Washington Manual Summary
"Acute kidney injury (AKI) is not a single disease but rather a syndrome with multiple potential mechanisms. The prognosis of AKI is determined more by the underlying cause and associated organ dysfunction than by the degree of renal impairment itself."
Washington Manual of Critical Care, 4th Ed. (Kollef & Witt, eds.) Wolters Kluwer 2023.Clinical Synopsis
- Prevalence: Marino (Ch.34, p.586) — "As many as 60% of ICU patients experience an acute deterioration in renal function." 15% require renal replacement therapy; up to 60% mortality in severe cases.
- AKD (NEW — KDIGO 2026): AKI persisting 7 days to 3 months = Acute Kidney Disease. CKD = >3 months. New intermediate entity with different management focus.
- Leading cause: Sepsis is responsible for ~50% of all AKI in the ICU (Marino Table 34.2)
- Serum creatinine caveat (Marino insight): ICU patients lose ~2% muscle mass per day → SCr underestimates GFR reduction. "Estimates of GFR based on SCr consistently overestimate the true GFR in critically ill patients." (Marino p.587)
AKI Staging (KDIGO)
| Stage | SCr Criterion | Urine Output | Approximate Mortality |
|---|---|---|---|
| 1 | ×1.5–1.9 baseline OR rise ≥0.3 mg/dL within 48h | <0.5 ml/kg/h × 6–12h | ~10–15% |
| 2 | ×2.0–2.9 baseline | <0.5 ml/kg/h × ≥12h | ~20–30% |
| 3 | ×3.0 baseline OR SCr ≥4.0 mg/dL OR initiation of RRT | <0.3 ml/kg/h × ≥24h OR anuria ×12h | ~40–60% |
Marino Physiology — How AKI Develops
"The serum creatinine can be an unreliable marker of the GFR in critically ill patients. This has important implications not only for the evaluation of renal function, but also for the appropriate dosing of drugs based on estimates of the GFR."
Marino PL. The ICU Book, 5th Ed. Chapter 34: Acute Kidney Injury, p.587. Wolters Kluwer; 2025.Step 1 — Glomerular Filtration Pressure (Marino Fig.34.2)
GFR is determined by: Filtration Gradient = (MAP − Pv) − P_PT where Pv = renal venous/CVP pressure, P_PT = proximal tubule pressure.
This predicts that GFR falls when:
- MAP decreases (hypotension — most common)
- Venous pressure increases (CVP elevated — over-resuscitation, right heart failure)
- Proximal tubule pressure increases (obstruction, cell sloughing in ATN)
This explains why fluid overload (↑CVP) is nephrotoxic — elevated venous pressure reduces the filtration gradient.
Step 2 — Sepsis-Related AKI Mechanism
Sepsis = leading cause of AKI (~50% of ICU cases). Principal mechanism: inflammatory (oxidative) injury involving both the capillary endothelium in the glomerulus AND the epithelial lining of the renal tubules.
Acute tubular necrosis (ATN): Damaged cells slough into the renal tubule lumen → luminal obstruction → ↑ proximal tubule pressure → ↓ GFR (tubuloglomerular feedback). This creates a self-perpetuating cycle of renal injury.
Marino (p.590): Major surgery AKI in >50% after liver transplant, 18% after cardiac surgery, 13% after major abdominal surgery.
Step 3 — The Serum Creatinine Trap
Critically ill patients lose ~2% muscle mass per day → ↓ creatine production → lower SCr DESPITE worsening GFR. As a result, serum creatinine consistently overestimates GFR in ICU patients. A "normal" SCr may hide significant renal impairment.
Cystatin C advantage (Marino p.588): "Serum levels of cystatin C are not influenced by muscle mass" → more accurate in critically ill. KDIGO 2026 now includes cystatin C as a recognised AKI criterion (rise ≥1.5× baseline).
Clinical implication: Drug doses based on SCr-estimated GFR will OVERESTIMATE renal clearance → drug accumulation → toxicity. This is particularly important for: vancomycin, aminoglycosides, meropenem, enoxaparin.
Step 4 — Cardiorenal Syndrome
Heart failure and renal dysfunction: 63% of hospitalized heart failure patients have renal dysfunction (Marino, in a review of 80,000 patients). Mechanisms: ↓ CO → ↓ MAP → ↓ renal perfusion pressure; AND ↑ venous congestion → ↑ renal venous pressure → ↓ filtration gradient. Treating the cardiac failure (diuretics, vasodilators) is the primary renal intervention.
KDIGO 2026 — Key Recommendations
A. Diagnosis — New Structural Criteria
B. Fluid Management
C. AKI Biomarkers — New Recommendations
D. RRT Timing — Deferred Strategy
Drug Dosing in AKI & CRRT Prescription
CRRT Settings (CVVHDF — Standard)
- Effluent dose: Prescribe 25 ml/kg/hr (delivers ~20 ml/kg/hr net accounting for filter downtime)
- Blood flow (Qb): 150–250 ml/min
- Dialysate flow: 50% of effluent (CVVHDF)
- Pre-dilution: Preferred (reduces clotting; slightly lower clearance)
- Net UF: Set per fluid balance goal (hourly target)
- Anticoagulation: Regional citrate first choice (controls iCa 0.25–0.35 post-filter, systemic 1.1–1.35 mmol/L)
- Access: Right IJV preferred; avoid subclavian
Drug Dosing in AKI & on CRRT
| Drug | Normal Dose | AKI (eGFR <30) | On CRRT | Key Note |
|---|---|---|---|---|
| Meropenem | 1g q8h | 1g q12–24h | 1g over 3h q12h | Extended infusion recommended (SSC 2026 Strong) |
| Pip-Tazobactam | 4.5g q6h | 2.25g q6h (eGFR<20) | 4.5g over 4h q8h | Avoid with Vancomycin (synergistic nephrotoxicity) |
| Vancomycin | Weight-based q8–12h | Load 25mg/kg; monitor | Load 25mg/kg; 1g q12–24h AUC 400–600 | AUC-guided dosing; avoid with Pip-Taz |
| Fentanyl | Infusion titrated | Safe — preferred opioid | Safe | No active metabolites — first choice in AKI |
| Morphine | Infusion | AVOID | AVOID | M6G accumulates → sedation, respiratory depression |
| Enoxaparin | 40mg SC OD | Use UFH | UFH preferred | Anti-Xa accumulation in AKI |
| Metformin | 500–1000mg BD | STOP if eGFR <30 | STOP | Lactic acidosis risk |
| Colistin | 9 MIU load, 4.5 MIU q12h | Reduce 50–75% | 4.5 MIU q12h variable | Nephrotoxic; last resort; monitor SCr daily |
Anticoagulation in CRRT
| Method | First Choice? | Protocol | Monitor | Avoid If |
|---|---|---|---|---|
| Regional Citrate (RCA) | YES — first choice | Citrate pre-filter → Ca²⁺ chelation in circuit; Ca replacement post-filter | Post-filter iCa 0.25–0.35; systemic iCa 1.10–1.35; Total/iCa <2.5 | Severe hepatic failure (citrate accumulation) |
| UFH systemic | If no citrate | 500–2000 IU/hr pre-filter | aPTT 45–60s | HIT; active bleeding |
| No anticoagulation | Active bleeding or INR >2.5 | Pre-dilution + saline flushes q30–60 min | Filter pressure; circuit life | — |
AKI Management — Step by Step
Identify AKI — Check Catheter First
Before ANY workup: confirm catheter is patent. Flush with 10 ml sterile water. Blocked catheter = most common cause of iatrogenic oliguria. Then: SCr criteria (×1.5 from baseline, or +0.3 mg/dL in 48h) OR UO <0.5 ml/kg/h ×6h OR damage biomarker elevated (KDIGO 2026).
Classify: Pre-renal, Intrinsic, or Post-renal
- Pre-renal: FeNa <1%, Uosm >500, bland urine sediment — volume/haemodynamic correction
- ATN: Muddy brown casts, FeNa >2%, nephrotoxin history — remove cause
- AIN: Drug exposure, WBC casts, mild proteinuria — stop offending drug
- Post-renal: Check ultrasound for hydronephrosis — relieve obstruction
Conservative Management
Stop nephrotoxins. Buffered crystalloids (KDIGO 2026 Strong 1B). MAP ≥65 mmHg (vasopressors if needed). Avoid fluid overload — monitor daily balance. Adjust drug doses (see table). Glucose 140–180 mg/dL. Normal protein nutrition (0.8–1.2 g/kg/day; 1.5–2 g/kg on CRRT).
Furosemide Stress Test (NEW KDIGO 2026)
If Stage 1–2 AKI and euvolaemic/hypervolaemic: Furosemide 1–1.5 mg/kg IV. Measure UO over 2h. UO <200 ml = high risk Stage 3/RRT (Sens 87%, Spec 84%). Plan for RRT access.
RRT Indications — AEIOU (Deferred Strategy)
Acidosis pH <7.1 refractory | Electrolytes K >6.5+ECG changes | Ingestion dialysable toxin | Overload refractory to diuretics | Uraemia (encephalopathy, pericarditis, bleeding). STARRT-AKI: do NOT initiate prophylactically — wait for absolute indication.
CRRT Prescription
CVVHDF: Effluent 25 ml/kg/hr prescribed (delivers 20 net). Blood flow 150–250 ml/min. Regional citrate anticoagulation (first choice). Net UF per fluid balance goal. Drug dose adjustment (see table — especially fentanyl preferred over morphine).
Renal Recovery & AKD Follow-Up
Trial off RRT when UO >400 ml/day off treatment + creatinine stable/improving. If dysfunction persists 7 days–3 months = AKD (KDIGO 2026 new entity) — arrange nephrology follow-up. AKD patients at high risk of CKD progression (30–40%).
Common Mistakes
Blocked urinary catheter is the most common cause of iatrogenic oliguria in ICU. Before any workup, flush catheter with 10 ml sterile water and confirm free flow. A kinked or blocked catheter can cause Stage 2–3 AKI within hours.
Marino (Ch.34, p.587): ICU patients lose ~2% muscle mass per day → SCr underestimates AKI. A "normal" SCr of 0.9 in a sarcopenic elderly patient may represent GFR of 20–30 ml/min. Always consider clinical context + cystatin C. Use Cockcroft-Gault with actual weight for drug dosing (not MDRD).
KDIGO 2026 Strong (1B): buffered crystalloids over 0.9% NaCl for AKI. Hyperchloraemic acidosis causes renal vasoconstriction, worsens AKI, and causes metabolic acidosis. Use Ringer's Lactate or PlasmaLyte. Exception: TBI patients.
Morphine-6-glucuronide (M6G) accumulates in AKI → prolonged sedation and respiratory depression. Marino (Table 6.2): "Avoid morphine in renal failure." Use fentanyl instead (no active metabolites, safe in all degrees of renal failure).
STARRT-AKI (2020) and KDIGO 2026: deferred (indication-based) strategy. No mortality benefit from accelerated RRT initiation. Unnecessary RRT = line complications, hypotension, anticoagulation risks, delays in renal recovery. Wait for AEIOU criteria.
KDIGO recommends ≥20 ml/kg/hr DELIVERED. Due to filter downtime (~20–25%), prescribe 25 ml/kg/hr. RENAL trial: >25 ml/kg/hr delivered = no additional benefit. Under-dosing causes inadequate clearance; critically ill patients are hypercatabolic.
Exam Pearls
Q: What is AKD and why is it new in KDIGO 2026?
AKD = Acute Kidney Disease — kidney dysfunction persisting 7 days to 3 months. New in KDIGO 2026 (not in 2012 guidelines). Bridges the gap between AKI (≤7 days) and CKD (>3 months). AKD patients need nephrology follow-up — 30–40% progress to CKD.
Q: KDIGO 2026 — what is new about AKI diagnosis?
Added STRUCTURAL criteria: elevated validated kidney damage biomarker (NGAL, TIMP-2×IGFBP7) = AKI even without SCr/UO changes. Cystatin C rise ≥1.5× baseline now recognised. Biomarker staging (B0 = no damage; B1 = damage present) added to severity system.
Q: Why is serum creatinine unreliable in ICU AKI? (Marino insight)
Marino (Ch.34, p.587): ICU patients lose ~2% muscle mass per day → ↓ creatinine production → SCr underestimates GFR reduction. A "normal" SCr can hide severe AKI. Drug doses based on SCr-GFR estimation will OVERESTIMATE clearance → drug accumulation → toxicity.
Q: Furosemide Stress Test — protocol and interpretation (KDIGO 2026)?
Euvolaemic Stage 1–2 AKI. Give furosemide 1–1.5 mg/kg IV (1 mg/kg if prior exposure). Measure UO over 2h. UO <200 ml = high risk of Stage 3 AKI + RRT requirement (Sensitivity 87%, Specificity 84%). KDIGO 2026 suggests using FST (conditional, 2C).
Q: Why is CVP elevation nephrotoxic?
Marino (Ch.34, p.589): Filtration Gradient = (MAP − Pv) − P_PT. Elevated CVP/venous pressure (Pv) reduces the filtration gradient → ↓ GFR. Fluid overload causes AKI by venous congestion, not just arterial hypotension. This is why diuresis in fluid-overloaded AKI patients can actually IMPROVE renal function.
Q: CRRT effluent dose — what to prescribe and why?
Prescribe 25 ml/kg/hr to deliver 20 ml/kg/hr net (filter downtime accounts for ~20–25%). RENAL trial: higher doses (>25 ml/kg/hr) = no additional mortality benefit. KDIGO minimum: 20 ml/kg/hr delivered. Underdosing = inadequate clearance in hypercatabolic septic patients.
References
- Marino PL. Marino's The ICU Book, 5th edition. Chapter 34: Acute Kidney Injury (pp.586–602). Philadelphia, PA: Wolters Kluwer; 2025. ISBN: 978-1-975176-71-6.
- KDIGO AKI Work Group (Ostermann M, James M, Co-Chairs). KDIGO 2026 Clinical Practice Guideline for Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD). Public Review Draft March 2026. kdigo.org
- KDIGO AKI Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2(1):1–138.
- STARRT-AKI Investigators, Bagshaw SM, Wald R, et al. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med. 2020;383(3):240–251.
- RENAL Replacement Therapy Study Investigators, Bellomo R, et al. Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients. N Engl J Med. 2009;361(17):1627–1638.
- Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults (SMART). N Engl J Med. 2018;378(9):829–839.
- Morabito S, Pistolesi V, Tritapepe L, Fiaccadori E. Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI. Clin J Am Soc Nephrol. 2014;9(12):2173–2188.
- Washington Manual of Critical Care, 4th Edition. Kollef MH, Witt CA (eds). Wolters Kluwer; 2023.
- Oh TE (ed). Oh's Intensive Care Manual, 8th edition. Chapter: Acute Kidney Injury. Elsevier; 2018.