Is RLS a Symptom or Result of CKD?
RLS is a secondary complication (result) of CKD, not merely a symptom—it develops as a distinct neurologic disorder triggered by the metabolic and physiologic derangements caused by chronic kidney disease, particularly iron deficiency and uremia. 1, 2
Understanding the Distinction
The American Geriatrics Society explicitly classifies RLS in CKD patients as secondary RLS, meaning it results from the underlying kidney disease rather than being a direct symptom of it. 1, 2 This is an important conceptual distinction:
- Secondary RLS develops from medical conditions that share iron deficiency as a common underlying mechanism, including end-stage renal disease, iron-deficiency anemia, and pregnancy. 1, 2
- Primary (idiopathic) RLS has a genetic basis, develops earlier in life, and has no identifiable associated conditions. 1, 2
Why CKD Causes RLS
The pathophysiology involves multiple CKD-related mechanisms:
- Iron metabolism dysfunction: CKD impairs iron storage and utilization, leading to reduced intracellular iron in the substantia nigra, which impairs dopamine transport—a critical mechanism in RLS development. 2, 3
- Uremia: Inadequate dialysis and uremic toxin accumulation contribute to RLS symptoms. 4, 5
- Metabolic derangements: Calcium/phosphate imbalances, hyperparathyroidism, and altered neurotransmitter systems (glutamate, dopamine, opioid receptors) play roles. 4, 5
Epidemiologic Evidence Supporting RLS as a Result of CKD
The prevalence data strongly supports RLS as a consequence rather than symptom of CKD:
- RLS affects up to 25% of dialysis patients when international diagnostic criteria are applied, compared to approximately 10% in the general population. 1, 6
- A meta-analysis demonstrated a sixfold increased risk of RLS in CKD patients compared to the general population (OR 5.64,95% CI 2.70-11.78). 7
- RLS prevalence is 2.6 times higher in end-stage kidney disease (26%) compared to CKD stage 3 (10%), suggesting progressive kidney impairment worsens or triggers RLS development. 5
- The increasing prevalence of RLS with age is partly attributable to the increasing presence of secondary causes like renal failure in aging populations. 1
Clinical Implications of This Distinction
Understanding RLS as a result rather than symptom changes clinical management:
- Independent predictors of RLS in CKD include: end-stage kidney disease status (OR 3.8), inadequate dialysis (OR 4.6), hyperparathyroidism (OR 5.1), and peripheral neuropathy (OR 5.6). 5
- RLS in CKD is associated with increased cardiovascular morbidity, sleep disturbance, decreased quality of life, and increased mortality risk—it functions as an independent complication requiring specific treatment. 4, 6
- Treatment approaches differ from primary RLS: renal transplantation and optimizing dialysis adequacy can resolve uremic RLS, whereas primary RLS requires lifelong management. 4
Common Pitfall to Avoid
Do not assume leg discomfort in CKD patients is simply "uremic symptoms"—apply formal RLS diagnostic criteria (urge to move legs with uncomfortable sensations, symptoms worsen with rest, relief with movement, circadian worsening in evening/night) to distinguish true RLS from other causes of leg discomfort like peripheral neuropathy, vascular disease, or arthritis. 2, 3