1. Dr. Ratan Jha (consultant nephrologist) Dr. Mohd Viquas Uddin Saim (DNB medicine resident) Medwin hospital

2. introduction Previously known as acute renal failure Sudden impairment of kidney function Retention of nitrogenous waste products Not a single disease Designation for conditions sharing common diagnostic features Increase in blood urea and serum creatinine Severity ranges from asymptomatic to fatal 3. Why term AKI preferred over ARF ? failure reflects only part of the spectrum of damage to the kidney In most cases damage is modest Modest damage is not nearly as omnious as frank kidney failure Frank kidney failure often requires acute dialysis therapies term renal is not well understood in the general population Hence kidney has replaced renal 4. epidemiology 57% of acute care hospital admissions 30% of admissions to the intensive care unit Major complication of diarrheal illnesses, malaria and leptospirosis markedly increased risk of death in hospitalized individuals mortality rates may exceed 50% in ICU patients 5. Etiology 6. Pre renal azotemia "azo," meaning nitrogen, and "-emia most common form of AKI rise in SCr or BUN concentration due to inadequate renal plasma flow and intraglomerular hydrostatic pressure to support normal glomerular filtration may coexist with other forms of intrinsic AKI When prolonged may lead to ischemic injury called Acute tubular necrosis prerenal azotemia involves no parenchymal damage to the kidney rapidly reversible once intraglomerular hemodynamics are restored. 7. Pathophysiology of prerenal AKI 8. Renal autoregulation Normal GFR is maintained by the relative resistances of the afferent and efferent renal arterioles Renal blood flow accounts for 20% of cardiac output renal vasoconstriction and salt and water reabsorption occur as a homeostatic response to decreased effective circulating volume or cardiac output to maintain blood pressure and increase intravascular volume to sustain perfusion to the cerebral and coronary vessels Mediators of this response include angiotensin II, norepinephrine, and vasopressin 9. Renal autoregulation Glomerular filtration can be maintained despite reduced renal blood flow by angiotensin IImediated renal efferent vasoconstriction Intrarenal biosynthesis of vasodilator prostaglandins (prostacyclin, prostaglandin E2 also increase in response to low renal perfusion pressure also accomplished by tubuloglomerular feedback decreases in solute delivery to the macula densa (specialized cells within the proximal tubule) elicit dilation of the juxtaposed afferent arteriole 10. Failure of autoregulation There is a limit to autoregulation in healthy adults, renal autoregulation usually fails once the systolic blood pressure falls below 80 mmHg Atherosclerosis, long-standing hypertension, and older age cause impaired capacity for renal afferent vasodilation NSAIDs inhibit renal prostaglandin production, limiting renal afferent vasodilation ACE inhibitors and angiotensin receptor blockers (ARBs) limit renal efferent vasoconstriction NSAIDs and ARBs should not be given together. 11. Intrinsic AKI most common causes of intrinsic AKI are sepsis, ischemia, and nephrotoxins In many cases, prerenal azotemia advances to tubular injury classically termed "acute tubular necrosis Other causes of intrinsic AKI are less common 12. Intrinsic AKI - Glomerular causes Post-infectious SLE ANCA associated Henoch schnolen purpura Cryoglobulinaemia TTP HUS Accounts for 5 % of cases 13. Intrinsic AKI - tubular causes (ATN) Ischemic (50%) kidneys are the site of one of the most hypoxic regions in the body, the renal medulla outer medulla is particularly vulnerable to ischemic damage AKI more commonly develops when ischemia occurs in the context of limited renal reserve or coexisting insults such as sepsis, Toxins (35%) kidney has very high susceptibility to nephrotoxins due to extremely high blood perfusion Endogenous nephrotoxins : hemoglobin, myoglobin Exogenous nephrotoxins : contrast agents, antibiotics, etc,. 14. Intrinsic AKI interstitial & vascular causes Acute interstitial nephritis Drugs : NSAIDs, allopurinol, methicillin Granulomatous : tuberculosis, sarcoidosis Infective : legionnaires disease, pyelonephritis Monosodium urate crystals Vascular causes Renal artery occlusion Renal vein thrombosis Cholesterol emboli 15. Post renal AKI occurs when the unidirectional flow of urine is acutely blocked either partially or totally leads to increased retrograde hydrostatic pressure and interference with glomerular filtration For AKI to occur in healthy individuals, obstruction must affect both kidneys unless Unilateral obstruction may cause AKI in the setting of significant underlying CKD Bladder neck obstruction is a common cause of postrenal AKI and can be due to prostate disease ,neurogenic bladder, or therapy with anticholinergic drugs Other causes of lower tract obstruction are blood clots, calculi, and urethral strictures 16. Post renal AKI- ureteric obstruction intraluminal obstruction (e.g., calculi, blood clots, sloughed renal papillae) infiltration of the ureteric wall (e.g., neoplasia) external compression (e.g., retroperitoneal fibrosis, neoplasia, abscess, or inadvertent surgical damage) pathophysiology of postrenal AKI involves hemodynamic alterations triggered by an abrupt increase in intratubular pressures Reduced GFR is due to underperfusion of glomeruli 17. Diagnostic evaluation presence of AKI is usually inferred by an elevation in the SCr concentration AKI is currently defined by a rise of at least 0.3 mg/dL or 50% higher than baseline within a 2448-hours period or a reduction in urine output to 0.5 mL/kg per hour for longer than 6 hours The distinction between AKI and chronic kidney disease is important for proper diagnosis and treatment 18. Diagnostic evaluation Features suggestive of CKD than AKI from radiologic studies (e.g., small, shrunken kidneys with cortical thinning on renal ultrasound, or evidence of renal osteodystrophy) laboratory tests such as normocytic anemia or secondary hyperparathyroidism with hyperphosphatemia and hypocalcemia, consistent with CKD distinction is straightforward when a recent baseline SCr concentration is available 19. Diagnostic evaluation : history & physical evaluation Prerenal azotemia : in the setting of vomiting, diarrhea, glycosuria causing polyuria, and several medications including diuretics, NSAIDs, ACE inhibitors, and ARBs Postrenal AKI : history of prostatic disease, nephrolithiasis, or pelvic or paraaortic malignancy . Abdominal fullness and suprapubic pain can accompany massive bladder enlargement A careful review of all medications is imperative in the evaluation of an individual with AKI 20. Diagnostic evaluation : Urine findings Anuria is seen in complete urinary tract obstruction, renal artery occlusion, overwhelming septic shock, severe ischemia, or severe proliferative glomerulonephritis or vasculitis oliguria, defined as