Kidney Stones Do Not Directly Cause RLS, But End-Stage Renal Disease Does
Kidney stones themselves do not lead to Restless Legs Syndrome (RLS), but the progression to chronic kidney disease (CKD) and end-stage renal disease (ESRD) that can result from recurrent nephrolithiasis is a well-established secondary cause of RLS. The connection is through renal dysfunction, not the stones themselves.
Understanding the Renal-RLS Connection
Secondary RLS from Kidney Disease
RLS is classified as either primary (idiopathic) or secondary, and secondary RLS can result from end-stage renal disease, which shares iron deficiency as a common pathophysiologic mechanism 1. The prevalence of RLS in dialysis patients reaches 15-30%, which is 2-3 times higher than the general population's 5-10% prevalence 2. A meta-analysis demonstrated a substantial sixfold increase in RLS likelihood among CKD patients compared to the general population (OR: 5.64,95% CI 2.70-11.78) 3.
The Pathway from Stones to RLS
The critical distinction is that kidney stones may contribute to CKD development, and it is the CKD/ESRD—not the stones themselves—that causes RLS 1. Emerging evidence links nephrolithiasis to increased risk of chronic kidney disease 1. The increasing prevalence of RLS with age occurs in association with secondary causes in the aging population, such as iron deficiency and renal failure 1.
Clinical Implications for Stone Patients
Risk Stratification
For patients with recurrent nephrolithiasis, assessment should include evaluation for CKD progression, as stone-related risks arise from obstruction, infection, and metabolic disorders that may impact renal function 1. Approximately 50% of recurrent stone-formers experience only one recurrence, while 10% have highly recurrent disease 1.
When to Screen for RLS
Screen for RLS symptoms in patients with:
- End-stage renal disease on dialysis 1, 4
- CKD stages 3-5 with iron deficiency 1, 4
- Nondialyzed CRF patients, particularly women with low transferrin saturation 5
The diagnosis is made by history, asking specifically about: (1) urge to move legs with uncomfortable sensations, (2) symptoms beginning or worsening during rest, and (3) partial or total relief with movement 1.
Management When RLS Develops in CKD
First-Line Approach: Iron Repletion
Check morning fasting ferritin and transferrin saturation first in all CKD patients with RLS 4. For dialysis patients, supplement with IV iron sucrose if ferritin <200 ng/mL AND transferrin saturation <20% 4. For non-dialysis CKD, consider supplementation if ferritin ≤75 ng/mL OR transferrin saturation <20% 4. The higher ferritin threshold in ESRD reflects altered iron metabolism and inflammation in advanced kidney disease 4.
Pharmacological Treatment
Gabapentin is conditionally recommended as first-line pharmacological treatment for ESRD patients with RLS 4. Start with 100 mg post-dialysis or at bedtime, with maximum dose of 200-300 mg daily in ESRD 4. This represents a 70-90% dose reduction from standard RLS doses to prevent severe toxicity 4. Gabapentinoids carry a 31-68% higher risk of altered mental status and falls in dialysis patients, even at low doses 4.
Dopamine agonists are NOT recommended as standard treatment due to high risk of augmentation—a paradoxical worsening of symptoms with earlier onset during the day and spread to other body parts 4.
Adjunctive Measures
Remove stimulants, review medications that worsen RLS, optimize dialysis adequacy, and correct hyperphosphatemia 4. Consider vitamin C supplementation specifically for ESRD patients 4. Pneumatic compression devices and good sleep hygiene may also be beneficial 4.
Critical Pitfalls to Avoid
Do not use standard RLS doses of gabapentin in kidney disease—this leads to severe toxicity 4. Independent predictors of RLS in nondialyzed CRF patients include female sex (OR: 10.7) and low transferrin saturation (OR: 0.6) 5. RLS in dialysis patients is associated with increased cardiovascular morbidity and mortality, making aggressive symptom management important for overall outcomes 4, 6.
The key clinical takeaway: evaluate stone patients for CKD progression, and if CKD/ESRD develops, screen for RLS symptoms and manage with iron repletion first, followed by low-dose gabapentin if needed 4.