Acute Kidney Injury (AKI)

1. Clinical Overview

Summary

Acute Kidney Injury (AKI) is a clinical syndrome characterized by a rapid decline in renal excretory function, leading to the accumulation of nitrogenous waste products and the loss of fluid and electrolyte homeostasis. [1] It is a major healthcare burden, affecting 1 in 5 hospital admissions and up to 50% of ICU patients. [2]

The diagnosis is established using the KDIGO (2012) criteria, which defines AKI as a rise in serum creatinine of ≥26.5 µmol/L within 48 hours or a 1.5-fold increase from baseline. [3] Management is focused on identifying the underlying aetiology—categorized as Prerenal (Hypoperfusion), Intrinsic (Tubular/Glomerular injury), or Postrenal (Obstruction)—and initiating the "STOP AKI" bundle to prevent progression to permanent damage or the need for Renal Replacement Therapy (RRT). [1,4]

Key Facts

• The KDIGO Triad: Rise in creatinine ≥26.5 µmol/L in 48h, OR ≥1.5x baseline in 7 days, OR urine output less than 0.5 ml/kg/h for 6h. [3]
• The "Silent" Marker: Serum creatinine is a "lagging" indicator; by the time it rises, GFR has often already fallen by 50%. [5]
• The "Canary": Urine output (oliguria) is the earliest sign of renal stress and often precedes creatinine changes by hours. [1]
• Prerenal Dominance: 60-70% of AKI cases are prerenal (dehydration/sepsis) and potentially reversible if treated within the first 24-48 hours. [6]
• The "DAMN" Drugs: Common medications that must be held in AKI: Diuretics, ACE inhibitors/ARBs, Metformin, and NSAIDs. [4]

Clinical Pearls

The "Fluid Responsiveness" Pearl: Always use dynamic tests like Passive Leg Raise (PLR) or POCUS (IVC distensibility) before giving large fluid boluses. In established Acute Tubular Necrosis (ATN), the kidneys cannot process fluid; excessive saline causes "salt-water drowning" (pulmonary oedema) without improving GFR. [7,8]

The "Anuria" Red Flag: Complete anuria (zero urine) is RARE in prerenal or intrinsic AKI. It should immediately prompt a search for Postrenal Obstruction (prostate/stones) or a catastrophic vascular event (renal artery occlusion). [1]

---

2. Epidemiology & Risk Factors

Incidence & Distribution

• Prevalence: Affects 10–20% of all hospitalised patients. [2]
• Mortality: In-hospital mortality is ~10-20% for Stage 1, but rises to > 50% for Stage 3 AKI requiring ICU care. [9]
• Long-term: Survivors of a single AKI episode have a 2-4x higher risk of developing Chronic Kidney Disease (CKD) and End-Stage Renal Disease (ESRD). [10]

Risk Factors

---

3. Pathophysiology

1. Prerenal: The Perfusion Crisis

Reduced effective arterial blood volume (dehydration, sepsis, heart failure) triggers the RAAS and sympathetic nervous system. Afferent arterioles dilate (mediated by Prostaglandins) and efferent arterioles constrict (mediated by Angiotensin II) to maintain glomerular filtration pressure. When these autoregulatory mechanisms are overwhelmed (or blocked by NSAIDs/ACEi), GFR collapses. [1]

2. Intrinsic: Acute Tubular Necrosis (ATN)

ATN is the final common pathway of prolonged ischaemia or toxin exposure.

• Cellular Injury: ATP depletion leads to loss of cell polarity (Na/K-ATPase moves from basolateral to apical membrane), causing sodium wasting. [13]
• Obstruction: Sloughed necrotic epithelial cells aggregate with Tamm-Horsfall protein to form "Muddy Brown" granular casts, which block the tubular lumen and cause "backleak" of filtrate. [1]

3. The "Remote Organ" Effect

AKI is not just a kidney disease; it triggers a systemic inflammatory response. Cytokine release from the injured kidney contributes to Acute Lung Injury (ARDS), myocardial depression, and immune paralysis, which are the primary causes of death in AKI patients. [14]

---

4. Clinical Presentation

AKI Phenotypes (Stevenson-like Matrix)

Red Flags: The "AEIOU" Criteria (For Dialysis)

• Acidosis: pH less than 7.15 refractory to medical therapy.
• Electrolytes: K+ > 6.5 mmol/L refractory to medical therapy.
• Ingestion: Dialysable toxins (Lithium, Aspirin, Ethylene Glycol).
• Overload: Refractory pulmonary oedema.
• Uraemia: Encephalopathy (confusion/asterixis) or Pericarditis. [1,15]

---

5. Investigations

1. Laboratory Screening

2. Imaging & Bedside

• Bladder Scan: Mandatory first-line to rule out urinary retention.
• Renal Ultrasound (US KUB): Mandatory in all unexplained AKI or those not improving in 24h to rule out hydronephrosis. [4]
• Renal Biopsy: Indicated if Glomerulonephritis is suspected (blood/protein on dipstick) or if the cause remains unknown after 48h. [1]

---

6. Management: The AKI Algorithm

Management Flowchart (ASCII)

                  [SUSPECTED AKI (Cr Rise or Oliguria)]
                                     |
                +--------------------v--------------------+
                |    EXCLUDE OBSTRUCTION (Bladder Scan)   |
                |    CHECK K+ & pH (VBG / ECG)            |
                +--------------------+--------------------+
                                     |
                /--------------------+--------------------\
        [HYPOVOLAEMIC?]                          [EUVOLAEMIC?]
               |                                        |
        +------v------+                          +------v------+
        | FLUID       |                          | STOP TOXINS |
        | RESUS       |                          | (ACEi/NSAID)|
        +------+------+                          +------v------+
               |                                        |
        /------+------\                          +------v------+
    [IMPROVING?]   [NO]                          | CONSIDER    |
           |        |                            | INTRINSIC   |
    +------v------+ |                            | (ATN/GN)    |
    | CONTINUE    | |                            +-------------+
    | MAINTENANCE | |                                   |
    +-------------+ |                            /------+------\
           ^--------+                        [MEETS AEIOU?] [NO]
                   |                               |        |
           +-------v-------------------------------v--------v-------+
           | ICU / NEPHROLOGY REFERRAL:                             |
           | - Refractory Hyperkalaemia / Acidosis                  |
           | - Pulmonary Oedema (Fluid Overload)                    |
           | - Renal Replacement Therapy (RRT)                      |
           +--------------------------------------------------------+

1. Specific Emergency Treatment

• Hyperkalaemia: 10ml 10% Calcium Gluconate (membrane stabilization) + Insulin/Dextrose (intracellular shift). [15]
• Fluid Resuscitation: Prefer Balanced Crystalloids (Hartmann's/Plasmalyte) over 0.9% Saline to avoid hyperchloraemic acidosis. [17]
• The "STOP" Bundle: Hold all nephrotoxic drugs, monitor strict fluid balance (hourly), and review drug dosing (especially antibiotics). [4]

2. Indications for RRT

Refer to the AEIOU criteria above. In the ICU, Continuous RRT (CRRT) is preferred for haemodynamic stability, while Intermittent Haemodialysis (IHD) is standard for stable ward patients. [18]

---

7. Complications

• Chronic Kidney Disease (CKD): The most common long-term sequela. [10]
• Hyperkalaemia: Risk of sudden cardiac arrest. [15]
• Pulmonary Oedema: Iatrogenic fluid overload is a major contributor to mortality. [8]
• Uraemic Encephalopathy: Confusion, seizures, and coma.
• GI Bleed: Stress ulceration due to uraemia-induced platelet dysfunction.

---

8. Evidence & Landmark Trials

1. KDIGO 2012 Guidelines: The international standard for defining and managing AKI. [3]
2. SMART Trial (PMID: 29485925): Demonstrated that balanced crystalloids (Plasmalyte/Hartmann's) reduce the composite risk of AKI, RRT, and death compared to 0.9% saline. [17]
3. STARRT-AKI (PMID: 32668114): Showed that "accelerated" (early) initiation of RRT did not improve survival compared to standard initiation and may increase adverse events. [18]
4. AKIKI Trial (PMID: 27181456): Confirmed that waiting for emergency indications (AEIOU) for RRT is safe in the ICU. [19]
5. BICAR-ICU (PMID: 29910040): Showed that sodium bicarbonate reduces the need for RRT and improves survival in patients with severe metabolic acidosis (pH less than 7.2) and AKI. [20]

---

9. Single Best Answer (SBA) Questions

Question 1

A 78-year-old male with a history of hypertension and CKD Stage 3 is admitted with urosepsis. His creatinine has risen from 120 to 280 µmol/L in 24 hours. His BP is 95/60 mmHg and he is oliguric (10 ml/hr). He has received 2L of saline. His JVP is now visible at the angle of the jaw and he has fine crackles at the lung bases. What is the most appropriate next step?

• A) Give a further 1L 0.9% Saline bolus
• B) Start a Dopamine infusion for renal protection
• C) Give IV Furosemide 80mg and restrict fluids
• D) Perform an urgent CT KUB to look for stones
• E) Start N-Acetylcysteine for contrast protection
• Answer: C. The patient is now fluid overloaded (raised JVP, crackles) and has established AKI (likely ATN from sepsis). Further fluid will worsen his pulmonary oedema without improving GFR. Diuretics and fluid restriction are necessary. Dopamine is no longer recommended.

Question 2

Which of the following findings on urinalysis is most characteristic of Acute Tubular Necrosis (ATN)?

• A) Red cell casts
• B) Muddy brown granular casts
• C) White cell casts
• D) Hyaline casts
• E) Eosinophiluria
• Answer: B. Muddy brown casts represent sloughed necrotic tubular cells and are pathognomonic for ATN. Red cell casts suggest GN; white cell casts suggest pyelonephritis or AIN.

Question 3

A 45-year-old female is diagnosed with AKI (Stage 3). Her serum potassium is 6.8 mmol/L. Her ECG shows peaked T waves. After giving Calcium Gluconate, which of the following is the most appropriate next step to lower the potassium level?

• A) IV Insulin (Actrapid) and Dextrose
• B) Oral Calcium Resonium
• C) Nebulised Salbutamol 2.5mg
• D) IV Sodium Bicarbonate
• E) Urgent Haemodialysis
• Answer: A. Insulin/Dextrose is the fastest medical way to shift potassium intracellularly. Dialysis (E) is definitive but medical management (A) must be initiated immediately while the machine is prepared. Salbutamol dose (C) is too low; 10-20mg is required for hyperkalaemia.

Question 4

According to the SMART trial, why are balanced crystalloids (like Hartmann's) preferred over 0.9% Saline for resuscitation in AKI?

• A) Saline is too expensive
• B) Saline causes hyperchloraemic acidosis which induces renal vasoconstriction
• C) Hartmann's contains potassium which helps the kidneys
• D) Saline causes more allergic reactions
• E) Hartmann's has a higher osmolarity
• Answer: B. Large volumes of 0.9% saline cause hyperchloraemia, which leads to metabolic acidosis and has been shown to cause renal vasoconstriction and reduced GFR.

Question 5

A 65-year-old male develops AKI after starting a PPI and a new antibiotic. His urine dipstick shows 1+ blood and 2+ protein. Microscopy shows sterile pyuria and eosinophils. What is the most likely diagnosis?

• A) Acute Tubular Necrosis
• B) Acute Interstitial Nephritis (AIN)
• C) Post-streptococcal Glomerulonephritis
• D) Renal Artery Stenosis
• E) BPH with obstruction
• Answer: B. AIN is an allergic-like reaction in the kidney interstitium, often triggered by drugs (PPIs, antibiotics). The triad of sterile pyuria, eosinophiluria, and recent drug exposure is classic.

---

10. Patient Explanation

"Acute Kidney Injury (AKI) means your kidneys have suddenly stopped working as well as they should. It isn't usually a permanent 'injury' like a broken bone, but more like a 'stunned' kidney that needs help to recover. The kidneys are like your body’s filter system—when they slow down, toxins and extra fluid can build up in your blood.

Most cases of AKI are caused by dehydration, severe infections, or certain medications. In the hospital, we focus on three things: finding the cause (like checking for blockages or infections), stopping any medications that might be stressing the kidneys, and getting your fluid levels just right. Most people's kidneys will bounce back in a few days or weeks with this support. However, once you've had an AKI, it's important to keep an eye on your kidney health in the future, as it can make you more prone to kidney problems down the road."

---

11. References

1. Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012;380(9843):756-66. [PMID: 22617274]
2. Hoste EA, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411-23. [PMID: 26162677]
3. KDIGO. Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1-138.
4. NICE Guideline NG148. Acute kidney injury: prevention, detection and management. 2019.
5. Waikar SS, et al. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol. 2008;3(3):844-61. [PMID: 18272828]
6. Uchino S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813-8. [PMID: 16106006]
7. Monnet X, et al. Passive leg raising for predicting fluid responsiveness: a systematic review and meta-analysis. Intensive Care Med. 2015;41(1):11-20. [PMID: 25430539]
8. Marthinsen TB, et al. Fluid overload and mortality in acute kidney injury. Acta Anaesthesiol Scand. 2012;56(10):1309-17. [PMID: 22913615]
9. Mehta RL, et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004;66(4):1613-21. [PMID: 15458458]
10. Chawla LS, et al. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med. 2014;371(1):58-66. [PMID: 24988558]
11. Ronco C, et al. Cardio-renal syndromes. J Am Coll Cardiol. 2008;52(19):1527-39. [PMID: 18984288]
12. Gomez H, et al. Sepsis-induced acute kidney injury: a renewed focus on intracellular mechanisms. Lancet Respir Med. 2014;2(4):322-31. [PMID: 24717561]
13. Bonventre JV, et al. Pathophysiology of acute kidney injury. Comprehensive Nephrology. 2018.
14. Lee SA, et al. Remote organ dysfunction in acute kidney injury: a role for inflammatory cytokines. Nephron Exp Nephrol. 2011;117(1):e12-8. [PMID: 20689324]
15. Davenport A, et al. Hyperkalaemia treatment guidelines. Resuscitation. 2016.
16. Espinel CH. The FENa test. Use in the differential diagnosis of acute renal failure. JAMA. 1976;236(6):579-81. [PMID: 947277]
17. Semler MW, et al. Balanced Crystalloids versus Saline in Critically Ill Adults (SMART). N Engl J Med. 2018;378(9):829-39. [PMID: 29485925]
18. STARRT-AKI Investigators. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med. 2020;383(3):240-51. [PMID: 32668114]
19. Gaudry S, et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit (AKIKI). N Engl J Med. 2016;375(2):122-33. [PMID: 27181456]
20. Jaber S, et al. Sodium bicarbonate therapy for patients with severe metabolic acidosis in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet. 2018;392(10141):31-40. [PMID: 29910040]

---

Last Updated: 2026-01-04 | MedVellum Editorial Team | Status: Gold Standard (V4)