At which stage of renal failure

dialysis should be started ?

Fitri Ashadi
Ka Unit Hemodialisa
RSUD Raja Ahmad Thabib Tanjungpinang
Historical Background
 The issue of the adequate or optimal time at
which renal replacement therapy (RRT) should be
INIATED for patients with advance or terminal
chronic renal failure (CRF) has been matter of
debate since the very first introduction of this
revolutionary therapeutic concept, now close to
50 years ago, and is not yet settled.

 The lack of means of treatments, due mainly to

economics constraints, continues to play a key
role in many areas of the world for retarding (or
denying) RRT for great number of patients with
CRF.
 However the issue remains controversial in countries
with good availability of therapeutics facilities, due
either to inadequate medical management of many
patients prior to the ultimate stage of renal insufficiency
or to conceptual/academic conflicts between different
lines of thought set forward by defendants of “early
dialysis” versus challengers advocating the advantages
and safety of dietary restrictions for delaying to a
significant extent the initiation of dialysis treatment.
Late Referral
 The clinical status at the start of dialysis is a major
factor among those involved in the vital and
functional prognosis of patients taken onto RRT.

 Despite more intensive information provided to

general practioners and various categories of
specialists pleading for an early referral of patients
with moderate renal insufficiency but sometimes
found a late refferal to competent nephrologist.

 Dialysis should be initiated to promote wellness and

not to rescue from illness.
 In many ways, a safe follow-up procedure for
patients with advance-stage uraemia can be
compared with that applied for smooth landing of
an aircraft at a “Dialysis initiation airport” using the
navigation instruments list in table 1 :
Table 1. Desirable clinical and biochemical profile of
patients with chronic renal failure at the time of
initiation of dialysis
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, …
The problem of measuring residual renal
function (RRF)
 Serial measurement of serum creatinine
concentration(Scr), or 1/Scr, or creatinine clearance
(Ccr) per body surface area (BSA) are currently
considered by many experts as less reliable
parameters than the calculation of the residual
glomerular filtration rate (GFR) according to the
formula :
[Ccr + urea clearance (ml/min/1.73 m2)/2].

 Walser and Hill found that, on average, the ‘true’

GFR was indeed about 25% lower than the
measured Ccr.
 The problem.....

 The overestimation of the RRF based on the Ccr in

patients with advanced CRF has to be stressed and
the use of a less imperfect indicator is highly
recommended

Keterangan pemeriksaan fungsi ginjal :

 Sederhana : kreatinin darah
 Tes klirens kreatinin (TKK) :
 Menilai kemampuan ginjal membersihkan
kreatinin darah
 TKK normal = 115 – 125 ml/menit
 Laju filtrasi glomerulus ~ TKK
LFG / laju filtrasi glomerulus
1. Formula Cockroft-Gault :

LFG
2. Menentukan bersihan kreatinin

LFG : kreatinin urin (mg/mL) x volume urin (mL/24 jam)

kreatinin serum (mg/dL) x 1440
Recommendation and guidelines
 According to the US National Kidney Foundation
Dialysis Outcomes Quality Iniative (DOQI)
guidelines → patients should be advised to initiate
some form of dialysis when the weekly renal
Kt/Vurea falls below 2.0”
 This corresponds to a renal Ccr that ranges
between 9 and 14 ml/min/1,73 m2 and a residual
GFR of about 10,5 ml/min/1,73 m2.
 The highly detrimental effect of malnutrition in
patients with severe renal insufficiency.
Conclusions : in this study, planned early initiation
of dialysis in patients with stage V chronic kidney
disease was not associated with an improvement in
survival or clinical outcomes.
Postulate and practice
 In several series of patients taken onto RRT in the
early years of the present decade, the RRF
expressed in terms of weekly Kt/V at the start
dialysis was actually markedly lower than the value
forward in the DOQI guidelines, ranging between
0.68, 0.72 and 1.05 in patients reviewed in the USA,
Canada and the UK respectively.

 If one assumes an average decline of residual urea

clearance 0f -0.333 ml/min/month, one would
have to start dialysis to maintain a weekly Kt/Vurea
of urea 2.0 between 20 and 11 months earlier.
 Postulate.....

 If the DOQI guidelines were implemented, of course

a heavy additional burden would fall on the health-
care budgets of developed countries. This looks
even more unrealistic in developing countries.
The concept of incremental dialysis
 Meanwhile, the revived debate on this issue has led
to the development of the concept of “incremental
dialysis”. This concept is based on the principle that
patients with advanced CRF should maintain a
constant weekly globalKt/Vurea of 2.0 by adding to
the RRF an adequately titrated dose of dialysis.

 This dose has to be increased over time according to

the progressive fall of the RRF and differs according
to the type of dialysis applied.
 The concept.........

 With haemodialysis this goal can be achieved

during 5 months with 1 weekly dialysis session
gradually increased from 1 to 8 h, followed up to
36 months by a weekly regimen of two
haemodialysis sessions with a gradually increased
duration from 1.5 to 6 h each.
Low protein diet – an alternative?
 Whether initiation of dialysis can be deferred for a more
or less prolonged period of time by a low (or very low)
protein diet supplemented by essential amino acids or
their keto-analogues has been extensively debated the
past 25 years.
 The advocates of restricted protein diets set forward
attractive benefits, such as the alleviationof uraemic
clinical symptoms and improvement of electrolyte and
acid-base disturbances,
 The sceptics : the high cost of pharmaceutical
supplements and the risk of more or less overt protein
malnutrition. Malnutrition has a well documented
adverse effect on patient outcome.
Persisting dilemmas
 Deferred versus early initiation of dialysis thus
currently remains a matter of controversy,
dividing the nephrological community into
believers and skeptics, and even opponennts, of
either concept.
 The presence of significant comorbidities has to
be carefully considered in making the decision of
an appropriate time for starting dialysis.
 The nephrologist should also not be too
favourably influenced for delaying the initiationof
dialysis by the improvement of the clinical status
alleged by patients whose anaemia is efficiently
corrected by Rh-Epo therapy.
 Summary
 From a practical point of view, it can be reasonably
stated that timely initiation of dialysis treatment
cannot be based merely on numerical data, but
should be decided according to the overall clinical
tolerance of each individual patient to his or her
advanced stage of uraemia.

 The most important parameters to be considered

being : adequate control of blood pressure and
quality of nutritional status.
 Summary...

 Initiating dialysis at the right time for a given

patient with the most appropriate technique
represents a sophisticated exercise of clinical
medicine, which remains, and will remain a
balanced mixture of Science and Art.
THANK YOU
Treatment Options for Renal
Replacement Therapy
ESRD Comfort Care

Hemodialysis Peritoneal Dialysis

Kidney Transplant
Treatment Options for Renal
Replacement Therapy
ESRD Comfort Care

Hemodialysis Peritoneal Dialysis

Kidney Transplant
Dialysis Options
Dialysis

Hemodialysis Peritoneal Dialysis

In-Center HD (3 x week) Manual (CAPD)

Home HD (short daily, nocturnal) Home
Cycler (CCPD)
Incident Patient Counts (USRDS)
by 1st Modality

USRDS 2013 ADR

Total Medicare ESRD
expenditures, by modality

Period prevalent ESRD patients.

USRDS 2013 ADR

Referral and Education for Patients
with Progressive CKD
• Refer patients early, when eGFR < 30 ml/min/1.73 m2
• Education about types of renal replacement therapy:
o Hemodialysis (vascular access +++)
o Peritoneal Dialysis (QOL advantage +++)
o Kidney Transplantation
• Refer when eGFR < 20 ml/min/1.73 m2
• Living kidney transplant (family, friends)
• Build time on list before dialysis initiation
• Even transplant before dialysis initiation (pre-
emptive)
• No PICC lines for patients with eGFR < 45 mL/min/1.73m2
Advantages of Timely Referral in
Patients with Progressive CKD
• Improves patient preparation for RRT
• Greater use of permanent vascular access
• Avoidance of emergent hemodialysis initiation
• Greater utilization of transplantation and self-care
dialysis (i.e., peritoneal dialysis or home hemodialysis)
• Management of medications which may help to delay
the need for RRT
• Gives the nephrologist adequate time to counsel
patients through this challenging transition in their
lives

KDIGO Transplant Guidelines

Medical Health and Wellness: Components
of Multidisciplinary Care in Progressive CKD
• Education and counseling about different RRT
modalities, transplant options, and vascular access
surgery
• Protocols for laboratory and clinic visits; with
attention to CKD and CVD-associated comorbidities
(e.g., high blood pressure)
• Ethical, psychological, and social care (e.g., social
bereavement, depression, anxiety)
• Dietary counseling and education on other lifestyle
modifications (e.g., exercise, smoking cessation)
• Vaccination program

KDIGO Transplant Guidelines

Early Vaccination for Hepatitis B: Too
Often Forgotten!
• Patients with ESRD have  response to vaccination
(Secondary to general suppression of immune system)
• After Hepatitis B vaccination in ESRD patients:
o 50 – 60 % develop antibodies, compared to > 90%
in patients without renal failure
o Have Lower titers
o Have protective levels for shorter duration

Stevens CE et al. NEJM 1984; 311: 496

Buti M et al. Am J Nephrol 1992; 112: 144
Other Considerations for Vaccination in
Patients with Progressive CKD
• Influenza vaccine annually, unless contraindicated.
• Polyvalent pneumococcal vaccine:
o eGFR <30 ml/min/1.73m2
o High risk of pneumococcal infection (e.g.,
nephrotic syndrome, diabetes, receiving
immunosuppression), unless contraindicated.
o Offer revaccination within 5 years.

KDIGO Transplant Guidelines

High Blood Pressure
• Common in both dialysis and transplant populations
• Target blood pressure:
o Dialysis:
• Predialysis: <140/90 mm Hg
• Postdialysis: <130/80 mm Hg
o Transplantation: 130/80 mm Hg
• Managing high blood pressure in dialysis requires
attention to fluid status and antihypertensive medications,
while minimizing intradialytic fluid accumulation
• Can be impacted by certain immunosuppressants in
kidney transplantation recipients. Monitor for adverse
effects and drug–drug interactions
KDIGO. Am J Transplant. 2009:9(suppl 3):S1-S155.
NKF KDOQI. Am J Kidney Dis. 2000; 35(suppl 2):S1-S3.
Alborzi et al. Clin J Am Soc Nepohrol. 2007;2:1228-1234
Hemodialysis (HD)
Principle of Hemodialysis
Vein

Artery
 Urea Mass Transfer During
Hemodialysis

Solids ICF ECF IV HD

Harmon W, Jabs K: Hemodialysis (chap 77) in Pediatric Nephrology, 4th ed

Barratt, Avner, Harmon (ed) Lippincott, 1999
Dialyzer
Hemodialysis Filter (Dialyzer)
Hemodialysis Vascular Access

Polytetrafluoroethylene
Arteriovenous (AV) Fistula
Which Vascular Access and
When Should It Be Placed?
Dialysis Access
• Provides location for easy access to patient’s blood for
dialysis
• Bane of dialysis physician’s existence
• Higher flows and cannulation can lead to stenosis or
thrombosis
• Maintenance of dialysis access patency is critical, at
times life-saving
o Patency is assessed while patient is on HD by multiple
parameters
• Early detection of stenosis can lead to intervention
before thrombosis occurs
Dialysis Access
• AV Fistula
o Vein cross-cut, attached end-to-side to artery
o High-pressure flow dilates and thickens vein
o Best alternative:
• Lowest infectious risk
• Longest lasting with least thromboses
o Drawbacks
• Takes 2-4 months to mature
• Only about 50% ever mature
o Goal for all dialysis patients
Dialysis Access
• AV Graft
o Tube made of biocompatible material (gortex) attached
end-to-side to artery and vein
o Often required in patients with vascular disease,
occluded distal veins
o Advantages
• Ready to use when swelling resolves (~2 weeks)
• Able to use in most patients
o Disadvantages
• High stenosis/thrombosis rate
• Moderate infectious risk
Dialysis Access
• Catheter (IJ most common)
o Tunnelled under skin to reduce communication from
skin flora with blood
o Advantages
• Ready for use immediately
o Disadvantages
• High infectious risk
• High thrombosis risk
• A/W increased mortality
• Can be a sign of poor pre-dialysis care or extensive vascular
disease
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.
o Avoid PICC lines
• 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)
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; 38:494-501.

SAVE the Non-Dominant ARM
for Vascular Access

• When GFR < 30 mL/min

o No BP measurement
o No IV
On Non-Dominant
Arm
o No Blood Draws

• Place vascular access within a year of

hemodialysis anticipation …
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
• Total of 75.9% of the patients in the late-start group started
dialysis when eGFR was > 7.0 mL/min/1.73m2, 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
mL/min/1.73m2)
•  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;18.7
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!
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:
o Overall, more likely to die over next 1-2 years
o 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
Pertanyaan :
Wanita, 47 th, keluhan utama : sesak napas sejak 1
minggu smrs.
PF : KU: sakit berat, Kes : CM TD : 210/100 mmHg,
N : 108 x/mnt, RR : 30 x/mnt, t: 36,8 C,
Paru : RBH (+) basal kedua paru,
Ekstremitas : edem pretibial(+)
Lab : Hb : 13,4 g/dL, Leukosit: 26.100
Trombosit : 337.000, GDS : 275 ,
Ureum/creatinin: 167/8,4 , Na/K : 137/8,4

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