EMODIALISI NOTTURNA
dr.ssa Patrizia Ondei
U.O. Nefrologia e Dialisi
A.O. Papa Giovanni XXIII Bergamo
XXII Corso Nazionale di Aggiornamento ANTE
31 Marzo- 2 Aprile 2014 Riccione
1943
first recovery of
an acute renal failure
patient treated with a
rotating drum hemodialysis
system
designed
by
WILLEM KOLFF.
This was the beginning of
what was to become an
important clinical reality:
artificial renal substitution
therapy.
The paradigm of hemodialysis has so evolved
from a life-saving treatment for a minority
of patients with acute kidney injury to a life
sustaining therapy for many thousand of
patients with chronic kidney disease stage 5
worldwide
The major developments in the next decades
related
to
improvements
in
membrane
biocompatibility and dialyzer design , volumetric
control, sophisticated monitoring systems that
provide online clearances dialysis, high flux
membrane and convective modalities such as
hemofiltration and hemodiafiltration
Adjusted mortality rates in ESRD and general
populations, age 65 and older
(per 1000 patient years at risk)
450
400
350
300
250
dialysis
transplant
cancer
200
diabetes
CHF
150
100
CVA/TIA
AMI
50
0
data from 2012 USRDS annual report
Adjusted survival in
incident dialysis
patients and
patients receiving a
first transplant
(between 2001 and 2005)
from day 91, by modality, adjusted for
age, gender, and primary diagnosis
Cardiovascular disease mortality in the general
population and dialysis patients
Parfrey et al. J Am Soc Nephrol (1999)
HEMO study
•1846 patients
•mean follow-up 2,84
years
•randomization to
either standard- or
high-dose goal and
either low or high-flux
dialyzer
Eknoyan et al. N Engl J Med (2002)
Hemodialysis Study Group Conclusions
•
“….
In summary, altough the effect of the dose and
level of membrane flux may vary among selected
subgroups of patients, the primary results of our
study indicate that, with a schedule of thrice-weekly
dialysis, neither an increased dose of dialysis nor use
of a high-flux membrane substantially improves
survival, reduces the rate of hospitalization, or
mantains serum albumin levels as compared with a
standard dose and use of low-flux membranes. “
Eknoyan et al. N Engl J Med (2002)
The "unphysiology" of dialysis:
a major cause of dialysis side effects?
Kjellstrand CM et al. Kidney Int 1975
We hold this truth to be self-evident
in dialysis: normal chemistries and
physiology are better than abnormal…a
lot better
In dialysis, it is more important that
body
chemistries
are
normal
(“physiologic”) than that an arbitrary
Kt/V is achieved.
The best way, we contemplated, to get rid of "un-physiology" is to
dialyze often – i.e., dialyze daily. There is no possibility of keeping
body chemistries within normal limits with three dialyses per week.
Foley RN et al. N Engl J Med (2011)
•data from the HEMO
study
•cubic spline interpolation
suggested that the risk
of mortality began to
increase at ultrafiltration
rates over 10 ml/h/kg
Kidney Int (2011) vol. 79
•national cohort of 10571 patients from a dialysis organization
•2382 pairs matched on age, gender, access, post-dialysis weight
Flythe et al. Kidney Int (2012)
•cross-sectional study
•46 patients on either
conventional HD; HD 5-6
times/week in a center and
at home or home nocturnal
HD
Jefferies et al. CJASN (2011) vol. 6
(2012) vol. 25 (1)
...The Hippocratic Oath tells us ‘‘to abstain from doing harm’’;
one must be concerned that standard HD, at least in some
patients, violates the primum non nocere tenet of medicine.
This literature and other recent studies seem to be building a
case for more careful consideration of alternatives to
conventional three times weekly in-center HD and movement
away from ‘‘cookie cutter’’ HD...
(2011) vol. 24 (6)
mmHg
mmHg
Improvement in hypertension control
systolic blood pressure
diastolic blood pressure
•randomized controlled trial: 52 patients, 6 months follow-up
•antihypertensive medications discontinued/reduced in 16/26 NHD
patients vs. 3/25 CHD patients (p<0,001)
Culleton et al. JAMA (2007) vol. 298 (11)
24h MAP (mmHg)
Improvement in hypertension control
CHD
NHD 1m
NHD 2m
•prospective observational study: 18 patients converted from CHD to
NHD for 2 months
•significant reduction in antihypertensive medications: 2,5->0,2
meds/patient, p<0,001
Chan T. et al. Hypertension (2003) vol. 42
mean LVMI g/m2
Regression of LVH
•52 patients randomized to NHD or CHD for 6 months
•LV mass assessed by cardiac MRI in 35 patients
Culleton et al. JAMA (2007) vol. 298 (11)
Regression of LVH
•observational cohort
study: 28 patients
converted from CHD to
NHD
•significant reduction in BP
and LVMI
LVMI g/m2
baseline
147±42
year 1
130±33
year 2
106±32
year 3
102±19
•LVMI correlated with
systolic BP
Chan et al. Kidney Int (2002) vol. 61 (6)
Reduction of sleep apnea
•conversion from CHD to
NHD in 14 patients (7 with
sleep apnea)
•reduction in the
frequency of apnea and
hypopnea, especially in the
7 patients with sleep apnea
•increase in pharyngeal
cross-sectional area may
play a role
Hanly et al. NEJM (2001) vol. 344
Beecroft et al. NDT (2008) vol. 23
Enhanced ESA responsiveness
NHD
CHD
p
Hb (g/dl)
12,4±4
12±4
0,30
EPO (U/kg/w)
90.5±22.1
167.2± 25.4
0,04
IL-6 (pg/ml)
3.9 ± 0.7
6.5 ±0.8
0,04
hsCRP (mg/L)
4.6 ± 1.3
8.4 ±1.8
0.14
•cross-sectional study on 14 NHD patients vs. 14 CHD patients
•matching for age and comorbidities and control for Hb
concentrations and iron status
Yuen et al. ASAIO Journal (2005) vol. 51
Improved phosphate control
• 51 patients randomized to CHD or NHD
• reduction in phosphate levels with fewer binders in HD
• variable effects on calcium and PTH
Walsh et al. Hemodialysis International (2010) vol. 14
American Journal of Kidney Diseases (2003) vol. 41
A 42-year-old man with ESRD was referred for conversion to
NHD therapy from CHD because of refractory intermittent
claudication secondary to peripheral arterial disease.
After conversion to NHD therapy (7.5 h/session five times
weekly), the patient became symptom free and had significant
clinical improvements in hemodynamics, measured by clinic
blood pressure and two-dimensional echocardiography;
biochemical profile, and a sustained improvement in arterial
Doppler flow measured by duplex Doppler ultrasound.
American Journal of Kidney Diseases (2003) vol. 41
Nutritional benefits
•15 patients converted from CHD to NHD
•minimum follow-up 8 months
•increase in protein intake, no dietary restrictions
•no change in BMI and upper arm muscle
circumference
Ipema et al. Ren Nutr (2012)
Improved pregnancy outcomes
•case series of 6 successful pregnancies in women on NHD
•putative improved fertility with NHD
•less severe pregnancy and fetal complications than those
reported in literature on CHD
•mean gestational age 36.2±3 weeks
•mean birth weight 2417.5±657 g
Barua et al. CJASN (2008) vol. 3
Better quality of life
•improvement in exercise capacity
Chan et al. NDT (2007)
•improved cognition
22% reduction in cognitive symptoms
32% improvement in attention and working memory
Jassal et al Kidney Int (2006)
• significant improvements in selected kidney-specific domains of
quality of life in NHD, without difference in overall quality of life
(EuroQol 5-D index)
Culleton et al. JAMA (2007)
Improved survival
Survival of NHD patients is comparable to recipients of deceased
donor kidney graft
Pauly et al. NDT (2009) vol. 24 (9)
FHN Nocturnal Trial
•87 patients randomized to either NHD or CHD,
12 month follow-up
•no significant difference in either of coprimary outcomes
(death or LVM measured by MRI)
•better
better control of hyperphosphatemia and hypertension in NHD
•no statistically significant differences for the other main
secondary outcomes ( physical health composite score, albumin,
ESA dose, non-access hospitalization)
•trend toward an increased rate of access complications in the
NHD arm
Rocco et al. Kidney Int 2011
FHN Nocturnal Trial: major limitations
•limited sample size
•lower adherence to the dialysis prescription in NHD arm
mean number of treatments 2,91±0,21 in CHD vs. 5,06±0,8 in
NHD
•consistent proportion of patients with residual urine output
>500 ml/day in 57,2% CHD patients and 46,7% NHD patients
•limited dialysis vintage
<1 year in 59,5% CHD and 44,4% NHD patients
Rocco et al. Kidney Int 2011
The Tassin paradigm
•1380 patients treated from
1968 to 2003
•3x8h/week
•mean delivered spKt/V >2 per
session
•low salt diet (average 5g/day)
•systematic antihypertensive
treatment withdrawal in
conjunction with lowering of
extracellular volume to achieve
dry weight
Charra B. Nefrologia (2005)
•98% of patients off
antihypertensive drugs
•average observed
mortality in Tassin
consistently about 45%
of the expected value
for US patients similar
in age, race and cause of
renal failure, in spite of
worsening of case mix
along the years
Charra B. Nefrologia (2005)
Bergamo INHD program
•started in January
2000
•1 nurse : 3 patients
•1 physician till 24.00
(afterwards on call)
•1 reverse osmosis
technician on call
INHD
CHD
frequency
(times/week)
3
3
duration (h)
8
3,5-4
QB ml/min
200-250
300-400
QD ml/min
300
500-800
dialyzer surface
(m2)
1,2-1,4
1,3-1,9
Bergamo INHD program
Patient population
•7 patients
•participation on
a voluntary basis
•motivation to
comply with the
treatment
schedule was
required
Cravedi et al. Int J Artif Organs (2009) vol. 32 (1)
Bergamo INHD program
Improved hypertension control
systolic blood pressure
diastolic blood pressure
•reduction in the mean number of
antihypertensive
drugs:
1,17±1,19
0,47±0,089
drugs/patient
•complete withdrawal of all blood
pressure lowering medications in
4 patients
Cravedi et al. Int J Artif Organs (2009) vol. 32 (1)
Bergamo INHD program
Increase in body weight
pre-HD
•significant increase in body
weight after conversion from
CHD to INHD
•no
significant
change
in
intradialytic weight reduction
post-HD
Cravedi et al. Int J Artif Organs (2009) vol. 32 (1)
Bergamo INHD program
Enhanced phosphate control
Cravedi et al. Int J Artif Organs (2009) vol. 32 (1)
Bergamo INHD program
Good treatment tolerance
•after 1 year of INHD, all patients declared that their mood
was either good (N=1) or very good (N=6)
•only 2 patients reported
difficulties
in
falling
asleep during the INHD
sessions,
however
sleeping
no
medications
were needed
Cravedi et al. Int J Artif Organs (2009) vol. 32 (1)
...The present thrice-weekly program was easy to establish and did
not significantly affect our unit’s activity. Indeed, it was started
with preexisting dialysis facilities. New dialysis machines, clinic
space, the development of home monitoring systems, or extensive
patient training were not required. However, extra payment for
nurses and technicians was required…
prospective observational study, 2 years of follow-up
746 patients starting INHD, matched 1:3 with CHD patients on
the basis of
• propensity score: age, gender, race, diabetes, dialysis
vintage, BMI, vascular access, albumin, hemoglobin,
phosphorus, calcium, white blood cell count
• geographic area
• incident patient status (vintage ≤90 days vs. >90 days)
J Am Soc Nephrol (2012) vol. 23 (4)
Patient survival
1-year mortality rate: 9% for INHD vs. 15% for CHD pts
2-year mortality rate: 19% in INHD vs. 27% in CHD pts
Lacson et al. J Am Soc Nephrol (2012) vol. 23 (4)
Secondary outcomes
•sustained significant
decline in phosphorus
levels from 5.73 to 5.02
mg/dl in INHD, p<0,001
•balanced increase in both interdialytic weight gain and
intradialytic weight loss for INHD patients that was not evident in
CHD patients
•better increase in albumin and hemoglobin in NHD patients, not
reaching statistical significance
Lacson et al. J Am Soc Nephrol (2012) vol. 23 (4)
•prospective observational
study on 247 INHD patients
from 10 HD centers operated
by Fresenius in Turkey
•12 months follow-up
•1:1 matching with CHD
patients on age, sex,
diabetes and dialysis vintage
NHD n=247
CHD n=247
age (years)
45,2±13,9
45,2
13,9
45,8±12,9
45,8
12,9
female (%)
31,9
31,9
dialysis vintage
(months)
60,6±44,9
59,5±44,4
AV fistula (%)
90,6
91,9
BMI (kg/cm2)
23,1±4,6
23,6±4,8
CV disease Hx (%)
14,3
13,9
Nephrol Dial Transplant (2011) vol. 26 (4)
Survival and adverse events
•one-year survival rate
98,4% in INHD
93,9% in CHD
•lower hospitalization rate
in the INHD group 5.43
vs 18.78 days/ 100
patient-months, p=0.002
•marked decrease in intradialytic hypotensions in INHD patients
Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)
Cardiovascular outcomes
• good BP control in both groups,
significantly reduced need for
antihypertensive medications (22->8%) only in INHD patients
•improvement in echocardiographic parameters only in the INHD group (↓ in
left atrium and left ventricle end-diastolic diameters, ↑ ejection fraction,
significant regression of left ventricular mass index)
•reduction of extracellular fluid documented in a subgroup of the INHD
study population by bioimpedance analysis
•lower progression rate of coronary artery calcification and improvement of
arterial stiffness documented in a subset of INHD patients, compared to
CHD
Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)
Mineral metabolism
better phosphate control in INHD patients with reduced use of binders
Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)
Nutritional status
•significantly higher time-averaged levels of serum
albumin, triglyceride and cholesterol in the INHD group
•higher time-averaged interdialytic weight gain in the INHD
than the CHD group
•increase in body weight after 1 year observed only in INDH
patients
Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)
Anemia and Inflammation
•significantly higher time-averaged mean
Hb level in the INHD group
•decrease in the percentage of patients on erythropoietin
treatment and dose of erythropoietin only in the INHD group
•lower time-averaged mean CRP levels in the INHD arm
after exclusion of patients with a baseline CRP level above 10
mg/dL
Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)
Psychometric measurements and QOL
INHD
CHD
memory functions
Rey Auditory Verbal
Learning Test
=
cognitive function
Mini Mental State
Examination
=
=
cognitive function
Trail Making Test B
=
=
health-related QOL
SF-36 Health Survey
=
§
depression/anxiety
Hospital Anxiety and
Depression Scale
=
=
§ significant deterioration in the bodily pain, mental health and vitality dimensions
Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)
age strata (years)
Gender and age distribution of incident HD patients
National registry
survey of 3702
USA nursing home
residents starting
dialysis between
June 1998 and
October 2000
K Tamura et al. N Engl J Med (2009) vol. 361 (16)
In conclusion, nursing
home residents who
are starting to
undergo dialysis have
a substantial and
sustained decline in
functional status in
addition to very high
mortality.
K Tamura et al. N Engl J Med (2009) vol. 361 (16)
The main aim of my
endeavors has always
been to restore people
to an enjoyable
existence. If it’s not
enjoyable, it should
not be done.
dr. Willem Johan Kolff