What is CAKUT?
CAKUT (Congenital Anomalies of the Kidney and Urinary Tract) represents a spectrum of structural malformations resulting from defects in kidney and urinary tract morphogenesis during fetal development, constituting the leading cause of end-stage kidney disease in children worldwide. 1, 2
Definition and Scope
CAKUT encompasses various structural malformations that arise from disruptions in normal kidney and urinary tract development during fetal life. 2, 3 These anomalies:
- Are the most commonly diagnosed malformations in the prenatal period 1
- Comprise 20-30% of all major birth defects 4
- Are included as components in more than 200 clinical syndromes 4
Developmental Timeline and Pathogenesis
The vulnerability window for CAKUT is extensive:
- Kidney formation begins at week 3 of gestation 2
- Nephrogenesis continues until week 36 2
- The kidneys and outflow tracts remain susceptible to environmental and genetic insults throughout this entire gestational period 2
The resultant clinical phenotypes depend on three critical factors: the timing of the insult, the penetrance of underlying gene mutations, and the severity and timing of any urinary tract obstruction. 3
Common Clinical Entities
The spectrum includes diverse anomalies, with posterior urethral valves (PUV) being the most commonly detected abnormality, accounting for 36.4% of cases in pediatric cohorts. 1 Other entities include vesicoureteral reflux, renal dysplasia, hydronephrosis, and various obstructive uropathies. 5, 1
Epidemiology and Genetic Patterns
Familial clustering occurs in approximately 14% of CAKUT cases, and syndromic CAKUT accounts for 31.8% of presentations. 1 The geographic distribution varies significantly:
- In high-income countries, congenital anomalies of the kidney and urinary tract account for approximately half of all chronic kidney disease cases in children 6
- In low- and lower-middle-income countries, CAKUT rates are lower due to inability to provide prenatal screening and higher rates of infective causes 6
Clinical Severity Spectrum
The severity ranges dramatically:
- In severe cases where kidneys do not form, fetal survival is not possible 2
- In less severe cases, patients may survive with combined kidney and outflow tract defects 2
- Some cases may only be identified in adulthood 2
- At presentation, 9.3% of pediatric CAKUT patients already have end-stage kidney disease, with 60% of these having PUV as their primary disease 1
Prognosis and Long-term Outcomes
Obstructive CAKUT cases present significantly earlier and progress to advanced chronic kidney disease stages more rapidly than non-obstructive forms. 1 The broad spectrum of outcomes depends on the specific anatomic defect, timing of diagnosis, and presence of associated anomalies. 3
Clinical Pitfalls
A critical related concept is low nephron number, which appears to arise by the same mechanisms as CAKUT but differs in the magnitude and timing of the gestational insult. 2 Low nephron number is much more common than severe CAKUT, with effects on kidney function becoming increasingly apparent as patients age. 2