Section 8.1: Acute Kidney Injury & Chronic Kidney Disease
Key Takeaways
- AKI is staged by KDIGO criteria based on serum creatinine rise or urine output decline; Stage 3 represents a threefold rise in creatinine, creatinine ≥4.0 mg/dL, anuria for ≥12 hours, or RRT initiation.
- Prerenal AKI presents with FeNa < 1% (or FeUrea < 35% with diuretics) and a BUN/Cr ratio > 20:1, while ATN shows muddy brown casts, FeNa > 2%, and a BUN/Cr ratio of 10-15:1.
- Emergent hemodialysis indications (AEIOU) include refractory metabolic acidosis, severe hyperkalemia with ECG changes, toxic alcohol/lithium ingestion, refractory volume overload, and symptomatic uremia.
- Anemia of CKD is managed with iron supplementation to target TSAT > 30% and ferritin > 500 ng/mL, followed by ESAs to target a hemoglobin of 10.0-11.0 g/dL.
- CKD-mineral bone disorder management involves dietary phosphate restriction, phosphate binders (non-calcium preferred if hypercalcemic), active vitamin D, and calcimimetics like cinacalcet.
Acute Kidney Injury: Staging and Diagnostic Framework
Acute kidney injury (AKI) is a rapid decline in glomerular filtration rate resulting in nitrogenous waste accumulation. The KDIGO guidelines standardize AKI staging: Stage 1 is a serum creatinine (Cr) rise of 1.5–1.9 times baseline (or ≥0.3 mg/dL within 48 hours) or urine output (UO) <0.5 mL/kg/h for 6–12 hours. Stage 2 is a serum Cr increase of 2.0–2.9 times baseline or UO <0.5 mL/kg/h for ≥12 hours. Stage 3 is a serum Cr increase of ≥3.0 times baseline, a Cr increase to ≥4.0 mg/dL, initiation of renal replacement therapy (RRT), or UO <0.3 mL/kg/h for ≥24 hours (or anuria for ≥12 hours).
The diagnostic workup begins by categorizing AKI into prerenal, intrinsic, or postrenal etiologies.
Prerenal AKI arises from renal hypoperfusion without structural parenchymal damage. Key causes include hypovolemia (hemorrhage, GI losses), decreased effective circulating volume (heart failure, cirrhosis), and hemodynamically mediated impairment (NSAIDs constricting the afferent arteriole, or ACE inhibitors/ARBs dilating the efferent arteriole). Diagnostic indicators include a fractional excretion of sodium (FeNa) < 1%, a fractional excretion of urea (FeUrea) < 35% (highly useful in patients receiving loop diuretics), urine sodium < 20 mEq/L, high urine osmolarity (>500 mOsm/kg), and a Blood Urea Nitrogen (BUN) to creatinine ratio > 20:1. Urinalysis typically reveals benign hyaline casts. Management focuses on restoring renal perfusion via isotonic crystalloids, optimizing cardiac output, and discontinuing offending drugs.
Intrinsic AKI involves structural damage to the renal parenchyma, subclassified into tubular, interstitial, glomerular, or vascular diseases. Acute Tubular Necrosis (ATN) is the most common cause in hospitalized patients, precipitated by ischemic or toxic injuries. Exogenous nephrotoxins include aminoglycosides, cisplatin, amphotericin B, and radiocontrast media. Endogenous toxins include myoglobin from rhabdomyolysis. Laboratory findings in ATN show a FeNa > 2% (FeUrea > 50%), urine sodium > 40 mEq/L, urine osmolarity < 350 mOsm/kg, and a BUN to creatinine ratio of 10–15:1. Urinalysis characteristically reveals "muddy brown" granular casts. Treatment is supportive, focusing on fluid balance and avoiding nephrotoxins.
Acute Interstitial Nephritis (AIN) is an immunologically mediated inflammatory infiltration of the renal interstitium, typically drug-induced (beta-lactams, cephalosporins, sulfonamides, NSAIDs, proton pump inhibitors). The classic triad of fever, rash, and eosinophilia is rare. Urinalysis demonstrates sterile pyuria, white blood cell casts, and eosinophiluria. Management relies on drug discontinuation; systemic corticosteroids may be initiated if kidney function fails to improve within several days.
Glomerulonephritis presents with hematuria, dysmorphic red blood cells, RBC casts, variable proteinuria, and hypertension. Diagnostics require serological workup (complements, ANA, ANCA, anti-GBM) and renal biopsy.
Postrenal AKI results from mechanical obstruction of urine outflow (BPH, neurogenic bladder, bilateral nephrolithiasis, pelvic tumors). Renal ultrasound is the initial imaging of choice, demonstrating hydronephrosis. Management necessitates urgent decompression via Foley or suprapubic catheter for lower tract obstruction, and ureteral stents or percutaneous nephrostomy tubes for upper tract obstruction. Following relief of obstruction, clinicians must monitor for post-obstructive diuresis. Severe cases require replacing 50% of hourly urine output with 0.45% saline to avoid volume depletion.
Indications for Emergent Renal Replacement Therapy
In the acute setting, the decision to initiate emergent hemodialysis is guided by clinical and laboratory parameters, summarized by the "AEIOU" mnemonic:
- Acidemia: Severe metabolic acidosis (pH < 7.1) refractory to medical therapy.
- Electrolytes: Severe, refractory hyperkalemia (K > 6.5 mEq/L) or rising levels with associated ECG changes (peaked T waves, QRS widening).
- Intoxication: Ingestion of dialyzable toxins (methanol, ethylene glycol, lithium, salicylates, theophylline).
- Overload: Volume overload (pulmonary edema) refractory to high-dose diuretics.
- Uremia: Symptomatic uremia (pericarditis, encephalopathy, neuropathy, or uremic bleeding due to platelet dysfunction).
Chronic Kidney Disease: Complications and Management
Chronic kidney disease (CKD) management focuses on slowing progression and treating complications. Anemia of CKD results from impaired erythropoietin production. Clinicians must first rule out and treat iron deficiency. Iron stores are assessed via transferrin saturation (TSAT) and serum ferritin; iron repletion is indicated if TSAT is ≤ 30% and ferritin is ≤ 500 ng/mL. Once iron is optimized, erythropoiesis-stimulating agents (ESAs) are initiated if hemoglobin (Hb) falls below 10 g/dL, targeting a range of 10.0–11.0 g/dL. Exceeding 11.0 g/dL increases the risk of stroke, venous thromboembolism, and cardiovascular events.
Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) pathophysiology begins with phosphate retention due to declining GFR. Hyperphosphatemia directly stimulates parathyroid hormone (PTH) secretion and binds free ionized calcium, causing hypocalcemia. Simultaneously, loss of renal mass impairs 1-alpha-hydroxylase activity, reducing active 1,25-dihydroxyvitamin D (calcitriol) and decreasing intestinal calcium absorption. The combination of hypocalcemia, hyperphosphatemia, and low calcitriol stimulates the parathyroid glands to hyper-secrete PTH, causing secondary hyperparathyroidism.
Treatment is stepwise: dietary phosphate restriction (800–1000 mg/day) and phosphate binders. Calcium-based binders (calcium acetate or calcium carbonate) are used if calcium is normal; non-calcium-based binders (sevelamer carbonate or lanthanum carbonate) are preferred if hypercalcemia or vascular calcification is present. Active vitamin D analogs (calcitriol, paricalcitol, doxercalciferol) are administered to suppress PTH once phosphate is controlled. Calcimimetics (cinacalcet) increase the sensitivity of parathyroid calcium-sensing receptors, reducing PTH without elevating calcium or phosphorus levels.
A 62-year-old man with a history of hypertension and osteoarthritis is admitted for acute onset of oliguria, fever, and a generalized maculopapular rash. Ten days ago, he was started on cephalexin for a mild skin infection. His current medications also include ibuprofen, which he takes daily for joint pain. Laboratory studies show a serum creatinine of 3.2 mg/dL (baseline 1.0 mg/dL). Urinalysis reveals sterile pyuria, mild proteinuria, and white blood cell casts. Eosinophiluria is noted on Hansel stain. What is the most appropriate next step in management?
A 54-year-old woman with stage 4 chronic kidney disease (eGFR 22 mL/min/1.73m2) presents to the clinic for routine follow-up. Her hemoglobin is 9.2 g/dL (previously 9.8 g/dL). She reports mild fatigue but no shortness of breath, chest pain, or dark stools. Iron studies reveal a transferrin saturation (TSAT) of 18% and a serum ferritin of 120 ng/mL. What is the most appropriate next step in the management of her anemia?
A 48-year-old man with end-stage kidney disease on maintenance hemodialysis is admitted with severe shortness of breath and orthopnea. He missed his last two dialysis sessions. His blood pressure is 185/104 mmHg, heart rate is 108/min, and oxygen saturation is 88% on a non-rebreather mask. Physical examination reveals diffuse bilateral crackles and 3+ lower extremity edema. Laboratory studies show a potassium of 6.2 mEq/L and a bicarbonate of 16 mEq/L. Electrocardiogram shows sinus tachycardia without peaked T waves or QRS widening. Which of the following is the most appropriate immediate management?