Renal Replacement Therapy in Acute Kidney Injury -time modality -Dr Ayman Seddik.pptx final 1.pptx

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

1. RRT in AKI T ime & 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

4. KDIGO/AKIN Classification

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

6. 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.

7. 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.

8. 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.

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

10. 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.

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

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

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

14. 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

15. 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.

16. 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  

17. 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.

18. 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

19. 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.

20. 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). When should we start renal replacement therapy in critically ill patients with acute kidney injury: do we finally have the answer?

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

22. 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

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

24. Thank You

25. APPENDIX FOR FURTHER READINGS

26. 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.

27. 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)

28. 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)

29. 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.

30. 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)

31. Risk factors for AKI :

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

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

34. 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.