Definition

There is no standard accepted definition of AKI. Generally accepted criteria (KDIGO modification to RIFLE and AKIN criteria) involve the following:

• <48 hours (abrupt) time course with 1 or more of the following:
  • Increase in serum creatinine of ≥0.3mg/dL.
  • Greater than 50% increase in serum creatinine from baseline.
  • Reduction in urine output of <0.5mL/kg/hr for ≥6 hours.

** AKI can also be stage 1-3 depending on severity.

Oliguria is defined as urine output <400mL/day, while anuria is <100mL/day.

Differential Diagnosis

An anatomic classification of etiologies is helpful (Table 1).

• Prerenal: accounts for 70% of community-acquired AKI and accounts for 40% of in-hospital AKI. Can progress to ATN if severe and/or prolonged.
  • Hypovolemia: vomiting, diarrhea, decreased fluid intake, diuretics, hemorrhage, osmotic diuresis (diabetes mellitus, hypercalcemia), burns, third spacing, adrenal crisis.
  • Decreased effective circulating volume: CHF (cardiorenal), cirrhosis (hepatorenal) (See section Renal Failure in Cirrhosis), nephrotic syndrome.
  • Changes in renal vascular tone: ACEI/ARBs, cyclosporine, NSAIDs.
• Intrarenal: classified according to site of injury within the kidney.
  • Vasculature:
    • Microvascular: HUS/TTP, preeclampsia, malignant hypertension, DIC.
    • Macrovascular: bilateral renal artery stenosis (can be seen after ACEI administration), dissecting AAA, thrombo- or atheroembolism, renal artery thrombosis, polyarteritis nodosa (PAN).
  • Interstitium: acute interstitial nephritis (AIN). 10% of intrinsic kidney disease. Classic triad includes fever, rash, and eosinophilia but occurs in minority of patients (~10-30%). (See section Acute Interstitial Nephritis.)
  • Glomeruli: glomerulonephritis (GN).
  • Tubules: acute tubular necrosis (ATN). The most common cause of intrinsic AKI among hospitalized patients – accounts for 85% of intrinsic disease. Main risk factors for ATN:
    • Ischemic: any prolonged and severe prerenal state; e.g. prolonged hypovolemia, vascular disease such as renal artery occlusion, severe heart failure.
    • Toxic: vancomycin, aminoglycosides, amphotericin, cisplatin, rhabdomyolysis, hemolysis, persistent hyperbilirubinemia (pigment nephropathy), myeloma protein, radiocontrast dye (see section Contrast Nephropathy).
    • Sepsis physiology (even without hypotension)
• Postrenal: important to exclude early, as failure to relieve obstruction leads to permanent kidney damage in a time-dependent manner.
  • Intratubular obstruction: various crystals (uric acid, calcium oxalate, acyclovir, indinavir).
  • Ureter (usually bilateral to cause AKI): bilateral calculi (see section Stone Disease), blood clot, cancer, external compression (lymphadenopathy and retroperitoneal fibrosis).
  • Bladder: neurogenic bladder, spinal cord injury, anticholinergic drugs, opiates, benign prostatic hyperplasia, obstructing bladder calculi, cancer, blood clot.
  • Urethra: stricture, congenital valve, BPH.

Table 1: Etiologies of Acute Kidney Injury

Evaluation

The initial evaluation should focus on a two-pronged approach:

1. 1) Identify potentially fatal complications of severe AKI (hyperkalemia, acidosis, fluid overload) that may require immediate renal replacement therapy (see section Indications for Dialysis).
2. 2) Diagnose and treat the underlying cause of AKI.

• History:
  • Underlying kidney function.
    • Baseline serum creatinine/GFR (pre-existing CKD is a strong factor for AKI), history of dialysis or stone disease, family history of renal disease.
  • Medication use.
  • Intake and output.
    • Dehydration due to diarrhea, nausea and/or decreased PO intake.
    • Oliguria, polyuria or anuria.
• Underlying medical conditions or recent procedures.
  • BPH, cancer/chemotherapy, SLE, recent intravascular contrast or surgery/anesthesia.
• Physical examination: assess for serious sequelae of renal failure and/or clues to underlying etiology. 
  • Uremia: pericardial friction rub, muffled heart sounds with increased JVP from pericardial effusion, confusion, asterixis.
  • Volume overload: pulmonary crackles, hypoxia, peripheral edema.
  • Obstruction: distended bladder, suprapubic tenderness, flank tenderness (stones).
  • Vasculitis: rash, purpura, livedo reticularis.
  • Dehydration: dry mucous membranes, orthostasis, flat neck veins.
  • Blood pressure: GN or vasculitis will cause new-onset hypertension.
  • Joint exam for rheumatologic disorders associated with renal disease: lupus, mixed connective tissue disease, gout, rheumatoid arthritis.
• Initial work-up: EKG (if K >5.4), chem 10, UA with microscopy, urine sediment exam, FENa, FEUrea, urine osmolality (UNa, UCr, UOsm+/- UUrea), spot UProt/UCr, renal U/S (see below).
• Consider screen for GN if high clinical suspicion or hematuria on UA: ANA, C3, C4, ANCA.
  • If exam and UA are consistent with GN, additional tests are recommended.
• Check CK if concern for rhabdomyolysis (heme without RBC on UA, elevated potassium).
• Note: elevated risk of ATN only when CK>15,000-20,000 (but may be seen at lower levels if concomitant sepsis, prerenal azotemia, or acidosis).
• Interpreting biochemical markers and urine electrolytes (table 2):
  • Calculate FENa [(UNa/PNa ÷ UCr/PCr) x 100] if patient is oliguric.
  • If patient has recently used diuretics, can calculate the FEUrea [(UUrea/PBUN ÷ UCr/PCr) x100].

Table 2: Classic Urinary Findings in AKI

**Pearl: urine needs to be collected fresh (voided or from clamped Foley and NEVER from Foley bag) and examined within 30-60 minutes to have highest sensitivity for casts.

• Renal US is to evaluate for:
• Hydronephrosis: a sign of obstruction, but may be falsely negative if the obstruction is acute, partial or with retroperitoneal fibrosis (retroperitoneal fibrosis can be seen by CT/MRI).
• Kidney size: normal size is somewhat dependent on the size of the individual, but generally 10-12cm in length. 
• Bilateral atrophic kidneys are seen in CKD and biopsy is likely of little yield in these patients.
• Large kidneys are seen in DM, amyloid, PCKD, HIV, infiltrative diseases (lymphoma).
• Asymmetric kidneys are seen in renal artery stenosis or congenital atrophy.

Management

• Management is primarily supportive:
• Manage fluid and transfusions carefully but do not shy away from bolus fluids if thought to be acute and likely purely prerenal +/- hypotension. Monitor for pulmonary edema.
• May need to use furosemide diuresis judiciously to avoid hemodialysis for volume overload.
• Monitor electrolytes closely, repleting potassium and calcium cautiously.
• Note the Ca x Phos product as patients may develop hyperphosphatemia. Ca x Phos product >70 can cause metastatic calcification (rare in acute setting).
• Phosphate binders reduce absorption of dietary PO4, rarely needed unless underlying CKD exists but consider if PO4 >7.
• Correction of significant acidosis (HCO3 <15) with IV or PO NaHCO3.
• Medical management of hyperkalemia.
• Strict I/Os as progression to oliguria is associated with a worse prognosis.
• If patient is unable to void spontaneously or is anuric, check post-void residual (PVR) and/or place Foley catheter to relieve potential lower tract or bladder obstruction.
• If Foley catheter is already present, flush to rule out obstructed catheter.
• Renal diet (low potassium and phosphorus). Consider nutrition consultation and therapy as these patients can be highly catabolic.
• Medications to avoid in AKI (see Drugs Requiring Adjustment in Renal Failure):
• Nephrotoxic: AVOID NSAIDS, contrast, aminoglycosides.
• Opioids: AVOID morphine, codeine, meperidine and propoxyphene.
• Safer to use: methadone and fentanyl safest followed by hydromorphone (dilaudid) and oxycodone. Levels may still increase and cause somnolence.
• Anti-hyperglycemics: AVOID metformin when Cr ≥1.4 (rare risk of lactic acidosis) in acute setting, glyburide (renally-cleared metabolite). Glipizide is preferred to other oral sulfonylureas when GFR is reduced.
• Specific targeted treatments:
• Prerenal: fluid challenge cautiously (unless patient hypotensive or orthostatic) and closely monitor ins and outs. Creatinine will lag behind renal recovery, so carefully measure and follow urine output.
• Intrarenal:
• ATN: focus on correcting underlying insult (hypotension, sepsis, nephrotoxins). Serum creatinine peaks between two and five days after insult and typically returns to baseline within two weeks.
• Rhabdomyolysis or acute uric acid nephropathy: hydration and alkalinization of the urine.
• Give 150mEq NaHCO3/L in 1L D5W IV at 100-150ml/hr, then titrate to high volume UOP with urine pH>6.
• If the patient is already oliguric, monitor volume status closely to avoid volume overload.
• Postrenal: catheterization to monitor UOP. If the obstruction is proximal, obtain urology consultation for ureteral stenting or percutaneous nephrostomy.
• Watch for post-obstructive diuresis (up to 500-1000ml/hr) leading to rapid fluid and electrolyte shifts because injured kidneys cannot filter urine appropriately. Do not replace urine output 1:1; however, can start MIVF to avoid Na wasting.
• Uremic platelet dysfunction: treat with transfusion (Hct>30% has better outcomes in uremic bleeding), DDAVP (0.3mcg/kg IV), estrogens or hemodialysis (best therapy).
• Treatments that have NOT been shown to beneficial:
• Diuretics have NOT been shown to improve either morbidity, LOS, or mortality and may be harmful with trend to higher creatinine after recovery.
• Low dose dopamine, calcium channel blockers, and mannitol have NOT been beneficial in the treatment of AKI.

Key Points

• An anatomic approach is useful for the basic DDx:
  • Prerenal (hypovolemia, decreased effective circulatory volume, change in renal vasculature).
  • Intrarenal (glomeruli, tubules, interstitium, vasculature).
  • Postrenal (tubules, ureters, bladder, urethra).
• Primary work-up (EKG, chem 10, UA with microscopy, urine sediment exam, urine lytes, spot UProt/UCr, renal US) is aimed at:
  • Quickly identifying potentially fatal complications of AKI (hyperkalemia, acidosis, volume overload).
  • Searching for and correcting underlying cause of AKI.

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