Tutor Lesson

Pre-renal AKI

Pre-renal AKI begins with reduced kidney perfusion rather than direct kidney damage. Lower blood flow decreases glomerular hydrostatic pressure and GFR. Consequently, less creatinine is filtered and less urine is produced.

Reduced renal perfusion can arise through three broad mechanisms: reduced effective arterial blood volume, altered renal-vessel tone, or obstruction of the renal artery.

• Cardiorenal syndrome occurs with heart failure. Left-ventricular dysfunction lowers cardiac output and mean arterial pressure, reducing effective arterial blood volume and kidney perfusion. Right-heart dysfunction raises central venous pressure, hinders blood leaving the kidneys, and produces venous congestion or congestive nephropathy. Patients commonly have hypervolemic findings such as pedal or pulmonary edema, ascites, and hypertension.
• Hepatorenal syndrome occurs with decompensated cirrhosis. Reduced albumin production lowers oncotic pressure, allowing fluid to leave the vessels and decreasing effective arterial blood volume. Portal hypertension also promotes systemic, especially splanchnic, vasodilation. Blood is diverted from the kidneys, blood pressure falls, and activation of RAAS and the sympathetic nervous system causes further renal vasoconstriction. Edema and ascites may be present.
• True hypovolemia follows direct fluid or blood loss. Important causes include severe diarrhea, excessive diuresis, dehydration, and acute blood loss. Reduced blood volume lowers preload, stroke volume, cardiac output, and ultimately renal perfusion. Findings can include poor skin turgor, dry mucous membranes, hypotension, and tachycardia.
• Septic, cardiogenic, and hypovolemic shock produce severe hypotension and a markedly low mean arterial pressure. The resulting loss of organ perfusion can cause kidney injury as part of multisystem organ dysfunction.

• Afferent arteriolar vasoconstriction restricts blood entering the glomerulus.
• NSAIDs inhibit prostaglandin I2, which normally supports afferent vasodilation. The resulting afferent constriction reduces glomerular blood flow and GFR.
• Tacrolimus can also constrict the afferent arteriole, although its mechanism is less clearly understood.
• Excessive efferent arteriolar dilation lets blood leave the glomerulus more readily, lowering glomerular pressure.
• ACE inhibitors and angiotensin receptor blockers oppose angiotensin II activity. This dilates the efferent arteriole, which can reduce glomerular pressure and GFR, raise creatinine, and lower urine output.

• Renal artery stenosis is commonly associated with atherosclerosis in patients older than 50 or fibromuscular dysplasia in those younger than 50.
• Reduced renal blood flow lowers GFR, increases serum creatinine, and decreases urine output.
• Possible clues include difficult-to-control hypertension and a bruit over a renal artery.
• Severe AKI generally requires bilateral stenosis or stenosis affecting a solitary kidney. ACE-inhibitor use further increases risk because efferent dilation compounds the fall in GFR.

Intra-renal AKI

Intra-renal AKI reflects direct nephron injury involving structures such as the glomeruli or renal tubules. It represents about 35–40% of AKI cases.

• Ischemic ATN follows a prolonged reduction in renal perfusion. Untreated pre-renal AKI, particularly severe hypotension or hypovolemia, can reduce oxygen delivery enough to kill tubular cells.
• Nephrotoxic ATN results from direct tubular injury by medications, toxins, pigments, crystals, or immunoglobulins.
• Medication and contrast triggers include vancomycin, aminoglycosides, amphotericin B, and iodinated contrast dye.
• Myoglobin released during rhabdomyolysis and hemoglobin released during hemolysis are toxic to tubular cells. Muscle injury and seizures can cause rhabdomyolysis.
• Uric acid crystals can injure tubules in tumor lysis syndrome, when rapid cancer-cell breakdown releases large quantities of uric acid.
• Bence Jones proteins, the immunoglobulin light chains associated with multiple myeloma, may deposit in and damage tubules.
• Muddy brown casts on urine microscopy are clumps of dead tubular cells and are a key clue to ATN.

• Frequent medication associations include NSAIDs, beta-lactam antibiotics, and proton pump inhibitors.
• Neutrophils, eosinophils, and lymphocytes enter the interstitium during the inflammatory response.
• The classic clinical pattern is fever, rash, and increased eosinophils in blood and urine.
• Urinalysis may reveal white blood cell casts, including eosinophil casts, but this finding has low sensitivity and specificity.

• Causes include ANCA-associated vasculitis, anti-glomerular basement membrane disease or Goodpasture syndrome, infectious glomerulonephritis, and immune-complex disorders such as lupus nephritis.
• ANCA-associated vasculitis and anti-GBM disease may produce a pulmonary-renal syndrome with hemoptysis and glomerulonephritis.
• Important findings are substantial proteinuria, hematuria, and red blood cell casts. Protein loss is often greater than 2 g and can exceed 3.5 g in the nephrotic range. Red blood cell casts strongly support glomerulonephritis and may indicate a rapidly progressive form.

• Associated disorders include hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and disseminated intravascular coagulation.
• The characteristic triad is hemolytic anemia, thrombocytopenia, and AKI.

Post-renal AKI

Post-renal AKI begins with urinary obstruction beyond the kidneys. Backed-up urine raises pressure in the tubules and Bowman's capsule. This capsular hydrostatic pressure opposes glomerular hydrostatic pressure, weakens the filtration gradient, and abruptly lowers GFR.

• Nephrolithiasis may obstruct a ureter or renal pelvis. AKI usually requires stones on both sides or a stone affecting the patient's only kidney.
• External compression can come from masses such as ovarian cancer, rectal cancer, or retroperitoneal fibrosis.
• Urine backup distends the ureter and collecting system, producing hydroureter and hydronephrosis. Flank pain, hematuria, nausea, and vomiting may occur.
• Ultrasound can demonstrate hydronephrosis and hydroureter. When the bladder remains normal-sized or empty, the pattern favors a proximal obstruction.

• Neurogenic bladder results from weak detrusor contraction or poor coordination between the bladder muscle and internal urethral sphincter.
• Possible causes include spinal cord disease, stroke, and Parkinson's disease.
• Anticholinergic medications can inhibit bladder contraction and cause urinary retention.
• Bladder outlet obstruction is a physical barrier to urine leaving the bladder.
• Benign prostatic hyperplasia is the most common cause in men, although prostate cancer may also obstruct the outlet.
• Distal blockage produces a distended bladder followed by hydroureter and hydronephrosis.
• Ultrasound shows the enlarged bladder in addition to hydronephrosis and hydroureter. A post-void residual above 200 mL supports distal obstruction, as does a marked increase in urine output after Foley catheter placement.

Metabolic Acidosis

• Mechanism: reduced GFR limits proton secretion and bicarbonate reabsorption. Retained organic acids, including sulfates and phosphates, add further protons.
• Result: protons rise, bicarbonate falls, and blood pH decreases. Severe AKI commonly produces an anion-gap metabolic acidosis with an anion gap above 12 mEq/L.
• Tachypnea or Kussmaul breathing increases respiratory rate and depth to remove carbon dioxide as compensation.
• Acidosis can worsen hyperkalemia because protons enter cells while potassium shifts into the bloodstream to preserve electroneutrality.
• Severe acidosis can weaken myocardial contraction and cause vasodilation. The resulting decreases in cardiac output and systemic vascular resistance lower blood pressure and reduce vasopressor effectiveness.

Hyperkalemia

A low GFR reduces renal potassium excretion, and accompanying acidosis can shift additional potassium out of cells. Serum potassium above 6 mEq/L can be life-threatening because of its cardiac effects.

• Peaked T waves are tall, narrow, pointed waves and may appear early.
• The PR interval lengthens as conduction between atrial and ventricular depolarization slows.
• P waves may disappear as atrial activity becomes disorganized or absent, with varying degrees of AV block.
• The QRS complex widens beyond 120 ms as ventricular depolarization is prolonged.
• A sine-wave pattern signals severe danger and can rapidly deteriorate into asystole or ventricular fibrillation and cardiac arrest.

Hypervolemia

When GFR falls, the kidneys cannot adequately filter and excrete sodium and water. Their retention expands blood volume.

• Pulmonary edema places fluid in the alveoli, while pleural effusions collect fluid in the pleural space.
• These changes can cause hypoxia, dyspnea, and crackles or rales, and may be visible on chest X-ray.
• Peripheral or pedal edema often pits, leaving a temporary indentation after pressure is applied.
• Expanded blood volume raises end-diastolic volume, stroke volume, and cardiac output, producing hypertension.
• Excess water retention can dilute serum sodium and cause hypervolemic hyponatremia.

Uremia

A substantial fall in GFR allows urea and other waste products to accumulate. Azotemia means a biochemical rise in BUN; uremia means that retained toxins are producing clinical symptoms.

• Uremic encephalopathy can involve brain swelling, altered mental status, confusion, lethargy, nausea, vomiting, and asterixis, the flapping tremor seen with extended hands.
• Uremic pericarditis is inflammation of the pericardium caused by retained toxins.
• Findings include inspiratory chest pain that improves on leaning forward and may radiate to the trapezius, a pericardial friction rub, pericardial effusion on echocardiography, diffuse concave ST elevation, and PR-segment depression.
• Uremic toxins impair platelet adhesion and aggregation, creating a bleeding tendency.
• Bleeding may appear as epistaxis, gingival bleeding, vaginal bleeding, or gastrointestinal bleeding. Severe blood loss can cause anemia.

Confirming AKI

• Serum creatinine supports AKI when it rises by at least 0.3 mg/dL over 48 hours or reaches at least 1.5 times baseline within 7 days.
• Urine output supports AKI when it is 0.5 mL/kg/hour or less for at least 6 hours. Oliguria can also be recognized as less than approximately 400–500 mL over 24 hours.

Differentiating the AKI Categories

1. Evaluate for post-renal AKI first because obstruction is comparatively straightforward to identify and requires prompt attention.
2. If obstruction is not found, use history, physical examination, urine studies, and microscopy to separate pre-renal from intra-renal causes.

• Renal and bladder ultrasound is the key imaging study for suspected obstruction.
• Hydronephrosis indicates dilation of the kidney from backed-up urine and may occur with either proximal or distal obstruction.
• Hydroureter is ureteral distension and may also appear in either location.
• An enlarged, distended bladder points toward distal obstruction.
• Flank pain, hematuria, nausea, vomiting, and a history of nephrolithiasis support proximal obstruction. Bilateral stones or a stone in a solitary kidney are especially concerning. Hydronephrosis with a normal or empty bladder also favors a proximal site.
• BPH, neurogenic bladder from spinal cord disease, stroke, or Parkinson's disease, and anticholinergic use support distal obstruction. A bladder post-void residual above 200 mL or improved urine output after Foley placement strengthens this conclusion.