Leading Cause of Chronic Renal Failure Worldwide
Diabetes is the leading cause of chronic kidney disease and end-stage renal disease (kidney failure) worldwide, accounting for approximately 40-50% of all cases requiring dialysis or transplantation. 1, 2
Primary Etiologies of End-Stage Kidney Disease
Diabetes as the Dominant Cause
Diabetic kidney disease (DKD) has become the single most common cause of kidney failure in the United States, Europe, and most developed countries, representing roughly 40% of new ESRD cases in the U.S. and approximately 50% globally. 1, 2
In the U.S., 66-86% of patients with end-stage kidney disease have a diagnosis of diabetes, with variation depending on age and race/ethnicity. 1
Both type 1 and type 2 diabetes contribute to this burden, though type 2 diabetes accounts for over half of diabetic patients starting dialysis due to its much greater prevalence in the population. 1
Hypertension as the Second Major Cause
Hypertension is the second leading cause of chronic kidney disease in developed countries, with approximately 70% of individuals with elevated serum creatinine having hypertension. 3
Hypertension creates a dangerous bidirectional relationship—it both causes kidney damage and results from kidney disease, accelerating the rate of GFR decline to 4-8 mL/min per year when poorly controlled. 3
Other Contributing Causes
Glomerulonephritis represents another significant cause, accounting for approximately 21.4% of CKD cases globally, with particular importance in younger populations and certain geographic regions. 3, 4
In China specifically, chronic glomerulonephritis and diabetes together account for more than 50% of CKD cases. 3
Clinical Implications and Risk Factors
Population-Specific Risks
There is considerable racial and ethnic variability in progression to ESRD, with Native Americans, Hispanics (especially Mexican-Americans), and African-Americans having substantially higher risks than non-Hispanic whites with type 2 diabetes. 1
Among diabetic patients, 20-40% develop evidence of nephropathy, though a smaller fraction of type 2 diabetics progress to ESRD compared to type 1 diabetics. 1
Timeline and Natural History
In type 1 diabetes, DKD typically develops after 10 years of disease duration, whereas in type 2 diabetes it may already be present at the time of diagnosis. 2, 3
Without intervention, 80% of type 1 diabetic patients with sustained microalbuminuria progress to overt nephropathy over 10-15 years, and 50% develop ESRD within several years thereafter. 1
Mortality Impact
The presence of diabetic kidney disease increases 10-year all-cause mortality from 11.5% in diabetic patients without kidney disease to 31% in those with kidney disease, with cardiovascular disease causing death more frequently than progression to kidney failure. 1, 2
Patients with diabetes on hemodialysis have the worst adjusted survival rates among the ESRD population, with only 55% surviving 3 years and 40% surviving 5 years after dialysis initiation. 1
Common Pitfalls to Avoid
Do not assume diabetes is the cause of kidney disease in every diabetic patient—up to 30% of patients with presumed diabetic kidney disease have other causes on kidney biopsy, particularly when atypical features are present (absence of retinopathy, short disease duration, rapid decline, active urinary sediment). 3
Do not overlook screening in type 2 diabetes at diagnosis, as 6.5% of newly diagnosed patients already have significant albuminuria and 28% already have hypertension. 3
Recognize that the contribution of diabetes to ESRD prevalence has begun to moderate in recent years, possibly reflecting improved management with renin-angiotensin system blockade and newer glucose-lowering agents. 1