Renal Replacement Therapy in Acute Kidney Injury -time and modality -Dr Ayman Seddik

1. RRT in AKI Time & Modality
Dr Ayman Seddik, MD, ECNeph, FASN
Prof. OF Nephrology Ain Shams University
Nephrology consultant Diaverum KSA

2. OUTLINE :
Definition of AKI
( what is new )
1
Q2
PATHOPHYSIOLOGY
of severe AKI
requiring RRT?
2
Q3
When ….. TIME TO
START RRT IN
AKI?
3
Q4
Which ……..
form of RRT?
4
Q1

3. OUTLINE :
Definition of AKI
( what is new )
1 2
Q3
3 4
Q1

6. KDIGO/AKIN Classification

8. OUTLINE :
1
Q2
PATHOPHYSIOLOGY
of severe AKI
requiring RRT?
2
Q3
3 4

9. Kellum, et al. Acute kidney injury. Nat Rev Dis Primers 7, 52 (2021).
Main principles of the pathophysiology of AKI.
A) Mild acute kidney injury (AKI), defined by a transient decline in urinary output or excretory function, involves no or minimal kidney cell necrosis or loss. Precedent and subsequent nephron
numbers remain identical and no persistent adaptive cellular responses are necessary. In the long term, the risk of cardiovascular disease (CVD) is somewhat increased, which may also depend on the
underlying cause of AKI.

10. Kellum, et al. Acute kidney injury. Nat Rev Dis Primers 7, 52 (2021).
Main principles of the pathophysiology of AKI.
B) Whenever AKI is associated with kidney cell or tubule necrosis, the affected cells are irreversibly lost during the phase of acute necroinflammation, as indicated by activated immune cells in the
interstitial compartment. Renal progenitor cells are more resistant to death and their clonal expansion may facilitate the structural and functional recovery of some injured nephrons. Nephrons in
which injured segments do not recover undergo atrophy, are irreversibly lost, and are replaced by fibrous tissue that stabilizes the structural integrity of remnant nephrons. Resulting hyperfiltration
requires an increase of the functional capacity of remnant nephrons achieved through an increase in their dimensions, with tubular epithelial cells (TECs) undergoing polyploidization, indicated by an
increased size of cytoplasm and cell nuclei. Depending on the number of remnant nephrons, their capacity for adaption (kidney reserve), and filtration load (dependent on body weight, fluid intake,
diet, and others), glomerular filtration rate (GFR) can return to baseline. This status already qualifies as CKD, even if GFR returns to baseline.
The adaptive changes of CKD imply a higher risk of CVD and possibly kidney cancer, and the irreversible loss of nephrons reduces kidney lifespan.

11. Kellum, et al. Acute kidney injury. Nat Rev Dis Primers 7, 52 (2021).
Main principles of the pathophysiology of AKI.
C) When severe AKI involves extensive tubule necrosis, the consequences on nephron number are substantial. Tubule recovery occurs only in those nephrons with surviving progenitor cells. Adaptation
to filtration and metabolic demands results in large increases in the dimensions of the few surviving nephrons (megalonephrons). Such adaptations frequently exceed the adaptive capacity of podocytes,
leading to secondary focal segmental glomerulosclerosis and subsequent loss of the remnant nephrons (that is, progressive CKD). Cellular adaptation-related polyploidization and senescence, as well as
nephron loss-related scarring, drive interstitial fibrosis and progressive kidney atrophy. These adaptive changes strongly increase the risk of CVD and possibly kidney cancer. Kidney lifespan is
drastically reduced and some patients remain on kidney replacement therapy.

12. Kellum, et al. Acute kidney injury. Nat Rev Dis Primers 7, 52 (2021).
Systemic consequences of AKI.

13. The kidneys maintain homeostasis; hence, acute kidney injury (AKI) affects almost all
systems of the body, albeit in different ways.
1- Fluid retention affects especially the lungs and the heart, frequently
with clinical signs of respiratory or circulatory failure. Fluid retention also compromises the
gastrointestinal system, for example, the liver or the intestine, promoting intestinal barrier
dysfunction and translocation of bacteria and bacterial toxins.
2- Impaired uremic toxin excretion affects the function
of the brain, the heart, the bone marrow, and the immune system, leading to neurocognitive
defects, anemia, and acquired immunodeficiency accompanied by persistent systemic
inflammation.
3-Kidney cell necrosis releases debris into the venous circulation,
which accumulates in the lungs and causes direct microvascular injury, thrombosis, and,
sometimes, acute respiratory distress syndrome.

14. OUTLINE :
1 2
Q3
When ….. TIME TO
START RRT IN
AKI?
3 4

15. Kellum, et al. Acute kidney injury. Nat Rev Dis Primers 7, 52 (2021).
Management of AKI.

16. Kellum, et al. Acute kidney injury. Nat Rev Dis Primers 7, 52 (2021).
Fluid management in acute kidney injury.

17. Joannidis, M., Meersch-Dini, M. & Forni, L.G. Acute kidney injury. Intensive Care Med 49, 665–668 (2023). https://doi.org/10.1007/s00134-023-07061-4

18. Both hypovolaemia (kidney hypoperfusion) and hypervolaemia (kidney congestion) compromise kidney
function. Impaired cardiac function adds to both problems as renal and cardiac dysfunction aggravate each
other, referred to as cardiorenal syndromes.
An injured kidney or heart increases the likelihood of developing clinical symptoms of hypovolaemia or
hypervolaemia compared with healthy organs. An increasing severity of symptoms requires escalating
therapeutic interventions. Hypotension frequently indicates kidney hypoperfusion despite clinically apparent
hypervolaemia whenever fluid redistributes to the venous system, into tissue interstitium or third
compartments, for example, in hepatorenal syndrome, congestive heart failure or capillary leakage during
sepsis.
Kidney and/or heart failure drastically decrease both organs’ capacity to maintain function during
hypovolaemia or hypervolaemia. In a euvolemic patient with AKI, a single bolus of buffered crystalloid fluid
can indicate the presence of subclinical hypovolaemia and hypoperfusion of the kidney (prerenal AKI).
Prolonged administration of balanced crystalloids should be handled with caution in order not to promote
oedema or congestion and not to decrease tissue oxygenation. Patients with hypervolaemia should not
receive fluids for AKI but loop natriuretics. In patients who are critically ill with suppressed vasomotor
response, vasopressors are frequently needed to improve cardiac output.

20. WHEN RRT
AKI
LATE
EARLY

26. hospital mortality and 90-day RRT dependence rates were higher in
the early RRT group than in the delayed RRT group. HOWEVER
WITHOUT STATISTICAL SIGNIFICANCE

27. Hemodynamic instability is a common complication during RRT, which can increase hospital mortality
and limit kidney recovery.
Many factors contribute to hemodynamic instability, including excessive ultrafiltration, rapid
osmotic/oncotic shifts, decreased cardiac output, and decreased peripheral resistance.
The incidence of hypotension was 15.7% and 11.0% in the early-strategy group and in the delayed-
strategy group, respectively.
studies that reported hypotension events all involved intermittent hemodialysis (IHD), which was more
likely to result in hemodynamic instability than CRRT.

28. A remarkable higher incidence of RRT-associated infection events was also
found in the early RRT group. Patients treated with RRT are more susceptible
to infection, as they are exposure to catheters and invasive treatments
Moreover, RRT may enhance the elimination of antibiotics, leading to
suboptimal antibiotic concentrations

29. Conclusions
• This meta-analysis suggested that early initiation of RRT was not associated with survival
benefit in critically ill patients with AKI.
• In addition, early initiation of RRT could lead to unnecessary RRT exposure in some
patients, resulting in a waste of health resources and a higher incidence of RRT-associated
adverse events.
• Maybe, only critically ill patients with a clear and hard indication, such as severe acidosis,
pulmonary edema, and hyperkalemia, could benefit from early initiation of RRT.
clinical outcomes were comparable between the two groups. In addition, results showed that
delayed RRT initiation could reduce the incidence of RRT-associated adverse events.
Undoubtedly, unnecessary RRT will increase the workload of medical staff, augment
treatment costs, and waste health resources. Therefore, it is reasonable to assume that
delayed initiation of RRT is a preferable approach for critically ill patients with AKI.

31. Bagshaw, S.M., Hoste, E.A. & Wald, R. When should we start renal-replacement therapy in critically ill patients with acute kidney injury: do we finally have the answer?. Crit Care 25, 179 (2021).
Whenshould we start renal replacement therapy in critically ill patients with acute
kidney injury: do we finally have the answer?

32. OUTLINE :
1 2 3
Q4
Which ……..
form of RRT?
4

33. Renal Replacement Therapy for AKI
peritoneal
dialysis
intermittent
hemodialysis
continuous
blood purification
• rarely used
• if no vascular
access can be
obtained
• equipment identical
to chronic renal
failure
• standard HD
treatments
• appropriate for
isolated AKI
NO other organs
involved
• dedicated
equipment
• mostly
hemofiltration
• therapy of choice
for complicated
ARF
WHICH modality of RRT IN AKI :
PIRRT
• prolonged
treatments with
(modified) HD
monitors
• appropriate for
severely ill patients
also

35. daily, intermittent haemodialysis
continuous haemodialysis
Therapy:
Continuous or Intermittent?

43. Key messages (when)
1.Early initiation of RRT was not associated with survival benefit in
critically ill patients with AKI.
2.Early initiation of RRT could lead to unnecessary RRT exposure
in some patients, resulting in a waste of health resources and a
higher incidence of RRT-associated adverse events, including
hypotension and infection.
3.Delayed initiation of RRT might be safe in the absence of life-
threatening conditions, such as acute pulmonary edema, severe
acidosis, and severe hyperkalemia.

46. Thank You

47. APPENDIX FOR FURTHER
READINGS

48. Prevention and Treatment of AKI
3.1.1: In the absence of hemorrhagic shock, we suggest
using isotonic crystalloids rather than colloids (albumin or
starches) as initial management for expansion of
intravascular volume in patients at risk for AKI or with AKI.
(2B)
3.1.2: We recommend the use of vasopressors in
conjunction with fluids in patients with vasomotor shock
with, or at risk for, AKI. (1C)
3.1.3: We suggest using protocol-based management of
hemodynamic and oxygenation parameters to prevent
development or worsening of AKI in high-risk patients in
the perioperative setting (2C) or in patients with septic
shock (2C).
KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138.

49. Prevention and Treatment
of AKI
3.3.1: In critically ill patients, we suggest insulin therapy
targeting plasma glucose 110–149mg/dl (6.1–8.3mmol/l).
(2C)
3.3.2: We suggest achieving a total energy intake of 20–30
kcal/kg/d in patients with any stage of AKI. (2C)
3.3.3: We suggest to avoid restriction of protein intake with
the aim of preventing or delaying initiation of RRT. (2D)
3.3.4: We suggest administering 0.8–1.0 g/kg/d of protein in
non catabolic AKI patients without need for dialysis (2D),
1.0–1.5 g/kg/d in patients with AKI on RRT (2D), and up to a
maximum of 1.7 g/kg/d in patients on (CRRT) and in hyper
catabolic patients. (2D)
3.3.5: We suggest providing nutrition preferentially via the
enteral route in patients with AKI. (2C)

50. 3.4.1: We recommend not using diuretics to prevent AKI. (1B)
3.4.2: We suggest not using diuretics to treat AKI, except in the
management of volume overload. (2C)
3.5.1: We recommend not using low-dose dopamine to prevent or treat
AKI. (1A)
3.5.2: We suggest not using fenoldopam to prevent or treat AKI. (2C)
3.5.3: We suggest not using atrial natriuretic peptide (ANP) to prevent
(2C) or treat (2B) AKI.
3.6.1: We recommend not using recombinant human (rh)IGF-1 to
prevent or treat AKI. (1B)
3.7.1: We suggest that a single dose of theophylline may be given in
neonates with severe perinatal asphyxia, who are at high risk of AKI.
(2B)

51. 3.8.1: We suggest not using aminoglycosides for the treatment of infections
unless no suitable, less nephrotoxic, therapeutic alternatives are available.
(2A)
3.8.2: We suggest that, in patients with normal kidney function in steady state,
aminoglycosides are administered as a single dose daily rather than multiple-
dose daily treatment regimens. (2B)
3.8.3: We recommend monitoring aminoglycoside drug levels when treatment
with multiple daily dosing is used for more than 24 hours. (1A)
3.8.4: We suggest monitoring aminoglycoside drug levels when treatment with
single-daily dosing is used for more than 48 hours. (2C)
3.8.5: We suggest using topical or local applications of aminoglycosides (e.g.,
respiratory aerosols, instilled antibiotic beads), rather than i.v. application,
when feasible and suitable. (2B)
3.8.6: We suggest using lipid formulations of amphotericin B rather than
conventional formulations of amphotericin B. (2A)
3.8.7: In the treatment of systemic mycoses or parasitic infections, we
recommend using azole antifungal agents and/or the echinocandins
(caspofungin ) rather than conventional amphotericin B, if equal therapeutic
efficacy can be assumed. (1A)
KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138.

52. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138.
3.9.1: We suggest that off-pump coronary artery bypass
graft surgery not be selected solely for the purpose of
reducing perioperative AKI or need for RRT. (2C)
3.9.2: We suggest not using NACETYL CYSTEINE to
prevent AKI in critically ill patients with hypotension.
(2D)
3.9.3: We recommend not using oral or i.v. NAC for
prevention of postsurgical AKI. (1A)

53. Risk factors for AKI :

55. Biomarkers of AKI
American Journal of Kidney Diseases 2020 76710-719DOI: (10.1053/j.ajkd.2020.03.016)

56. Kellum, et al. Acute kidney injury. Nat Rev Dis Primers 7, 52 (2021).
Severity of AKI and long-term kidney outcome

57. Certain biomarkers indicate early kidney injury or subclinical acute kidney injury (AKI) as a risk
factor for proceeding to AKI according to the Kidney Disease Improving Global Outcomes
(KDIGO) definitions. AKI itself is indicated by injury markers in blood and urine before any
impairment of kidney function (as measured by serum creatinine levels and urine output)
occurs.
The three stages of AKI are defined by the extent of renal function impairment. Patients with
AKI in which structural damage causing irreversible nephron loss does not occur may fully
recover. AKI with structural damage frequently lasts >7 days, which is classified as acute kidney
disease (AKD), and the irreversible nephron loss precludes restoration of the baseline
glomerular filtration rate (GFR), resulting in chronic kidney disease (CKD) or persistent kidney
failure.
Cys-C, cystatin C; IGFBP-7, insulin-like growth factor-binding protein 7; IL-18, interleukin 18;
KIM-1, kidney injury molecule; sCr, serum creatinine level; TIMP-2, metalloproteinase inhibitor.