10.1 Acute Kidney Injury & Chronic Kidney Disease
Key Takeaways
- Acute Kidney Injury (AKI) is defined by KDIGO criteria as an increase in serum creatinine by >=0.3 mg/dL within 48 hours, >=1.5 times baseline within 7 days, or urine volume <0.5 mL/kg/h for 6 consecutive hours.
- Prerenal AKI features a BUN/Cr ratio >20:1, Fractional Excretion of Sodium (FENa) <1% (or FEUrea <35% in patients taking diuretics), and urine osmolality >500 mOsm/kg.
- Intrinsic AKI (e.g., Acute Tubular Necrosis [ATN]) demonstrates a BUN/Cr ratio <15:1, FENa >2%, urine sodium >40 mEq/L, urine osmolality <350 mOsm/kg, and muddy brown granular casts.
- Chronic Kidney Disease (CKD) diagnosis requires persistent evidence of kidney damage or GFR <60 mL/min/1.73 m² for at least 3 months, with Stage 5 CKD (End-Stage Renal Disease) defined as GFR <15 mL/min/1.73 m².
- High-yield urgent indications for hemodialysis are remembered by the mnemonic AEIOU: Acidosis (pH <7.1 refractory), Electrolytes (hyperkalemia >6.5 mEq/L or with ECG changes), Ingestions (Salicylates, Lithium, Isopropanol, Methanol, Ethylene glycol), Overload (volume refractory to diuretics), and Uremia (pericarditis, encephalopathy, or neuropathy).
Acute Kidney Injury Definitions & Classification
Acute Kidney Injury (AKI) represents an abrupt decline in renal function occurring over hours to days, leading to the accumulation of nitrogenous waste products (azotemia) and perturbations in fluid, electrolyte, and acid-base homeostasis. On the USMLE Step 2 CK, diagnostic evaluation begins by categorizing AKI according to standardized consensus definitions and hemodynamic pathophysiology.
KDIGO Diagnostic Criteria
According to the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, AKI is formally diagnosed when a patient meets any one of the following three objective criteria:
- An increase in serum creatinine by >=0.3 mg/dL (>=26.5 umol/L) within 48 hours.
- An increase in serum creatinine to >=1.5 times baseline, which is known or presumed to have occurred within the prior 7 days.
- Urine volume <0.5 mL/kg/h for 6 consecutive hours.
[ Suspected Acute Kidney Injury ]
|
[ Step 1: Renal Ultrasound ]
|
+--------------------------+--------------------------+
| |
[ Hydronephrosis / Obstruction ] [ No Obstruction ]
| |
(Postrenal AKI) |
-> Foley Catheter / [ Step 2: Urine Spot ]
Nephrostomy Tube (FENa / FEUrea / Osm)
|
+-------------------------------------+-------------------------------------+
| |
[ FENa <1% / FEUrea <35% ] [ FENa >2% / FEUrea >50% ]
[ Urine Osm >500 mOsm/kg ] [ Urine Osm <350 mOsm/kg ]
| |
(Prerenal AKI) (Intrinsic AKI)
-> Fluid Bolus / Restor Perfusion -> Identify Parenchymal Etiology
(ATN vs AIN vs Glomerulonephritis)
Diagnostic Differentiation: Prerenal, Intrinsic & Postrenal AKI
Determining the etiology of AKI requires evaluating urine chemistry, urine osmolality, and microscopic urinalysis. The table below outlines the classic laboratory findings used to distinguish prerenal hypoperfusion from intrinsic renal parenchymal damage.
| Diagnostic Parameter | Prerenal Azotemia | Intrinsic AKI (Acute Tubular Necrosis) | Postrenal Obstruction |
|---|---|---|---|
| BUN / Serum Creatinine Ratio | >20:1 | <15:1 | Variable (>20:1 early, <15:1 late) |
| Fractional Excretion of Na (FENa) | <1% | >2% | >2% (late stage) |
| Fractional Excretion of Urea (FEUrea) | <35% (use if patient takes diuretics) | >50% | >50% |
| Urine Sodium Concentration | <20 mEq/L | >40 mEq/L | >40 mEq/L |
| Urine Osmolality | >500 mOsm/kg | <350 mOsm/kg | <350 mOsm/kg |
| Urinary Sediment | Hyaline casts or normal | Muddy brown granular casts, tubular cells | Normal, RBCs, or crystals |
Prerenal Azotemia
Prerenal AKI results from compromised renal perfusion without structural renal parenchymal injury. Common etiologies include intravascular volume depletion (hemorrhage, gastrointestinal fluid loss, excessive diuresis), effective arterial volume depletion (systolic heart failure, decompensated cirrhosis), and intrarenal hemodynamics altered by medications (ACE inhibitors/ARBs dilate efferent arterioles; NSAIDs constrict afferent arterioles). The renal tubules remain functionally intact, appropriately reabsorbing sodium and water to expand intravascular volume, yielding low FENa (<1%) and concentrated urine (>500 mOsm/kg).
Intrinsic Renal Parenchymal Disease
Intrinsic AKI involves structural damage to glomeruli, tubules, interstitium, or renal vasculature. Acute Tubular Necrosis (ATN) accounts for over 85% of intrinsic AKI cases in hospitalized patients. ATN stems from either prolonged ischemic injury (unresolved prerenal state, septic shock) or direct nephrotoxic exposure:
- Exogenous Nephrotoxins: Aminoglycosides (gentamicin), radiocontrast agents, cisplatin, amphotericin B, and vancomycin.
- Endogenous Nephrotoxins: Myoglobin (rhabdomyolysis following crush injury or prolonged immobilization), hemoglobin (hemolysis), and uric acid/light chains (tumor lysis syndrome or multiple myeloma).
Pathologically, necrotic tubular epithelial cells slough off into the tubular lumen, forming diagnostic muddy brown granular casts on urine microscopy.
Postrenal Urinary Tract Obstruction
Postrenal AKI occurs when urinary outflow is acutely obstructed bilaterally (or unilaterally in a patient with a single functioning kidney). Causes include benign prostatic hyperplasia (BPH), prostate cancer, bilateral nephrolithiasis, neurogenic bladder, or retroperitoneal fibrosis. Renal ultrasound is the diagnostic procedure of choice to visualize hydronephrosis and urinary bladder distension. Immediate bladder catheterization or percutaneous nephrostomy tube placement is therapeutic.
Chronic Kidney Disease (CKD) & Complications
Chronic Kidney Disease (CKD) is defined as abnormalities of kidney structure or function present for >=3 months, with implications for health. It is staged primarily by Estimated Glomerular Filtration Rate (eGFR):
- Stage 1: eGFR >=90 mL/min/1.73 m² with persistent proteinuria/kidney damage.
- Stage 2: eGFR 60–89 mL/min/1.73 m².
- Stage 3a/3b: eGFR 45–59 (3a) and 30–44 (3b) mL/min/1.73 m².
- Stage 4: eGFR 15–29 mL/min/1.73 m² (severely decreased; prepare for vascular access/dialysis).
- Stage 5 (ESRD): eGFR <15 mL/min/1.73 m² (end-stage renal disease requiring renal replacement therapy).
Major Systemic Complications of CKD
- Normocytic Normochromic Anemia: Decreased erythropoietin production by renal peritubular interstitial cells. Treatment involves erythropoiesis-stimulating agents (ESAs) like epoetin alfa, provided serum ferritin (>100 ng/mL) and transferrin saturation (>20%) confirm adequate iron stores.
- CKD-Mineral and Bone Disorder (CKD-MBD): Failing kidneys decrease phosphate excretion (hyperphosphatemia) and produce less active 1,25-dihydroxyvitamin D (calcitriol) due to loss of 1-alpha-hydroxylase. Low calcitriol causes hypocalcemia. Combined hyperphosphatemia and hypocalcemia stimulate parathyroid hormone secretion (secondary hyperparathyroidism), leading to high-turnover bone disease (osteitis fibrosa cystica). Treatment includes dietary phosphate restriction, oral phosphate binders (sevelamer, calcium acetate), and active vitamin D analogs.
- Calciphylaxis (Calcific Uremic Arteriolopathy): Painful, necrotic skin ulcers caused by vascular calcification and thrombosis in patients with advanced ESRD and severe hyperphosphatemia.
- Uremic Platelet Dysfunction: Accumulated uremic toxins impair platelet adhesion and aggregation, causing mucosal bleeding and prolonged bleeding time with normal platelet count, PT, and PTT. First-line therapy for acute bleeding is desmopressin (DDAVP).
Indications for Urgent Hemodialysis
When medical management fails in patients with acute or chronic renal failure, urgent renal replacement therapy (hemodialysis) is indicated. High-yield emergency indications are recalled using the classic AEIOU mnemonic:
- A (Acidosis): Refractory metabolic acidosis with pH <7.1 despite sodium bicarbonate therapy.
- E (Electrolytes): Severe hyperkalemia (K+ >6.5 mEq/L) or hyperkalemia with ECG changes refractory to medical stabilization.
- I (Ingestions): Toxic exposures to dialyzable drugs (SLIME: Salicylates, Lithium, Isopropanol, Methanol, Ethylene glycol).
- O (Overload): Refractory volume overload / pulmonary edema unresponsive to intravenous loop diuretics.
- U (Uremia): Symptomatic uremia, specifically uremic pericarditis (pericardial friction rub), uremic encephalopathy (asterixis, altered mental status), or uremic neuropathy.
A 68-year-old male with a history of hypertension and heart failure is admitted to the intensive care unit with severe septic shock secondary to pneumonia. Over the past 24 hours, his urine output has decreased to 15 mL/h. Laboratory results reveal a serum creatinine of 2.4 mg/dL (baseline 0.9 mg/dL) and Blood Urea Nitrogen (BUN) of 62 mg/dL. Urinalysis demonstrates high urine osmolality (620 mOsm/kg), a urine sodium of 12 mEq/L, and a Fractional Excretion of Sodium (FENa) of 0.4%. Hyaline casts are noted on urine microscopy. Which of the following is the most appropriate initial management step?
A 58-year-old female with Stage 4 Chronic Kidney Disease (eGFR 22 mL/min/1.73 m²) secondary to long-standing type 2 diabetes mellitus presents to the emergency department with oozing from a peripheral venipuncture site and recurrent epistaxis over the last 12 hours. Laboratory evaluation shows a hemoglobin of 9.2 g/dL, platelet count of 210,000/mm³, Prothrombin Time (PT) of 12 seconds, Activated Partial Thromboplastin Time (aPTT) of 31 seconds, and a significantly prolonged Bleeding Time. Which of the following is the best initial step in management to control her acute bleeding?
A 34-year-old construction worker is brought to the emergency department after being trapped under concrete rubble for 8 hours following a building collapse. On physical examination, his lower extremities are severely swollen, tender, and ecchymotic. Laboratory evaluation reveals a serum creatinine of 3.8 mg/dL, BUN of 45 mg/dL, and serum potassium of 6.8 mEq/L. An electrocardiogram (ECG) shows tall, peaked T waves in precordial leads with subtle widening of the QRS complex. Which of the following is the most urgent initial step in managing this patient?