What is the recommended treatment for a patient with diabetic nephropathy and a history of diabetes?

Treatment of Diabetic Nephropathy

Start an ACE inhibitor or ARB immediately as first-line therapy, optimize blood glucose control to near-normal levels, and target blood pressure <130/80 mmHg, while restricting dietary protein to 0.8 g/kg/day. 1

Pharmacologic Management: ACE Inhibitors and ARBs

First-Line Therapy Selection

ACE inhibitors and ARBs are the cornerstone of treatment, providing renoprotection beyond blood pressure lowering alone by reducing intraglomerular pressure and proteinuria. 2

• For Type 1 diabetes with any degree of albuminuria: ACE inhibitors are preferred and delay nephropathy progression in both hypertensive and normotensive patients, reducing risk of death, dialysis, and transplantation by 50% and risk of doubling serum creatinine by 48%. 1, 2

• For Type 2 diabetes with microalbuminuria (30-299 mg/g): Either ACE inhibitors or ARBs delay progression to macroalbuminuria in hypertensive patients. 1, 2

• For Type 2 diabetes with macroalbuminuria (≥300 mg/g) and elevated serum creatinine: ARBs are specifically indicated and reduce progression to end-stage renal disease more effectively than other antihypertensive classes. 1, 3

Critical Implementation Points

• If one class is not tolerated, substitute the other—never combine ACE inhibitor with ARB, as the VA NEPHRON-D trial demonstrated increased hyperkalemia and acute kidney injury without additional benefit. 2, 3

• Uptitrate to maximally tolerated dose rather than focusing on which specific agent within the class. 2

• Maintain ACE inhibitor or ARB as the foundation even when adding additional antihypertensive agents to reach blood pressure targets. 2

Blood Pressure Control

Target blood pressure <130/80 mmHg using ACE inhibitor or ARB as first-line therapy. 1, 2, 4

• If additional agents are needed, add non-dihydropyridine calcium channel blockers, β-blockers, or diuretics. 1, 4

• Dihydropyridine calcium channel blockers as initial monotherapy are not more effective than placebo in slowing nephropathy progression and should only be used as add-on therapy. 1, 2

Glycemic Control

Optimize glucose control to near-normoglycemia (HbA1c <7%) through intensive diabetes management. 1, 4

• Intensive glycemic control reduces development and progression of microalbuminuria by 34-43%. 4

• This intervention delays onset of microalbuminuria and progression to macroalbuminuria in both Type 1 and Type 2 diabetes. 1

Dietary Protein Restriction

Prescribe protein intake of 0.8 g/kg/day (the adult RDA, approximately 10% of daily calories) in patients with overt nephropathy. 1, 4

• Once GFR begins to fall, further restriction to 0.6 g/kg/day may slow GFR decline in selected patients. 1

• Common pitfall: Nutrition deficiency may occur with excessive restriction and may be associated with muscle weakness—protein-restricted meal plans should be designed by a registered dietitian familiar with diabetes management. 1

Monitoring Strategy

Initial Monitoring

• Check serum creatinine and potassium within 7-14 days of ACE inhibitor/ARB initiation or dose change. 2

• Accept creatinine increases up to 30% from baseline. 2

• Discontinue if potassium >5.5 mEq/L despite dietary restriction and diuretic adjustment. 2

Ongoing Surveillance

• Monitor serum potassium every 3-4 months, as both ACE inhibitors and ARBs can exacerbate hyperkalemia, particularly in patients with advanced renal insufficiency. 1, 2, 4, 3

• Recheck urine albumin-to-creatinine ratio every 6 months to assess response to therapy and disease progression. 4

• Calculate eGFR at least annually to detect declining kidney function. 4

Additional Management Considerations

Standard Renal Disease Modalities

• Implement sodium and phosphate restriction when indicated. 1

• Use phosphate binders for management of renal osteodystrophy. 1

Nephrotoxin Avoidance

• Radiocontrast media are particularly nephrotoxic in diabetic nephropathy—carefully hydrate azotemic patients before any procedures requiring contrast that cannot be avoided. 1

• Monitor renal function when coadministering NSAIDs (including COX-2 inhibitors), as they may cause deterioration of renal function, including possible acute renal failure, particularly in elderly or volume-depleted patients. 3

Specialist Referral

Refer to a physician experienced in diabetic renal disease when GFR falls to <60 mL/min/1.73 m² or when difficulties occur managing hypertension or hyperkalemia. 1, 4

• Clinical trials demonstrating ACE inhibitor benefit excluded patients with eGFR <30 mL/min/1.73 m², as structural kidney damage is often irreversible at this stage. 2