13.1 Acute Kidney Injury (AKI) & Chronic Kidney Disease (CKD)

Acute Kidney Injury (AKI) & Chronic Kidney Disease (CKD)

PANCE High-Yield Focus: Renal medicine is highly tested on the PANCE, with Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) representing core concepts. You must be able to classify AKI into prerenal, intrinsic, and postrenal types using clinical history, physical exam findings, and lab indices like the blood urea nitrogen-to-creatinine (BUN/Cr) ratio, fractional excretion of sodium (FeNa), and urine microscopy. For CKD, focus on the stages of kidney disease, cardiovascular risk reduction, and the management of complications such as renal osteodystrophy and anemia of chronic disease.

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Acute Kidney Injury (AKI)

Acute Kidney Injury (AKI) is defined by the Kidney Disease: Improving Global Outcomes (KDIGO) consensus as an abrupt decline in kidney function, clinically identified by:

1. An increase in serum creatinine of >= 0.3 mg/dL within 48 hours;
2. An increase in serum creatinine to >= 1.5 times baseline within the prior 7 days;
3. Urine output < 0.5 mL/kg/hour for at least 6 consecutive hours.

The diagnostic workup of AKI requires classification into one of three distinct etiologic categories: prerenal, intrinsic, or postrenal.

1. Prerenal AKI (Hypoperfusion)

Prerenal AKI is the most common cause of acute renal failure in both outpatient and inpatient settings. It results from a decrease in effective renal blood flow, leading to a reduced GFR, without causing structural damage to the kidney parenchyma.

• Pathophysiology and Risk Factors: Risk factors include volume depletion (vomiting, diarrhea, hemorrhage, excessive diuresis), systemic vasodilation (sepsis, anaphylaxis), and localized renal hypoperfusion (heart failure, cirrhosis, bilateral renal artery stenosis). In response to low perfusion, the kidneys activate the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system to retain water and sodium. Glomerular pressure is maintained by prostaglandin-mediated afferent arteriole vasodilation and Angiotensin II-mediated efferent arteriole vasoconstriction.
• Nephrotoxic Traps: Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, causing afferent vasoconstriction. ACE inhibitors and ARBs block Angiotensin II, causing efferent vasodilation. Both drug classes can precipitate acute prerenal kidney failure in hypoperfused patients and must be held.
• Diagnostics: Because the renal tubules remain functional, they aggressively reabsorb water and electrolytes.
  • BUN/Cr Ratio: > 20:1 (urea is passively reabsorbed along with sodium and water, whereas creatinine is not).
  • Fractional Excretion of Sodium (FeNa): < 1% (indicates intact sodium conservation). Use Fractional Excretion of Urea (FeUrea) < 35% if the patient is taking diuretics.
  • Urine Sodium (UNa): < 20 mEq/L.
  • Urine Osmolality: > 500 mOsm/kg (intact urinary concentrating ability).
  • Urine Sediment: Characterized by hyaline casts (composed of Tamm-Horsfall mucoprotein, a non-specific finding).
• Clinical Management: Focuses on restoring renal perfusion. Administer intravenous isotonic crystalloids (normal saline or lactated Ringer's) for hypovolemia. Optimize cardiac output in heart failure and avoid all nephrotoxins.

2. Intrinsic AKI (Structural Damage)

Intrinsic AKI involves structural damage to the glomerular, tubular, interstitial, or vascular compartments of the kidney.

Acute Tubular Necrosis (ATN)

ATN is the most common form of intrinsic AKI, representing death of the renal tubular epithelial cells.

• Etiology: Ischemic ATN is caused by prolonged, uncorrected prerenal hypoperfusion (sepsis, shock). Nephrotoxic ATN is caused by exposure to substances that are directly toxic to tubular cells.
  • Exogenous toxins: Aminoglycoside antibiotics (e.g., gentamicin), intravenous iodinated contrast media (contrast-induced nephropathy), amphotericin B, cisplatin, and acyclovir.
  • Endogenous toxins: Myoglobin (from rhabdomyolysis), hemoglobin (from hemolysis), and Bence-Jones proteins (in multiple myeloma).
• Diagnostics: Damaged, necrotic tubules cannot reabsorb water, sodium, or urea.
  • BUN/Cr Ratio: < 15:1.
  • FeNa: > 2%.
  • Urine Sodium: > 40 mEq/L.
  • Urine Osmolality: < 350 mOsm/kg (urine is isosthenuric, matching serum osmolality).
  • Urine Sediment: Characterized by muddy brown granular casts and sloughed renal tubular epithelial cells.
• Clinical Management: Supportive care, including volume management, avoidance of further nephrotoxins, and correction of electrolyte disturbances (e.g., hyperkalemia). Diuretics do not improve recovery or mortality but may help manage hypervolemia.

3. Postrenal AKI (Obstructive)

Postrenal AKI arises from mechanical obstruction of urinary outflow anywhere from the renal pelvis to the urethra.

• Etiology: Benign prostatic hyperplasia (BPH) is the most common cause in elderly males. Other causes include nephrolithiasis (bilateral or in a solitary kidney), pelvic malignancies (e.g., cervical, prostate, colorectal cancer), and neurogenic bladder.
• Diagnostics:
  • Renal Ultrasound: The initial imaging study of choice to evaluate for hydronephrosis or hydroureter.
  • Foley Catheterization: Diagnostic and therapeutic for bladder outlet obstruction.
• Management: Relieve the obstruction. Interventions include bladder catheterization, ureteral stenting, or percutaneous nephrostomy tube placement.

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Chronic Kidney Disease (CKD)

Chronic Kidney Disease is defined as kidney damage (e.g., albuminuria) or a GFR < 60 mL/min/1.73m2 persisting for >= 3 months. In the United States, diabetes mellitus is the leading cause of CKD, followed by hypertension.

KDIGO Staging Criteria

CKD staging is based on GFR categories (G1 to G5) and Albuminuria categories (A1 to A3).

Pathophysiology & Management of CKD Complications

As GFR declines below 30-45 mL/min/1.73m2, the kidneys' endocrine and excretory capacities are severely compromised.

1. Cardiovascular Risk: Cardiovascular disease is the most common cause of death in patients with CKD, preceding progression to end-stage renal disease (ESRD). Aggressive blood pressure control (goal < 130/80 mmHg) is vital. ACE inhibitors or ARBs are first-line for patients with CKD and albuminuria (A2 or A3) because they dilate the efferent arteriole, lowering intraglomerular pressure and reducing proteinuria.
2. Anemia of CKD: This is typically a normocytic, normochromic anemia.
   • Pathophysiology: Decreased synthesis of erythropoietin (EPO) by renal peritubular interstitial cells.
   • Management: Exclude other causes of anemia. If iron stores are insufficient (defined as Transferrin Saturation [TSAT] < 20% or ferritin < 100 ng/mL in non-dialysis patients), oral or intravenous iron therapy is initiated first. Erythropoiesis-Stimulating Agents (ESAs, e.g., epoetin alfa, darbepoetin alfa) are indicated when hemoglobin drops < 10 g/dL. Target hemoglobin should be maintained between 10 and 11 g/dL; correcting above 11.5 g/dL is associated with an increased risk of stroke, myocardial infarction, and thromboembolic events.
3. Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD): Formerly known as renal osteodystrophy.
   • Pathophysiology:
     1. Decreased glomerular filtration of phosphorus leads to hyperphosphatemia.
     2. Elevated serum phosphorus binds free calcium, causing hypocalcemia.
     3. Declining GFR causes a loss of renal 1-alpha-hydroxylase activity, preventing the conversion of 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D (calcitriol). This further worsens hypocalcemia by reducing gastrointestinal calcium absorption.
     4. Chronic hypocalcemia, hyperphosphatemia, and low calcitriol levels stimulate the parathyroid glands to hypersecrete parathyroid hormone (PTH) (secondary hyperparathyroidism).
     5. High PTH levels stimulate osteoclastic activity, leading to bone resorption (osteitis fibrosa cystica), fractures, and calciphylaxis (painful systemic medial arterial calcification).
   • Management:
     • Dietary phosphorus restriction is the initial step.
     • Phosphate binders are taken with meals to limit intestinal absorption. Calcium-based binders (e.g., calcium acetate, calcium carbonate) are used when calcium levels are normal or low. Non-calcium-based binders (e.g., sevelamer, lanthanum carbonate) are preferred if the patient is hypercalcemic or has vascular calcifications.
     • Active Vitamin D (Calcitriol) or Vitamin D analogs (paricalcitol) are used to suppress PTH secretion.
     • Calcimimetics (Cinacalcet) activate calcium-sensing receptors on the parathyroid glands to inhibit PTH release.

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Classic PANCE Traps & Clinical Pearls

• The Urgency Dialysis Mnemonic: Memorize AEIOU for the indications for urgent hemodialysis:
  • Acidosis: Refractory metabolic acidosis (pH < 7.1).
  • Electrolytes: Refractory hyperkalemia (K+ > 6.5 mEq/L or with ECG changes).
  • Intoxications: Toxic levels of dialyzable drugs (Salicylates, Lithium, Isopropanol, Methanol, Ethylene glycol).
  • Overload: Volume overload refractory to diuretics (e.g., acute pulmonary edema).
  • Uremia: Uremic complications (pericarditis, encephalopathy with asterixis, neuropathy, or bleeding).
• Bilateral Renal Artery Stenosis: While ACEis and ARBs are renal-protective in proteinuric CKD, they are absolutely contraindicated in patients with bilateral renal artery stenosis. In this condition, GFR is highly dependent on Angiotensin II-mediated efferent vasoconstriction. Blocking this pathway causes an acute GFR collapse and severe prerenal AKI.