Acute Kidney Injury

Definitions
Sudden loss of kidney function resulting in retention of nitrogenous waste as well as electrolyte and volume homeostasis abnormalities with or without oliguria (urine output <500 mL/d)


Physiology

Classification

Risk (R)	Cr x 1.5	GFR ↓ by 25%	UO <0.5 mL/kg/h for 6 hours
Injury (I)	Cr x 2.0	GFR ↓ by 50%	UO <0.5 mL/kg/h for 12 hours
Failure (F)	Cr x 3.0	GFR ↓ by 75%, or SeCr >4 mg/dL with acute increase of >0.5 mg/dL	UO <0.3 mL/kg/h for 24 hours, or anuria for 12 hours
Loss (L)		Persistent ARF, complete loss of kidney function >4 weeks
End-stage kidney disease (E)		Loss of kidney function >3 months

The RIFLE classification of ARF

Aetiology

Prerenal (~55%):	Decreased effective arterial blood volume - Hypovolemia, CHF, liver failure, sepsis Renal arterial disease - Renal arterial stenosis (atherosclerotic, fibromuscular dysplasia), embolic disease (septic, cholesterol) Perinatal hemorrhage - Twin-twin transfusion, complications of amniocentesis, abruptio placenta, birth trauma Neonatal hemorrhage - Severe intraventricular hemorrhage, adrenal hemorrhage Perinatal asphyxia and hyaline membrane disease (newborn respiratory distress syndrome) both may result in preferential blood shunting away from the kidneys (ie, prerenal) to central circulation.
Intrarenal (~40%):	ATN, ischemia, toxins (eg, aminoglycosides, radiocontrast, heme pigments, cisplatin, myeloma light chains, ethylene glycol) Interstitial diseases - Acute interstitial nephritis, drug reactions, autoimmune diseases (eg, systemic lupus erythematosus [SLE]), infiltrative disease (sarcoidosis, lymphoma), infectious agents (Legionnaire disease, hantavirus) (HUS) often is cited as the most common cause of ARF in children. The most common form of the disease is associated with a diarrheal prodrome caused by E coli O157:H7. Acute glomerulonephritis Vascular diseases - Hypertensive crisis, polyarteritis nodosa, vasculitis
Postrenal (~5%)	Tubular obstruction from crystals (eg, uric acid, calcium oxalate, acyclovir, sulfonamide, methotrexate, myeloma light chains) Ureteral obstruction - Retroperitoneal tumor, retroperitoneal fibrosis (methysergide, propranolol, hydralazine), urolithiasis, papillary necrosis Urethral obstruction - Benign prostatic hypertrophy; prostate, cervical, bladder, colorectal carcinoma; bladder hematoma; bladder stone; obstructed Foley catheter; neurogenic bladder; stricture

Pathophysiology

Prerenal	Pathology secondary to decreased renal perfusion leading to a decrease in glomerular filtration rate (GFR); reversible if factors decreasing perfusion are corrected; otherwise, it can progress to an intrarenal pathology known as ischemic ATN.
Renal	Pathology secondary to pathology within the kidney; acute tubular necrosis (ATN) is the most common cause via ischemic or nephrotoxic injury to the kidney; 75% of ATN is a complication of prerenal etiology.
Postrenal	Pathology secondary to extrinsic or intrinsic obstruction of the urinary collection system

Epidemiology
5% and 30% of hospital and ICU admissions, respectively, have a diagnosis of acute renal failure (ARF). 25% of patients develop ARF while in the hospital, and 50% of those cases are iatrogenic.

Risk Factors
Comorbidities (e.g., liver failure, heart failure, diabetes)
Advanced age
Radiographic contrast material exposure
Nephrotoxic medications (e.g., aminoglycosides, nonsteroidal anti-inflammatory drugs [NSAIDs], angiotensin-converting enzyme [ACE] inhibitors)
Volume depletion (e.g., sepsis, hemorrhage)
Surgery
Rhabdomyolysis
Solitary kidney (risk in nephrolithiasis)
Benign prostatic hypertrophy (BPH)
Malignancy

Presentation
General: PO intake, urine output, body weight, and baseline creatinine measurement (to assess how far from baseline the current creatinine is), lethargy, seizures, asterixis, myoclonus, pericardial friction rub, peripheral neuropathies

Prerenal	Thirst, orthostatic dizziness, mental status change Tachycardia, decreased jugular venous pressure (JVP), orthostatic hypotension, dry mucous membranes, decreased skin turgor; look for stigmata of associated comorbidities such as liver and heart failure, as well as sepsis
Renal	Nephrotoxic medications, radiocontrast material, other toxins; fever, arthralgias, and pruritic rash suggest allergic interstitial nephritis, although systemic effects are not always seen in this pathology. Edema, hypertension, and oliguria with nephritic urine sediment points to glomerulonephritis or vasculitis. Livedo reticularis, subcutaneous nodules, and ischemic toes and fingers despite good pulses suggest atheroembolization. Flank pain suggests occlusion of the renal artery or vein. Pruritic rash, livedo reticularis, subcutaneous nodules, ischemic digits despite good pulses
Post-Renal	Colicky flank pain that radiates to the groin suggests a ureteric obstruction such as a stone. Nocturia, frequency, and hesitancy suggest prostatic disease. Suprapubic and flank pain are usually secondary to distension of the bladder and collecting system. Ask about anticholinergic drugs that could lead to neurogenic bladder. Enlarged prostate

Investigation

Urinalysis	If normal- suspect: HUS, TTP Transparent hyaline casts—prerenal etiology; pigmented granular/muddy brown casts—ATN; WBC casts—acute interstitial nephritis; RBC casts—glomerulonephritis Eosinophiluria - Acute allergic interstitial nephritis, atheroembolism Crystalluria - Acyclovir, sulfonamides, methotrexate, ethylene glycol toxicity, radiocontrast agents (can be a normal finding)
FBC	Leukocytosis - ARF. Leukopenia and thrombocytopenia -SLE or TTP. Anemia and rouleaux formation - multiple myeloma. Microangiopathic anemia -DIC, TTP, or atheroemboli. Eosinophilia - allergic interstitial nephritis, polyarteritis nodosa, or atheroemboli. Coagulation disturbances- liver disease, DIC, TTP, or hepatorenal syndrome
BUN	differentiate prerenal failure from other etiologies of ARF.
Creatinine	estimation of GFR
Cystatin C	biomarker for early kidney injury.
Blood chemistry	Creatine phosphokinase elevations- rhabdomyolysis ,MI Elevations in liver transaminase - liver failure and hepatorenal syndrome. Hypocalcemia is common in ARF; marked hypocalcemia is more typical of chronic renal failure. Hyperkalemia is a common and important complication of ARF.
Fractional excretion of sodium (FeNa)	FeNa = (urine Na/plasma Na)/(urine creatinine/plasma creatinine) FeNa <1% suggests prerenal ARF FeNa >1% suggests ATN
Imaging	Renal U/S- hydronephrosis, obstruction, small kidney(chronic renal failure) CXR- volume overload, Wegener/Goodpasture
ECG	hyperkalemia and arrhythmias, ischemia, and infarction.
Renal biopsy	if unknown causes

Management
Treatment of acute renal failure (ARF) ideally should begin before the diagnosis of ARF is firmly established.

Emergency	ABCs of resuscitation Treat hyperkalemia emergently, especially with ECG changes. If volume depleted, give IV fluids. Place a Foley catheter.
Oliguria	a fluid challenge may be appropriate with diligent monitoring for volume overload fluid restriction of 400 mL + yesterday's urine output (unless there are signs of volume depletion or overload)
ARF	Furosemide(Studies show that it is ineffective in preventing and treating ARF)
Antimicrobial therapy	eg, penicillin does not appear to prevent the development of GN, except if given within the first 36 hours.
Hyperkalemia:	IV calcium, sodium bicarbonate, and glucose with insulin, hemodialysis
Acidosis	Sodium bicarbonate 1–2 mEq/kg per dose (1–2 mmol/kg per dose) IV or p.o.
Contrast-induced ARF	can be prevented by N-acetylcysteine 600 mg PO b.i.d. on day prior to and day of contrast and isotonic NaHCO3 3 mL/kg/h × 1 h before administration of contrast material and 1 mL/kg/h × 6 h after contrast material
Correct causes	Flomax or other selective α-blockers for bladder outlet obstruction secondary to BPH Calcium channel blockers may have a protective effect in posttransplant ATN. Review drug list: Stop nephrotoxic drugs and renally adjust others. Always record ins and outs and daily weights. Watch for complications, including hyperkalemia, pulmonary edema, and acidosis—all potential reasons to start dialysis. Ensure good cardiac output and subsequent renal blood flow. Follow nutrition suggestions and be aware of infections; treat aggressively if they occur. Start patients on H2 inhibitors or proton pump inhibitors, and avoid aspirin to avoid bleeding tendency
Diet	Total caloric intake should be 35–50 kcal/kg/d to avoid catabolism. Sodium should be restricted to 2 g/d Potassium intake should be restricted to 40 mEq/d. Phosphorus should be restricted to 800 mg/d. If it becomes high, treat with calcium carbonate or other phosphate binder Magnesium compounds should be avoided.

Complications
Death, sepsis, infection, seizures, paralysis, peripheral edema, CHF, pulmonary edema, arrhythmias, uremic pericarditis, bleeding, GI bleed, hypotension, anemia, hyperkalemia, uremia

Prognosis
Depending on the cause, comorbid conditions, and age of patient, mortality ranges from 5–80%.
In cases of prerenal and postrenal failure, there are very good rates of recovery positively correlated with shorter duration of renal failure. Intrarenal etiologies usually take more time to recover from. Overall average recovery takes from days to a few months.
20–60% of patients experiencing ARF require dialysis during their hospital stay
25% requiring long-term renal replacement therapy