strategies

1. Dehydration and Hypotension

💡 Why it happens? SGLT-2 inhibitors increase urinary glucose excretion, leading to osmotic diuresis and volume depletion.
📌 How to manage?

  • Monitor blood pressure and electrolytes
  • Educate patients to increase fluid intake if experiencing dehydration symptoms

2. Acute Kidney Injury (AKI) Risk

💡 Why it happens? Volume depletion can trigger transient declines in eGFR.
📌 How to manage?

  • Temporary dose reduction or discontinuation during acute illnesses (e.g., severe dehydration, vomiting, diarrhea)
  • Resume therapy once the patient is clinically stable

3. Increased Risk of Genitourinary Infections

💡 Why it happens? Elevated glucose levels in urine create a favorable environment for bacterial and fungal growth.
📌 How to manage?

  • Encourage proper hygiene practices
  • Promptly treat urinary tract or genital infections

4. Euglycemic Diabetic Ketoacidosis (eDKA)

💡 Why it happens? SGLT-2 inhibitors promote ketogenesis, which can lead to DKA even with normal blood glucose levels.
📌 How to manage?

  • Avoid SGLT-2 inhibitors in Type 1 diabetes
  • Monitor ketone levels in high-risk patients

Future Research and Outlook

🔍 1. Expansion to Lower eGFR Ranges

  • Studies on SGLT-2 inhibitor efficacy in patients with eGFR <20 mL/min/1.73m² are needed.

🔍 2. Disease-Specific Applications

  • Effectiveness in glomerulonephritis, polycystic kidney disease, and lupus nephritis requires further validation.

🔍 3. Cost-Effectiveness and Accessibility

  • Long-term health-economic impact should be assessed to ensure broad accessibility.

🔍 4. Long-Term Outcomes Beyond CKD Progression

  • Research on hospitalization rates, cardiovascular mortality, and quality of life improvements will further solidify the role of SGLT-2 inhibitors in CKD management.

Conclusion: A Game-Changer in CKD Management

SGLT-2 inhibitors have revolutionized the treatment paradigm for CKD, offering significant renoprotective and cardioprotective benefits. Their efficacy extends beyond glycemic control, making them a cornerstone therapy in both diabetic and non-diabetic CKD.

However, proper patient selection, monitoring, and risk management are essential to maximize benefits while minimizing adverse effects. Personalized treatment approaches integrating SGLT-2 inhibitors, RAS inhibitors, and lifestyle modifications will be key to improving CKD patient outcomes in the coming years.

References

  1. The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2025;392(8):777-787.
  2. Heerspink HJL, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446.
  3. Perkovic V, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306.

 

 

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Chronic Kidney Disease (CKD) Diagnosis in Elderly Patients: Understanding eGFR Interpretation and Age-Specific Cutoffs

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1. Introduction: The Growing Burden of CKD in an Aging Society

Chronic Kidney Disease eGFR interpretation in elderly patients, With the rapid aging of populations worldwide, the prevalence of chronic kidney disease (CKD) among elderly patients is also increasing. Traditionally, CKD has been diagnosed when the estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73m². However, distinguishing age-related decline in kidney function from pathological CKD remains a significant challenge.

Applying a strict eGFR <60 criterion to elderly individuals may lead to overdiagnosis, classifying age-related physiological decline as a disease. This article explores the importance of age-specific eGFR cutoffs, albuminuria, and comorbidities such as diabetes in diagnosing CKD in elderly patients.

2. eGFR Declines with Aging—Is It Always CKD?

(1) Understanding eGFR

  • The estimated glomerular filtration rate (eGFR) is a key marker of kidney function, typically calculated using serum creatinine or cystatin C.
  • While an eGFR below 60 mL/min/1.73m² is traditionally classified as CKD, aging must be considered when interpreting these values.

(2) The Problem with a Fixed eGFR <60 Criterion in Elderly Patients

  • Among patients in their 70s and 80s, it is common to observe eGFR values between 50–55 mL/min/1.73m², even in the absence of significant complications.
  • Using a fixed 60 mL/min/1.73m² threshold could lead to the misclassification of age-related decline as CKD, resulting in unnecessary tests and treatments.

3. Why Are Albuminuria and Comorbidities Important in CKD Diagnosis?

(1) The Role of Albuminuria (UACR)

  • Albuminuria (urinary albumin-to-creatinine ratio, UACR) is a sensitive marker of kidney damage.
  • If eGFR is low but albuminuria is absent, the decline may be due to natural aging rather than CKD. Conversely, patients with albuminuria, even with relatively preserved eGFR, have a higher risk of CKD progression.

(2) The Impact of Diabetes, Obesity, and Cardiovascular Risk

  • Comorbid conditions such as diabetes, obesity, and hypertension can accelerate kidney function decline beyond what is expected with normal aging.
  • Diabetes significantly increases the risk of albuminuria, making early detection and close monitoring essential for elderly diabetic patients.

(3) Greater eGFR Decline in Patients with Comorbidities

  • Patients with diabetes, obesity, and microalbuminuria exhibit a more rapid eGFR decline than their healthy counterparts.
  • Understanding eGFR trajectories over time is crucial to distinguishing between normal aging and pathological CKD.

4. Age-Specific eGFR Cutoffs: Benefits and Limitations

(1) Benefits

✔ Prevention of Overdiagnosis: Helps differentiate normal age-related eGFR decline from true CKD, avoiding unnecessary treatments.
✔ Personalized Risk Assessment: In an 80-year-old, an eGFR of 50 mL/min/1.73m² might be within an expected range, whereas the same value in a 40-year-old may indicate serious kidney disease.

(2) Limitations

❌ Lack of Official Guidelines: Leading organizations such as KDIGO still use a fixed eGFR threshold of 60 mL/min/1.73m² for CKD diagnosis.
❌ Risk of Missing Severe Cases: If age-specific cutoffs are too lenient, some patients who require dialysis or kidney transplantation may be overlooked.
❌ Individual Variability: Muscle mass, nutrition, medications, and overall health impact eGFR, making a one-size-fits-all approach problematic.

5. Practical Applications: How Should We Interpret eGFR in Elderly Patients?

5.1 Use KDIGO Standards with Additional Markers

  • In clinical practice, eGFR <60 mL/min/1.73m² + albuminuria remains the primary CKD diagnostic criterion.
  • However, in elderly patients, using age-specific eGFR cutoffs can help reduce overdiagnosis.

5.2 Comprehensive Risk Assessment: Comorbidities, Albuminuria, and Decline Rate

  • Assessing diabetes, hypertension, cardiovascular disease, and albuminuria alongside eGFR provides a more accurate risk evaluation.
  • The rate of eGFR decline over time is more important than a single measurement—gradual declines suggest aging, while rapid declines suggest pathology.

5.3 Managing CKD in Elderly Patients: Conservative vs. Dialysis Approaches

  • Kidney transplantation is often not feasible in patients aged 65+, necessitating a careful approach to dialysis initiation.
  • Lifestyle modifications, medication adjustments, and patient-centered care should be prioritized to maximize remaining kidney function.
  • The decision between dialysis and conservative management should be made collaboratively between physicians and patients, considering quality of life and overall prognosis.

6. Conclusion: Moving Beyond a Fixed eGFR 60 Threshold

  • Age-related eGFR decline is not always indicative of CKD, and a rigid application of the 60 mL/min/1.73m² threshold may lead to overdiagnosis.
  • However, albuminuria, diabetes, cardiovascular conditions, and eGFR decline rates should be carefully evaluated before ruling out CKD.
  • Age-specific eGFR cutoffs provide useful reference points but should not replace comprehensive patient evaluation.

Ultimately, a patient-centered approach—rather than relying solely on a single eGFR value—is the key to optimizing kidney disease management in elderly populations.

References

  1. Herold JM, et al. “Population-based reference values for kidney function and kidney function decline in 25- to 95-year-old Germans without and with diabetes.” Kidney International, 2024;106(4):699–711.
  2. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl, 2024;105(4S):S117–S314.

Disclaimer: This article summarizes research findings and clinical guidelines for general informational purposes only. For specific diagnosis and treatment, consult a medical professional.

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