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For further information, see CMDT Part 24-19: Diabetic Nephropathy

KEY FEATURES

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

  • Evidence of diabetes mellitus, typically over 10 years

  • Incidence of chronic kidney disease (CKD) is about 30% in both types 1 and 2 diabetes mellitus

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

  • Those with a family history of kidney disease are at higher risk

  • Albuminuria usually precedes decline in glomerular filtration rate (GFR)

CLINICAL FINDINGS

  • Diabetic retinopathy is common

  • Develops about 10 years after the onset of diabetes mellitus

  • May be present at the time type 2 diabetes mellitus is diagnosed

  • Kidney size usually enlarged until disease becomes advanced

  • Patients with diabetes prone to other kidney diseases, such as

    • Papillary necrosis

    • Chronic interstitial nephritis

    • Type 4 (hyporeninemic hypoaldosteronemic) renal tubular acidosis

    • Acute kidney injury (AKI) from many insults (eg, intravenous contrast material and concomitant use of an angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor blocker [ARB] with nonsteroidal anti-inflammatory drug [NSAID])

  • Mortality rates are higher for patients with diabetes and kidney disease compared to those without CKD

DIAGNOSIS

  • First stage of diabetic nephropathy is hyperfiltration, with an increase in GFR, followed by the development of moderate albuminuria (30–300 mg/d)

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

  • Yearly screening for moderate albuminuria is recommended for all patients with diabetes; diabetic nephropathy less commonly can present as nonproteinuric CKD

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

    • Sudden onset of proteinuria

    • Nephritic features

    • Massive proteinuria (> 10 g/d)

    • Urinary cellular casts

    • Rapid decline in GFR

TREATMENT

  • Moderate albuminuria requires aggressive treatment

  • Strict glycemic control should be emphasized early, with recognition of risk of hypoglycemia as CKD becomes advanced

  • Blood pressure goals should be tailored:

    • ACCORD trial: blood pressure lowering below 140/90 mm Hg in patients with moderate albuminuria (30–300 mg/d) and preserved GFR and those with significant cardiovascular disease did not confer survival benefit

    • 2021 Kidney Disease Improving Global Outcomes practice guidelines: targeting < 120/80 mm Hg in patients with diabetes and CKD, regardless of degree of albuminuria

  • ACE inhibitors and ARBs

    • Recommended in those with moderate albuminuria to

      • Decrease rate of progression to overt proteinuria

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

    • Not absolutely indicated in diabetic patients without albuminuria

    • With initiation or up titration of therapy, close monitoring within ∼2 weeks 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 AKI)

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

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

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