How should I treat a >80‑year‑old diabetic with stage 4 chronic kidney disease (eGFR ≈ 28 mL/min/1.73 m²), albuminuria, proteinuria, lower‑leg edema and hypertension (160/68 mm Hg) who is currently on amlodipine 5 mg, perindopril 8 mg and indapamide 2.5 mg?

Management of an Octogenarian with Diabetes, Stage 4 CKD, and Hypertension

Stop metformin immediately, add an SGLT2 inhibitor (empagliflozin 10 mg or dapagliflozin 10 mg daily) for renal and cardiovascular protection, optimize the current antihypertensive regimen by continuing perindopril 8 mg with careful monitoring, and address volume overload with loop diuretics rather than indapamide at this level of kidney function.

Immediate Medication Adjustments

Discontinue Metformin

• Metformin must be stopped at eGFR 28 mL/min/1.73 m² because it is contraindicated below 30 mL/min/1.73 m² due to lactic acidosis risk. 1, 2
• The FDA-revised labeling explicitly restricts metformin use to eGFR ≥30 mL/min/1.73 m², and this patient falls below that threshold. 2

Initiate SGLT2 Inhibitor Therapy

• Start empagliflozin 10 mg daily or dapagliflozin 10 mg daily immediately for organ protection, independent of glucose-lowering effect. 1
• KDIGO 2024 provides a Grade 1A recommendation (the highest level) to treat adults with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m² with an SGLT2 inhibitor. 1
• At eGFR 28 mL/min/1.73 m², SGLT2 inhibitors reduce the composite outcome of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51–0.72). 3
• Continue the SGLT2 inhibitor even if eGFR falls below 20 mL/min/1.73 m², provided the patient tolerates it and kidney replacement therapy is not imminent. 1, 3
• Expect a transient, reversible eGFR decline of 2–5 mL/min/1.73 m² within the first 2–4 weeks; this hemodynamic effect does not warrant discontinuation. 3, 4
• Withhold the SGLT2 inhibitor during prolonged fasting, surgery, or acute illness to reduce the rare risk of euglycemic diabetic ketoacidosis. 1, 3

Blood Pressure and Antihypertensive Management

Continue Perindopril with Dose Monitoring

• Maintain perindopril 8 mg daily because ACE inhibitors provide renoprotection in diabetic CKD, even at eGFR 28 mL/min/1.73 m². 1, 5
• The FDA label for perindopril states that for creatinine clearance <30 mL/min (approximately eGFR 28), the initial dose should be 2 mg/day and should not exceed 8 mg/day. 5
• Since this patient is already on 8 mg and tolerating it (creatinine 143 µmol/L is stable), continue the current dose but monitor creatinine and potassium every 2–4 weeks. 1, 5
• Do not discontinue perindopril unless serum creatinine rises >30% within 4 weeks or hyperkalemia becomes unmanageable. 1
• The combination of perindopril and indapamide reduced urinary albumin excretion and prevented nephropathy progression in diabetic patients, independently of blood pressure control. 6, 7

Reassess Indapamide Use

• Consider switching from indapamide 2.5 mg to a loop diuretic (furosemide 20–40 mg daily) to manage lower-leg edema more effectively at this level of kidney function. 4
• Thiazide-like diuretics (including indapamide) lose efficacy when eGFR falls below 30 mL/min/1.73 m², whereas loop diuretics remain effective in stage 4 CKD. 4
• If blood pressure remains elevated (160/68 mmHg systolic is above target), the loop diuretic will provide both volume control and additional blood pressure reduction. 4

Continue Amlodipine

• Maintain norvasc (amlodipine) 5 mg daily because calcium channel blockers are safe and effective in advanced CKD and complement ACE inhibitor therapy. 8
• In hypertensive patients with diabetic CKD, the combination of perindopril and a calcium antagonist effectively controlled blood pressure and preserved renal function over 2 years. 8

Blood Pressure Target

• Target blood pressure <130/80 mmHg in this diabetic CKD patient. 1, 4
• The current systolic pressure of 160 mmHg is significantly above target and requires intensification of therapy. 1, 4
• Lowering systolic blood pressure below 120 mmHg in diabetic patients with CKD was associated with progressively lower rates of renal events, with no identifiable threshold below which renal benefit is lost. 7

Additional Glycemic Management

Add GLP-1 Receptor Agonist if Needed

• If individualized glycemic targets (typically HbA1c 7.0–8.0% in an octogenarian) are not met after 3 months of SGLT2 inhibitor therapy, add a long-acting GLP-1 receptor agonist (dulaglutide 0.75–1.5 mg weekly or liraglutide 1.2–1.8 mg daily). 1, 2
• GLP-1 receptor agonists are the preferred add-on agents after SGLT2 inhibitors because they reduce cardiovascular events by 12–26% and can be used safely down to eGFR 15 mL/min/1.73 m². 3, 2
• Liraglutide showed significantly greater cardiovascular risk reduction in patients with eGFR <60 mL/min/1.73 m² compared to those with higher eGFR. 2

Alternative: DPP-4 Inhibitor

• If GLP-1 receptor agonists are not tolerated or affordable, add linagliptin 5 mg daily, which requires no dose adjustment at any level of renal function. 3, 2
• However, DPP-4 inhibitors lack proven cardiovascular and renal protective effects and are positioned as second- or third-line options. 3

Avoid Sulfonylureas

• Do not use sulfonylureas (e.g., glyburide, glimepiride) at eGFR 28 mL/min/1.73 m² because they markedly increase hypoglycemia risk due to accumulation of active metabolites and reduced renal gluconeogenesis. 3, 2

Consideration of Nonsteroidal Mineralocorticoid Receptor Antagonist

Finerenone for Albuminuria

• If albuminuria is present (UACR ≥30 mg/g) and persists despite maximum tolerated ACE inhibitor and SGLT2 inhibitor therapy, consider adding finerenone 10 mg daily (starting dose for eGFR 25–59 mL/min/1.73 m²). 1, 9
• KDIGO 2022 provides a Grade 2A recommendation for nonsteroidal MRA in adults with type 2 diabetes, eGFR >25 mL/min/1.73 m², normal serum potassium, and albuminuria despite RAS inhibitor therapy. 1
• The CONFIDENCE trial demonstrated that initial therapy with finerenone plus empagliflozin led to a 29–32% greater reduction in urinary albumin-to-creatinine ratio than either treatment alone. 9
• Monitor serum potassium closely: check at 1 week, 1 month, then every 4 months; hold finerenone if K⁺ >5.5 mmol/L. 1

Monitoring Protocol

Renal Function and Electrolytes

• Check eGFR, serum creatinine, and potassium 2–4 weeks after initiating the SGLT2 inhibitor, then every 3–6 months. 1, 3, 4
• Increase monitoring frequency to every 2–4 weeks if finerenone is added or if potassium trends upward. 1

Albuminuria Assessment

• Measure urine albumin-to-creatinine ratio (UACR) at baseline and every 3–6 months to assess treatment response. 1, 4
• Persistent albuminuria (UACR ≥30 mg/g) despite therapy indicates high risk for CKD progression and cardiovascular events, warranting consideration of finerenone. 1, 9

Glycemic Control

• Recheck HbA1c every 3–6 months, targeting 7.0–8.0% in this elderly patient with advanced CKD to balance glycemic control against hypoglycemia risk. 3, 2
• Continuous glucose monitoring may be beneficial when HbA1c becomes unreliable in advanced CKD. 2

Edema Management

Loop Diuretic for Volume Overload

• Initiate furosemide 20–40 mg daily (or equivalent loop diuretic) to address lower-leg edema, which is common in stage 4 CKD and exacerbated by amlodipine. 4
• Loop diuretics are more effective than thiazide-like diuretics when eGFR <30 mL/min/1.73 m² and will also contribute to blood pressure control. 4
• Monitor for hypokalemia if loop diuretics are used, especially in combination with perindopril, which may cause hyperkalemia. 4

Albumin and Nutritional Status

• The serum albumin of 34 g/L is low-normal and may reflect either malnutrition or urinary protein loss; ensure adequate protein intake (0.8 g/kg/day) unless proteinuria is severe. 1

Common Pitfalls and Caveats

Therapeutic Inertia

• Delaying initiation of SGLT2 inhibitor therapy forfeits proven renal and cardiovascular benefits in eligible diabetic CKD patients. 3, 4
• Most patients with diabetes and CKD have high residual risks of CKD progression and cardiovascular disease despite standard therapy; multiple interventions are needed simultaneously. 1

Premature Discontinuation of ACE Inhibitor

• Do not stop perindopril if creatinine rises <30% or if hyperkalemia can be managed with dietary potassium restriction or potassium binders. 1
• Continue ACE inhibitor therapy even when eGFR falls below 30 mL/min/1.73 m², unless symptomatic hypotension or uncontrolled hyperkalemia develops. 1

NSAID Avoidance

• Absolutely avoid NSAIDs (ibuprofen, naproxen, ketorolac) in stage 4 CKD because they accelerate renal function decline and increase cardiovascular risk. 4, 2

Contrast Nephropathy Prevention

• Minimize exposure to iodinated contrast; ensure adequate hydration and consider N-acetylcysteine prophylaxis when imaging is required. 4

Hypoglycemia Risk

• The risk of hypoglycemia increases substantially at eGFR <45 mL/min/1.73 m² due to decreased renal gluconeogenesis and reduced clearance of insulin and oral agents. 2
• If the patient is on insulin or sulfonylureas and meeting glycemic targets, reduce or withdraw these medications when adding SGLT2 inhibitors to prevent hypoglycemia. 2