Respiratory Function ESRDRespiratory Function, ESRD, and Nocturnal Hemodialysis

Mark Unruh MD MSRenal-Electrolyte DivisionUniversity of Pittsburgh Medical CenterQuotidian DialysisQuotidian Dialysis ASN 2009

•Normal and abnormal sleep in d ltadults

•Measurement and consequences of sleep apnea•Recognize the prevalence of•Recognize the prevalence of sleep disorders among those with ESRD•Nocturnal Dialysis and SleepNocturnal Dialysis and Sleep

Fun Pittsburgh fact

Identify the neurophysiologist who theorized that the reticular activating gsystem has an amplifying and sustaining feature for sensory g ystimulation transduction (otherwise, we would fall asleep with sensory p yreduction)?

SFun Pittsburgh Sleep Fact

Dr. Starzl began his career as a neurophysiologist before becomingneurophysiologist before becoming interested in surgery and immunology.

Sleep quality: an important and persistent problem for ESRD

An increase in energyAn increase in energy level (94%) and improvement in sleep p p(57%) were the most common potential benefits that would justify DHD

19% ld d19% would undergo DHD for an increase in survival of < or =3 years.

Unruh JAGS 2008Ramkumar et. al. HI 2005

?What is sleep?

BehavioralPostureClosed eyesReduced response to external stimuli

A complex collection of

to external stimuliReversible

Physiologicalphysiological and behavioral processes that are organized around behaviors such as

PhysiologicalPolysomnography criteriaaround behaviors such as

quiet recumbency with closed eyes -Carskadon

f SDefining Sleep

Behavioral Rest – Activity CyclesD d i l dit iDecreased visual, auditory responsivenessEyes closedRhythmic breathingRhythmic breathing

PhysiologicEEG: stages 1-4, REMEOG: to characterize REM, other stagesEMG: to characterize REM; measure pathological movements during sleeppathological movements during sleep

STAGE 1 SLEEP

Stage 1Usually first stage of sleep encounteredUsually first stage of sleep encounteredSleep onset is usually NOT sharp; lack full consensus on what constitutes sleep onsetLower voltage mixed amplitudeLower voltage, mixed amplitude

Note: slow, rolling eye- movementsmixed frequency EEG

S G SSTAGE 2 SLEEP

K complex Sleep spindle

S GSTAGE 3 AND 4EEG

EEG

EOG

Note slo (delta) a es in EEG and EOG channels

EOG

Note slow (delta) waves in EEG and EOG channelsKnown as slow wave sleep or Delta sleepMost prominent in children and adolescents D ith ft 30Decreases with age after ~30Defined by frequency and voltage criteria

S GSTAGE REM

Small amplitude, desynchronized waves (replacement of higher amplitude“synchronous” EEG waves with lower amplitude higher frequencysynchronous EEG waves with lower amplitude, higher frequency waves) Rapid eye movements (phasic REM) and periods of minimal (tonic)eye movementSkeletal muscle inhibition

?Why we sleep?

Avoid sleepiness and drowsinessMetabolic effects –energy conservationImmunologicMemory and learningCardiovascular h l hhealth

Subjective and objective sleep findings may have a substantial impact

Health and functioning (Bliwise). Poor cognitive performance, increased l i f di b t dsleepiness, presence of diabetes and

hypertension, and premature death [IOM REPORT].REPORT]. Few studies have examined subjective and objective sleep among the community dwelling aged population.

My Home ExperienceMy Home Experience

Unruh AJKD 2008

Short and disturbed sleep in SESRD

SSummary

HD shorter sleep, less efficient sleep, and insomnia

Poor sleep was not explained by agePoor sleep was not explained by age or chronic health conditions

Implications

Poor sleep multi-factorialN t l hi t fNatural history of sleep in ESRD remains unclearremains unclearPoor sleep may contribute to morbidity and mortality of patients with ESRDwith ESRD

f SImpact of Dialysis on Sleep

Timing –DiurnalTemperatureTemperature Type – Hemodialysis vs. Peritoneal DialysisDialysisTiming –Nocturnal with Automated P it l Di l i d N t lPeritoneal Dialysis and Nocturnal Hemodialysis

Sleep Apnea in ESRD

“Very lazy …

p p

y yjust eats and sleeps

… rotund and l hf l”slothful” Pokemon et

al, 2000Obesity, neck size y,>17 inchesMale genderAgeAgeSnoringCraniofacial abnormalities

What is Obstructive Sleep Apnea?

Repetitive episodes of upper airway obstruction.Reduction in blood oxygen saturation.Arousal from sleep.pSymptoms of snoring and sleepiness.

SSleep Apnea: A Primer

Apnea: cessation in breathing > 10 secObstructive if there is effortCentral if effort is absent

Hypopnea: reduction in breathingHypopnea: reduction in breathing AHI: Apnea + Hypopnea IndexOb t ti Sl A HObstructive Sleep Apnea Hypopnea Syndrome: 5 or more respiratory event / hr of sleepevent / hr of sleep

f OSPrevalence of OSA

Women 30-60 yrs Men 30-60 yrs

AHI >5/hr 9.0%AHI>10/hr 5.0%

AHI >5/hr 24%AHI>10/hr 15%

AHI>15/hr 4.0% AHI>15/hr 9.1%

Young, et al., NEJM 1993

SSleep apnea outcomes

Sleepiness

S i

Depression

Snoring

Hypertension

Quality of Life

Hypertension

Cardiovascular

Impotence/loss of libido

diseaseAnxiety

Cognitive Deficits

Cardiovascular sleep apnea consequencesCardiovascular sleep apnea consequences

Copyright restrictions may apply.Shamsuzzaman, A. S. M. et al. JAMA 2003;290:1906-1914.

Sleep apnea associated with premature death

Punjabi et. al. PLOS MED 2009

How common is sleep apnea among hemodialysis patients?

Sl l i tSleep complaints common

Sleep apnea improves with treatment of uremic patients

SA 60% from symptomatic populations. y p p p

SLEEP APNEA AND KIDNEY FAILURE

Highly prevalent in hemodialysis patients (Kimmel 1989)

Not associated with typical risk factors (Kimmel 1989)Not associated with typical risk factors (Kimmel 1989)

Sleep doctors can treat: Short-term response to CPAP (Pressman 1993)(Pressman 1993)

Kidney doctors can treat: Improvement with nocturnal h di l i (H l 2001)hemodialysis (Hanly 2001)

Zoccali et al – JASN 2002

G SGGraphic PSG DataREM

MOV AWK11234

100

SaO2

100

70Cn.A +5

Ob.AMx.AHyp

+5+5+5Hyp

Uns +5

Unruh – JASN 2006

Predictors of severe sleep apnea in HD population

HD Crude Severe SHHS Crude SA Severe SA

Age per year 0.96 (0.90-1.02) 1.02 (0.97,1.07)

Sex (Female vs. male)

0.19 (0.04-1.01) 0.28 (0.06,1.27)

Race (white vs. black)

0.69 (0.21-2.33) 1.58 (0.53,4.7)

BMI 1 08 (0 96-1 21) 1 17 (1 07 1 28)BMI 1.08 (0.96-1.21) 1.17 (1.07,1.28)

DM meds 2.4 (0.68-8.49) 0.58 (0.07,4.7)

CVD 1.06 (0.30-3.72) 4.9 (1.5,15.7)

Non traditional Risk Factors for Sleep Apnea in Patients with Kidney Failure?

Neuropathy secondary to uremic toxin(s)

Myopathy secondary to uremic t i ( )toxin(s)

Effect of acid/base disturbances on ventilatory drive

Altered lung volumes

Upper airway edema Beecroft 2007

Or is it simply that we see older patients or patients with shared risk factors

Beecroft Sleep Med 2008

fTreatment of sleep apnea

Alcohol cessation and weight lossSleep position – HMO solutionSleep position HMO solutionMandibular advancementP iti AiPositive Airway pressureNocturnal Dialysis?

“Never, ever, think outside of the box.”

Peritoneal dialysis, nocturnal hemodialysis, kidney tx

Nocturnal Dialysis Improves Sleep Apnea

Hanly NEJM 2001

NHD IncreasesIn pharyngeal size

3.17 ± 0.68 to 3.86 ± 0.67 cm2

Beecroft et al – NDT 2008

Bradley et al – Am J Resp Crit Care Med 2009

Peritoneal dialysis at home, now can be done during sleep

Sleep apnea in peritoneal dialysis

Determined whether nocturnal PD was associated with lessassociated with less sleep apnea

Uremia clearance similarNo change in pulmonary functionNPD decreased body water

Tang JASN 2006

Tang et al CJASN 2009

ECF volume overload: upper airway edema?

Normal Subject Sleep Apnea

Change in apnoea-hypopnoea index following kidney transplantation (post) in patients with apnoea-hypopnoea index >10 prior to transplantation (pre)apnoea-hypopnoea index >10 prior to transplantation (pre)

Beecroft, J. M. et al. Nephrol. Dial. Transplant. 2007 22:3028-3033; doi:10.1093/ndt/gfm309

Copyright restrictions may apply.

SummarySummary

Long-term Implications f Sl T t t i ESRDof Sleep Treatment in ESRD

Need To Diagnose and MonitorScreen for Sleep Apnea, Sleepiness, PLMD, RLS

Informed treatment selectionKidney TransplantationNocturnal DialysisUse of CPAP

Treatment EffectsImproved daytime functioningImproved BP and LVH

GGrant support

NKF Western PennsylvaniaNKF Young Investigator GrantNKF Young Investigator GrantNIDDK ASN ASP HARTFORD FOUNDATIONASN-ASP HARTFORD FOUNDATIONPaul Teschan Research Foundation (DCI)Satellite Research Coplonp

Thanks for all of the helpp

Christos Argyropolous MD, PhD

Manisha Jamb MD

Lee Anne MandichSheena DoharLauren Kester

Anne NewmanMaria-Eleni Roumelioti MD

Khaled Abdel-Kader MD

Sarah Ramer

Anne Newman Beth PirainoDan BuysseMary Amanda DewMark Sanders

Tom Rice MD

Nizar Younas MD

Pat Strollo/Charlie AtwoodChris Chan Tica HallHEMO Study InvestigatorsCHOICE STUDY

Manju Mavanur MDCHOICE STUDYSleep Heart Health StudyFHN StudyCKID Study InvestigatorsParticipants