This document discusses restless leg syndrome (RLS) and its prevalence and treatment in chronic kidney disease (CKD) patients on hemodialysis. It summarizes a study that found switching CKD patients from conventional hemodialysis to short daily hemodialysis (SDHD) resulted in significant and sustained improvements in RLS symptoms and sleep quality over 12 months, especially for those with moderate to severe RLS initially. The improvements were greater than typically seen with RLS medication alone. However, the study was limited by potential selection bias and lack of a control group.

1. Bader AlMasaad
Restless leg syndrome in CKD

2. Restless leg syndrome.
 Neurological movement disorder often
accompanied by sleep disorder.
 Characterized by an irresistible urge to move
ones body to stop an uncomfortable or odd
sensation.
 Moving the body provides temporary relief.
 Often under diagnosed
 RLS affects 5-15% of the general population in
the US.
 Can occur at any age, even infants.
 More common in women 2:1

3. Restless leg syndrome
 Pathogenesis is unknown.
 Most accepted theory is impairment of cortical
and sub cortical dopamine pathways and iron
homeostasis, with a genetic component.
 Primary or secondary
 Primary : 50-75% are familial (autosomal
dominant or recessive)

4. Restless leg syndrome
 Secondary:
 Iron deficiency
 Peripheral neuropathy
 Folate or magnesium deficiency
 Amyloidosis
 DM
 Rheumatoid arthritis
 MGUS
 Uremia
 Vitamin B12 deficiency

5. Restless leg syndrome
 Morbidity:
 Decreased quality of life
 85% have sleep disturbance ( deprivation,
fragmentation)
 Chronic headache
 Prone to developing hypertension
 Learning and memory difficulties
 More prone to developing pneumonia and
myocardial infarctions.

6. Restless leg syndrome
 Clinical presentation
 "pins and needles," an "internal itch," or a
"creeping or crawling" sensation.
 Criteria for diagnosis of RLS are based on those
developed by the International RLS Study Group
in 1995. The following 4 basic elements must be
present to make the diagnosis:
 A compelling urge to move the limb
 Motor restlessness
 Symptoms that worsen or are exclusively present
at rest with temporary relief on movement
 Circadian variation in symptoms.

7. Restless leg syndrome
 Treatment is symptomatic.
 Secondary RLS can by cured
 Dopaminergic agents ( eg pramipexole,
ropinirole)
 Benzodiazepines
 Opioids
 Anticonvulsants ( eg gabapentin and pregabalin)
 Iron replacement vital in patients with iron
deficiency

8. Prevalence of RLS in CKD
 Much higher than the general population, all of these
had end stage renal disease on regular hemodialysis.
 50.22%, riyadh, saudi arabia (1)
 21%, Italy (2)
 14%, Hungary (3)
 48%, Brazil (4)
1. Saudi J Kidney Dis Transpl. 2009 May;20(3):378-85.
2. Sleep Med. 2004 May;5(3):309-15
3. Nephrol Dial Transplant. 2005 Mar;20(3):571-7.
Epub 2005 Jan 25
4. Rev Assoc Med Bras. 2007 Nov-Dec;53(6):492-6

9. Imptact of short daily hemodialysis on restless
legs syndrome and sleep disturbances
 Observational studies have linked restless leg
syndrome to premature discontinuation of
dialysis, impaired QOL, increased risk of
cardiovascular events and increased risk of
death.
 Poor sleep quality is also common among
patients on conventional HD. Ranging from 41-
83%.
 The FREEDOM study (1) is an ongoing multi-
centre , prospective , cohort study of SDHD with
a planned 12 month follow up.
 The aim is to assess if SDHD ( 6 treatments per
week) was beneficial in improving RLS and sleep
disturbances.

10. Method
 Inclusion criteria:
 Adults (age >18) with ESRD requiring dialysis
who were being initiated on SDHD.
 Exclusion criteria:
 Current use of SDHD
 Current enrollment in an investigational drug or
device trial.
 Low likelihood of surviving the first 4-6 months

11. Method
 At enrollment demographic data was collected as well
as clinical data on co-morbid conditions, duration of
dialysis, vascular access type, prior renal replacement
therapy, laboratory data, prescribed medications
related to RLS.
 The presence of RLS was evaluated at enrollment, at
4 months and at 12 months.
 This was done using the IRLS ( international restless
leg syndrome study group rating scale)
 Scored from 0 to 24, depending on severity of
symptoms. Moderate to severe RLS defined as IRLS
score above 15.
 Assessment of sleep disturbances was through the
MOS sleep scale manual.
 Baseline characteristics were compared using the chi-
squared test and variables were compared using the
paired t test.

12. Population
 Between Jan. 2006 and Dec 2008, 235
participants were enrolled from 28 different sites
 108 discontinued before the 12 months follow up
period. This was due to death, renal transplant,
recovery of kidney function, transfer to another
centre.
 Mean age was 52 yrs, 65% were men, 66%
were white, 43% were diabetic and 55% had an
AV fistula.
 At enrollment, 40% of the participants had RLS.
These participants had worst scores on the MOS
sleep scale manual.

13. Results
 At enrollment, the mean IRLS score was 9, with
65 % of the RLS participants with a score of >15.
 SDHD resulted in a decrease in IRLS score from
baseline of 5 points at 4 months (p=0.002) and 7
points at 12 months ( p=0.0001)
 In moderate to severe RLS, SDHD resulted in a
larger decrease in IRLS score of 8-9 points at 4
and 12 months.
 SDHD resulted in a significant improvement in the
majority of the individual components of the sleep
survey at 4 months and 12 months.

14. Percentage reporting RLS symptoms
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Baseline 12 months
RLS
no RLS

15. Percentage suffering moderate to severe RLS
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
baseline 12 months
RLS
no RLS

16. Conclusion
 SDHD resulted in sustained and clinically
significant improvement in restless leg symptoms
and sleep disturbances, especially in those with
moderate to severe RLS. (IRLS score above 15)
 Among those with moderate to severe RLS, a
switch to SDHD resulted in an impressive
improvement of 8-9 points on the IRLS compared
to 6 points that was the average improvement
found in trials studying the medications used in
RLS treatment.

17. Conclusion
 Strengths of study: large population size, from 28
different sites across the US, the use of 2
validated surveys to asses QOL measures of
interest and the 12 months follow up.
 Limitations of the study: selection bias as evident
by the recruitment of relatively younger
population, and the absence of a control group.
1. Clin J Am Soc Nephrol. 2011 May; 6(5): 1049-
1056