What are the most common causes of chronic kidney disease (CKD) in individuals younger than 40 years?

Causes of Chronic Kidney Disease in Young Age

In individuals younger than 40 years, congenital anomalies of the kidneys and urinary tract (CAKUT) are the predominant cause of CKD, accounting for the majority of cases, followed by hereditary diseases, steroid-resistant nephrotic syndrome, and chronic glomerulonephritis. 1, 2

Primary Causes in Young Adults and Children

Congenital and Structural Abnormalities

• Congenital anomalies of the kidneys and urinary tract (CAKUT) represent the leading cause of early-onset CKD, encompassing renal dysplasia, reflux-associated kidney damage, and obstructive uropathy. These conditions together account for over 70% of CKD diagnoses in individuals under 25 years when combined with other pediatric-specific etiologies. 1, 2
• Obstructive uropathy contributes to approximately 6.9% of CKD cases and should be considered in young patients with structural urinary tract abnormalities. 3

Hereditary and Genetic Disorders

• Over 200 different monogenic genes have been identified as causes of early-onset CKD, making genetic disorders a major contributor to disease in this age group. 1
• Autosomal dominant polycystic kidney disease (ADPKD) accounts for approximately 1.5% of CKD cases and represents one of the most common hereditary causes. 3
• Alport syndrome causes progressive proteinuria and CKD through inherited collagen-IV defects, particularly in young males with family history of kidney disease and hearing loss. 4, 5
• Renal cystic ciliopathies are among the four most common diagnostic groups causing CKD before age 25. 1

Glomerular Diseases

• Steroid-resistant nephrotic syndrome is one of the four most frequent causes of early-onset CKD, often presenting with heavy proteinuria and foamy urine. 1
• Chronic glomerulonephritis accounts for approximately 21.4% of CKD cases overall and represents a significant proportion in younger populations, particularly when including IgA nephropathy (Berger disease). 4, 3
• Primary focal segmental glomerulosclerosis (FSGS) can cause progressive CKD in young adults while maintaining normal kidney size on imaging in early stages. 6

Secondary Causes in Younger Adults

Diabetes and Hypertension

• While diabetes is the leading cause of CKD in adults overall (30-40% of cases), it typically develops after 10 years of disease duration in type 1 diabetes, making it less common in very young patients but increasingly relevant in young adults with longstanding disease. 6, 7
• Hypertension accounts for approximately 19.5% of CKD cases and becomes more prevalent as a cause in the older end of the "young adult" spectrum (ages 30-40). 7, 3

Other Contributing Factors

• Chronic interstitial nephritis contributes to 3.6% of CKD cases, often related to medication exposure, infections, or autoimmune conditions. 3
• Approximately 25% of teenagers and young adults with CKD present directly to adult services after age 16, often with previously undiagnosed congenital or hereditary conditions. 4

Key Diagnostic Considerations

When to Suspect Genetic or Congenital Causes

• Family history of kidney disease is highly significant in young patients, suggesting possible genetic disorders such as Alport syndrome, thin basement membrane disease, or APOL1-related nephropathy. 6
• Absence of typical adult risk factors (diabetes, hypertension) in a young patient with CKD strongly suggests congenital or hereditary etiology. 4, 1
• Bilateral small kidneys or structural abnormalities on imaging point toward CAKUT or hereditary conditions rather than acquired disease. 6

Essential Workup for Young Patients

• Measure both eGFR and urinary albumin-to-creatinine ratio (UACR) to confirm CKD diagnosis, as either abnormality persisting ≥3 months establishes the diagnosis. 6, 8
• Renal ultrasound is the best initial imaging modality to assess kidney size, position, and screen for structural abnormalities or cystic disease. 4
• Kidney biopsy may be necessary in up to 30% of cases when the etiology remains unclear, particularly to diagnose glomerulonephritis, hereditary nephropathies, or atypical presentations. 6
• Genetic testing should be considered in young patients with CKD of unclear etiology, especially when family history is positive or clinical features suggest hereditary disease. 1

Common Pitfalls to Avoid

• Do not assume diabetes or hypertension as the cause in young patients without confirming adequate disease duration and typical features, as congenital and hereditary causes are far more likely in this age group. 4, 1
• Do not rely on kidney size alone to exclude CKD, as conditions like diabetic nephropathy and infiltrative disorders can present with normal-sized kidneys despite significant dysfunction. 6
• Do not skip family history assessment, as many hereditary kidney diseases have autosomal dominant inheritance patterns that may not be immediately apparent. 6
• Refer to nephrology early when eGFR <30 mL/min/1.73 m², UACR ≥300 mg/g, unclear etiology, or atypical features are present, as specialized evaluation including potential kidney biopsy may be needed. 6, 8