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Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), and Dialysis

Sources: Harrison's Principles of Internal Medicine 22E, Brenner and Rector's The Kidney, Comprehensive Clinical Nephrology 7th Edition, Fischer's Mastery of Surgery 8th Edition, Textbook of Family Medicine 9e

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Part 1: Acute Kidney Injury (AKI)

Definition

• A rise in serum creatinine (SCr) ≥0.3 mg/dL within 48 hours, OR
• A rise in SCr to ≥1.5× baseline within 7 days, OR
• Urine output <0.5 mL/kg/h for ≥6 hours

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Staging (KDIGO / AKIN / RIFLE)

• Brenner and Rector's The Kidney, Table 29.2

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Etiology and Classification

1. Prerenal Azotemia (most common)

• Results from inadequate renal plasma flow and reduced intraglomerular hydrostatic pressure
• Common causes: hypovolemia, decreased cardiac output (CHF, liver failure), medications impairing renal autoregulation (NSAIDs, ACE inhibitors, ARBs, cyclosporine)
• No parenchymal damage - rapidly reversible when perfusion restored
• Prolonged prerenal state -> ischemic tubular injury -> ATN
• Autoregulatory mediators involved: angiotensin II, norepinephrine, vasopressin, prostaglandins (prostacyclin, PGE2), nitric oxide
• Note: SGLT-2 inhibitors do not appear to increase AKI risk and may have a protective effect
• Harrison's Principles of Internal Medicine 22E, Ch. 321

2. Intrinsic Renal AKI

• Tubular (ATN): ischemia or nephrotoxins (aminoglycosides, cisplatin, contrast, amphotericin B, PPIs, NSAIDs, immune checkpoint inhibitors)
  • Exogenous: iodinated contrast, cisplatin, aminoglycosides, amphotericin B
  • Endogenous: hemolysis, rhabdomyolysis, myeloma, intratubular crystals
  • SCr rise with aminoglycosides/cisplatin is characteristically delayed 3-5 days to 2 weeks
• Glomerular: acute glomerulonephritis
• Vascular: vasculitis, malignant hypertension, TTP-HUS
• Interstitial: acute interstitial nephritis (AIN) - drug-induced allergic reaction

3. Postrenal (Obstructive)

• Bladder outlet obstruction (benign prostatic hyperplasia most common in men)
• Bilateral pelvoureteral obstruction (or unilateral if solitary functioning kidney)
• Brenner and Rector's The Kidney, PATHOPHYSIOLOGY section

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Evaluation

• Volume status: orthostatic hypotension, JVP, mucous membrane dryness
• Drug history: NSAIDs, diuretics, ACE-I/ARBs, contrast agents
• Review of prior creatinine trends

• Brenner and Rector's The Kidney, Table 29.4

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Management

Prerenal AKI

• IV fluid resuscitation for hypovolemia (normal saline or balanced crystalloids)
• Discontinue NSAIDs, ACE-I, ARBs
• Optimize cardiac output in heart failure
• Hepatorenal syndrome: terlipressin (or norepinephrine) + midodrine + IV albumin (25-50 g, max 100 g/day)

Intrinsic AKI

• ATN: supportive care - no agent has proven efficacy (atrial natriuretic peptide, dopamine, erythropoietin, endothelin antagonists, growth factors all failed in trials)
• Glomerulonephritis/vasculitis: immunosuppressants, anti-complement therapy, plasmapheresis
• Allergic interstitial nephritis: stop offending drug; glucocorticoids used (not RCT-proven)
• Scleroderma renal crisis: ACE inhibitors
• TTP: plasma exchange (medical emergency); atypical HUS: complement blockade (eculizumab)
• Rhabdomyolysis: early aggressive volume repletion (up to 10 L/day); alkaline fluids (75 mmol/L NaHCO3 in 0.45% saline) to alkalinize urine and prevent cast formation

Postrenal AKI

• Bladder catheterization for urethral/bladder outlet obstruction
• Percutaneous nephrostomy or ureteric stent for ureteral obstruction
• Post-obstructive diuresis expected after relief; monitor and replace fluids/electrolytes

Supportive measures

• Volume management: restrict fluid/Na; loop diuretics (furosemide bolus 200 mg then IV drip 10-40 mg/h ± thiazide); no evidence that forced diuresis changes AKI natural history
• Hyperkalemia: calcium gluconate (cardiac protection), insulin/dextrose, sodium bicarbonate, kayexalate - then dialysis if refractory
• Nutrition: avoid protein restriction; standard enteral nutrition preferred
• Harrison's Principles of Internal Medicine 22E, Ch. 321

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Part 2: Chronic Kidney Disease (CKD)

Definition

• Textbook of Family Medicine 9e, Ch. 40

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Staging (GFR-based)

• Cockcroft-Gault: CrCl = [(140 - age) × weight] / (72 × SCr), ×0.85 if female
• MDRD: GFR = 1.86 × (SCr)^-1.154 × (age)^-0.203 × 0.742 (female) × 1.210 (Black)
• Modern clinical practice uses CKD-EPI (not shown in older textbook editions)

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Causes / Risk Factors

1. Diabetic nephropathy (most common in developed world)
2. Hypertension (hypertensive nephrosclerosis)
3. Glomerulonephritis (IgA nephropathy, FSGS, membranous, lupus)
4. Polycystic kidney disease (autosomal dominant)
5. Obstructive uropathy
6. Repeated episodes of AKI -> CKD progression
7. HIV-associated nephropathy (associated with APOL1 variants)

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Complications by Stage

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Management

• BP control: target <130/80 mmHg; ACE inhibitors or ARBs first-line in proteinuric CKD (reduce intraglomerular pressure and proteinuria)
• Glycemic control in diabetics (HbA1c ~7%)
• SGLT-2 inhibitors (e.g., empagliflozin, dapagliflozin) - now a pillar of CKD management in diabetic and non-diabetic CKD; reduces progression and cardiovascular events
• Protein restriction: 0.6-0.8 g/kg/day in later stages
• Avoid nephrotoxins, NSAIDs, contrast without prehydration
• Smoking cessation

• Anemia: erythropoiesis-stimulating agents (ESAs: epoetin alfa, darbepoetin); IV iron supplementation; target Hb 10-12 g/dL
• CKD-MBD (mineral-bone disease): phosphate binders (calcium carbonate, sevelamer, lanthanum), vitamin D analogs (calcitriol), calcimimetics (cinacalcet)
• Metabolic acidosis: sodium bicarbonate supplementation (target serum bicarb >22 mmol/L)
• Hyperkalemia: dietary K restriction, patiromer or sodium zirconium cyclosilicate (ZS-9)
• Hypertension/volume: loop diuretics, salt restriction
• Dyslipidemia: statins (though benefit in dialysis patients not clearly established)

• Early referral to nephrology (GFR <30)
• AV fistula placement at least 6 months before anticipated dialysis start
• Peritoneal dialysis catheter placement 4-6 weeks before start
• Renal transplant evaluation (preferred modality if eligible)

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Part 3: Dialysis

Indications for Renal Replacement Therapy (RRT)

1. Volume overload unresponsive to diuretic therapy (most common indication in AKI)
2. Persistent hyperkalemia despite medical therapy
3. Severe metabolic acidosis
4. Overt uremic symptoms: encephalopathy, pericarditis (late, urgent sign; can progress to tamponade), uremic bleeding diathesis

• Progressive azotemia without uremic manifestations
• Persistent oliguria
• BUN >60-100 mg/dL (no hard threshold; initiation before profound uremia is preferred)

"Uremic pericarditis can progress to tamponade if hemorrhage is seen. It is best to initiate RRT with elevated circulating nitrogen levels before clinical evidence of profound uremia." - Fischer's Mastery of Surgery 8e

Transplantation is a form of RRT for ESKD but plays no role in AKI management. - Brenner and Rector's The Kidney, block 16

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Principles of Dialysis

1. Ultrafiltration: Water and solutes cross a semipermeable membrane via a transmembrane pressure gradient. Rate depends on membrane surface area, transmembrane pressure, and membrane permeability.
2. Diffusion: Solutes move from high to low concentration. Dialysate runs countercurrent to blood. The dialysate composition is adjusted to the patient's electrolytes (e.g., potassium in dialysate lower than plasma -> potassium moves out of blood).
3. Convection: Solutes are dragged through the membrane with water (solvent drag). Pore size of the membrane determines which solutes can pass (important for larger "middle molecules").

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Modalities Comparison

• Fischer's Mastery of Surgery 8e, p. 226-227; Comprehensive Clinical Nephrology 7e, Ch. 95

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Hemodialysis (HD)

• Blood is pumped through an extracorporeal circuit at 300-500 mL/min, across a semipermeable dialyzer membrane
• Dialysate flows countercurrent at 500-800 mL/min
• Vascular access: AV fistula (preferred) > AV graft > central venous catheter (CVC; highest infection risk)
• AV fistula should be created ≥6 months before anticipated dialysis start
• Standard dose: Kt/V ≥1.2 per session (K = urea clearance, t = time, V = volume of distribution)
• Complications: hypotension (most common), muscle cramps, disequilibrium syndrome, infection (CVC-related bacteremia), cardiovascular events

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Peritoneal Dialysis (PD)

• Uses the peritoneal membrane as the dialyzer
• Dialysate (glucose-based) is instilled into the peritoneal cavity and drained after a dwell time
• CAPD (continuous ambulatory PD): 4 manual exchanges/day
• APD (automated PD): overnight machine cycling
• Advantages: home-based, preserves residual renal function longer, no vascular access needed, better hemodynamic stability, superior health-related quality of life
• PD preferred as first choice in Hong Kong (75% of prevalent dialysis) unless absolute contraindications
• Technique failure causes: infection (peritonitis), mechanical problems, inadequate dialysis, social reasons
• Late technique failure primarily due to social factors; infection-related failure carries higher short-term mortality (mainly cardiac)
• Comprehensive Clinical Nephrology 7e, Ch. 95

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CRRT (Continuous Renal Replacement Therapy)

• Runs 24 hours/day at low blood flow rates (100-200 mL/min)
• Preferred in hemodynamically unstable ICU patients
• Subtypes:
  • CVVH (continuous veno-venous hemofiltration) - convection only
  • CVVHD (continuous veno-venous hemodialysis) - diffusion only
  • CVVHDF (continuous veno-venous hemodiafiltration) - both
• Requires continuous anticoagulation (heparin or citrate)
• Less effective at rapid solute removal vs. iHD, but causes far less hemodynamic perturbation
• No evidence that CRRT is superior to iHD for survival in AKI

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Timing of RRT in AKI: Early vs. Late

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Choice of Dialysis Modality for ESKD

• Preference for home therapy
• Remote location / limited HD access
• Residual renal function to preserve
• Better QoL reported
• Vascular access difficulties

• Prior abdominal surgery / adhesions (relative contraindication to PD)
• Active IBD / abdominal hernias (relative contraindication to PD)
• Poor manual dexterity or social support (can't manage PD exchanges)
• Severe protein-energy malnutrition (PD causes protein loss)

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AKI to CKD Progression

• Incomplete tubular repair -> fibrosis and tubular atrophy
• ET-1/ET-A receptor upregulation after transient ischemia drives progressive injury
• ET-A receptor antagonism (but not ET-B) prevents progressive kidney injury in animal models - Brenner and Rector's The Kidney, block 6

• Aggressive early AKI management
• Avoiding nephrotoxin re-exposure after recovery
• Long-term nephrology follow-up after AKI episodes (SCr checks at 3 and 12 months)

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Quick Reference Summary