dialysis (RRT) in acute kidney injury, when to start, when to stop dialysis?, what dose to give and what modality to use?

1. Dialytic management of AKI
Mahmoud Naguib
Assistant lecturer of nephrology - Mansoura university

2. Introduction
• In a metanalysis that included about 49 million patients in 312 studies the
pooled rate of AKI was 10.7%
• When restricted to the 154 studies (about 3.5 million patients) that used a
KDIGO-equivalent AKI definition, the pooled rate of AKI was 23.2%
• The rate of dialysis requirement was 2.3 %
• the pooledAKI-associated all-cause mortality rate was 23.0%
• The mortality rate reaches up to 49.4% in AKI patients who required dialysis
“World incidence of AKI: a meta-analysis.” CJASN vol. 8,9 (2013): 1482-93.

3. “World incidence of AKI: a meta-analysis.” CJASN vol. 8,9 (2013): 1482-93.

4. “World incidence of AKI: a meta-analysis.” CJASN vol. 8,9 (2013): 1482-93.

5. • 199 AKI patients
• 67 patients (33.7 %) received dialysis:
• 49.1% maintained on hemodialysis
• 50.9% stopped hemodialysis
• 23% no renal recovery
• 13% Mortality
Nephron. 2018;140(3):185-193. doi: 10.1159/000492063. Epub 2018 Sep 11. PMID:
30205406.

6. Dialysis in
AKI
When to start ??
When to stop ??
What modality to use ??
What dose to give ??

7. Dialysis in
AKI
When to start ??

8. When to start ?

11. Early versus late dialysis
• Until recently, there were only a few small RCTs and a number of observational and
cohort studies examining the timing of initiation of RRT, with some showing the
beneficial effects of “early” RRT.
• However, there is heterogenicity between these studies and they used different
definitions for “early” and “late”
• Definitions across published studies include physiologic parameters (e.g.,urine
output (UO)), functional biomarkers (e.g., creatinine, urea), time from AKI
development and hospital or ICU admission, or occurrence of classical (urgent)
indications (e.g.hyperkalemia, metabolic acidosis, fluid overload resistant to
diuretics, and uremia)
A comparison of early versus late initiation of renal replacement therapy in critically ill patients
with acute kidney injury: a systematic review and meta-analysis. Crit Care 15, R72 (2011).
Moreover, the terms
“early”
and “late” are relative,
and what may represent
early RRT in one case
could be late in another

14. Early versus late dialysis
• Some RCTs were published between 2015 and 2016, which compared
early (or “accelerated”) and late RRT (defined by the KDIGO criteria).
• However, there was differences in methodology and conflicting results
between these studies.

15. • 100 patients with KDIGOAKI stage 2 and (NGAL) more than 400 ng/mL
were randomized into “accelerated” arm and “standard” arm.
• In the “accelerated” arm, RRT started within 12 h of reaching the inclusion
criteria, whereas in the “standard” group, initiation of RRT was determined
by classic indications.
• There was no difference in mortality.
• 30% of patients in “standard” arm didn’t require dialysis.

16. • that included 231 mainly cardiac surgical patients:
• Early group ( started RRT within 8 hours of diagnosis of KDIGO stage 2; n = 112)
• Delayed group ( started RRT within 12 hours of stage 3 AKI or no initiation; n = 119).
• 90-day all-cause mortality was significantly lower in early group [39.3% (44/112)] than
in patients in the “late” group [54.7% (65/119)].
• Also, early RRT produced significant benefits for several secondary endpoints,
including duration of RRT, recovery of renal function, duration of mechanical
ventilation, length of hospital and ICU stay, and requirement of RRT at day 90, along
with a decrease in interleukin (IL)-6 and IL-8 plasma concentrations.
all patients were treated with a standardized
CRRT protocol, which included citrate
anticoagulation

20. • larger multi-center, randomized AKIKI (Artificial Kidney Initiation in Kidney Injury) trial included 620
critically ill patients, all with KDIGO stage 3 AKI.
• “Early” group initiated RRT within 6 h of the start of mechanical ventilation and/or catecholamine infusion.
• “Delayed” group initiated RRT when absolute/urgent indications were fulfilled (severe hyperkalemia,
metabolic acidosis, pulmonary edema, BUN level >112 mg/dl, or oliguria >72 hours).
• There was no significant difference in overall survival at day 60 (primary outcome)
• The main secondary outcomes also were not significantly different between the two groups.
• in the AKIKI trial, 49% of patients enrolled in the delayed arm did not receive any RRT (compared to 9% in
the ELAIN)
• the predominant treatment modality used initially was intermittent hemodialysis (HD) (55%), and only
30% of patients received CRRT as the sole method.

24. Early versus late dialysis
• although the AKIKI and the ELAIN trials have been conducted with a high level of scientific quality and
good study designs, the significant differences in patient populations, severity of renal injury, and extra-
renal organ insufficiency, along with RRT modality and timing, prevent the possibility of reaching
definitive conclusions about early or late RRT benefits in patients with AKI.
• Moreover, an important aspect that physicians have to consider is whether the criteria to start RRT used
in these trials are in agreement with routine clinical practice
• Publication of these two large studies confirmed that the timing of RRT initiation is an unanswered but
important issue for critically ill AKI patients.
• Evidence from the literature suggests that timing of initiation of RRT is a very complex decision,
involving considerations beyond isolated variables, such as “clock-time” or a specific metabolic
parameter. Indeed, a more personalized approach will likely be required, as recently advocated by the
Acute Disease Quality Initiative (ADQI) workgroup
Renal replacement therapy for AKI:When? How much?When to stop?, Best Practice & Research Clinical Anaesthesiology,Volume 31, Issue 3,2017,

27. Dialysis in
AKI
When to start ??
When to stop ??
What modality to use ??
What dose to give ??

28. Dialysis in
AKI
When to stop ??

29. When to stop ?
• While an increasing body of evidence indicates that a significant portion of patients are left with
some degree of chronic kidney disease after AKI, most patients who survive an episode of RRT-
requiring AKI regain sufficient kidney function to avoid the need for long-term dialysis.
• unnecessary prolongation of RRT may impair renal recovery, especially when side effects
occur: (treatment-associated hemodynamic instability, vascular catheter-related bacteremia and
sepsis, and cytokine activation by bioincompatible membranes)

30. When to stop ?
The lack of specificity for these statements indicates that clear factors that may help
physicians in predicting successful cessation of RRT are still lacking

31. • Success in discontinuing dialysis was defined as cessation from dialysis for at least
30 days
• 304 postoperative patients who underwent acute renal replacement therapy
• 94 patients (30.9%) weaned from acute dialysis for more than 5 days
• 64 of these (21.1%) were successfully weaned for at least 30 days.
• Less urine output, longer duration of dialysis, age over 65 years, and higher disease
severity score were predictive of a patient's re-dialysis after initial weaning from
acute dialysis.

32. • Included 529 ICU patients who survived initial treatment with CRRT
• “successful” group (n=216) was defined as the avoidance of CRRT for at
least 7 days after original termination
• UO (during the 24 h before stopping CRRT) was identified as significant
predictor of successful discontinuation, although its predictive ability was
negatively affected using diuretics

33. • In the AKIKI study for both the early and late groups, discontinuation of RRT was
considered when the spontaneous UO was >500 mL/24, highly recommended
when the spontaneous UO was higher than 1000 mL/24 h in the absence of diuretic
therapy (>2000 mL/24 h in patients who were receiving diuretic therapy), and
mandatory if diuresis was sufficient to allow for a spontaneous decrease in serum
creatinine concentration
• In the ELAIN study, RRT was discontinued if renal recovery occurred (defined by
UO >400 mL/24 h without diuretic treatment (2100 mL/24 h with diuretic
treatment) and creatinine clearance >20 mL/min.

34. • Retrospective single-center cohort study of (67 patients) treated with IHD for at least
7 days and four dialysis sessions forAKI
• (37 patients) were weaned and (30 patients) not weaned
• Blood and urinary markers were recorded on the day of the last IHD in the ICU for
unweaned patients and 2 days after the last IHD for weaned patients.
• Concluded that a daily urinary urea excretion > 1.35 mmoL/kg was the best indicator
for successful weaning, followed by UO > 8.5 mL/kg/24 h

36. • studied 54 surviving AKI patients in which a weaning of RRT was tried. On the
day of weaning (D0) and the following 2 days (D1 and D2), SAPS II and SOFA
scores, 24-h diuresis, 24-h urinary creatinine and urea (UCr and UUr),
creatinine and urea generation rates (CrGR and UrGR) and clearances (CrCl
and UrCl) were collected.
• in 26 successful RRT weaning attempts (remained free of RRT 15 days after
its discontinuation), multivariate analysis demonstrated that 24-h urinary
creatinine on day 1 after weaning was the most powerful predictor
• A 24-h UCr ≥5.2 mmol was associated with a successful weaning in 84 % of
patients

37. • Retrospective study included 85 patients who received CRRT in intensive care unit
and had a 2h-CrCl measurement performed in the 12 hours preceding CRRT
cessation.
• 2h-CrCl was a better predictor of remaining CRRT free at day 7, than urine output,
serum creatinine or age.
• Concluded that 2h-CrCl may be a useful measurement to help guide
discontinuation from CRRT.

38. When to stop RRT?
• Requires regular (at least daily) assessment.
• Average duration of RRT in AKI is 7 - 12 days.
• Assessment of underlying renal function during RRT can be difficult.
• Especially for intermittent haemodialysis (IHD) where variable rebound in Ur, SCr, and
electrolytes may occur between treatments.
• An increase in urine output is particularly helpful, although the use of diuretics will
need to be factored in (routine administration of diuretics to increase UO and
facilitate earlier cessation of RRT is not recommended)
• •Trends in SCr, Ur, and electrolytes need to be carefully considered (and allowance
made for non-renal confounding factors, such as the patient's catabolic state and
volume status).

39. When to stop RRT?
• Theoretically, serial measurements of urinary Cr excretion might be helpful but are
very rarely undertaken in practice.
• Cessation of RRT does not have to be an absolute. It might be wise to initially adjust
the duration and frequency of treatment or to consider a modality change (e.g. step
down from CRRT on ITU to IHD on a renal unit).
• Occasionally, specially in a critical care setting, more fundamental issues concerning
the uselessness of further treatment will need to be included in the decision-making

40. Dialysis in
AKI
When to start ??
When to stop ??
What modality to use ??
What dose to give ??

41. Dialysis in
AKI
What modality to use ??

42. • The study analyzed 15 RCTs including (1550 patients)
• Comparing IHD and CRRT in ARF
• CRRT did not differ from IRRT with respect to in‐hospital mortality, ICU
mortality, number of surviving patients not requiring RRT, haemodynamic
instability or hypotension and need for escalation of pressor therapy
• Patients on CRRT were likely to have significantly higher mean arterial
pressure, and higher risk of clotting dialysis filters

44. Advantages and disadvantages of different modalities

45. Advantages and disadvantages of different modalities

46. What modality to use ??

47. What modality to choose?
• The ideal modality of RRT in AKI is unknown. In practice, the choice will be based
primarily upon: (i) the availability of different treatments and (ii) a patient's
haemodynamic status and overall clinical condition
• PD use in AKI is infrequent, except in paediatric practice and in areas where
resources are constrained
• One size does not fit all. No single modality of RRT is ideal for all patients in all
situations.
• It is important to be aware of the advantages and disadvantages of available
techniques and to tailor treatment to a particular clinical context.
• The treatments should not be considered competitive but complementary.
• It should also be acknowledged that availability may influence choice to a greater or
lesser extent.

48. What modality to choose?
• In the patient with haemodynamic instability, CRRT is preferred to standard IHD.
• CRRT is also preferred in patients with AKI who cannot tolerate fluctuations in fluid
status (e.g. cardiogenic shock).
• In a critically ill patient with multi-organ involvement, particularly in an HDU/ITU
setting, the adaptability of CRRT means that it is generally preferred to IHD.
• CRRT is preferred for a patient with acute brain injury where IHD may worsen
neurological status ( decreased BP >>> cerebral oedema >> decrease cerebral
perfusion pressure).
• CRRT is preferred in combined liver-kidney failure (possible advantage for
prevention of increased intracranial pressure).
• SLED may be better tolerated than IHD, particularly if other forms
• of CRRT are unavailable.

49. Dialysis in
AKI
What dose to give ??

50. What dose to give ??
• The optimal dose of renal replacement therapy (RRT) in acute kidney injury
(AKI) remains controversial.
• Kt/V urea, Although widely used for evaluation of RRT in CKD, it has important
limitations as a tool for RRT dosing in AKI, as AKI patients are metabolically
unstable, with variations in urea generation.

51. What dose to give ??
• This observational study was the first to explore the relationship between delivered
Kt/V and outcome in a series of 842 AKI patients who received different forms of RRT
• Patients receiving a relatively high delivered dose of HD (Kt/V > 1.0 per treatment)
had a significantly higher hospital survival than patients receiving a lower dose.

52. • RCT of 160 patients with AKI were assigned to receive daily or conventional
alternate day IHD.
• patients in the daily HD group had a significantly lower mortality than those
in the alternate-day group
• mortality was significantly higher in patients with a cumulative (weekly)
Kt/V < 3.0 in comparison to patients with a cumulative Kt/V > 6.0

53. • A RCT of 156 patients with AKI requiring renal replacement therapy were randomly
assigned to receive standard dialysis [dosed to maintain plasma urea levels between
120 and 150 mg/dL (20–25 mmol/L)] or intensified dialysis [dosed to maintain
plasma urea levels <90 mg/dL (<15 mmol/L)]
• Outcome measures were survival at Day 14 (primary) and survival and renal
recovery at Day 28 (secondary)
• There was no differences between both groups in survival or renal recovery

55. • 1124AKI patients were randomized into 2 groups (intensive and less intensive RRT)
• In both study groups, hemodynamically stable patients underwent IHD, and
hemodynamically unstable patients underwent CRRT or SLED
• Intensive group : IHD or SLED 6 times/w or CRRT at 35 ml/kg/h
• Less intensive group : IHD or SLED 3 times/w or CRRT at 20 ml/kg/h
• Conclusion: Intensive renal support in critically ill patients with AKI did not decrease
mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ
failure

57. • RRT of 1508 critically ill AKI patients randomized into:
• Higher-intensity: effluent flow: 40 ml/kg/h
• Lower-intensity: effluent flow 25 ml/kg/h
• There was no difference in 90-day mortality between both groups

59. What dose to give ??