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Bader AlMasaad
Restless leg syndrome in CKD
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
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)
Restless leg syndrome
 Secondary:
 Iron deficiency
 Peripheral neuropathy
 Folate or magnesium deficiency
 Amyloidosis
 DM
 Rheumatoid arthritis
 MGUS
 Uremia
 Vitamin B12 deficiency
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.
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.
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
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
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.
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
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.
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.
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.
Percentage reporting RLS symptoms
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Baseline 12 months
RLS
no RLS
Percentage suffering moderate to severe RLS
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
baseline 12 months
RLS
no RLS
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.
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

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Restless leg syndrome in ckd

  • 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