What is diabetic nephropathy?

Diabetic Nephropathy

Diabetic nephropathy is a serious kidney complication of diabetes characterized by persistent albuminuria and progressive decline in renal function, occurring in approximately 20-30% of patients with type 1 or type 2 diabetes. 1

Definition and Pathophysiology

• Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in the United States and Europe, accounting for about 40% of new ESRD cases 1
• The condition develops due to chronic hyperglycemia causing damage to kidney blood vessels, particularly affecting the glomeruli 1
• Diabetic nephropathy is characterized by a progressive increase in urinary albumin excretion and declining glomerular filtration rate (GFR) 1

Natural History and Progression

Early Stage (Incipient Nephropathy)

• The earliest clinical evidence is microalbuminuria, defined as urinary albumin excretion of 30-299 mg/24h or 20-199 μg/min 1, 2
• Without intervention, 80% of type 1 diabetes patients with sustained microalbuminuria progress to overt nephropathy over 10-15 years 1
• Hypertension typically develops alongside increasing albuminuria 1

Advanced Stage (Overt Nephropathy)

• Characterized by clinical albuminuria (macroalbuminuria) ≥300 mg/24h or ≥200 μg/min 1, 2
• Once overt nephropathy occurs, GFR gradually declines at a variable rate (2-20 ml/min/year) 1
• Without specific interventions, ESRD develops in 50% of type 1 diabetic patients with overt nephropathy within 10 years and in 75% by 20 years 1

Differences Between Type 1 and Type 2 Diabetes

• In type 1 diabetes, nephropathy typically develops after 10-15 years of diabetes duration 1
• In type 2 diabetes, microalbuminuria and overt nephropathy may be present shortly after diagnosis because diabetes often exists for years before diagnosis 1
• Without intervention, 20-40% of type 2 diabetes patients with microalbuminuria progress to overt nephropathy 1
• By 20 years after onset of overt nephropathy, only about 20% of type 2 diabetes patients will have progressed to ESRD 1

Risk Factors

• Racial/ethnic variations exist with higher risks in Native Americans, Hispanics (especially Mexican-Americans), and African-Americans compared to non-Hispanic whites 1
• Male sex and prolonged duration of diabetes increase risk 1
• Poor glycemic control and hypertension accelerate progression 1
• Early decrease in GFR, elevated uric acid levels, and presence of albuminuria are predictors of progression 1

Clinical Implications

• Albuminuria is not only a marker of kidney disease but also indicates greatly increased cardiovascular morbidity and mortality 1
• Mortality rates are 30 times higher in diabetic patients with nephropathy compared to those without nephropathy 3
• The majority of patients with diabetic nephropathy die from cardiovascular disease before reaching ESRD 3

Diagnosis

• Screening for microalbuminuria should be performed annually, starting 5 years after diagnosis in type 1 diabetes and at diagnosis in type 2 diabetes 4
• Diagnosis requires confirmation with 2 of 3 specimens collected within a 3-6 month period 2
• Standard hospital laboratory assays for urinary protein are often not sensitive enough to detect microalbuminuria; specific assays are needed 2
• Assessment should include both urinary albumin excretion and estimated glomerular filtration rate (eGFR) 2

Treatment Approach

• Aggressive control of blood pressure and blood glucose are cornerstones of treatment 2
• Angiotensin receptor blockers (ARBs) like losartan have been shown to slow the progression of nephropathy in type 2 diabetes patients 5
• Losartan specifically reduces the risk of doubling of serum creatinine by 25% and ESRD by 29% in type 2 diabetes patients with nephropathy 5
• Early intervention is crucial as treatments have their greatest impact when instituted early in the course of nephropathy 1

Prevention Strategies

• Regular monitoring of blood glucose and kidney function is essential 2
• Comprehensive cardiovascular risk factor management (including lipid control, smoking cessation, and exercise) is recommended upon finding microalbuminuria 1
• Strict blood pressure control, particularly with medications targeting the renin-angiotensin system, is critical 4

Special Considerations

• Some patients, particularly with type 2 diabetes, may have kidney disease without albuminuria (non-proteinuric diabetic nephropathy) 4
• About 40% of type 2 diabetes patients with microalbuminuria show typical diabetic nephropathy changes on biopsy, while approximately 30% have normal or near-normal findings despite having albuminuria 2
• Consider non-diabetic kidney disease in patients with atypical presentations 2