Acute Kidney Injury (Adult)

1. Overview

Acute Kidney Injury (AKI) is a clinical syndrome characterized by a rapid decline in renal excretory function, leading to the accumulation of nitrogenous waste (Urea/Creatinine) and the loss of fluid and electrolyte homeostasis. It is not a single disease but a unified clinical endpoint for diverse insults classified as Pre-renal, Intrinsic, and Post-renal. [1]

The clinical significance of AKI is profound: it affects up to 20% of hospitalized adults and > 50% of ICU patients. Even "mild" AKI is independently associated with an increased risk of hospital mortality and long-term progression to Chronic Kidney Disease (CKD). [2]

The 2024 management paradigm focuses on early recognition via electronic alerts, the judicious use of Balanced Crystalloids (SMART/SALT-ED evidence), and the avoidance of "nephrotoxic synergy" (e.g., Vancomycin + Pip-Taz). Standard staging is provided by the KDIGO criteria, while the Furosemide Stress Test (FST) has emerged as a critical functional tool to predict progression. [3]

2. Epidemiology

The Hospital Burden

• Incidence: 1 in 5 hospital admissions involve AKI.
• The "Creatinine Lag": Clinical AKI is often preceded by subclinical damage that is undetectable by creatinine for 24-48 hours.
• Mortality: Stage 3 AKI requiring RRT carries a mortality rate exceeding 50%. [4]

High-Risk Profiles

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3. Aetiology & Pathophysiology

⚠️ THE 7-STEP MOLECULAR MECHANISM (Intrinsic/ATN)

1. Haemodynamic Insult: Prolonged pre-renal ischaemia or direct toxins cause a precipitous drop in medullary blood flow.
2. Bioenergetic Failure: Tubular epithelial cells (especially in the S3 segment of the proximal tubule) are highly metabolic. ATP depletion leads to the failure of the Na+/K+ ATPase pump.
3. Cytoskeletal Disruption: Loss of cell polarity occurs; the actin cytoskeleton collapses, and brush border microvilli are shed into the tubular lumen.
4. Acinar Necroptosis: Cells undergo programmed necrosis (Necroptosis), releasing Damage-Associated Molecular Patterns (DAMPs) into the interstitium.
5. TLR4-Mediated Inflammation: DAMPs activate Toll-like receptors (TLR4) on resident macrophages, triggering the NF-κB pathway and a local "Cytokine Storm" (TNF-α, IL-6).
6. Intra-tubular Obstruction: Shed epithelial cells and inflammatory debris form "Muddy Brown" Granular Casts, which physically obstruct the lumen, increasing retrograde pressure and further reducing GFR.
7. G1/S Cell Cycle Arrest: Surviving cells enter G1/S arrest to preserve energy. If this arrest is prolonged, it activates profibrotic pathways (TGF-β), leading to the irreversible transition from AKI to CKD. [5, 6, 7]

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4. Clinical Presentation

Clinical Categories

• Pre-renal (60%): History of losses (vomiting, diarrhoea, bleeding) or low-output (HF).
• Intrinsic (30%): ATN (Sepsis/Toxins), AIN (Drug allergy), or GN.
• Post-renal (10%): History of BPH, stones, or pelvic malignancy.

Physical Signs

1. Volume Status: Flat JVP/Dry membranes (Pre-renal) vs. Raised JVP/Crackles (Intrinsic/Fluid Overload).
2. Uraemic Stigmata: Asterixis (flapping tremor), pericardial friction rub, and "uraemic frost" (rare).
3. Skin Signs: Livedo reticularis (Cholesterol emboli); Purpua (Vasculitis).

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5. Investigations

The "Liquid Biopsy" (Urinalysis)

• Hyaline Casts: Suggest Pre-renal state.
• Muddy Brown Casts: Diagnostic for ATN.
• RBC Casts: Diagnostic for Glomerulonephritis.
• White Cell Casts & Eosinophils: Suggest AIN. [8]

Urine Chemistry: FENa vs. FEUrea

• FENa less than 1%: Suggests Pre-renal (kidneys are avidly retaining sodium).
• FENa > 2%: Suggests ATN (tubules are damaged and losing sodium).
• FEUrea less than 35%: More reliable than FENa if the patient is already on Diuretics.

The Furosemide Stress Test (FST)

Administer 1.0 mg/kg (naïve) or 1.5 mg/kg (previous user) of IV Furosemide. Success: Urine output > 200 mL in the first 2 hours. Failure: Identifies patients at high risk of progressing to Stage 3 AKI and RRT. [9]

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6. Management: The Acute Protocol

1. The "DAMN" Drug Hold

Immediately suspend: Diuretics, ACE inhibitors/ARBs, Metformin, NSAIDs. [10]

2. Fluid Selection: The Balanced Rule

• Balanced Crystalloids (Hartmann's or Plasmalyte) are preferred.
• 0.9% Saline should be avoided where possible as high chloride concentrations cause Hyperchloraemic Acidosis and renal vasoconstriction (SMART/SALT-ED trials).

3. Indications for RRT (The "AEIOU" Mnemonic)

1. Acidosis (pH less than 7.1 refractory to treatment).
2. Electrolytes (K+ > 6.5 refractory to treatment).
3. Intoxications (Lithium, Ethylene Glycol, Methanol, Salicylates).
4. Overload (Pulmonary oedema refractory to diuretics).
5. Uraemia (Encephalopathy or Pericarditis). [11]

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7. Evidence: Landmark Trials

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8. Single Best Answer (SBA) Questions

Question 1

A 70-year-old male with sepsis has a creatinine of 350 (baseline 90). He is on a Furosemide infusion for pulmonary oedema. You wish to calculate his fractional excretion of an analyte to distinguish pre-renal from ATN. Which test is most appropriate?

• A) Fractional Excretion of Sodium (FENa)
• B) Fractional Excretion of Urea (FEUrea)
• C) Fractional Excretion of Creatinine
• D) Urine Osmolality
• E) 24-hour Creatinine Clearance
• Answer: B. FENa is unreliable in patients taking diuretics as the drug forced sodium excretion. FEUrea less than 35% remains a sensitive marker of pre-renal physiology in this setting.

Question 2

What is the primary molecular target that is downregulated in the "initiation phase" of ischaemic ATN?

• A) VEGF
• B) Na+/K+ ATPase
• C) TGF-β
• D) Aquaporin-2
• E) Renin
• Answer: B. ATP depletion causes the Na+/K+ ATPase pump to relocate from the basolateral membrane, leading to loss of cellular polarity and ion handling failure.

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9. Viva Scenario: The "Sick Day" Protocol

Examiner: "Your patient with CKD Stage 3b is being discharged after a bout of gastroenteritis that caused a Stage 1 AKI. What is your advice regarding their medications?"

Candidate:

1. The SADMANS List: I would provide the "Sick Day Rules," advising them to temporarily stop SGLT2i, ACEi/ARBs, Diuretics, Metformin, ARBs, NSAIDs, and Sulfonylureas during any illness involving vomiting, diarrhoea, or fever.
2. Rationale: These drugs either exacerbate hypovolaemia or interfere with the kidney's autoregulatory compensation, potentially turning a mild dehydration into severe AKI.
3. Restarting: They should restart these medications only 48 hours after they have returned to normal eating and drinking.
4. Follow-up: I would arrange a repeat U&E in 7-14 days to ensure the creatinine has returned to its baseline.

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10. Patient Explanation

"Acute Kidney Injury is a 'sudden shock' to your kidneys. They have stopped cleaning your blood properly, often because of an infection or a lack of fluids. Think of it like a filter that has become temporarily clogged. Most of the time, the kidneys can repair themselves, but we need to protect them while they heal by stopping certain 'harsh' medications and keeping your fluid levels perfectly balanced. We will monitor your blood every day until we see the levels returning to normal."

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11. References

1. KDIGO. Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012. KDIGO
2. The STARRT-AKI Investigators. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med. 2020. [PMID: 32668107]
3. Self WH, et al. Balanced Crystalloids versus Saline in Critically Ill Adults (SMART). N Engl J Med. 2018. [PMID: 29485925]
4. Chawla LS, et al. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013. [PMID: 24053420]
5. NICE NG148. Acute kidney injury: prevention, detection and management. 2019. NICE

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Last Updated: 2026-01-05 | MedVellum Editorial Team