How does diabetes affect the kidneys?

How Diabetes Damages the Kidneys

Diabetes damages the kidneys through chronic high blood glucose levels that injure the small blood vessels in the glomeruli (the kidney's filtering units), leading to progressive structural damage including thickening of the glomerular basement membrane, mesangial expansion, glomerulosclerosis, and tubulointerstitial fibrosis—ultimately resulting in declining kidney function, albuminuria (protein in urine), and potentially kidney failure. 1, 2

Primary Mechanisms of Kidney Damage

Vascular and Structural Injury

• High blood glucose directly damages the small blood vessels (capillaries) within the kidney's glomeruli, impairing their ability to filter waste and fluids effectively 1
• The glomerular basement membrane undergoes homogenous thickening, which disrupts normal filtration 1
• Mesangial expansion occurs as the supporting cells and matrix between capillaries in the glomeruli proliferate abnormally 1
• Glomerulosclerosis develops as scarring replaces functional kidney tissue 1

Filtration Barrier Breakdown

• Diabetes damages the glomerular filtration barrier, a highly specialized three-layer structure consisting of fenestrated endothelium, glomerular basement membrane, and epithelial podocytes 3
• This barrier normally permits highly selective ultrafiltration of blood plasma, but diabetes disrupts this selectivity 3
• The result is albuminuria—abnormal leakage of albumin protein into the urine, which is the hallmark clinical sign of diabetic kidney damage 1, 3

Tubular Damage

• Beyond glomerular injury, diabetes causes damage to both glomerular and tubular compartments of the kidney 1
• Tubulointerstitial fibrosis develops as scar tissue replaces normal kidney tubule structure 1

Clinical Progression Pattern

Early Stage Changes

• The disease begins with glomerular hyperfiltration—the kidneys initially filter too much blood as they attempt to compensate 3
• This hyperfiltration phase can be reversible if diabetes is controlled early 3
• Kidney size may remain normal initially, particularly in type 2 diabetes, despite progressive functional decline 4

Progressive Stages

• Stage 1-2: Normal or mildly decreased kidney function (GFR ≥60 mL/min/1.73m²) with evidence of kidney damage 5, 4
• Stage 3: Moderate decrease in kidney function (GFR 30-59 mL/min/1.73m²) 5
• Stage 4: Severe decrease in kidney function (GFR 15-29 mL/min/1.73m²) 5
• Stage 5: Kidney failure (GFR <15 mL/min/1.73m² or requiring dialysis) 5

Timeline of Development

• In type 1 diabetes, diabetic kidney disease typically develops after 10 years of disease duration 5, 4
• In type 2 diabetes, kidney disease may be present at the time of diagnosis because the diabetes itself often goes undetected for years 5, 4
• Approximately 20-40% of diabetic patients develop microalbuminuria within 10-15 years, and 80-90% of those progress to more advanced stages 3, 5

Contributing Factors Beyond Glucose

Hypertension

• High blood pressure is both a cause and consequence of diabetic kidney disease, creating a dangerous cycle that accelerates kidney function decline 4, 2
• Hypertension dramatically accelerates progression, with GFR decreasing at rates greater than 10 mL/min/year in those with poorly controlled blood pressure and macroalbuminuria 4

Other Risk Factors

• Genetic predisposition plays a role in determining who develops kidney disease 1
• Aging-related nephron loss compounds the damage from diabetes 2
• Lifestyle factors including smoking contribute to progression 3

Clinical Consequences

Mortality and Cardiovascular Risk

• All-cause mortality in individuals with diabetic kidney disease is approximately 30 times higher than in diabetic patients without kidney disease 6
• The presence of kidney disease is associated with a sharp increase in 10-year cumulative all-cause mortality from 11.5% among individuals with diabetes without kidney disease up to 31% among those with kidney disease 7
• Most patients with diabetic kidney disease will die from cardiovascular disease before reaching end-stage kidney disease 6
• Individuals with chronic kidney disease have twice the risk of cardiovascular disease compared to those without kidney disease 7

End-Stage Kidney Disease

• Diabetic kidney disease is the single leading cause of end-stage kidney disease in the United States, accounting for approximately 35% of cases 5
• It is the most common cause of kidney failure requiring dialysis or transplantation worldwide 7
• In advanced stages, patients require dialysis or kidney transplant to sustain life 1

Quality of Life Impact

• Progression of kidney disease is associated with reduced quality of life from the patient's perspective 7
• The condition represents a significant social and economic burden globally 6

Key Clinical Pitfall

A critical misconception is that diabetic kidney disease always follows a predictable pattern of albuminuria followed by declining kidney function. In reality, reduced kidney function without albuminuria is becoming increasingly common in both type 1 and type 2 diabetes, meaning kidney disease can present without the traditional albuminuria progression pathway 4. Additionally, up to 30% of patients with clinical diabetic kidney disease may have other causes of kidney disease on biopsy, requiring different management approaches 7.