Causes of Chronic Kidney Disease in Young Children
Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic kidney disease in young children, accounting for approximately half of all pediatric CKD cases in high-income countries. 1
Primary Causes by Geographic and Economic Context
High-Income Countries
- Congenital causes (50% of cases):
- Genetic disorders:
Low and Lower-Middle-Income Countries
- Infectious causes (may exceed congenital causes):
- HIV nephropathy
- Hepatitis B-related nephropathy
- Post-infectious glomerulonephritis
- Iatrogenic causes (medication-related)
- Congenital anomalies (less frequently diagnosed due to limited prenatal screening) 1
Risk Factors for CKD Progression in Children with CAKUT
- Male gender (associated with higher CKD stages) 2
- Premature birth (significantly associated with CKD stage ≥ II) 2
- Abnormal prenatal ultrasound (associated with more severe CKD - GFR <30 ml/min/1.73 m²) 2
Long-Term Implications
Children with a history of kidney disease, even those who appear to have normal renal function in adolescence, have a significantly increased risk of developing end-stage renal disease (ESRD) in adulthood:
- 4.19 times higher risk of ESRD compared to those without childhood kidney disease 3
- 10.40 times higher risk of early-onset ESRD (before age 40) 3
Acute Kidney Injury as a Precursor to CKD
The etiology of acute kidney injury (AKI) in children also varies by geographic region:
High-Income Countries
- Hospital-acquired AKI related to:
- Cancer treatments
- Cardiac surgery
- Solid organ transplantation
- Multi-organ failure
Low and Lower-Middle-Income Countries
- Community-acquired AKI related to:
- Acute gastroenteritis causing dehydration
- Postinfectious glomerulonephritis
- Severe malaria
- Envenomation (snake and insect bites) 1
Diagnostic Approach for Suspected Genetic Causes
For children with very-early-onset or rapidly progressive cystic kidney disease:
- Genetic testing is recommended for:
- Infants with very-early-onset symptomatic disease (regardless of family history)
- Children with progressive disease (increasing cyst number or kidney volume) and negative family history 1
- Multi-gene panel testing is preferred over single-gene testing due to phenotypic overlap between different cystic kidney diseases 1
- Panels should include coverage of PKD1, PKD2, PKHD1, DZIP1L, HNF1B, and genes for other ciliopathies 1
Management Considerations
- Blood pressure monitoring is essential as hypertension is one of the most common complications of pediatric CKD (20% prevalence) 1
- Ambulatory blood pressure monitoring is preferred when feasible, especially in children at high risk 1
- Transition planning from pediatric to adult nephrology services is critical for adolescents with CKD 1
- Treatment options to slow CKD progression include:
- Blood pressure control (ACE inhibitors or ARBs)
- Glycemic control in diabetes
- Management of metabolic disturbances (acidosis, hyperphosphatemia, vitamin D deficiency) 4
Common Pitfalls in Pediatric CKD Management
- Missing the diagnosis in children with a single cyst or mild manifestations
- Assuming normal kidney function in adolescence means no risk of future kidney disease
- Inadequate transition from pediatric to adult nephrology care
- Failure to recognize the increased cardiovascular risk associated with CKD, even in children
- Underestimating the importance of early diagnosis and intervention to slow progression
Understanding the etiology of CKD in children is essential for appropriate management, monitoring, and potentially slowing disease progression to improve long-term outcomes.