Integrated renal replacement therapy

1. TAREK ELERAKY
Consultant Nephrologist

3. • For all CKD complications, prognosis will vary depending on:
• Cause of CKD;
• GFR category;
• Albuminuria category;
• Other risk factors and comorbid conditions.
• The risk associations of GFR and albuminuria categories appear to be largely
independent of one another. Therefore, neither the category of GFR nor the
category of albuminuria alone can fully capture the prognosis for a patient with
CKD.
• All of the parameters above have an impact on life expectancy and quality of life
and contribute substantially to predicting the prognosis of CKD.
• Key to color grid:
Colors indicate groups of patients at higher risk of major outcomes:
• Green represents low risk. If the patient does not have other markers of kidney
disease, then CKD is not diagnosed or confirmed.
• Compared with the Green box (eGFR>60 ml/min/1.73 m2 and ACR<30 mg/g [<3
mg/mmol]):
• Yellow = is one step away from normal down or across. It represents moderately increased
risk.
• Orange = is two steps away from normal: down two, across two, or down one/across one. It
represents high risk.
• Red = is three steps away from normal. It represents very high risk.

5. Integrated Care Settings (ICS)
provide a holistic approach to the
transition from chronic kidney
disease into renal replacement
therapy (RRT), offering at least both
types of dialysis.

6. Initiation of dialysis
Many researchers thought that early dialysis
initiation would improve patient QOL and patient
survival by reducing the complication of dystrophy.
Furthermore, it was also believed that a decreased
glomerular filtration rate GFR at dialysis initiation
was associated with an increased probability of
hospitalization and death.
They held the idea that early dialysis initiation was
indispensable for preventing and reversing the
deteriorated nutritional status associated with
progressive uremia.

8. All of the studies and guidelines that were supporting early
dialysis have all been promoted as conventional wisdom (CW).
The CW can be summarized as follows:
• (1) low levels of dialytic and endogenous renal
clearance are associated with improved morbidity
and mortality;
• (2) Nutrition can be improved with the early
initiation of dialysis;
• (3) Dialysis should be initiated earlier in diabetics
than in nondiabetics; and
• (4) Dialysis initiated at eGFRs below 6 mL/min per
1.73 m2 is potentially dangerous.

9. • Recently, certain registry and observational studies
that included a total of > 900000 analyzable patients
all demonstrated that late dialysis initiation was
associated with improved survival.
• The Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)
• In 2002, Traynor et al….. In 2012, Yamagata et al...... In 2014, Crews et al
The IDEAL study
• The randomized controlled trial of early vs late
initiation of dialysis (IDEAL) study[ showed no
difference in mortality between the early and late
groups.

10. The IDEAL study
• The early group was expected to start dialysis when the CC (calculated
with the CG equation) was 10-14 mL/min per 1.73 m2, and the late group
was expected to start dialysis at 5-7 mL/min per 1.73 m2.
• It was allowed to start dialysis based on clinical indications,
disregardfulness CC in either group.
• The average CC values were 12.0 and 9.8 mL/min per 1.73 m2 at the time
of dialysis initiation in the early and late groups, respectively.
• Compared with the early group, the late group showed a 6-mo delay in
initiation. However, 76% of the patients who were allocated to the late
group actually commenced dialysis with a higher CC, and the mean
difference in the estimated GFR between the late and early groups was
only 2.2 mL/min.
• The gap between the 2 groups was too small to generate a difference in
the mortality rates.
• However, for some patients, who started RRT after their eGFR values
dropped below 5-7 mL/min per 1.73 m2, no harm was detected.
• In other words, initiating dialysis late might be safe for some patients
with fluid overload or other accompanying complications if they are
carefully monitored.

11. Recommendations that support late dialysis
• Many guidelines, including the ERBP 2002, the
Australia 2005
• and the United Kingdom 2009
• , recommend that RRT should be initiated before
the GFR reaches 6 mL/min per 1.73 m2.
• The ERBP 2002 recommends that dialysis
preparation should be initiated at a GFR of 8
mL/min per 1.73 m2 and that dialysis must be
initiated at a GFR of 6 mL/min per 1.73 m2.
• The CSN 2014 clinical practice guidelines
suggest that chronic dialysis should be
initiated when the eGFR drops to 6
mL/min per 1.73 m2, even if there are no
clinical indications.

13. • In a Chinese study in Taiwan, the median eGFR level at
dialysis initiation was 4.7 mL/min per 1.73 m2 from July
2001 to December 2004 in > 23000 incident patients.
• Based on the eGFR level at dialysis initiation, patients
were divided into quintiles, and the best survival was
observed at < 3.29 mL/min per 1.73 m2. Impact of the clinical conditions at
dialysis initiation on mortality in incident haemodialysis patients: a national cohort study in Taiwan.Hwang SJ, Yang WC, Lin MY, Mau LW, Chen HC,
Taiwan Society of Nephrology.
• Nephrol Dial Transplant. 2010 Aug; 25(8):2616-24.
• In another report, the best survival was achieved in
patients with eGFRs of between 0 and 5 mL/min per
1.73 m2 among American subjects. This study included
81176 uremic subjects, aged 20-64 with no substantial
comorbidities other than hypertension, from the
USRDS dataset. Rosansky SJ, Eggers P, Jackson K, Glassock R, Clark WF. Early start of hemodialysis may be harmful. Arch
Intern Med. 2011;171:396–403.

14. Renal replacement therapy (RRT) modalities
Renal replacement therapy (RRT) modality
distribution in a given country is determined by a
constellation of patient, physician, and system-
related factors that interact in complex ways to
ultimately determine both patient outcomes and
treatment costs.
It should first be acknowledged that there is no
single perfect form of RRT, and that each of the
existing options has its own inherent strengths
and limitations.

15. MODALITY OPTIONS FOR RRT
Renal transplantation
Transplantation remains the preferred mode of
renal-replacement therapy with respect to both
outcomes and cost effectiveness. As its initial
cost is high, its long term cost savings make it a
dominant economic strategy in any financial
environment, including developing countries.

16. In general, preemptive living donor
transplantation is the preferred
strategy when feasible, as it appears to
be associated with improved patient
survival, and minimizes the impact on
health-related quality of life.

17. Hemodialysis
Conventional 3-times per week, in-center hemodialysis
(HD) is the most prevalent and costly form of RRT in use.
Home HD currently comprises less than 1% of all RRT
in the United States, yet surveyed nephrologists believe
that it should comprise more than 10% of an optimal
modality mix.
While home HD is associated with a greater up-front
cost, it appears to be cost effective in the long term when
compared with in-center HD, and is associated
with superior outcomes.

18. Alternate HD schedules
Frequent HD schedules such as
Short daily HD (1.5–2.5 hr/session, 5 or more days/week),
Daily nocturnal HD (6–10 hr/session, 5 or more
days/week),
and long intermittent HD (8 hr, 3 days or nights/week)
appear to offer a number of benefits over the
conventional HD regimen.
The improved hemodynamic stability, and improved
small and large solute clearance afforded by these
therapies appear to confer a number of important
physiologic benefits that may ultimately prove to improve
patient survival.

19. Peritoneal dialysis (PD)
Peritoneal dialysis remains highly cost effective, costing as
little as 53% as much as in-center HD in the United
States.
Despite this, the United States and Canada
have seen an overall decline in PD
prevalence, which remains difficult to
understand on the basis of outcomes and
cost analyses.
The rapid growth of large dialysis organizations
in the United States, and their tendency to promote
HD have likely contributed to the demise of PD in the
United States.

20. Peritoneal dialysis may fare better in the early
years because of the tendency to use HD over PD at
the initiation of RRT for sicker patients as well as
better preservation of residual renal function in PD
during the first 1–3 years.
In later years of PD, with loss of residual renal
function and membrane failure, complications such as
volume overload, hypertension, reduced clearance,
and accelerated atherosclerosis (because of the long
term atherogenic effect of most kinds of current PD
solutions) may supervene, resulting in better
outcomes with HD.

21. More recent and well-designed
observational studies based on
USRDS data have suggested that
patients beginning RRT with known
atherosclerotic heart disease or
congestive heart failure have a
greater relative risk of death on PD
than with HD at 2 years

22. Despite this, it has become relatively
clear from the existing data that the
apparent benefits for one modality over
the other are modest compared with the
influence of other more important
prognostic factors such as age,
diabetes, and heart disease.

23. The importance of residual renal
function in dialysis patients.
Preserving residual renal function has always been
the primary clinical goal for every nephrologist
managing patients with chronic kidney disease.
There is no reason why this important goal should
not extend to patients with stage 5 chronic kidney
disease receiving dialysis.
Indeed, there is now clear evidence that
preserving residual renal function remains
important after the commencement of dialysis.

24. Residual renal function contributes
significantly to the overall health and well-
being of dialysis patients.
It not only provides small solute clearance
but also plays an important role in
maintaining fluid balance, phosphorus
control.
Removal of middle molecular uremic
toxins,
It shows strong inverse relationships with
valvular calcification and cardiac
hypertrophy in dialysis patients.

25. • Decline of residual renal function
also contributes significantly to
anemia, inflammation, and
malnutrition in patients on dialysis.
• More importantly, the loss of
residual renal function, especially in
patients on peritoneal dialysis, is a
powerful predictor of mortality.

26. • In addition, there is increasing
evidence that residual renal and
peritoneal dialysis clearance
cannot be assumed to be
equivalent qualitatively, thus
indicating the need to preserve
residual renal function in patients
on dialysis.

27. Progressive loss of RKF in incident dialysis patients
is associated with increased death risk over time.
Nevertheless, mortality is the highest in the first
several months of dialysis therapy when most
patients starting kidney replacement therapy have
their highest RKF.
The loss of RKF is faster in patients on HD than
those receiving peritoneal dialysis (PD).

28. HD may cause episodic ischemic damage to the kidneys,
leading to repetitive bouts of ischemic events similar to acute
kidney injury (AKI).
The causal link between AKI and subsequent CKD and that the
use of the term “AKI” may not be appropriate for the
mechanism of the faster loss of RKF in HD patients, the
cumulative effect of repetitive ischemic events may accelerate
the decline in RKF.
Consistent with this hypothesis, the recent Frequent
Hemodialysis Network (FHN) study showed that frequent
nocturnal HD may accelerate loss of RKF.

29. • Intense dialysis therapy
may also remove the
stimulus for the
hyperfunctioning of the
remaining nephrons,

30. Conservative kidney management
(CKM)
• Personalisation of choice in ESKF care has been
an explicit policy goal. Increasing emphasis has
been given to preparation for ESKF and choice of
treatments including conservative kidney
management (CKM). The majority of patients
with stage 4 chronic kidney disease (CKD4) or
CKD5 approaching ESKF are now seen in
multidisciplinary renal clinics, where risk factors
for progression and major cardiovascular events
are managed, advanced CKD metabolic
abnormalities and symptoms are treated and
preparation for RRT is organised.

31. The term CKM to describe the management of
ESKF without RRT, but with active symptom
management, communication and advanced
care planning (ACP), interventions to delay
progression and minimise complications,
psychological support, social and family support,
and spiritual care.

32. • It is not simply a ‘no dialysis’ option.
• Maximum care to slow disease progression,management
of other comorbidities,
• assessment and active management of symptoms (e.g. by
correcting anaemia and acidosis,
• maintaining fluid balance and treating troublesome
symptoms with drugs) including dietary restrictions,
• optimising communication and ACP,
• and improving care at the end of life,
• are all recommended.
• Services have increasingly been developed to focus on
optimising conservative care.

33. Incremental peritoneal dialysis: a 10
year single-centre experience
Incremental dialysis consists in
prescribing a dialysis dose aimed
towards maintaining total solute
clearance (renal + dialysis) near the
targets set by guidelines. Incremental
peritoneal dialysis (incrPD) is defined
as one or two dwell-times per day on
CAPD, whereas standard peritoneal
dialysis (stPD) consists in three-four
dwell-times per day.

35. PATIENTS AND METHODS
• Single-centre cohort study. Enrollement
period: January 2002-December 2007; end of
follow up (FU): December 2012.

37. INCLUSION CRITERIA
Incident patients with FU ≥6 months, initial
residual renal function (RRF) 3-10 ml/min/1.73
sqm BSA, renal indication for PD.

38. RESULTS
• Median incrPD duration was 17 months (I-III Q: 10; 30).
• There were no statistically significant differences between 29
patients on incrPD and 76 on stPD regarding: clinical, demographic
and anthropometric characteristics at the beginning of treatment,
• adequacy indices,
• peritonitis-free survival (peritonitis incidence: 1/135 months-
patients in incrPD vs. 1/52 months-patients in stPD) and patient
survival.
• During the first 6 months, RRF remained stable in incrPD (6.20 ± 2.02
vs. 6.08 ± 1.47 ml/min/1.73 sqm BSA; p = 0.792)
• Whereas it decreased in stPD (4.48 ± 2.12 vs. 5.61 ± 1.49; p < 0.001).
Patient survival was affected negatively by ischemic cardiopathy
(HR: 4.269; p < 0.001), peripheral and cerebral vascular disease
(H2.842; p = 0.006) and cirrhosis (2.982; p = 0.032) and positively by
urine output (0.392; p = 0.034). Hospitalization rates were
significantly lower in incrPD (p = 0.021). Eight of 29 incrPD patients
were transplanted before reaching full dose treatment.

41. CONCLUSIONS
• IncrPD is a safe modality to start
PD; compared to stPD, it shows
similar survival rates, significantly
less hospitalization, a trend towards
lower peritonitis incidence and
slower reduction of renal function.

42. Incremental HD dialysis: Can it make a
difference for residual renal function?
• Currently, in some countries, including India and China,
over half of HD patients receive ≤2 treatments per
week. Some patients are dialyzed even less frequently,
e.g. once weekly to even once a month.
• This practice pattern may largely reflect limited
resources and financial constraints. Nevertheless it
may be associated with improved outcomes in some
patients.
• In a seven-year observational study in Taiwan, patients
dialyzed twice (n= 23) versus thrice (n=51) weekly had
a slower decline of RKF, as indicated by higher urine
output and better creatinine clearance.
• Patients dialyzed twice weekly also had lower levels
of serum beta-2-microglobulin, fewer intra-dialytic
hypotensive episodes, and fewer hospitalizations.

43. • There are other important reasons to
perform twice-weekly HD upon
initiating dialysis therapy.
• First, having two sessions a week
means less frequent cannulations of a
new ateriovenous fistula or graft, which
may prolong its longevity.
• In addition, incremental HD may offer
a compromise and reconciliation
between the two camps of early vs.
late dialysis initiation in lieu of the
traditional approach of initiating thrice-
weekly HD.

44. • Criteria for candidates that may benefit from incremental
hemodialysis (IHD)
• Good residual renal function with urine output > 0.5 L/d (or KRU>3
ml/min)
• Limited fluid retention between two conservative HD treatments
with fluid gain < 2.5 kg (or < 5% of ideal dry weight) without HD for 3-
4 days
• Limited or readily manageable cardiovascular or pulmonary
symptoms without clinically significant fluid overload
• Suitable body size relative to renal residual kidney function
• Hyperphosphatemia (P> 5.5 mEq/L) is infrequent or readily
manageable
• Good nutrition status
• Lack of profound anemia
• Infrequent hospitalizations and easily manageable comorbid
conditions
• Satisfactory health-related quality of life
• Use of the criteria on 2x/week HD therapy patients should be re-
evaluated once a month.

45. Implementation Strategies
• In order to initiate and maintain 2x/wk HD,
the patient should meet the first criterion
(urine output >0.5 Lit/day) plus most (5 out
of 9) of the other criteria.
• Examine these criteria every month in all
2x/wk HD patients and compare outcome
between 2x/wk and 3x/wk HD to assure
outcome non-inferiority for continuation of
2x/wk HD
• Consider transition from 2x/wk to 3x/wk HD
regimen if patient’s urine output drops (<0.5
L/day) or if patient’s nutritional status or
general health condition shows a
deteriorating trend over time

46. Take home messages
(1) Early referral to CKD programs should be promoted,
as it is associated with improved outcomes and
preservation of renal function.
(2) Chronic kidney disease care should include aggressive
medical management to delay the progression
of chronic renal failure as well as reduce cardiovascular disease
burden, and control the complications of chronic renal failure.
(3) Preemptive living donor transplantation should be
promoted as the first-line treatment for ESRD.
modality, when and if required.
(4) RRF is very precious and all efforts should be done to keep them as
long as possible