Renal Replacement Therapy – What the Non-Nephrologist
Should Know
Bernard G. Jaar, MD, MPH, FASN,FNKFJohns 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 …
Coresh, J. et al. JAMA 2007;298:2038-2047
Prevalence of CKD Stages in US Adults Aged 20 Years or Older:
NHANES 1988-1994 and NHANES 1999-2004
ESRD Prevalence – The Forecast Projected growth overall ESRD prevalence (5% / yr)
Gilbertson et al. JASN 2003
Number of patients (millions)
Year
0.4 million
0.7 million
1.3 million
2.2 million (60% diabetic)
2000 2010 2020 20301978
3.0
2.0
1.0
0
618,160 pts (2011)
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)
• PE:– Unremarkable, except:– Weight 230 lbs (BMI 33) – BP 138 / 85– 2+ LE edema
• Treatment:– ACE inhibitor– Thiazide diuretics
Initial Nephrology Clinic Visit
Case Presentation (III)
• Labs:
Albumin 2.5 T. cholesterol 398 mg/dLSerology w-u (-)UA: protein 4+, 0-2 RBC, 0-2 WBCSpot u. prot. / creat. 413 mg/dL / 41 mg/dL 10
Initial Laboratory Data
12.3
41.0 7490 333
1413.6
10728
182.4
95
eGFR 37 cc/min/1.73m2
CKD Progression ESRD
05
10152025303540
Dates
eGFR
cc/
min
/1.7
3m2
Initial presentation:HTN, CKD, proteinuria
RRT
Kidney Bx: FSGS
“Uremic”ESRD
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
Hemodialysis
Kidney Transplant
Peritoneal Dialysis
Comfort Care
ESRD Treatment Options
ESRD
Hemodialysis
Kidney Transplant
Peritoneal Dialysis
Comfort Care
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
05
10152025303540
Dates
eGFR
cc/
min
/1.7
3m2
Initial presentation:HTN, CKD, proteinuria
RRT
“Uremic”ESRD
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)
CKD Education
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
Too Ofte
n Forgotte
n !
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.Central venous cuffed catheter2.Arteriovenous graft3.Arteriovenous fistula4.Temporary central venous catheter
Which Vascular Access and When Should It Be Placed?
CKD Progression
05
10152025303540
Dates
eGFR
cc/
min
/1.7
3m2
Initial presentation:HTN, CKD, proteinuria
HD
Vascular Access (AVF)
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
Astor B. et al. Am J Kidney Dis 2001; 38 (3): 494-501
Patients who started using an AV access by timing of first referral to a nephrologist
N=356 hemodialysis patients
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 non-dominant 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
Place vascular access within a year of hemodialysis anticipation …
On Non-Dominant Arm
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 RegimensMultiple 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 RegimensPD 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.Ultrafiltration failure2.Malnutrition3.Peritonitis4.Non-adherence to the treatment regimen
Cumulative percentage of PD patients by time from 1st dialysis to
1st switch to HD
Jaar BG et al. BMC Nephrol 2009; 10: 3
25% of PD patients
switched to HD within 5-7 years
Causes of PD Technique Failure (Switching from PD to HD)
47%
19%
15%
15%4%
Peritonitis
Ultrafiltration Failure
Malnutrition
Abdominal Surgery
Psychological Issues
Jaar BG et al. BMC Nephrol 2009; 10: 3
Which Dialysis Modality Provides the Best Outcomes?
Factors Influencing Dialysis Choice
Dialysis Modality
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:Late Referral,
…
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
Dialysis Modality
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:Late Referral,
…
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: Ontario, CanadaEnrollment Years: 7-1-1998 to 3-31-2006Follow-Up: 8 yearsPopulation Type: Incident – Elective Outpatient
(databases @ Institute for Clinical Evaluative Sciences)
Sample Size: HD: 4,538 PD: 2,035Switching Modality: NoModel(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)
Quinn RR et al. J Am Soc Nephrol 2011; 22: 1534-1542
Adjusted HR: 0.96, p = 0.44
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 HDBeyond Survival
• In considering choice of dialysis technique, other issues must be considered …
Factors Influencing Dialysis Choice
Dialysis Modality
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:Cost of Care,Late Referral,
…
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
• 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
CHOICE - Quality of Life: PD vs HD (II)
Factors Influencing Dialysis Choice
Dialysis Modality
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:Late Referral,
…
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
Ledebo I., Ronco C. NDT Plus 2008; 6:403-408
1. PD
2. HD in-center
3. HD home/ self-care
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 damage2.BMI > 303.Residual urine output of > 500 cc / day4.Colon cancer5.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
Cooper BA et al. N Engl J Med 2010;363:609-619
• 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
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: 396Shemin D et al. Am J Kidney Dis 2001; 38: 85Szeto C et al. Nephrol Dial Transplant 2003; 18: 977
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
Cumulative Incidence of All-Cause Mortality in 579 HD Patients by Urine Status at 1 Year (CHOICE)
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
Mange K et al. N Engl J Med 2001;344:726-731
K-M Estimates of Allograft Survival According to the Use or Nonuse of Long-Term Dialysis before
Kidney Transplantation from a Living DonorAdjusted Rate Ratio (95% CI): 0.16 (0.07–0.35)
P = 0.009
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 under-reporting
• 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-Pertussis-Tetanus
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 cost-effective 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
488,938 ESRD patients representing less than 1% Medicare population
USRDS ADR 2012
ESRD Cost$32.9 (6.3%)
Total Medicare Costs$522.8
Total Medicare ESRD expenditures per person per year, by modality
USRDS ADR 2012
Period prevalent ESRD patients Patients with Medicare as secondary payor are excluded
$87,561
$66,751
$32,914
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?