What is the management of diabetic nephropathy?

Management of Diabetic Nephropathy

The cornerstone of diabetic nephropathy management is initiating ACE inhibitors or ARBs titrated to maximum tolerated doses combined with SGLT2 inhibitors, alongside optimizing glycemic control (HbA1c individualized between <6.5% to <8.0%) and blood pressure control (target <130/80 mmHg). 1

Pharmacological Management Algorithm

First-Line Therapy: RAS Inhibition

All patients with diabetes, hypertension, and albuminuria (albumin-to-creatinine ratio >30 mg/g) must receive either an ACE inhibitor or ARB, titrated to the highest approved dose tolerated. 2, 1

• Type 1 diabetes: ACE inhibitors are proven effective in both hypertensive and normotensive patients with any degree of albuminuria to delay nephropathy progression 2
• Type 2 diabetes with microalbuminuria: Both ACE inhibitors and ARBs delay progression to macroalbuminuria 2
• Type 2 diabetes with macroalbuminuria and renal insufficiency (serum creatinine >1.5 mg/dl): ARBs specifically delay nephropathy progression 2, 3
• If one class is not tolerated, substitute with the other 2

Critical caveat: Monitor serum potassium and creatinine within 2-4 weeks of initiation or dose changes 2. Accept creatinine increases up to 30% unless volume depletion is present 1. Never combine ACE inhibitors with ARBs—this increases risks of hyperkalemia, acute kidney injury, and hypotension without additional benefit. 3, 1

Second-Line: SGLT2 Inhibitors

For patients with type 2 diabetes, CKD, and eGFR ≥30 mL/min/1.73 m², add an SGLT2 inhibitor regardless of glycemic control status due to significant renoprotective and cardiovascular benefits. 2, 1

• SGLT2 inhibitors should be used alongside metformin as foundational therapy 2
• These agents reduce CKD progression and cardiovascular events independent of glucose-lowering effects 2, 1

Third-Line: GLP-1 Receptor Agonists

If glycemic targets are not achieved with metformin and SGLT2 inhibitors, or if these medications cannot be used, add a long-acting GLP-1 receptor agonist. 2, 1

• GLP-1 RAs reduce cardiovascular events, particularly in patients with atherosclerotic CVD, and may prevent macroalbuminuria or slow eGFR decline 2

Glycemic Control Targets

Target HbA1c between <6.5% to <8.0% based on individual hypoglycemia risk, age, diabetes duration, and comorbidities. 2, 1

• HbA1c remains accurate for monitoring down to eGFR 30 mL/min/1.73 m² 2
• Below eGFR 15 mL/min/1.73 m², shortened erythrocyte lifespan biases HbA1c low; consider continuous glucose monitoring or self-monitoring of blood glucose 2
• Intensive glycemic control (A-level evidence) reduces risk and slows nephropathy progression 2

Blood Pressure Management

Target blood pressure <130/80 mmHg in all patients with diabetes and CKD. 1

• Aggressive blood pressure control (A-level evidence) reduces risk and slows nephropathy progression 2
• For isolated systolic hypertension ≥180 mmHg, lower gradually in stages 1
• If RAS inhibitors alone are insufficient, avoid dihydropyridine calcium channel blockers as initial add-on therapy—they are not more effective than placebo for slowing nephropathy progression 2
• Consider non-dihydropyridine calcium channel blockers, beta-blockers, or diuretics as additional agents 2

Dietary Modifications

Prescribe protein intake of 0.8 g/kg body weight/day (10% of daily calories) for patients with overt nephropathy not on dialysis. 2, 1

• Once GFR begins declining, further restriction to 0.6 g/kg/day may slow GFR decline in selected patients 2
• Warning: Monitor for nutritional deficiency and muscle weakness; protein-restricted plans require registered dietitian involvement 2
• For dialysis patients, increase protein to 1.0-1.2 g/kg/day 1

Restrict sodium intake to <2 g sodium per day (<5 g sodium chloride per day). 2, 1

• Emphasize a balanced diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, and unsaturated fats 2, 1
• Limit processed meats, refined carbohydrates, and sweetened beverages 2

Lifestyle Interventions

Prescribe moderate-intensity physical activity for cumulative duration of at least 150 minutes per week. 2, 1

Advise all tobacco users to quit immediately. 2, 1

Monitoring and Specialist Referral

Screen annually for microalbuminuria in type 1 diabetes patients with disease duration ≥5 years and all type 2 diabetes patients starting at diagnosis. 2

Refer to nephrology when: 2, 1

• eGFR falls to <30 mL/min/1.73 m² (or <60 mL/min/1.73 m² per some guidelines) 2, 1
• Difficulties managing hypertension or hyperkalemia arise 2
• Uncertain etiology of kidney disease or rapidly progressing disease 1

Management of Complications

Hyperkalemia on RAS Inhibitors

Do not discontinue RAS inhibitors for minor creatinine increases (≤30%) without volume depletion. 1

If hyperkalemia develops: 1

• Moderate dietary potassium intake
• Initiate diuretics
• Use sodium bicarbonate for metabolic acidosis
• Add gastrointestinal cation exchangers

Other Renal Complications

Implement sodium and phosphate restriction with phosphate binders when indicated for complications like osteodystrophy. 2

Exercise extreme caution with radiocontrast media—these are particularly nephrotoxic in diabetic nephropathy. 2

• Carefully hydrate azotemic patients before any unavoidable contrast procedures 2

Critical Pitfalls to Avoid

• Never use dual RAS blockade (ACEi + ARB or either with aliskiren in diabetes)—this increases hyperkalemia and acute kidney injury without benefit 3, 1
• Do not use RAS inhibitors for primary prevention in diabetic patients with normal blood pressure, normal albumin excretion (<30 mg/g), and normal eGFR 2, 1
• Do not delay nephrology referral when eGFR <30 mL/min/1.73 m² or with rapidly declining function 1
• Adjust medications as eGFR declines, particularly glycemic agents 1