Nephropathy, Diabetic

Key Features

• Most common cause of end-stage kidney disease (ESKD) in United States

• Prior evidence of diabetes mellitus, typically more than 10 years duration

• Incidence is about 30% in both types 1 and 2 diabetes mellitus

• Males, African Americans, and Native Americans are at higher risk

Clinical Findings

• Diabetic retinopathy is common

• Microalbuminuria develops within 10–15 years after onset of diabetes and progresses over the next 3–7 years to overt proteinuria

• Kidney size usually enlarged

Diagnosis

• First stage of diabetic nephropathy is hyperfiltration, with an increase in glomerular filtration rate (GFR), followed by the development of microalbuminuria (30–300 mg/day)

• With progression, albuminuria increases to > 300 mg/day and can be detected on a urine dipstick as overt proteinuria; GFR subsequently declines over time

• Renal biopsy is not required in most patients unless atypical findings are present

  • Sudden onset of proteinuria

  • Nephritic spectrum features

  • Massive proteinuria (> 10 g/day)

  • Urinary cellular casts

  • Rapid decline in GFR

Treatment

• Microalbuminuria requires aggressive treatment

• Strict glycemic control

• Blood pressure goals should be tailored:

  • 140/90 mm Hg in patients with microalbuminuria (30–300 mg/day) and preserved GFR and in patients with significant cardiovascular disease

  • < 130/80 mm Hg in patients with overt proteinuria (especially when > 1 g/day)

• ACE inhibitors and ARBs

  • Recommended in those with microalbuminuria to

    • Lower the rate of progression to overt proteinuria

    • Slow progression to ESKD by reducing intraglomerular pressure and by antifibrotic effects

  • Not absolutely indicated in diabetic patients with normal blood pressure and no microalbuminuria

  • May provide benefit in patients with markedly diminished GFR

  • With initiation or uptitration of therapy, close monitoring to exclude resultant hyperkalemia or decline in GFR of > 30%

  • Combination ARB and ACE inhibitor therapy is not recommended due to lack of efficacy and increased adverse events (hyperkalemia and acute kidney injury)

• Canagliflozin, empagliflozin, and dapagliflozin (sodium glucose cotransporter 2 [or SGLT-2] inhibitors)

  • Slow progression of diabetic nephropathy in addition to having cardioprotective effects

  • Use is limited to patients who have type 2 diabetes mellitus with eGFR > 30 mL/min

• Treatment of other cardiovascular risk factors and obesity is crucial

• Patients who are relatively healthy benefit from kidney transplantation