1. PreRenal Acute Kidney Injury Mini-Lecture David Aymond 2/21/2012

2. Nephron Anatomy

3. Definition Prerenal kidney injury is characterized by preserved renal parenchymal function responding appropriately to diminished perfusion. Because the integrity of the renal parenchyma is preserved, timely restoration of perfusion corrects GFR. Although there is a continuum from renal hypoperfusion  prerenal injury with reduced GFR  ischemic ATN Clinically: an abrupt ( 0.3mg/dL, increase in Cr > 50%, or UOP 6hrs

4. Pathogenesis Decreased perfusion of the kidney *Immediate systemic and renal compensatory responses directed at maintaining GFR Once these compensatory mechanisms are overwhelmed, the pre-renal state has arrived

5. Etiology 1.Intravascular volume depletion- hemorrhage, NG suction, dysphagia, diarrhea, vomiting, hyperthermia, “Third-Spacing” (pancreatitis, hypoalbuminemia, crush syndrome, intestinal obstruction, hip fracture) 2.Decreased Cardiac Output/effective circulating volume: CHF, Sepsis, Cirrhosis 3.Renal Vasoconstriction: hepatorenal, sepsis, hypercalcemia 4.Iatrogenic: ACE-I, ARB’s, NSAIDS, and contrast

6. History and Physical Orthostasis, Episodes of BP swings Weight gain, edema, and periorbital swelling in the a.m. (CHF) Ascites, hypoalbuminemia, low platelets, elevated PT/INR, neutropenia, encephalopathy (Liver cirrhosis) Review for nephrotoxic meds

7. Diagnosis Urinalysis: Bland (no protein/blood), large amount of hyaline casts, Specific Gravity >1.020 Urine Studies: only effective if oliguric (must write NOW on order sheet) -Fractional Excretion of Sodium (FENa) [(urine Na/plasma Na)/ (urine creatinine/plasma cr)] x 100 -Fractional Excretion of Urea (FEUrea): when is this appropriate? -Urine Na: what is cut off? -Plasma BUN:Cr ratio -Serologic Biomarkers? Serum neutrophil gelatinase assocated lipocalin (NGAL) and Interleukin 18

8. Treatment Restoration of Effective Circulatory Volume with Crystalloid; why not Colloid (Albumin or Dextrans)? Treatment of Underlying cause -Sepsis: Early goal directed therapy -Special attention to CHF and Cirrhosis Stop all ACE’s, ARB’s, NSAIDS, and COX-2 Diuretics: only if volume overloaded and AKI; important to note that higher than standard doses must be used for loop diuretics to be effective Inc Dose with Inc Cr, initial effective IV lasix dose=30 x Cr, max dose is 160-200mg IV bolus

9. Tips on Diuretics 1.Daily Weight is most effective way of measuring successful diuresis 2.Loop Diuretics: response is related to amt. of drug excreted toward threshold=dose response curve; once diuresis is met, increasing dose no help, inc. frequency helps *adequate diuresis met at different doses depending on Disease state and GFR NL GFR: -CHF: 40-80mg IV -Cirrhosis: 40mg IV Abnl GFR: 30 x Cr dose (see previous slide) IV dosing is 2x as potent as PO dosing; how do you switch from IV to PO dosing? Can use a continuous infusion if the patient has refractory edema, but need to bolus first: The enhanced diuresis with a continuous infusion compared to bolus therapy is related to maintenance of an effective rate of drug excretion and therefore of inhibition of sodium chloride reabsorption in the loop of Henle over time. In contrast, bolus therapy is associated with initially higher and then lower rates of diuretic excretion; as a result, sodium excretion may be at near maximal levels for the first two hours but then gradually falls until the next dose is given (enhances urine output and dec rate of ototoxicity compared with bolus) Can co-administer with Albumin if Albumin 2 Adding Thiazide potentiates the response to Loop diuretics (unless GFR<30, exception is Metolazone which works at all GFR’s); very important in refractory edema in CHF Critical Care Setting: use CVP and urine output, if CVP >12 and decreased urine output, give Lasix 40-80mg IV (assuming normal GFR) Liver Cirrhosis: pt needs Spironolactone + Lasix in a 2.5:1 ratio to conserve potassium; Spironolactone used b/c of the high Aldo state in Cirrhosis *Recommendations for Step Wise approach to Diuresis