ACUTE KIDNEY INJURY APPROACH AND MANAGEMENT

AKI

1. APPROACH TO AKI

2. AKI is defined by a rise in the serum creatinine concentration or a decline in urine output that has developed within hours to days. The KDIGO (Kidney Disease: Improving Global Outcomes criteria for AKI include an increase in serum creatinine by ≥0.3 mg/ dL (27 micromol /L) within 48 hours or an increase to ≥1.5 times the presumed baseline value that is known or presumed to have occurred within the prior seven days, or a decrease in urine volume to <0.5 mL/kg/hour over six hours. DEFINITION

3. STAGING Using the KDIGO criteria, AKI is staged as follows: •Stage 1 – Increase in serum creatinine to 1.5 to 1.9 times baseline, or increase in serum creatinine by ≥0.3 mg/ dL (≥26.5 micromol /L), or reduction in urine output to <0.5 mL/kg/hour for 6 to 12 hours. •Stage 2 – Increase in serum creatinine to 2.0 to 2.9 times baseline, or reduction in urine output to <0.5 mL/kg/hour for ≥12 hours. •Stage 3 – Increase in serum creatinine to 3.0 times baseline, or increase in serum creatinine to ≥4.0 mg/ dL (≥353.6 micromol /L), or reduction in urine output to <0.3 mL/kg/hour for ≥24 hours, or anuria for ≥12 hours, or the initiation of renal replacement therapy, or, in patients <18 years, decrease in estimated glomerular filtration rate ( eGFR ) to <35 mL/min/1.73 m2

4. CAUSES Common Causes of Acute Kidney Injury Prerenal Volume depletion Blood loss GI fluid loss (e.g., vomiting, diarrhea) Overzealous diuretic use Volume overload with reduced renal perfusion Congestive heart failure Low-output with systolic dysfunction “High-output” (e.g., anemia , thyrotoxicosis) Hepatic cirrhosis Severe hypoproteinemia Renovascular disease Drugs NSAIDs, cyclosporine, tacrolimus , ACE inhibitors, ARBs, cisplatin , aminoglycosides Other Hypercalcemia ( e.g., pancreatitis, systemic inflammatory response), hepatorenal syndrome )

5. Intrinsic ATN Hypotension or shock, prolonged prerenal azotemia , postoperative sepsis syndrome, rhabdomyolysis , Radiocontrast , aminoglycosides, cisplatin Other tubulointerstitial disease Allergic interstitial nephritis Pyelonephritis (bilateral, or unilateral in single functional kidney) Heavy metal poisoning Atheroembolic disease—after vascular procedures, thrombolysis, or Anticoagulation Glomerulonephritis 1. ANCA-associated: granulomatosis with polyangiitis (GPA), idiopathic pauciimmune GN, PAN 2. Anti-GBM disease; isolated or with pulmonary involvement ( Goodpasture’s syndrome) 3. Immune complex–mediated Subacute bacterial endocarditis, SLE, postinfectious GN (classically poststreptococcal ) IgA nephropathy and Henoch-Schönlein purpura Glomerular endotheliopathies Thrombotic microangiopathy , malignant hypertension

6. Postrenal (Urinary Tract Obstruction) Bladder neck obstruction, bladder calculi Prostatic hypertrophy Ureteral obstruction due to compression Pelvic or abdominal malignancy, retroperitoneal fibrosis Nephrolithiasis Papillary necrosis with obstruction The most frequent causes were: ●ATN – 45 percent ● Prerenal disease – 21 percent ●Acute superimposed on CKD – 13 percent (mostly due to ATN and prerenal disease) ●Urinary tract obstruction – 10 percent (most often older men with prostatic disease) ●Glomerulonephritis or vasculitis – 4 percent ●AIN – 2 percent ● Atheroemboli – 1 percent

7. Clinical features D epend on the etiology of renal disease. Patients with prerenal azotemia due to volume depletion usually demonstrate orthostatic hypotension, tachycardia, low jugular venous pressure, and dry mucous membranes. Patients with prerenal azotemia and CHF (“ cardiorenal syndrome”) may show jugular venous distention , an S3 gallop, and peripheral and pulmonary edema . Patients with intrinsic renal disease present with varying complaints. GN is often accompanied by hypertension and mild to moderate edema (associated with Na retention and proteinuria, and sometimes with gross hematuria ). An antecedent prodromal illness and/or prominent extrarenal symptoms and signs may occur if GN occurs in the context of a systemic illness, e.g., vasculitis or SLE; these may include hemoptysis or pulmonary hemorrhage ( vasculitis and Goodpasture’s syndrome), arthralgias /arthritis ( vasculitis or SLE), serositis (SLE )

8. Unlike patients with GN, patients with interstitial diseases are less likely to have hypertension or proteinuria. A notable exception is NSAID-associated acute interstitial nephritis, which can be accompanied by proteinuria due to an associated minimal-change glomerular lesion. Hematuria and pyuria may present on Urine analysis. Patients with postrenal AKI due to urinary tract obstruction are usually less severely ill than pts with prerenal or intrinsic renal disease, and their presentation may be delayed until azotemia is markedly advanced (BUN >54 μmol /L [150 mg/ dL ], Cr >1060–1325 μmol /L [12–15 mg/ dL ]). Pain can occur in obstruction due to stones In men, there is frequently a history of lower urinary tract symptoms, e.g., hesitancy, urgency, or frequent nocturia . Physical examination may reveal an enlarged bladder by percussion over the lower abdominal wall Prostatic hypertrophy can be determined by digital rectal examination.

9. There are three major diagnostic approaches that are used to distinguish prerenal disease from ATN and from other causes of AKI ● Urinalysis . The urinalysis with sediment examination by urine microscopy is normal or near normal in prerenal disease, unless it is superimposed on another cause of renal disease. In comparison, the classic urinalysis in ATN reveals muddy brown granular, epithelial cell casts, and free renal tubular epithelial cells ●Fractional excretion of sodium ( FENa ) and, to a lesser degree, the urine sodium concentration. The fractional excretion of urea may be helpful in patients being treated with diuretics The urine-sodium concentration tends to be low in prerenal disease (less than 20 mEq /L) in an appropriate attempt to conserve sodium and high in ATN (more than 40 to 50 mEq /L) due, in part, to impaired tubular function induced by the tubular injury [32]. PRE RENAL VS ATN

10. ●Response to fluid repletion in patients who have evidence of volume depletion, which is the gold standard for the diagnosis of prerenal disease. If sufficient fluid is given to reverse any signs of volume depletion ( eg , hypotension, cool extremities, low FENa and urine-sodium concentration), return of the serum creatinine to the previous baseline within 24 to 72 hours is considered to represent correction of prerenal disease, whereas persistent AKI is considered to represent ATN. OTHER CRITERIAS BUN/CREATININE RATIO URINE VOLUME URINE OSMOLARITY

11. TREATMENT Hypovolemic patients Intravenous fluid therapy should be administered to patients with a clinical history consistent with fluid loss (such as vomiting and diarrhea ), a physical examination consistent with hypovolemia (hypotension and tachycardia), or oliguria. If hypovolemia is confirmed by clinical assessment, we administer 1 to 3 liters of crystalloid (preferably buffered crystalloid) with assessment of clinical response. For volume responsive patients with a robust response in urine output and improvement in GFR, and with persistent evidence of hypovolemia or inability to maintain fluid balance, we continue maintenance isotonic fluids at 75 mL/hour or greater depending upon the ongoing losses. Clinical parameters including heart rate, blood pressure, urine output, skin turgor, mucus membrane integrity, and mental status should be continuously followed during fluid replacement to assess the efficacy of volume replacement.

12. Hypervolemic patients In diuretic-naïve patients, we start with 80 mg of intravenous (IV) furosemide, or equivalent, and assess for response. Patients who were on diuretics prior to the onset of AKI should receive a dose that is at least double their prior (home) dose. If there is no definite augmentation in the urine output within two hours of an IV diuretic dose, then we administer double the initial dose (maximum of 200 mg in a single dose of IV furosemide or equivalent). Addition of a thiazide diuretic such as chlorothiazide (500 to 1000 mg IV) is sometimes given in conjunction with furosemide to augment urine output. Lack of response to a 200 mg dose of IV furosemide or equivalent, with or without a thiazide diuretic, may suggest the need for extracorporeal removal of excess volume. Among patients who respond to diuretics, we continue to give repeated doses to avoid hypervolemia if kidney function is improving or improvement is thought to be imminent. However, even among those patients who respond to diuretics, the urine output may be too meager to avoid worsening hypervolemia. In such situations, or if improvement is not imminent, we generally avoid using diuretics to postpone the initiation of RRT, since dialysis and ultrafiltration offer the most efficient method of volume removal in patients with AKI from any cause.

13. Renal replacement therapy U rgent indications for RRT in patients with AKI generally include: ●Refractory fluid overload ●Severe hyperkalemia (plasma potassium concentration >6.5 mEq /L) or rapidly rising potassium levels ●Signs of uremia , such as pericarditis, encephalopathy, or an otherwise unexplained decline in mental status ●Severe metabolic acidosis (pH <7.1) ●Certain alcohol and drug intoxications

14. Managing electrolyte imbalances Calcium directly antagonizes the membrane actions of hyperkalemia , while hypocalcemia increases the cardiotoxicity of hyperkalemia 1.Hyperkalemia The usual dose of calcium gluconate is 1000 mg (10 mL of a 10 percent solution) infused over two to three minutes, with constant cardiac monitoring. The usual dose of calcium chloride is 500 to 1000 mg (5 to 10 mL of a 10 percent solution), also infused over two to three minutes, with constant cardiac monitoring. The dose of either formulation can be repeated after five minutes if the ECG changes persist or recur. Insulin administration lowers the serum potassium concentration by driving potassium into the cells, primarily by enhancing the activity of the Na-K-ATPase pump in skeletal muscle . Glucose is usually given with insulin to prevent the development of hypoglycemia .

15. Commonly used regimen for administering insulin and glucose is 10 to 20 units of regular insulin in 500 mL of 10 percent dextrose, given intravenously over 60 minutes. Hyperphosphatemia Restrict dietary phosphorous to <2 g per day in all patients with AKI, except those with hypophosphatemia. C alcium-containing phosphate binders such as calcium acetate or calcium carbonate may be given to control serum phosphate levels. If the serum ionized calcium concentration is high, non-calcium phosphate binders, such as lanthanum carbonate, sevelamer , or aluminum hydroxide (Al(OH)3), should be given

16. A symptomatic patient who has moderately reduced kidney function ( ie , estimated glomerular filtration rate of 15 to 30 mL/min per 1.73 m2) and severe hypomagnesemia should be treated with 2 to 4 g of IV magnesium sulfate given slowly over 4 to 12 hours. The plasma magnesium should be checked prior to subsequent doses, and daily if doses are given less frequently. ●Asymptomatic patients who have severe hypomagnesemia and moderately decreased kidney function may be treated with approximately half the dose of the selected oral preparation that is recommended for the patient with normal kidney function. The plasma magnesium concentration should be measured before giving a subsequent dose. Hypomagnesemia Managing nutrition Protein energy wasting is common among critically ill patients with AKI and contributes to mortality Nondialysis patients with only mild to moderate illness require only 0.8 to 1.2 g/kg per day, critically ill patients or patients who are on RRT generally require 1.2 to 1.5 g/kg per day or more

17. TREATMENT OF URINARY TRACT OBSTRUCTION

18. MONITORING AND FOLLOW-UP Serum creatinine , electrolytes, ionized calcium, total serum calcium, and phosphate should be measured daily in stable patients. The serum calcium and ionized calcium should be measured more frequently (twice daily) in patients who require calcium or bicarbonate. Serum potassium should be checked more frequently in patients who have an elevated serum potassium on presentation or who are oliguric or hemodynamically unstable.

19. LEARNING POINTS The two major causes of acute kidney injury (AKI) developing in the hospital are prerenal disease and acute tubular necrosis (ATN) The principal diagnostic measures are urinalysis, response to fluid repletion, and fractional excretion of sodium ( FENa ). Fluid replacement in hypovolemic patients Dosage and monitoring of diuretics in hypervolemic patients Indications for RRT Electrolyte imbalances with AKI Management of Urinary tract obstruction Monitoring and follow up parameters

20. REFERENCES UPTO DATE HARRISONS MANUAL OF MEDICINE 20 TH EDITION