Acute Kidney Injury (AKI) Epidemiology

Epidemiology of Acute Kidney Injury (AKI)

By Dr. Usama Ragab
Lecturer of Internal Medicine

I have discussed the epidemiology, etiology of acute kidney injury

1. AKI Epidemiology Dr. Usama Ragab Youssif, MD Lecturer of Medicine Zagazig University

2. History William Heberden described ARF, then known as ischuria renalis , for the first time in 1802. ARF, then known as Acute Bright's disease, was described in William Osler's Textbook for Medicine (1909) as occurring "as a result of toxic agents, pregnancy, burns, trauma, or kidney operations.“ During WWI, the syndrome was known as war nephritis and was reported in several publications. Crush syndrome was largely forgotten until the WWII, when Bywaters and Beall published their seminal paper on the subject. Because of histological evidence of patchy necrosis of renal tubules at autopsy, this clinical entity was labelled as acute tubular necrosis (ATN). Homer W. Smith who is credited for the introduction of the term acute renal failure, in a chapter on Acute renal failure related to traumatic injuries in his 1951 textbook The kidney-structure and Function in Health and Disease.

3. Definition

4. AKI not ARF

5. Oliguria is usually, but not invariably, a feature

6. Urine output? 50 kg i.e., 25mls/ hr. 120 kg i.e., 60mls/ hr. 0.5 ml/kg/hour looks different for different individuals

7. Why is it important to identify? AKI is associated with increased risks of adverse outcomes such as progression to chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality. Therefore, early diagnosis, treatment, and proper follow-up are essential.

8. ARF or AKI J Am Soc Nephrol 18: 1987–1994, 2007

9. Risk Factors: Adults

10. Risk factors: children and young people

11. Assessing Risk of AKI

12. Epidemiology

13. Epidemiology (cont.)

14. Causes

15. Before we proceed

16. I- Prerenal: (correctable, i.e., normal kidney with ↓↓ perfusion)

17. I- Prerenal: (correctable, i.e., normal kidney with ↓↓ perfusion) Decreased effective circulatory volume (Hypovolemia) Reduced COP Hemorrhage : Traumatic, surgical, postpartum, gastrointestinal GI). GI fluid loss : Vomiting, diarrhea, surgical drainage. Kidney loss : Diuretic therapy, osmotic diuresis in diabetes, and adrenal insufficiency. Vasodilatory loss of the extravascular compartments : Sepsis syndromes, acute pancreatitis, peritonitis, severe trauma, burns, and severe hypoalbuminemia. Diseases of the myocardium, valves, and pericardium; arrhythmias; massive pulmonary embolism; positive–pressure mechanical ventilation

18. I- Prerenal: (correctable, i.e., normal kidney with ↓↓ perfusion) Vascular abnormalities Impaired renal autoregulation and hypoperfusion Vasodilation : Sepsis, hypotension caused by antihypertensive medications (including drugs that reduce afterload), and general anesthesia. Vasoconstriction : Hypercalcemia, norepinephrine, epinephrine, tacrolimus, cyclosporine (INN cyclosporin), and amphotericin B. COX inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and direct renin inhibitors.

19. I- Prerenal: (correctable, i.e., normal kidney with ↓↓ perfusion) Hyperviscosity syndrome Renal vessel occlusion Multiple myeloma Waldenström macroglobulinemia Polycythemia. Renal artery occlusion: Atherosclerosis, thromboembolism, dissecting aneurysm, and systemic vasculitis. Renal vein occlusion: Thromboembolism and external compression.

20. Pathogenesis of prerenal failure

21. II- Intrinsic Renal Causes Small vessel disease Acute tubular necrosis (ATN) Thrombotic microangiopathy (TMA) (hemolytic–uremic syndrome [HUS], thrombotic thrombocytopenic purpura [TTP]), cholesterol crystal embolization, disseminated intravascular coagulation (DIC), preeclampsia or eclampsia, malignant hypertension, systemic lupus erythematosus (SLE), and progressive systemic sclerosis (scleroderma renal crisis). Ischemia : Prolonged prerenal AKI. Exogenous toxins : Radiographic contrast agents, cyclosporine, antibiotics ( eg , aminoglycosides), chemotherapy (cisplatin), ethylene glycol, methanol, and NSAIDs. Endogenous toxins : Myoglobin, hemoglobin, monoclonal proteins ( eg , in multiple myeloma). Crystals : Uric acid, oxalic acid (a metabolite of ethylene glycol), acyclovir (INN aciclovir ) (particularly IV), methotrexate, sulfonamides, and indinavir.

22. II- Intrinsic Renal Causes Acute interstitial nephritis (AIN) Glomerulonephritis (GN) Allergic : Beta–lactam antibiotics, sulfonamides, trimethoprim, rifampin (INN rifampicin), NSAIDs, diuretics, captopril, and proton pump inhibitors. Infectious : Bacterial (legionella, leptospirosis), viral (cytomegalovirus, BK virus), and fungal (candidiasis). Infiltrative : Malignant (lymphoma, leukemia), granulomatous (sarcoidosis), and idiopathic. Autoimmune : Sjögren syndrome, tubulointerstitial nephritis with uveitis (TINU) syndrome, IgG4-related kidney disease (IgG4-RKD), SLE. Anti–glomerular basement membrane (GBM) disease (sometimes referred to as Goodpasture syndrome or disease). Antineutrophil cytoplasmic antibody (ANCA)-associated GN (granulomatosis with polyangiitis [formerly Wegener granulomatosis]), Churg-Strauss syndrome, microscopic polyangiitis). Immune complex–mediated GN (SLE, postinfectious, cryoglobulinemia, and primary membranoproliferative GN).

23. II- Intrinsic Renal Causes Other causes Acute graft rejection following renal transplantation. Acute renal cortical necrosis Chinese herb nephropathy Acute phosphate nephropathy Warfarin-related nephropathy Loss of the solitary functioning kidney.

24. III- Post-renal causes Intrinsic Extrinsic Intra-luminal: e.g. stone, blood clot, papillarynecrosis Intra-mural: e.g. urethral stricture, prostatic hypertrophy or malignancy, bladder tumour , radiation fibrosis Pelvic malignancy Retroperitoneal fibrosis

25. Prerenal acute kidney injury and acute tubular necrosis account for approximately 65% to 75% of acute kidney injury cases in hospitalized patients.

26. Another classification Pharmacological Non-Pharmacological

27. Pharmacological causes Pre-renal Volume depletion SGLT2 inhibitors, diuretics Intrarenal/afferent arteriolar vasoconstriction NSAIDs (including COX-2 inhibitors); amphotericin B; calcineurin inhibitors; iodinated radiocontrast agents Efferent arteriolar vasodilation Renin inhibitors; ACE inhibitors; ARBs

28. Pharmacological causes (cont.) Intrinsic Acute tubular necrosis Aminoglycosides; vancomycin, particularly in combination with piperacillin-tazobactam; polymyxins; lithium; amphotericin B; pentamidine; cisplatin; foscarnet; tenofovir; cidofovir; carboplatin; ifosfamide; zoledronate; contrast agents. sucrose; immune globulins; mannitol; hydroxyethyl starch; dextran; synthetic cannabinoids; amphetamines Acute interstitial nephritis Etiologies of acute interstitial nephritis are like those for chronic tubulointerstitial nephritis. Acute interstitial nephritis may lead to chronic tubulointerstitial nephritis with protracted exposure Acute glomerulonephritis ANCA-associated drugs, such as minocycline and levamisole (veterinary antihelminthic used in some cocaine preparations) Acute vascular syndromes Drug-induced TMA: quinine; cancer therapies (gemcitabine, mitomycin, bortezomib, sunitinib); calcineurin inhibitors (cyclosporine, tacrolimus); drugs of abuse (cocaine, ecstasy, intravenous extended-release oxymorphone); clopidogrel; anti-angiogenesis drugs; interferon; mTOR inhibitors Intratubular obstruction Crystals: sulfonamides; triamterene; ciprofloxacin; ethylene glycol; acyclovir; indinavir; atazanavir; methotrexate; orlistat; large doses of vitamin C; sodium phosphate purgatives

29. Natural history

30. Natural history (cont.)

31. There are 4 phases that can be distinguished in the natural history of AKI Initiation phase: This phase presents with normal urine output as it commences from the initial impact of the insult (cause) until the point of actual kidney damage. The duration of this phase is usually several hours and varies depending on the causative factor. Oliguria (urine output 100-400 mL/d) or anuria (urine output <100 mL/d): This phase occurs when urine output is typically between 50 and 400 mL/d. It develops in ~50% of patients and lasts an average of 10 to 14 days but can vary from 1 day to 8 weeks.

32. There are 4 phases that can be distinguished in the natural history of AKI (cont.) Polyuria: This phase begins with rapidly increasing urine output over several days after a period of oliguria or anuria. It occurs due to tubular dysfunction and is manifested by sodium wasting and polyuria. Serum creatinine and urea levels may not decrease for several days. The duration of polyuria is proportional to the duration of oliguria/anuria and may last up to several weeks. This phase of AKI is associated with considerable risk of dehydration and severe loss of electrolytes, particularly potassium and calcium. Recovery phase: During this phase urine output gradually returns to normal and serum creatinine and urea begin to normalize. It may take up to several months for complete recovery or for a new baseline function to be established.

33. Presentation

34. Classification Systems

35. The RIFLE criteria for AKI (2002) The distinction between acute and chronic renal failure, or even acute-on-chronic renal failure, cannot be readily apparent in a patient presenting with uraemia. In view of these difficulties, the Acute Dialysis Quality Initiative group proposed the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria utilizing either increases in serum creatinine or decreases in urine output. It characterizes three levels of renal dysfunction (R, I, F) and two outcome measures (L, E). These criteria indicate an increasing degree of renal damage and have a predictive value for mortality.

36. Acute Kidney Injury Network (AKIN) classification (2004) 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.

37. 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, and it is likely that this definition will become the accepted standard.

38. KDIGO Classification KDIGO stage Serum creatinine criteria Urine output criteria 1 1.5 – 1.9 times baseline OR ≥0.3mg/dL (>26.4 μ 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

39. AKI → AKD

40. Risk Assessment (KDIGO Guided) 2.2.1: We recommend that patients be stratified for risk of AKI according to their susceptibilities and exposures. (1B) 2.2.2: Manage patients according to their susceptibilities and exposures to reduce the risk of AKI (see relevant guideline sections). (Not Graded) 2.2.3: Test patients at increased risk for AKI with measurements of SCr and urine output to detect AKI. (Not Graded) Individualize frequency and duration of monitoring based on patient risk and clinical course. (Not Graded)

41. Evaluation 2.3.1: Evaluate patients with AKI promptly to determine the cause, with special attention to reversible causes. (Not Graded) 2.3.2: Monitor patients with AKI with measurements of SCr and urine output to stage the severity, according to Recommendation 2.1.2. (Not Graded)

42. Evaluation 2.3.3: Manage patients with AKI according to the stage (see Figure 4) and cause. (Not Graded) 2.3.4: Evaluate patients 3 months after AKI for resolution, new onset, or worsening of pre-existing CKD (Not Graded) If patients have CKD, manage these patients as detailed in the KDOQI CKD Guideline (Guidelines 7–15). (Not Graded) If patients do not have CKD, consider them to be at increased risk for CKD and care for them as detailed in the KDOQI CKD Guideline 3 for patients at increased risk for CKD. (Not Graded)

43. AKI Stage Centered Approach Avoid subclavian catheters if possible High Risk Discontinue all nephrotoxic agents when possible Consider invasive diagnostic workup Consider Renal Replacement Therapy 1 2 3 Non-invasive diagnostic workup Ensure volume status and perfusion pressure Check for changes in drug dosing Consider functional hemodynamic monitoring Monitor Serum creatinine and urine output Consider ICU admission Avoid hyperglycemia Consider alternatives to radiocontrast procedures

44. Referral to nephrologist

45. Consider RRT if

46. Prognosis The overall mortality in patients with AKI is high, and AKI is considered an independent risk factor for mortality. Mortality rates are population-dependent, ranging between 10% and 80%. Patients with uncomplicated AKI have mortality rates of ~10%. Patients presenting with AKI and multiorgan failure have mortality rates >50%.

47. Prognosis In patients requiring RRT mortality rises to >80%. Death is usually a result of the severity of the underlying disease-causing AKI rather than the renal injury itself. It has been shown that from 20% to 50% of patients with AKI progress to CKD and 3% to 15% develop ESRD, even those who initially recover sufficient kidney function to discontinue dialysis.

48. Mortality

49. Selected differential features of AKI and CKD AKI CKD History suggestive of CKD No Yes Kidney size Normal Small Dynamics of serum creatinine increases High Low CBC Normal Anemia Calcium‑phosphate metabolism Mild or moderate disturbances (depending on AKI etiology) High phosphate level, increased alkaline phosphatase level, radiographic signs of renal osteodystrophy and/or soft tissue calcifications Fundoscopy Usually normal Frequently lesions typical of diabetes mellitus or chronic hypertension

50. Thanks