What causes simple renal cysts?

What Causes Simple Renal Cysts

Simple renal cysts are benign lesions that arise from the renal parenchyma through age-related processes, with their exact molecular mechanisms remaining undetermined, though they likely result from tubular obstruction, cellular proliferation, and abnormal fluid accumulation within distended tubular cavities. 1, 2

Primary Pathogenic Mechanisms

The development of simple renal cysts involves several interconnected pathological processes:

• Tubular obstruction is the leading historical hypothesis, first proposed by Hepler in 1930, suggesting that blockage of renal tubules initiates cyst formation 3
• Cellular proliferation and dedifferentiation occur, with cyst epithelium composed of moderately dedifferentiated, immature epithelial cells that proliferate abnormally 2
• Abnormal fluid transport develops as cyst epithelium secretes fluid rather than absorbing it (the normal tubular function), leading to progressive fluid accumulation and cavity distension 2
• Extracellular matrix remodeling accompanies cyst formation, including basement membrane thickening, interstitial mononuclear cell infiltration, and interstitial fibrosis 2

Age-Related Development

Simple renal cysts are fundamentally age-related lesions:

• Their occurrence, number, and bilaterality increase progressively with advancing age 1
• They are uncommon in pediatric patients, with the vast majority occurring in adults 3
• The mean age in longitudinal studies is approximately 58 years 4

Potential Contributing Factors

While the molecular mechanisms remain incompletely understood, several factors may contribute:

• Metabolic abnormalities may play a role, particularly in pediatric cases, where hypercalciuria and/or hypocitraturia are present in a significant proportion (63% in one study), suggesting a possible relationship with genetic predisposition to kidney stones 3
• Genetic or environmental insults may trigger the cascade of events leading to cyst formation, though specific mutations have not been identified for simple cysts (unlike hereditary polycystic kidney diseases) 5
• Disrupted nephrogenesis processes can lead to cyst formation when normal tubular development is interrupted 5

Important Clinical Distinctions

Simple cysts must be distinguished from other cystic entities:

• Simple cysts are acquired and sporadic, not hereditary, unlike autosomal dominant polycystic kidney disease (ADPKD) which is caused by PKD1 or PKD2 gene mutations 6
• They are not associated with end-stage renal disease, unlike acquired cystic disease (ACD) which develops specifically in the setting of chronic kidney disease and dialysis 6
• Simple cysts typically remain asymptomatic and benign, with 86% increasing in size over time but none developing complex features or malignant transformation in longitudinal studies 4

Natural History and Clinical Significance

• Simple cysts grow at an average rate of approximately 6.5% per year in axial diameter, with most (78%) increasing by ≥6% in volume annually 4
• Complications are rare but can include hemorrhage, infection, or rupture, which transform simple cysts into complex cysts with calcification and irregular demarcation 1
• No follow-up imaging is indicated for enlarging asymptomatic simple renal cysts, as growth does not indicate malignant potential 4