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Key Features

  • Most common cause of end-stage renal disease in United States

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

  • Type 1 diabetes mellitus carries a 30–40% risk of nephropathy after 20 years

  • Type 2 diabetes carries a 15–20% risk after 20 years

  • 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 ESRD 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)

  • Newer antidiabetic agents show early promise in slowing the progression of diabetic nephropathy, including

    • Canagliflozin and empagliflozin (SGLT-inhibitors)

    • Linagliptin (DPP-4 inhibitor)

    • Liraglutide (GLP-1 receptor antagonist)

  • Treatment of other cardiovascular risk factors and obesity is crucial

  • Patients who are relatively healthy benefit from kidney transplantation

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