What adjustments should be made to the medication regimen of a patient with CKD stage 3 and diabetes, currently on spironolactone and furosemide, to avoid further kidney damage and slow CKD progression?

Medication Adjustments for CKD Stage 3 with Diabetes on Spironolactone and Furosemide

In patients with CKD stage 3 and diabetes currently on spironolactone and furosemide, you should discontinue spironolactone due to high risk of hyperkalemia and worsening renal function, continue furosemide for volume management only if clinically indicated, add an SGLT2 inhibitor (if eGFR ≥20 mL/min/1.73 m²) as first-line therapy to slow CKD progression, and initiate or optimize an ACE inhibitor or ARB for blood pressure control targeting <130/80 mmHg. 1

Immediate Action: Discontinue Spironolactone

Spironolactone should be stopped in CKD stage 3 patients unless there is a compelling indication like heart failure with reduced ejection fraction. The evidence strongly argues against its use:

• Spironolactone causes hyperkalemia risk that increases with impaired renal function, requiring monitoring within 1 week of initiation and regularly thereafter, with more frequent monitoring needed in CKD patients. 2
• Recent high-quality evidence from a 2024 randomized controlled trial showed that two-thirds of CKD stage 3b patients discontinued spironolactone within 6 months, predominantly due to safety concerns including decreased eGFR (35.4%), treatment side effects (18.9%), and hyperkalemia (8.0%). 3
• Spironolactone provided no cardiovascular benefit in stage 3b CKD (hazard ratio 1.05,95% CI: 0.81-1.37) and should not be used without another explicit treatment indication. 3
• The FDA label explicitly warns that spironolactone can cause excessive diuresis leading to symptomatic dehydration, hypotension and worsening renal function, particularly in patients taking ACE inhibitors or ARBs. 2

Furosemide: Continue Only If Volume Overload Present

Furosemide should be continued only for active volume management, not for CKD prevention or treatment:

• Loop diuretics like furosemide are recommended for symptom control in volume overload but have no role in slowing CKD progression. 1, 4
• Monitor serum electrolytes (particularly potassium), CO2, creatinine and BUN frequently during the first few months and periodically thereafter, as furosemide influences electrolyte balance. 5
• Furosemide combined with ACE inhibitors or ARBs may lead to severe hypotension and deterioration in renal function, requiring dose adjustment or interruption. 5
• A 2020 study comparing spironolactone versus furosemide in resistant hypertension showed furosemide was associated with faster eGFR decline (-3.2±5.6 vs -2.1±4.8 mL/min/1.73 m²/year). 6

Add SGLT2 Inhibitor as Primary Kidney-Protective Agent

SGLT2 inhibitors are the cornerstone of CKD progression prevention in type 2 diabetes:

• For people with type 2 diabetes and CKD, use of an SGLT2 inhibitor with demonstrated benefit is recommended to reduce CKD progression and cardiovascular events in individuals with eGFR ≥20 mL/min/1.73 m². 1
• The 2023 American Diabetes Association guidelines give this recommendation the highest level of evidence (Class A). 1
• SGLT2 inhibitors reduce intraglomerular pressure, albuminuria, and slow GFR loss through mechanisms independent of glycemia, including reducing oxidative stress by >50% and blunting angiotensinogen increases. 1
• The CREDENCE trial demonstrated that canagliflozin reduced the risk of kidney failure and cardiovascular events in patients with diabetic kidney disease. 1

Optimize RAS Blockade for Blood Pressure and Albuminuria Control

ACE inhibitors or ARBs remain essential for slowing kidney disease progression:

• In adults with hypertension and CKD stage 3 or higher, treatment with an ACE inhibitor is reasonable to slow kidney disease progression, with ARBs as an alternative if ACE inhibitors are not tolerated. 1
• Target blood pressure should be <130/80 mmHg in adults with hypertension and CKD. 1
• Monitor serum creatinine and potassium 7-14 days after initiation or dose change, then at routine visits. 1
• Continue RAS blockade for mild to moderate increases in serum creatinine (≤30%) in individuals without signs of volume depletion. 1

Critical Monitoring Parameters

Establish a rigorous monitoring schedule to prevent complications:

• Check serum potassium, creatinine, and eGFR within 1-2 weeks after stopping spironolactone and starting/adjusting other medications. 2, 1
• Monitor for hyperkalemia more frequently when combining ACE inhibitors/ARBs with SGLT2 inhibitors, though SGLT2 inhibitors may actually reduce hyperkalemia risk. 1
• Assess volume status regularly to avoid excessive diuresis and hypotension. 2, 5
• Monitor urine albumin-to-creatinine ratio with a goal of ≥30% reduction to slow CKD progression. 1

Diabetes Medication Adjustments in CKD Stage 3

Modify diabetes medications to prevent hypoglycemia:

• Metformin can be continued in CKD stage 3 but should not be initiated if eGFR <45 mL/min/1.73 m² and must be discontinued if eGFR <30 mL/min/1.73 m². 1
• If using sulfonylureas, prefer glipizide or gliclazide as they lack active metabolites and don't increase hypoglycemia risk in CKD, unlike first-generation agents which must be avoided. 1, 7
• Consider GLP-1 receptor agonists for additional cardiovascular risk reduction if SGLT2 inhibitors alone don't achieve glycemic targets. 1
• Patients with CKD stage 3 have increased hypoglycemia risk due to decreased clearance of insulin and oral agents, plus impaired renal gluconeogenesis requiring close glucose monitoring. 1

Additional Considerations

Address other modifiable risk factors:

• Dietary protein intake should be 0.8 g/kg body weight per day for non-dialysis-dependent stage 3 CKD. 1
• Refer to nephrology if eGFR continuously decreases, albuminuria continuously increases, or eGFR falls <30 mL/min/1.73 m². 1
• Consider nonsteroidal mineralocorticoid receptor antagonists (like finerenone) if eGFR ≥25 mL/min/1.73 m² and albuminuria persists despite optimal therapy, as these have better safety profiles than spironolactone. 1