Learning Objectives

By the end of this chapter, learners will be able to:
– Describe the epidemiology, definitions, and staging of acute kidney injury (AKI) in the ICU.
– Identify common causes and pathophysiologic mechanisms of AKI in critical illness.
– Apply a structured diagnostic approach to AKI, including urine microscopy and pragmatic use of indices and biomarkers.
– Implement hemodynamic optimization and fluid strategies that balance resuscitation with avoidance of fluid overload.
– Select and tailor renal replacement therapy (RRT) modalities, dosing, anticoagulation, and access in critically ill adults.
– Recognize and manage key electrolyte and acid–base disorders in the ICU, including safe correction limits.
– Adjust drug dosing in fluctuating renal function and during RRT, using therapeutic drug monitoring where available.
– Anticipate complications, monitor recovery, and plan transitions of care after critical illness–associated AKI.

30.1 Epidemiology, Definitions, and Staging of AKI in Critical Illness

• AKI affects approximately one-third to one-half of ICU patients; a substantial minority require RRT. It is independently associated with increased morbidity, mortality, and long-term CKD risk.
• AKI is defined by an acute rise in serum creatinine (SCr) and/or a reduction in urine output (UO). Staging commonly incorporates:
• SCr increase from baseline within 48 hours or over 7 days.
• UO thresholds over defined time periods (e.g., <0.5 mL/kg/h for ≥6 hours).
• Limitations in the ICU:
• SCr is a delayed and dilution-sensitive marker (hemodilution from fluids, reduced creatinine generation from low muscle mass).
• Baseline SCr is often unknown; trend and clinical context are critical.
• UO is sensitive but nonspecific; oliguria may reflect hypovolemia, obstruction, or intrinsic injury.

30.2 Etiologies and Pathophysiology of AKI in Critical Illness

• Sepsis-associated AKI: systemic inflammation, endothelial injury, microcirculatory dysfunction, altered tubular energetics, and hemodynamic changes.
• Hemodynamic/ischemic injury: hypovolemia, vasodilation, cardiogenic shock; prolonged insult progresses from prerenal azotemia to acute tubular injury.
• Nephrotoxic exposures: aminoglycosides, vancomycin, amphotericin B, calcineurin inhibitors, NSAIDs, iodinated contrast, chemotherapeutics.
• Cardiorenal interactions: venous congestion and reduced forward flow impair renal perfusion.
• Abdominal compartment syndrome: intra-abdominal pressure ≥20 mmHg with organ dysfunction reduces renal blood flow and GFR.
• Rhabdomyolysis: myoglobin-mediated tubular toxicity and obstruction; volume depletion and acidosis exacerbate injury.
• Other ICU contributors: pancreatitis, liver failure, tumor lysis syndrome, thrombotic microangiopathy, atheroembolism, obstruction (catheter malposition, prostatic enlargement).

30.3 Diagnostic Approach

• History and examination: fluid balance, hemodynamics, medications (including recent contrast), systemic illness, obstructive symptoms, bladder scan.
• Laboratory testing:
• Serum: electrolytes, bicarbonate, anion gap, lactate, CK (rhabdomyolysis), uric acid (tumor lysis), drug levels where applicable.
• Urinalysis and microscopy:
  • Muddy brown granular casts: acute tubular injury.
  • RBCs/RBC casts: glomerulonephritis; dysmorphic RBCs suggest glomerular source.
  • WBCs/WBC casts ± eosinophils: interstitial nephritis (nonspecific).
  • Crystals: oxalate (toxic alcohol), uric acid (tumor lysis), drug-related crystals.
• Indices:
  • Fractional excretion of sodium (FENa) and urea (FEUrea) can aid differentiation but are confounded by diuretics, sepsis, and CKD; interpret cautiously.
• Imaging: kidney ultrasound to exclude obstruction and assess size/echogenicity; Doppler if vascular concern.
• Biomarkers: NGAL, KIM-1, and [TIMP-2]•[IGFBP7] may detect stress/injury earlier than SCr; their routine use varies by institution and availability.

30.4 Hemodynamic Optimization and Fluid Management

• Initial resuscitation:
• Use isotonic crystalloids; balanced crystalloids are generally favored over high-chloride solutions to reduce hyperchloremic acidosis and potential renal vasoconstriction.
• Assess fluid responsiveness dynamically (e.g., passive leg raise, stroke volume variation) rather than by static pressures.
• Vasopressors and inotropes:
• Target a mean arterial pressure (MAP) commonly around 65 mmHg, individualized to chronic hypertension and organ perfusion.
• Norepinephrine is first-line in distributive shock; vasopressin can be added to reduce catecholamine dose. Consider inotropes (e.g., dobutamine) in cardiogenic shock.
• De-resuscitation:
• After stabilization, avoid positive cumulative balance. Use diuretics for congestion if responsive; consider RRT for refractory fluid overload.
• Diuretics:
• Do not treat AKI per se; use to manage volume overload. High-dose loop diuretics may be required in reduced GFR; monitor for ototoxicity and electrolyte losses.
• Furosemide stress test (FST): 1–1.5 mg/kg IV (higher if prior exposure). Low 2-hour urine output after FST predicts progression and may inform RRT planning; not a standalone indication.
• Abdominal compartment:
• Measure bladder pressure if suspected; manage with evacuation of intra-abdominal contents, optimizing abdominal perfusion pressure, and surgical decompression when indicated.

30.5 Renal Replacement Therapy (RRT) in the ICU

• Indications (A–E–I–O–U), generally when refractory to medical management:
• Acidosis: severe metabolic acidemia with hemodynamic compromise.
• Electrolyte: life-threatening hyperkalemia or other critical derangements.
• Intoxications: selected dialyzable toxins (e.g., lithium, salicylates, methanol, ethylene glycol) in consultation with toxicology/nephrology.
• Overload: pulmonary edema or right heart strain not responsive to diuretics.
• Uremia: complications such as pericarditis, encephalopathy, refractory bleeding.
• Timing:
• Initiation is individualized; clear indications warrant prompt therapy. In equivocal cases, early vs delayed strategies should consider trajectory, catabolic state, and complications risk.
• Modalities:
• Intermittent hemodialysis (IHD): rapid solute/volume removal; higher risk of intradialytic hypotension in unstable patients.
• Continuous RRT (CRRT): CVVH (convection), CVVHD (diffusion), CVVHDF (combined). Preferred for hemodynamic instability or severe fluid management needs.
• Sustained low-efficiency dialysis (SLED): prolonged intermittent treatments (6–12 h) with improved tolerability vs IHD.
• Peritoneal dialysis (PD): option in resource-limited settings or select patients; less common in adult ICUs.
• Dose and fluid management:
• For CRRT, target a delivered effluent dose approximately 20–25 mL/kg/h. Higher doses have not shown mortality benefit and increase electrolyte/protein losses.
• Prescribe and monitor net ultrafiltration (UFNET) rates according to hemodynamics and congestion (e.g., 0–200 mL/h commonly), reassessing frequently.
• Anticoagulation:
• Regional citrate anticoagulation reduces filter clotting and bleeding risk and is often preferred if citrate metabolism is adequate.
• Systemic heparin is an alternative; consider no anticoagulation in high bleeding risk with acceptance of shorter filter life.
• Vascular access:
• Non-tunneled double-lumen dialysis catheters for acute therapy.
• Right internal jugular is typically preferred; femoral is acceptable (especially in coagulopathy), with careful infection prevention; avoid subclavian due to stenosis risk in those with potential future fistula needs.
• Complications:
• Hemodynamic instability (especially with IHD), hypothermia, bleeding (from anticoagulation), catheter-related bloodstream infection, circuit clotting.
• Electrolyte and nutrient losses during CRRT: hypophosphatemia, hypomagnesemia, water-soluble vitamins, amino acids—anticipate and replace.

30.6 Electrolyte and Acid–Base Disturbances in Critical Illness

• Hyperkalemia:
• Stabilize myocardium (IV calcium for ECG changes), shift K+ intracellularly (insulin/glucose; beta-agonists), remove K+ (loop diuretics if responsive, cation exchangers, RRT).
• Recheck potassium and glucose frequently; manage precipitating causes.
• Hypokalemia:
• Replace enterally when possible; IV replacement if severe or symptomatic. Correct concomitant magnesium deficiency.
• Hyponatremia:
• Define chronicity and symptoms. For severe symptoms, administer hypertonic saline boluses and reassess.
• Limit correction to generally ≤8 mEq/L per 24 hours (lower targets in high-risk patients such as malnutrition, liver disease, alcoholism); frequent monitoring and use of desmopressin may be required to prevent overcorrection.
• Hypernatremia:
• Calculate free water deficit; correct gradually to avoid cerebral edema. Common targets are ≤10–12 mEq/L per 24 hours (slower if chronic).
• Metabolic acidosis:
• Treat underlying cause. Consider bicarbonate for severe acidemia with hemodynamic compromise or hyperkalemia; ventilation must permit CO2 elimination. RRT for refractory cases.
• Metabolic alkalosis:
• Address volume/chloride depletion (isotonic fluids), stop causative diuretics if feasible, replace potassium and chloride, consider acetazolamide in volume-overloaded alkalemia.

30.7 Drug Dosing and Pharmacotherapy

• Estimating renal function:
• Creatinine-based equations are unreliable in dynamic AKI. Consider trends, urine output, timed urine creatinine clearance where feasible, and clinical judgment.
• Principles:
• Loading doses often unchanged or increased (expanded volume of distribution).
• Maintenance doses adjusted to renal function and RRT clearance; reassess daily or more frequently.
• Use therapeutic drug monitoring for narrow-index agents (e.g., vancomycin AUC-based approaches, aminoglycosides); consider beta-lactam TDM where available.
• RRT-specific considerations:
• Drug removal depends on modality, filter, protein binding, and effluent dose. CRRT often requires higher maintenance dosing than anuric non-dialysis states.

30.8 Special Situations

• Rhabdomyolysis:
• Early volume resuscitation to maintain urine output; avoid hyperchloremic acidosis. Consider urine alkalinization selectively; evidence is mixed. Monitor K+, Ca2+, and phosphorus.
• Initiate RRT for standard indications; myoglobin itself is not a sole indication.
• Tumor lysis syndrome:
• Aggressive prevention and monitoring; manage hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia; RRT for refractory or severe derangements.
• Hepatorenal physiology:
• Vasodysregulation and low effective arterial blood volume; albumin infusions and vasoconstrictors may be used under specialist guidance; avoid nephrotoxins.
• Cardiorenal syndrome:
• Venous decongestion is central; adjust UFNET prudently, consider right ventricular function.
• Intoxications:
• For dialyzable toxins, consult toxicology/nephrology for modality selection and end points of therapy.

30.9 Monitoring, Recovery, and Follow-up

• Daily reassessment:
• Indications for RRT, hemodynamics, fluid balance, electrolytes, acid–base status, and medication dosing.
• Nutrition:
• Provide adequate protein (commonly 1.3–1.7 g/kg/day in critical illness; higher needs during CRRT due to losses), with dietitian input.
• Avoid further injury:
• Review and minimize nephrotoxins, ensure appropriate contrast precautions, maintain glycemic control, and prevent catheter complications.
• Post-ICU:
• Monitor for kidney recovery or progression to CKD; arrange follow-up, medication reconciliation, and patient education.

SUMMARY

• AKI is common in the ICU and arises from multifactorial insults including sepsis, hemodynamic instability, and nephrotoxins; both SCr and UO have limitations in this setting.
• Diagnosis relies on clinical context, urine microscopy, cautious interpretation of fractional excretion indices, and selective use of biomarkers and imaging.
• Hemodynamic optimization includes balanced crystalloids for resuscitation, early vasopressor support to an individualized MAP, and timely de-resuscitation to avoid fluid overload.
• RRT should be initiated promptly for clear indications (A–E–I–O–U); modality and dose are tailored to hemodynamic status and goals, with CRRT often preferred in instability and a delivered effluent dose around 20–25 mL/kg/h.
• Expect and proactively manage CRRT-associated electrolyte and nutrient losses; choose vascular access sites that balance efficacy and future dialysis needs.
• Manage electrolyte and acid–base disorders with attention to safe correction limits; use RRT for refractory derangements.
• Drug dosing in AKI and during RRT requires frequent reassessment, understanding of pharmacokinetics, and therapeutic drug monitoring when available.
• Plan for recovery and long-term kidney health after critical illness.

CLINICAL PEARLS

• Urine output trends are often the earliest signal of AKI; intervene before SCr rises.
• Urine microscopy adds actionable information rapidly at the bedside.
• FENa and FEUrea are frequently misleading in sepsis or with diuretics; integrate with the whole clinical picture.
• After initial resuscitation, a neutral or negative fluid balance generally improves outcomes; reassess volume status daily.
• In distributive shock, earlier vasopressor use to achieve target MAP may reduce unnecessary fluid loading.
• CRRT offers better hemodynamic tolerability than IHD; SLED can be a practical alternative where CRRT is unavailable.
• During CRRT, monitor phosphate and magnesium at least daily and replace proactively.
• Regional citrate anticoagulation extends filter life and reduces bleeding but requires monitoring of ionized calcium and acid–base status.
• Right internal jugular is the preferred acute dialysis catheter site in most adults; avoid subclavian when long-term access may be needed.
• Revisit all medication doses daily; assume kidney function is changing until proven otherwise.

VISUAL MATERIALS

• Flowchart: Diagnostic approach to AKI in the ICU (history, labs, urine microscopy, imaging, decision nodes for obstruction vs intrinsic vs hemodynamic).
• Table: Comparison of RRT modalities (IHD, SLED, CVVH, CVVHD, CVVHDF) with pros/cons, typical settings, hemodynamic impact, and indications.
• Diagram: Pathophysiology of sepsis-associated AKI (inflammation, microcirculation, tubular stress).
• Algorithm: Fluid management across resuscitation, optimization, and de-resuscitation phases; integration of vasopressors and diuretics.
• Checklist: Safe correction targets for sodium disorders and common ICU electrolyte replacement strategies.
• Table: CRRT prescription elements (access, modality, dose, anticoagulation, UFNET, monitoring).

MULTIPLE CHOICE QUESTIONS

1) In a hemodynamically unstable patient with septic shock and oliguric AKI, which RRT modality is most appropriate initially?
A) Intermittent hemodialysis (IHD)
B) Continuous venovenous hemodiafiltration (CVVHDF)
C) Peritoneal dialysis (PD)
D) Hemoperfusion only

Answer: B) Continuous venovenous hemodiafiltration (CVVHDF)
Explanation: CRRT modalities (e.g., CVVHDF) provide gradual solute and fluid removal, improving hemodynamic tolerability in unstable patients.

2) Which statement about fluid therapy in the ICU is most accurate regarding kidney protection?
A) Hyperoncotic starch solutions reduce AKI risk
B) Balanced crystalloids may reduce hyperchloremic acidosis compared with high-chloride saline
C) Colloids are preferred to crystalloids for initial resuscitation in all patients
D) Hypotonic fluids are recommended for initial resuscitation

Answer: B) Balanced crystalloids may reduce hyperchloremic acidosis compared with high-chloride saline
Explanation: Balanced crystalloids are generally favored in initial resuscitation to limit chloride load and acid–base disturbances.

3) A patient with severe AKI has K+ 7.0 mEq/L and ECG changes despite temporizing measures. Which is the strongest indication for urgent RRT?
A) Elevated BUN alone
B) Severe hyperkalemia refractory to medical therapy
C) Anemia
D) Mild metabolic alkalosis

Answer: B) Severe hyperkalemia refractory to medical therapy
Explanation: Life-threatening hyperkalemia refractory to medical management is a classic indication for urgent RRT.

4) Regarding CRRT dosing in severe AKI, which prescription target is most appropriate in adults?
A) Effluent 10 mL/kg/h delivered
B) Effluent 20–25 mL/kg/h delivered
C) Effluent 35–40 mL/kg/h delivered for all
D) No need to specify dose; machines auto-adjust

Answer: B) Effluent 20–25 mL/kg/h delivered
Explanation: A delivered effluent dose around 20–25 mL/kg/h achieves adequate clearance without excess losses; higher routine doses have not improved outcomes.

5) Which scenario most strongly supports hypertonic saline bolus therapy for hyponatremia?
A) Chronic asymptomatic Na+ 127 mEq/L
B) Acute symptomatic hyponatremia with seizures
C) Hypernatremia with confusion
D) Mild chronic hyponatremia in stable outpatient

Answer: B) Acute symptomatic hyponatremia with seizures
Explanation: Severe symptomatic hyponatremia warrants prompt hypertonic saline to control cerebral edema, followed by careful correction limits.

6) Which bedside test helps predict progression of AKI and potential RRT need but is not itself an indication for dialysis?
A) Furosemide stress test (FST)
B) FEUrea <35%
C) Plasma NGAL level
D) Renal ultrasound

Answer: A) Furosemide stress test (FST)
Explanation: Low urine output after a standardized furosemide dose predicts progression; decisions still require clinical integration.

7) For acute dialysis catheter placement in an adult with potential future need for long-term access, the preferred site is:
A) Right internal jugular vein
B) Left subclavian vein
C) Femoral vein in all cases
D) External jugular vein

Answer: A) Right internal jugular vein
Explanation: Right IJ provides reliable flow and minimizes risk of central venous stenosis that could jeopardize future access; subclavian sites are generally avoided.

8) During CRRT with regional citrate anticoagulation, which parameter requires routine monitoring to ensure safety?
A) Serum ammonia only
B) Ionized calcium pre- and post-filter
C) Serum ferritin
D) Procalcitonin

Answer: B) Ionized calcium pre- and post-filter
Explanation: Citrate chelates calcium; monitoring ionized calcium ensures adequate anticoagulation and systemic safety.

9) Which of the following is the safest general limit for sodium correction in a high-risk patient with chronic severe hyponatremia?
A) 2 mEq/L per 24 hours
B) 6 mEq/L per 24 hours
C) 12–15 mEq/L per 24 hours
D) No limit if asymptomatic

Answer: B) 6 mEq/L per 24 hours
Explanation: In high-risk patients, more conservative limits (around 4–6 mEq/L per 24 h) reduce the risk of osmotic demyelination.

10) Which CRRT-associated abnormality is commonly overlooked and should be proactively replaced?
A) Hyperphosphatemia
B) Hypophosphatemia
C) Hypermagnesemia
D) Hypernatremia

Answer: B) Hypophosphatemia
Explanation: CRRT removes phosphate and magnesium, often causing hypophosphatemia that requires scheduled replacement.

POWERPOINT PRESENTATION

Slide 1: Nephrology in Critical Care – Setting the Stage
– AKI is common in the ICU and impacts outcomes
– Goals: diagnose early, optimize hemodynamics, tailor RRT, prevent complications

Slide 2: Definitions and Staging of AKI
– SCr and UO criteria; pitfalls in the ICU
– Creatinine lag and dilution effects; use trends

Slide 3: Etiologies and Pathophysiology
– Sepsis, hemodynamic injury, nephrotoxins, congestion, rhabdomyolysis
– Microcirculatory and tubular mechanisms

Slide 4: Diagnostic Strategy
– Focused history/exam; urinalysis and microscopy
– Cautious use of FENa/FEUrea; role of ultrasound and selective biomarkers

Slide 5: Hemodynamic Optimization and Fluids
– Balanced crystalloids; dynamic assessments
– Early vasopressors; de-resuscitation and diuretics; FST as a prognostic tool

Slide 6: RRT Indications and Timing
– A–E–I–O–U framework; initiate when refractory to medical therapy
– Individualize timing based on trajectory and complications

Slide 7: Choosing and Dosing RRT
– IHD vs SLED vs CRRT; when to choose each
– CRRT dose (20–25 mL/kg/h delivered) and UFNET targets

Slide 8: Anticoagulation and Access
– Regional citrate vs heparin; monitoring ionized calcium
– Preferred access sites; infection prevention

Slide 9: Electrolyte and Acid–Base Disorders
– Hyperkalemia algorithm; sodium correction limits
– Anticipate hypophosphatemia/hypomagnesemia during CRRT

Slide 10: Drug Dosing in AKI and RRT
– Loading vs maintenance; unreliable eGFR in dynamic AKI
– TDM for narrow-index drugs; RRT-specific dosing

Slide 11: Special Situations and Recovery
– Rhabdomyolysis, tumor lysis, hepatorenal/cardiorenal
– Nutrition, nephrotoxin avoidance, post-ICU follow-up

Slide 12: Key Takeaways
– Early recognition, judicious fluids, timely RRT, daily reassessment
– Prevent complications and plan for recovery

Educational disclaimer: This chapter is for educational purposes for healthcare professionals. Management should be individualized and guided by local protocols, patient-specific factors, and specialist consultation where appropriate.

Visual learning: Nephrology in Critical Care

Presentation resource: The Kidney Hub clinical-series PowerPoint for Chapters 22–30 accompanies these chapters for teaching use.