Acute Kidney injury slides education .pptx

Good decision for AKI

1. Overview of A cute Kidney injury Dr. Victor O. Onyenokwe

2. outline Introduction Definition Historical Limitations and Grading Epidemiology Pathophysiology Clinical features Investigations Prevention Management Biomarkers Conclusion References

3. Introduction Acute kidney injury (AKI) (formerly acute renal failure) is the syndrome arising from a rapid fall in GFR (over hours to days). It is characterized by: retention of both nitrogenous (including Ur and Cr) and non-nitrogenous waste products of metabolism. as well as disordered electrolyte, acid–base , and fluid homeostasis.

4. Introduction There is evidence that even relatively small acute reductions in kidney function are associated with poorer outcomes including : Increased mortality, higher risk of long-term dialysis. longer hospital stay

5. Historical limitations Despite a relative insensitivity to acute changes in GFR, most definitions of acute renal dysfunction have been based on Serum Cr , either as an absolute value or as a change from baseline . urine output (UO) or the need for dialysis support . A 2004 survey of 598 participants at a critical care nephrology conference revealed 199 different criteria to define AKI and 90 for the initiation of renal replacement therapy .

6. Historical limitations This lack of consensus had implications for collection and comparison of epidemiological data, and consistency of clinical practice. In response, the Acute Dialysis Quality Initiative established a multilayered definition of AKI called the RIFLE criteria

7. Grading of AKI The RIFLE criteria for AKI AKI is stratified into five stages, based on severity and outcome of renal injury: Risk , Injury , Failure , Loss , and End-stage disease. Many studies (>0.5 million patients) have validated these criteria. RIFLE-defined AKI is associated with significantly reduced survival (with increasing RIFLE stage leading to greater risk of death).

8. THE RIFLE CRITERIA RIFLE category SCr /GFR criteria Urine output criteria Risk Increase SCr ≥ 150 – 200% (1.5 – 2-fold) OR decrease of GFR >25% <0.5mL/kg/h for 6h Injury increase SCr >200 – 300% (>2 – 3-fold) OR decrease of GFR >50% <0.5mL/kg/h for 12h Failure Increase SCr >300% (>3-fold) from baseline OR decrease of GFR >75% OR SCr≥350μmol/L (≥4.0mg/ dL ) with an acute rise of at least 45μmol/L (0.5mg/ dL ). Or on RRT. <0.3mL/kg/h for 24h OR anuria for 12h Loss Complete loss of renal function for >4 weeks End-stage kidney disease Need for RRT for >3 months

9. Limitations to RIFLE CRITERIA Baseline SCr is necessary to define and classify AKI -ADQI propose estimating baseline SCr using MDRD assuming baseline GFR of 75mls/min/1.73m2. The MDRD formula has been validated in CKD patients with stable renal function not AKI. The sensitivity and specificity of UO can be significantly changed by the use of diuretics. The UO can only be determined in patients with a bladder catheter in place and this not frequent in most hospitalized patients

10. Acute Kidney Injury Network (AKIN) classification More recently, AKIN (an international network of AKI experts) modified RIFLE to incorporate small changes in SCr occurring within a 48h period and to remove changes in GFR as diagnostic criteria

11. Acute Kidney Injury Network (AKIN) classification AKIN stage Serum creatinine criteria Urine output criteria 1 SCr ≥ 26.4μmol/L (0.3mg/ dL ) in ≤ 48h OR increased SCr ≥ 150 – 200% (1.5 – 2-fold) from baseline <0.5mL/kg/h for >6h 2 SCr >200 – 300% (2 – 3-fold) from baseline <0.5mL/kg/h for >12h 3 SCr ≥ 300% (3-fold) from baseline OR SCr ≥ 354μmol/L (>4mg/ dL ) with an acute rise of ≥ 44μmol/L (0.5mg/ dL ) OR treatment with RRT <0.3mL/kg/h for 24h OR anuria for 12h

12. Strengths of AKIN classification AKI definition is only considered after an adequate status of hydration is achieved. Therefore, the AKIN classification unlike RIFLE, adds important aetiological information. The AKIN classification is based on SCr and not on GFR changes. The AKIN classification does not need baseline SCr to define AKI, although it requires at least two SCr determinations within 48hrs.

13. Limitations of the AKIN classification It does not allow the identification of AKI when SCr elevation occurs in a time frame higher than 48hrs. Stage 3 includes three diagnostic criteria(Cr, UO and RRT), however, -The extreme variability in the beginning and cessation of RRT -RRT modality used among different physicians ,hospitals and countries could significantly limit the prognostic acuity of this classification.

14. KDIGO AKI definition (2012) AKI, classified by either of the earlier listed criteria, may identify slightly different patients: RIFLE may not detect ~ 10% of AKIN-identified cases, and AKIN may miss ~ 25 % RIFLE cases. KDIGO have recently produced a definition that incorporates the key elements of both .

15. Key elements of KDIGO AKI defi nition Increase in SCr by ≥ 26.5μmol/L ( ≥ 0.3mg/ dL ) within 48h. Increase in SCr by ≥ 1.5 x baseline (known or presumed to have occurred within prior 7d ). Urine volume <0.5mL/kg/h for 6h Only one criterion needs to be present to fulfill the definition

16. KDIGO classification Stage Serum creatinine criteria Urine output criteria 1 1.5 – 1.9 times baseline OR ≥ 0.3mg/ dL (>26.5μ mol /L) in ≤ 48h <0.5mL/kg/h for 6 – 12h 2 2 – 2.9 times baseline <0.5mL/kg/h for ≥ 12h 3 ≥ 3 times baseline OR increase in SCr to ≥ 4.0mg/ dL (354 μ mol /L) OR initiation of RRT <0.3mL/kg/h for ≥ 24h OR anuria for ≥ 12h

17. Epidemiology Hospital 5 – 10% of general admissions. 20 – 25% of patients with sepsis and ~ 50 % with septic shock. 50 % of all ICU admissions (where it acts as an independent risk factor for mortality of 20 – 60%, depending on AKI stage).

18. Community KDIGO estimate a worldwide AKI prevalence of ~ 2,100 pmp , the majority of which are community-acquired. The burden of AKI may be highest in developing countries. Incidence of dialysis-dependent AKI: ~ 200 pmp annually.

19. A 4yrs retrospective review done in 2015 by Wachukwu et al at UPTH showed that of the 3841 patients admitted to the medical wards , 590(15.4%) has renal disease and AKI constituted 12.4% of this admission. Ekwere found the incidence to be 2.1 % of medical admissions in OAUTHC Ile-Ife. Okunola reported an incidence of 19.6% of ICU admissions in OAUTHC Ile-Ife .

20. Classification of AKI Urine Volume Medical Specialty Aetiological classification

21. AKI Urine Volume Specialty Aetiological Oliguric Non-oliguric Medical Surgical Obstetric or Gynae Pre- renal Renal / Intrinsic Post - renal ICU

22. AKI Urine Volume Specialty Aetiological Oliguric Non-oliguric Medical Surgical Obstetric or Gynae Pre- renal Renal or Intrinsic Post - renal Hypotension Hypovolaemia Fluid Loss Blood Loss Poor Pump Function Cadiogenic Shock CCF Pericardial effusion Haemodynamic Contrast Neph Prostaglandin Inhibition CyA, Tac, ACE Inhibitors HRS Vascular Renal infarction, RAS, RVT Malignant HT, Tubular Ischaemic Nephrotoxic Glomerular AGN Vasculitis Thrombotic microangiopathy Pre Eclamptic Toxaemia Interstitium Drug induced TIN Tumour infilteration ICU Intra ureteral obstruction Stones, Clots, crystals, tumour , papillae etc Extra ureteral obstruction Tumour RPF Prostate BPH, Ca , Prostatitis Urinary Bladder Ca , Stones, Clots, Urethra Stricture, Ca , stones

23. Peculiar aetiological factors in our environment Nephrotoxins Native herbs Drugs Cholera Septicaemia CuSo4 (green water)

24. PATHOGENESIS The pathogenesis of AKI is best explained by the aetiology of the AKI. Noteworthy is that there are four clinical phases in the pathogenesis of AKI: -Initiation phase -Extension phase -Maintenance phase -Recovery phase

25. PRE-RENAL AZOTEMIA Prerenal azotemia, is the most common cause of AKI, accounting for 30–50% of all cases. characterized by a diminished renal blood flow , primarily due to decreased effective arterial blood flow. - either from an absolute reduction in the volume of extracellular fluid ( e.g , hypovolemia) - or in conditions in which the effective circulating volume is reduced despite a normal total extracellular fluid volume ( e.g , congestive heart failure).

26. There is physiological response to the decreased effective arterial blood flow. -Systemic response -Renal autoregulatory response

27. Systemic response Baro /chemo-receptors senses systemic hypoperfusion Activation of : -Sympathetic Nervous system -RAAS -Increased Arg.vasopressin (ADH)

28. This maintains BP and RBF: -Vasoconstriction in ‘dispensable ’ vascular beds (e.g. cutaneous). - increase cardiac output and heart rate. - increase thirst and decrease sweating. - increase renal conservation of salt and water

29. Renal response (renal autoregulation ) GFR is initially maintained because intraglomerular pressure is preserved despite the fall in systemic BP through renal autoregulation . If perfusion continues to fall, pre-renal AKI will result . Below a mean arterial pressure (MAP) of ~ 80mmHg, GFR falls rapidly and urine falls as well.

30. Intrarenal Acute Kidney Injury Intrinsic AKI is subdivided into four categories: tubular disease , glomerular disease, interstitial disease, and vascular disease. ATN accounts for 80 – 90% of all intrinsic AKI . - The diagnosis implies that pre-renal and post-renal factors have been excluded (or corrected) and that other causes of intrinsic AKI, such as vasculitis or TIN, are deemed unlikely.

31. Acute tubular necrosis (ATN) ATN subdivided by cause Ischaemic (incl. septic) ANY cause decrease renal perfusion: - Hypotension. - Shock: • Haemorrhagic . • Cardiogenic. • Septic. - Devascularization (incl. aortic cross-clamping).

32. Nephrotoxic: - Myoglobin. - Haemoglobin . - Aminoglycosides. -Contrast . - Amphotericin. - Cisplatin .

33. Pathophysiology of ATN Vessels and endothelium - Blood flow is not uniform within the kidney: pO2 falls progressively from cortex to medulla despite higher metabolic activity in the latter. Any cause of decrease RBF or endothelial injury may decrease delivered O2,rendering vulnerable segments of the nephron relatively hypoxic.

34. As a result of endothelial cell injury -Increase afferent arteriolar cytosolic Ca2 + leads to increase sensitivity to vasoconstrictor and sympathetic stimulation leading to impaired glomerular auto regulation. - Endothelial cell swelling compounds decrease flow leading to decrease O2 delivery . - Activated leucocytes leading to local inflammation and local injury -decrease endothelial nitric oxide production + increase endothelin and prostaglandin synthesis resulting to enhanced vasoconstriction,further decrease RBF.

35. Tubular cells Hypoxic proximal tubular cells (PTC) now become increase energy-deplete. Injured PTC generate proinflammatory mediators leading to recruitment of leucocytes into the interstitium , with subsequent inflammation. decrease O2 delivery leads to increase Ca2 + entry into energy-depleted cells. increase Ca 2+ -dependent cysteine protease activity leading to actin breakdown and cytoskeletal disruption with loss of cell polarity.

36. Loss of polarity leads to decrease basolateral Na + /K + ATPase pumps and decrease proximal Na + absorption. More Na + is delivered to the distal nephron and sensed at the macula densa . This triggers tubuloglomerular feedback decrease GFR. Apical relocation of integrins and loss of cell–cell adhesion leads to tubular cell desquamation and cast formation with tubular obstruction and decrease GFR . Desquamation of PTC exposes the basement membrane and provides a route for misdirected filtrate , with further increase interstitial congestion.

37. Repair Post-reperfusion, sub lethally injured cells starts to repair and proliferation Non-viable cells die (necrosis and apoptosis) and exfoliate Growth factors (IGF-1, EGF, TGF- B ) cause proliferation and differentiation of tubular cells, restoring the epithelium to health

38. Clinical features Oliguria Uraemia GIT Heart CNS Haematological Dermatology Oedema

39. Investigations Urine volume / microscopy Urinalysis Urinary electrolytes Serum chemistry eg creatinine, urea, K,Ca,PO4 Haematology including serology LFT CK Microbiology immunology Imaging eg USS, IVU, RUCG etc Renal biopsy

40. Distinguishing the different causes of AKI Type Urinalysis Urine SG Urine Micro U Na ( Mmol /L) FE Na (%) Fe UN (%) BUN/Cr ratio Pre-Renal Normal High Hyaline < 20 < 1 ≤ 35 >20:1 A.T.N Normal Low Muddy brown > 40 > 1 > 50 ≤ 20:1 Vascular Normal Normal Haematuria > 20 Variable G.N Proteinuria Normal Haemat / RBC casts < 20 < 1 TIN Mild prot WBCs / casts / Eosino . > 20 > 1 Post Renal Normal Normal WBcs , RBcs , granular casts > 20 Variable ≥ 20:1

41. Prevention of AKI Many cases of AKI can be prevented or reversed at an early stage. Who is at risk ? increase age. Pre-existing CKD. Surgery (esp. if with another risk factor) Diabetes mellitus (esp. if established diabetic nephropathy with decrease eGFR ). Volume depletion (NBM, bowel obstruction, vomiting, burns). LV dysfunction and other cardiac disease. Other causes of d effective arterial volume (cirrhosis). Drugs that cause renal vasomotor changes (NSAIDs, ACE-I, ARB ). • Multiple myeloma

42. Reducing AKI risk perioperatively Three principles 1. Avoid dehydration. 2. Avoid nephrotoxins ( contrast, NSAIDs, aminoglycosides). 3. Review clinical (esp. volume) status and renal function if at risk

43. Management of AKI Treat precipitating event / condition Conservative Management RRT

44. AKI Management Conservative Treat Primary Condition RRT Fluid Balance Electrolytes Electrolytes Diet Acute Intermittent Continuous APD AHD Intermittent PD Intermittent HD Intermittent HF SLED EDD CAVHD CVVHD CAPD CAVHDF CVVHDF

45. Fluid Management Limit fluid intake to insensible loss (500-1200mls/day) Replace volume of urine / other documented losses in the previous 24 hours Avoid Potassium containing fluids Diuretics may be useful in pre-renal AKI

46. Electrolyte management Hyperkalaemia Biochemical confirmation ECG appearance Force K into cells Glucose-Insulin Infusion Glucose Infusion Antagonise K Effects on heart 10% Calcium gluconate Remove K from circulation Dialysis Ion exchange resin

47. Diet and Calorie High calorie low protein in acute phase High calorie normal protein in recovery phase Parenteral hyperalimentation may become necessary in prolonged cases

48. Newer Treatment modalities Modulating Vasoconstriction Calcium channel antagonists eg Transplant, CyA exposure, Radiocontrast Nephropathy Dopamine – Not effective from studies ANP may initiate diuresis in oliguric patients Endothelin blockade Nitric oxide modulation N acetyl cysteine use

49. Newer Treatment modalities Limiting Inflammation Inhibition of chemokine production eg α -MSH Anti Adhesion strategies Anti ICAM Anti Integrins PPAR ligands eg etomoxir Biocompatible membranes Cytokine absorbing membranes

50. Indications for RRT Clinical Biochemical Features of hypercatabolism

51. Biomarkers Creatinine high molecular weight proteins tubular proteins or enzymes lack specificity and no standardized assays. Neutrophil Gelatinase -Associated Lipocalin ( NGAL , also known as lcn2 ) Very promising

52. Cystatin C Interleukin-18 Kidney injury molecule-1 Retinol binding protein.

53. Conclusion AKI is a medical emergency with increase risk of mortality, prompt diagnosis and early institution of management is a key.

54. References Harrison’s Principles of internal medicine, 20 th Edition. Oxford Handbook of Nephrology and Hypertension, 2 nd Edition Current Diagnosis and Treatment-Nephrology and Hypertension, 2020. Ekwere TG, Pattern of Acute renal failure in Ile- Ife, FMCP (Nephrology subspecialty) Dissertation November 1996 . Okunola O,A study of the aetiologial factors, management and outcome ot acute renal failure at the intensive care unit, FMCP (Nephrology subspecialty) Dissertation May 2005