Diabetic kidney disease

Definition

Diabetic nephropathy (diabetic kidney disease) is glomerular sclerosis and fibrosis caused by the metabolic and hemodynamic changes of diabetes mellitus. It manifests as slowly progressive albuminuria with worsening hypertension and progressive chronic kidney disease.

Occurrence & epidemiology

Diabetic nephropathy is the most common cause of kidney failure worldwide and the most common cause of nephrotic syndrome in adults. Because type 2 diabetes often remains unrecognized for years, nephropathy may already be present at diagnosis; about 25% of people with type 2 diabetes have microalbuminuria 10 years after diagnosis.

Aetiopathogenesis

Risk factors and pathogenesis

Risk factors are the duration and degree of hyperglycemia, arterial hypertension, dyslipidemia, smoking, family history and genetic factors such as polymorphisms of the renin-angiotensin-aldosterone system or a reduced number of glomeruli.

The process begins with microangiopathy. Glycation of glomerular proteins, cytokines such as TGF-β, proliferation of mesangial cells and matrix and altered glomerular hemodynamics lead to thickening of the basement membrane and sclerosis. An early functional abnormality is glomerular hyperfiltration.

Clinical features

Typical course over years: glomerular hyperfiltration, then moderately increased albuminuria (30–300 mg/24 h, formerly microalbuminuria), later severely increased albuminuria (> 300 mg/24 h) and often nephrotic syndrome, followed several years later by kidney failure. Early stages are asymptomatic; persistent microalbuminuria is the earliest warning sign.

In the course, most patients develop hypertension and edema. Uremic symptoms often appear at a higher GFR than in other kidney diseases. Papillary necrosis, type 4 renal tubular acidosis and urinary tract infections occur more often.

Histology

Thickened glomerular basement membrane, diffuse or nodular intercapillary glomerulosclerosis (the nodular form is called the Kimmelstiel-Wilson lesion), marked hyalinosis of afferent and efferent arterioles, and interstitial fibrosis and tubular atrophy. The extent of mesangial expansion correlates with progression to kidney failure.

Diagnosis

• Albumin-to-creatinine ratio in a spot urine, ideally mid-morning: a value ≥ 30 mg/g in at least 2 of 3 samples within 3–6 months indicates moderately increased albuminuria, provided infection or exercise has been excluded as the cause.
• If the dipstick is already positive for protein, severely increased albuminuria is usually present.
• eGFR and urine sediment; on ultrasound the kidneys are usually normal-sized or enlarged.
• The presence of diabetic retinopathy supports the diagnosis as a sign of microangiopathy.

The diagnosis is usually clinical. Another kidney disease is considered in case of heavy proteinuria with a short duration of diabetes, absent retinopathy, rapid onset of heavy proteinuria, gross hematuria, red blood cell casts, rapid decline in GFR or small kidneys; a kidney biopsy then clarifies the cause.

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Diabetic Nephropathy
2. MSD Manual Professional: Evaluation of the Patient With Renal Issues

Cross-references