Causes of Chronic Kidney Disease
Primary Causes
Diabetes is the single largest cause of CKD and kidney failure in the United States, accounting for 30-40% of end-stage kidney disease cases. 1, 2 Diabetic kidney disease typically develops after 10 years in type 1 diabetes but may already be present at the time of diagnosis in type 2 diabetes. 1, 2
Hypertension is the second leading cause of CKD in developed countries and creates a dangerous bidirectional relationship—it both causes kidney damage AND results from kidney disease, accelerating progression. 1, 2, 3 This vicious cycle is particularly devastating when blood pressure remains uncontrolled. 3
Other Major Causes
Glomerular diseases represent a significant cause of CKD, particularly in certain geographic regions:
- Chronic glomerulonephritis is especially common in Asia and sub-Saharan Africa 2, 3
- In China specifically, chronic glomerulonephritis and diabetes together account for more than 50% of CKD cases 2, 3
- Primary focal segmental glomerulosclerosis (FSGS) and minimal change disease can cause progressive CKD 2
Vascular diseases affecting kidney blood supply contribute to CKD development 1
Tubulointerstitial diseases including chronic interstitial nephritis and autosomal dominant tubulointerstitial kidney diseases lead to progressive fibrosis 1, 2
Cystic kidney diseases such as polycystic kidney disease cause progressive kidney function decline 1, 2
Risk Factors and Susceptibility
Modifiable Risk Factors
- Hyperglycemia in diabetes is a fundamental cause of vascular complications including kidney disease 1
- Uncontrolled hypertension dramatically accelerates progression, with GFR decreasing at rates greater than 10 mL/min/year when combined with macroalbuminuria 2, 3
- Dyslipidemia contributes to kidney damage 1
- Obesity increases CKD risk 4
- Smoking accelerates progression 5
Non-Modifiable Risk Factors
- Family history of diabetic kidney disease, hypertension, or cardiovascular disease increases risk 1, 3
- Age—CKD typically begins late in life 1
- Genetic alterations predispose to certain forms of kidney disease 6
Additional Contributing Factors
- Acute kidney injury (AKI) is now recognized as a risk factor for developing CKD de novo or worsening existing CKD 7
- Reduced blood supply to kidneys from various causes 6
- Urinary tract obstruction (though this accounts for less than 3% of cases) 3
- Kidney infections and infiltrative disorders 1, 2
- Nephrotoxic drug exposure including NSAIDs, aminoglycosides, and certain antibiotics 5, 8
Critical Clinical Pitfalls
Never assume normal-sized kidneys on imaging exclude CKD—diabetic kidney disease, minimal change disease, and early FSGS all present with normal kidney size despite significant dysfunction. 2, 3 Up to 30% of patients with presumed diabetic kidney disease have other causes on biopsy. 2
Avoid the "triple whammy" combination of ACE inhibitors/ARBs, diuretics, and NSAIDs, especially in elderly patients, as this dramatically increases acute kidney injury risk. 3
Screening Recommendations
All patients with type 2 diabetes should be screened immediately at diagnosis using urinary albumin-to-creatinine ratio (UACR) and estimated GFR (eGFR), as 6.5% already have urinary albumin >50 mg/L and 28% already have hypertension at diagnosis. 2, 3, 8
Type 1 diabetes patients should begin screening after 5 years of disease duration. 3
Patients with hypertension require regular kidney function monitoring given the high risk of CKD development. 2, 8
Pathophysiological Mechanisms
The progression of CKD involves common pathways regardless of initial cause 6, 4: