Transcript Renal Replacement Therapy – What the Non-Nephrologist Should Know Bernard G. Jaar, MD, MPH, FASN,FNKF Johns Hopkins Medical Institutions Nephrology Center of Maryland.

Renal Replacement Therapy –
What the Non-Nephrologist
Should Know
Bernard G. Jaar, MD, MPH, FASN,FNKF
Johns Hopkins Medical Institutions
Nephrology Center of Maryland
Why is this topic relevant
to you?
Kidney Disease is a Public
Health Problem
Trends in Kidney Disease
Burden …
Prevalence of CKD Stages in US Adults Aged
20 Years or Older:
NHANES 1988-1994 and NHANES 1999-2004
Coresh, J. et al. JAMA 2007;298:2038-2047
ESRD Prevalence – The Forecast
Projected growth overall ESRD prevalence (5% / yr)
Number of patients (millions)
3.0
2.2 million
(60% diabetic)
2.0
618,160 pts
(2011)
1.3 million
1.0
0.7 million
0.4 million
0
1978
2000
2010
Year
2020
2030
Gilbertson et al. JASN 2003
Objectives
• Describe treatment options for renal
replacement therapy
• Understand the general principles of
dialysis modalities & compare their
outcomes
• Importance of residual renal function
• Describe kidney transplantation process
Case Presentation (I)
• 39 y/o AA man
• PMHx: none
• Routine physical exam:
– BP 142 / 100
– LE edema
– 4+ proteinuria (dipstick)
Case Presentation (II)
Initial Nephrology Clinic Visit
• PE:
–
–
–
–
Unremarkable, except:
Weight 230 lbs (BMI 33)
BP 138 / 85
2+ LE edema
• Treatment:
– ACE inhibitor
– Thiazide diuretics
Case Presentation (III)
Initial Laboratory Data
• Labs:
12.3
7490
333
41.0
141
3.6
107
28
18
2.4
95
Albumin 2.5
eGFR 37 cc/min/1.73m2
T. cholesterol 398 mg/dL
Serology w-u (-)
UA: protein 4+, 0-2 RBC, 0-2 WBC
Spot u. prot. / creat. 413 mg/dL / 41 mg/dL  10
CKD Progression  ESRD
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ESRD
Dates
Initial presentation:
HTN, CKD, proteinuria
RRT
Indications for Renal
Replacement Therapy
•
•
•
•
•
Hyperkalemia
Metabolic acidosis
Fluid overload (recurrent CHF admissions)
Uremic pericarditis (rub)
Other non specific uremic symptoms:
anorexia and nausea, impaired nutritional
status, increased sleepiness, and
decreased energy level, attentiveness, and
cognitive tasking, …
What are the Treatment
Options for Renal Replacement
Therapy for our Patient?
ESRD Treatment Options
ESRD
Comfort Care
Peritoneal Dialysis
Hemodialysis
Kidney Transplant
ESRD Treatment Options
ESRD
Hemodialysis
Comfort Care
Peritoneal Dialysis
Kidney Transplant
Dialysis options
Dialysis
Hemodialysis
Peritoneal Dialysis
In-Center HD (3 x week)
Home HD (short daily, nocturnal)
CAPD
CCPD
Home
Incident Patient Counts (USRDS)
by 1st Modality
USRDS 2013 ADR
CKD Education
CKD Progression  ESRD
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CKD
Education
Dates
Initial presentation:
HTN, CKD, proteinuria
RRT
CKD Education
 Refer patients early, when eGFR < 30 cc/min
 Education about types of renal replacement
therapy:
– Hemodialysis (vascular access +++)
– Peritoneal Dialysis (QOL advantage +++)
– Kidney Transplantation
• Refer when eGFR <20
• Living kidney transplant (family, friends)
• Build time on list before dialysis initiation
• Even transplant before dialysis initiation
(pre-emptive)
Early Vaccination for Hepatitis B!
 Patients with ESRD have  response to
vaccination
(2ary to general suppression of immune system)
 After Hepatitis B vaccination in ESRD patients:
– 50 – 60 % develop antibodies, compared to
> 90% in patients without renal failure
– Have Lower titers
– Have protective levels for shorter duration
Stevens CE et al. NEJM 1984; 311: 496
Buti M et al. Am J Nephrol 1992; 112: 144
Early Vaccination for Hepatitis B!
 Patients with ESRD have  response to
vaccination
(2ary to general suppression of immune system)
 After Hepatitis B vaccination in ESRD patients:
– 50 – 60 % develop antibodies, compared to
> 90% in patients without renal failure
– Have Lower titers
– Have protective levels for shorter duration
Stevens CE et al. NEJM 1984; 311: 496
Buti M et al. Am J Nephrol 1992; 112: 144
Hemodialysis (HD)
Principle of Hemodialysis
Vein
Artery
Hemodialysis Filter (Dialyzer)
Hemodialysis Filter (Dialyzer)
Hemodialysis Vascular Access
Polytetrafluoroethylene
Arteriovenous (AV) Fistula
Question 1
• Which type of vascular access is associated
with better outcomes in hemodialysis
patients? (choose one answer):
1.
2.
3.
4.
Central venous cuffed catheter
Arteriovenous graft
Arteriovenous fistula
Temporary central venous catheter
Which Vascular Access and
When Should It Be Placed?
CKD Progression
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Vascular
Access
(AVF)
Dates
Initial presentation:
HTN, CKD, proteinuria
HD
Adjusted* Relative Risk of Death
by Type of Vascular Access
Diabetes
No Diabetes
Cohort: 5,507 patients, followed for 2 years
*Adjusted for age, race, gender, BMI, history of smoking, PVD, CAD, CHF, neoplasm, ability to
ambulate and education level.
Prevalent diabetic pts: CVC vs. AVG (P = 0.42). Incident diabetic pts: CVC vs. AVG (P = 0.48).
Prev. nondiabetic pts: CVC vs. AVG (P < 0.0001). Inc. nondiabetic pts: CVC vs. AVG (P = 0.82).
Dhingra RK et al. Kidney Int 2001; 60: 1443–1451
Adjusted* Relative Risk of Death due to
Infection by VA Type and Diabetes Status
Cohort: 5,507 patients, followed for 2 years
*Adjusted for age, race, gender, BMI, history of smoking, PVD, CAD, CHF, neoplasm, ability to
ambulate and education level.
Prevalent diabetic pts: CVC vs. AVG (P = 0.81)
Prevalent nondiabetic pts: CVC vs. AVG (P < 0.13)
Dhingra RK et al. Kidney Int 2001; 60: 1443–1451
Patients who started using an AV access
by timing of first referral to a nephrologist
N=356 hemodialysis patients
Astor B. et al. Am J Kidney Dis 2001; 38 (3): 494-501
VASCULAR ACCESS GUIDELINES
 Arm veins suitable for placement of vascular access
should be preserved, regardless of arm dominance.
Arm veins, particularly the cephalic veins of the nondominant arm should not be used.
 Dorsum of the hand could be used for IV.
 A Medic Alert bracelet should be worn to inform
hospital staff to avoid IV cannulation of essential
veins.
 Subclavian vein catheterization should be avoided
for temporary access in all patients with CKD
( stenosis  preclude use of ipsilateral arm for
vascular access)
SAVE the Non-Dominant ARM
for Vascular Access
 When GFR < 30 mL/min
– No BP measurement
– No IV
– No Blood Draws
On Non-Dominant
Arm
 Place vascular access within a year of
hemodialysis anticipation …
Peritoneal Dialysis (PD)
Principle of PD Treatment
• Abdominal cavity is lined by peritoneal membrane
which acts as a semi-permeable membrane
• Diffusion of solutes (urea, creatinine, …) from blood
into the dialysate contained in the abdominal cavity
• Removal of excess water (ultrafiltration) due to
osmotic gradient generated by glucose in dialysate
Types of PD Catheters
• Overall PD catheter survival : +/- 90% at 1 year
• No particular catheter is superior
Placement of Peritoneal Dialysis
Catheter
Placement of PD Catheter
Exit Site
PD Catheter Exit Site
Peritoneal Dialysis (PD)
PD
Continuous
Intermittent
Continuous PD Regimens
Multiple sequential exchanges are performed during the day
and night so that dialysis occurs 24 hours a day, 7 days a week
CAPD: Continuous
Ambulatory PD
CCPD: Continuous
Cyclic PD
Intermittent PD Regimens
PD is performed every day but only during certain hours
DAPD: Daytime
Ambulatory PD.
Multiple manual exchanges
during waking hours
NPD: Nightly PD.
Performed while patient
asleep using an automated
cycler machine.
Sometimes,
1 or 2 day-time manual
exchanges are added to
enhance solute clearances
CCPD Treatment Setup
Question 2
• What is the most common cause of
technique failure in peritoneal dialysis?
(choose one answer):
1.
2.
3.
4.
Ultrafiltration failure
Malnutrition
Peritonitis
Non-adherence to the treatment regimen
Cumulative percentage of PD
patients by time from 1st dialysis to
1st switch to HD
25% of PD
patients
switched to HD
within 5-7 years
Jaar BG et al. BMC Nephrol 2009; 10: 3
Causes of PD Technique Failure
(Switching from PD to HD)
Psychological Issues
4%
Abdominal Surgery 15%
47%
Peritonitis
Malnutrition 15%
19%
Ultrafiltration Failure
Jaar BG et al. BMC Nephrol 2009; 10: 3
Which Dialysis Modality
Provides the Best Outcomes?
Factors Influencing Dialysis Choice
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Late Referral,
…
Dialysis Modality
Absolute contraindications for PD
• Documented loss of peritoneal function or
extensive abdominal adhesions (previous abd.
Surgeries)  limit dialysate flow
• Uncorrectable mechanical defects
(e.g., diaphragmatic hernia)
• In the absence of a suitable assistant, a
patient who is physically or mentally incapable
of performing PD.
NKF K/DOQI Guidelines 2000
Peritoneal Adhesions
Factors Influencing Dialysis Choice
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Late Referral,
…
Dialysis Modality
Best Study Design to Compare
Dialysis Modalities
• Prospective, randomized, clinical trial
• Significant barriers to performing this type of study1
• We are left with the analysis of observational data
from well-conducted prospective studies
1Korevaar JC et al. KI 2003; 64(6): 2222-2228
Quinn RR et al. 2011 (I)
Country:
Enrollment Years:
Ontario, Canada
7-1-1998 to 3-31-2006
Follow-Up:
8 years
Population Type:
Incident – Elective Outpatient
(databases @ Institute for Clinical
Evaluative Sciences)
Sample Size:
Switching Modality:
HD: 4,538 PD: 2,035
No
Model(s)
Intention-to-Treat (baseline
modality)
Quinn RR et al. J Am Soc Nephrol 2011; 22: 1534-1542
Adjusted Survival between PD and HD,
(received > 4 months of predialysis care
and Started as outpatient)
Adjusted HR: 0.96, p = 0.44
Quinn RR et al. J Am Soc Nephrol 2011; 22: 1534-1542
Biases
• Residual confounding: limited adjustment for
known factors associated with mortality (e.g.,
comorbidities, lab data [albumin, …])
• Short follow-up (1-2 years) in some studies
• Lead-time bias: baseline GFR
• Selection bias: patient characteristics
• Statistical Methodology:
– Center Effect: confounding by clinic as patient
characteristics varied by center and treatment
– How to handle modality switching: As-Treated
vs Intention-to-Treat
• No causal relationship, just association!
Other Issues: PD vs HD
Beyond Survival
• In considering choice of dialysis technique,
other issues must be considered …
Factors Influencing Dialysis Choice
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Cost of Care,
Late Referral,
…
Dialysis Modality
CHOICE - Quality of Life:
PD vs HD (I)
• PD patients reported better QOL then HD
patients in the following domains:
– Bodily pain
– Travel
– Diet restrictions
– Dialysis access
– Financial well-being
– Physical functioning (only at baseline, not at 1
year)
Wu A et al. JASN 2004; 15: 743-753
CHOICE - Quality of Life:
PD vs HD (II)
• At one year,
– HD patients improved more on aspects of
general health-related QOL than patients on
PD
– HD patients had greater improvement on:
• Physical functioning
• Sexual functioning
• General health perceptions
Wu A et al. JASN 2004; 15: 743-753
Factors Influencing Dialysis Choice
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Late Referral,
…
Dialysis Modality
CHOICE - Treatment Satisfaction:
PD vs HD
• PD patients were significantly more likely to give
excellent ratings of dialysis care overall
compared to HD patients (85% vs 56%).
• Also PD patients were more likely to give excellent
ratings for specific aspects of care:
– information on choosing a dialysis modality
– information on fluid removal
– staff and nephrologist availability
– coordination with other physicians
– caring of nurses or staff
–…
Rubin HR et al. JAMA 2004; 291: 697-703
Implications
• Each modality has distinct advantages or
disadvantages
• Physicians should be as explicit as possible in
describing specific tradeoffs and attempt to elicit
individual preferences at start of dialysis
• Although there is no conclusive evidence that the
choice of PD or HD provide a specific survival
advantage:
– Better selection of PD patients (PD underutilized)
– PD patients should be monitored closely after the 2nd or
3rd year of dialysis
– Consider a “timely” transfer to HD (if or when PD
problems arise)
What is the best long-term treatment?
1. PD
2. HD in-center
3. HD home/
self-care
Ask the nephrology providers which dialysis modality they
would select if they had ESRD?
What is the best long-term treatment?
Opinion vs Reality
1. PD
2. HD in-center
3. HD home/
self-care
Ledebo I., Ronco C. NDT Plus 2008; 6:403-408
Question 3
• Which one of the following patient’s
characteristic or comorbidity is associated
with better overall outcome on dialysis
(choose one answer):
1.Diabetes Mellitus + end-organ damage
2.BMI > 30
3.Residual urine output of > 500 cc / day
4.Colon cancer
5.Early initiation of dialysis (eGFR > 15)
Is Timing of Dialysis
Initiation Important in
ESRD Patients?
(Controversial)
IDEAL Study: K–M Curves for Time to the
Initiation of Dialysis & for Time to Death
• Between July 2000 &
November 2008
• Australia / New Zealand
• 828 adults
• Early start:
eGFR 10-14 cc/min
• Late start:
eGFR 5-7 cc/min
• mean age 60.4 years
• 542 men & 286 women
• 355 with diabetes
• Median follow-up 3.6
years
Cooper BA et al. N Engl J Med 2010;363:609-619
Implications
• A total of 75.9% of the patients in the late-start group
started dialysis when eGFR was > 7.0 cc/minute,
owing to the development of symptoms!
• In this study, planned early initiation of dialysis in
patients with stage V CKD was not associated with an
improvement in survival or clinical outcomes (QOL)
•  OK to delay initiation of dialysis (eGFR < 7-10 cc/min)
•  Dialysis initiation should be based upon clinical
factors (symptoms) rather than eGFR alone
Cooper BA et al. N Engl J Med 2010;363:609-619
Why is Residual Renal
Function Important in
Dialysis Patients?
Why is baseline residual renal
function important?
• Remaining GFR at start of dialysis make a
significant contribution to the removal of
potential uremic toxins
• Also facilitates regulation of fluid, electrolytes,
and may enhance nutritional status and QOL
• Offers survival advantage in both HD and PD
Suda T et al. Nephrol Dial Transplant 2000; 15: 396
Shemin D et al. Am J Kidney Dis 2001; 38: 85
Szeto C et al. Nephrol Dial Transplant 2003; 18: 977
Cumulative Incidence of All-Cause Mortality in 579
HD Patients by Urine Status at 1 Year (CHOICE)
Adjusted Hazard Ratio: 0.70 (0.52-0.93) p = 0.02
Shafi T., Jaar B., et al. Am J Kidney Dis. 2010;56:348-58
Implications
• Try to preserve residual renal function in
dialysis patients!
•  Less dietary restriction
•  Better quality of life
•  Better survival
• Try to avoid nephrotoxins if your dialysis
patient still makes urine!
Kidney Transplantation
Principle of Kidney Transplantation
Iliac Fossa
Question 4
• Which one of the following statements is
correct? (choose one answer):
1. CKD patients can be referred to a transplant
center when their GFR is < 20 cc/min/1.73m2
2. Pre-emptive and live kidney transplants are
associated with better graft survival
3. Most common cause of kidney transplant loss
is death with a functional transplant
4. All of the above
Trends in Transplantation:
patients age 20 years & older
USRDS ADR 2012
Adjusted Relative Risk of Death among 23,275
Recipients of a 1st Cadaveric Transplant
Wolfe RA et al. N Engl J Med 1999;341:1725-1730
K-M Estimates of Allograft Survival According to
the Use or Nonuse of Long-Term Dialysis before
Kidney Transplantation from a Living Donor
Adjusted Rate Ratio (95% CI): 0.16 (0.07–0.35)
P = 0.009
Mange K et al. N Engl J Med 2001;344:726-731
Acute Rejection within
the 1st Year Post-Transplant
Patients age 18
& older with a
functioning
graft at
discharge.
USRDS ADR 2012
Cumulative incidence of
post-transplant diabetes
Patients
receiving a
first-time,
kidney-only
transplant,
2003–2007
combined.
USRDS ADR 2012
Causes of Death in Kidney Transplant
Patients with Functioning Graft
2006–2010
First-time,
kidney-only
transplant
recipients,
age 18 &
older, 2006–
2010, who
died with
functioning
graft.
USRDS ADR 2012
Posttransplant Malignancy
• Risk is 4X to 100X compared rates of
malignancy in the general population
• No comprehensive reporting system
• Available data suggesting 2- to 3-fold underreporting
• The precise rate is UNKNOWN
• Accounts for 10% of deaths in kidney
recipients with functioning graft
•  SCREENING is KEY!
Immunization for Kidney Transplant
Recipients
Recommended
 Influenza types A and B
(yearly)
 Pneumovax (every 3-5
years)
 Diphteria-PertussisTetanus
 Haemophilus influenza B
 Hepatitis A and B
 Inactivated polio
 Meningococcus
Not Recommended









Varicella zoster
Intranasal influenza
BCG
Live oral typhoid
Measles, Mumps, Rubella
Oral polio
Yellow fever
Smallpox
Live Japanese B
encephalitis vaccine
Key Concepts (I)
• Kidney transplantation is the most costeffective modality of renal replacement
• Transplanted patients have a longer life
and better quality of life
• Early transplantation (before [pre-emptive]
or within 1 year of dialysis initiation) yields
the best results
• Living donor kidney outcomes are superior
to deceased donor kidney outcomes
Key Concepts (2)
• Early transplantation is more likely to occur in
patients that are referred early to nephrologists
• Refer for transplant evaluation when eGFR <
20 cc/min/1.73m2
• Success of transplantation results from a
delicate balance between the suppression of
the immune system to prevent rejection and the
long-term side-effects of immunosuppression
Key Concepts (3)
• The most common cause of transplant loss is
death with a functional transplant due to
– Heart disease +++
– Infections
– Malignancies
• Immunosuppressants are essential to prevent
immunological loss of the transplant but side
effects can also lead to transplant loss
What are the Costs of the
Different Renal Replacement
Therapy Modalities?
Costs (in Billion) of Medicare and
ESRD Programs in 2010
ESRD Cost
$32.9 (6.3%)
Total Medicare Costs
$522.8
488,938 ESRD patients representing
less than 1% Medicare population
USRDS ADR 2012
Total Medicare ESRD expenditures
per person per year, by modality
$87,561
$66,751
$32,914
Period prevalent ESRD patients
Patients with Medicare as secondary payor are excluded
USRDS ADR 2012
What About No Renal
Replacement Therapy Option?
Starting Dialysis in the
Elderly…Or Not?
• Among patients > 75 yrs with stage 5 CKD who
chose NOT to start dialysis:
– Overall, more likely to die over next 1-2 years
– But if they had ischemic heart disease or other
significant comorbidity  NO DIFFERENCE in
survival
• Active disease management and supportive care
may be appropriate without starting dialysis in the
ill elderly
• Must have end-of-life discussions!
Murtagh, et al. Nephrol Dial Transplant. 2007; 22(7): 1955-1962
The Future …
• Regenerative Medicine …
• Stem Cell Therapy …
• Wearable Artificial Kidney
Thank You !
QUESTIONS?