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)
- Vasculature:
- 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.
Prerenal |
Hypovolemia
|
Decreased effective circulating volume
|
|
Change in renal vascular tone
|
|
Intrarenal |
ATN (85% of intrinsic disease)
|
AIN (10% of intrinsic disease)
|
|
GN (5% of intrinsic disease)
|
|
Vascular
stenosis, dissecting AAA, atheroembolism, renal artery thrombosis |
|
Postrenal |
Tubules
|
Ureters
|
|
Bladder
|
|
Urethra
|
Table 1: Etiologies of Acute Kidney Injury
Evaluation
The initial evaluation should focus on a two-pronged approach:
- 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) 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 kidney function.
- 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].
Type |
Uosm |
UNa |
FENa |
FEUrea |
BUN/Cr |
Urine Examination |
Prerenal |
>500 |
<10 |
<1% |
<35% |
>20 |
Bland, few cells, hyaline casts |
Intrarenal |
<350 |
>20 |
>1% |
>45% |
<15 |
ATN: S.G. 1.010, minimal proteinuria, muddy brown casts, coarse granular casts, tubular epithelial cells |
AIN: WBC casts or eosinophils. WBCs with negative LE may be a clue to eosinophiluria, <1-2g/d proteinuria |
||||||
GN: dysmorphic RBCs, RBC casts, proteinuria may reach nephrotic range (>3.5g/day) |
||||||
Postrenal |
<350 |
>40 |
>4% |
>45% |
>15 |
Often normal but may contain RBC, WBC and crystals in stone disease |
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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