L2- Acute Kidney Injury

What is the functional unit of the kidney?

The nephron.

What are the two main components of a nephron and what are their functions?

1. Glomerulus (filtration)

2. Tubule (reabsorption and secretion to modify the filtrate)

What regulates glomerular filtration in the nephron?

• Afferent arteriole

• Efferent arteriole

Approximately how many nephrons are present in each kidney?

~1 million nephrons.

What percentage of nephrons are located in the cortex vs medulla?

• Cortex- About 85%.

• Medulla- About 15%.

What 3 structures are located in the renal cortex?

• Glomeruli

• Bowman’s capsule

• proximal and distal tubules of

  the juxtamedullary nephrons

What structures are found in the renal medulla?

• Renal pyramids

• Renal columns

• Loop of Henle

• Vasa recta

• Collecting ducts of

  the juxtamedullary nephrons

Which part of the kidney is most susceptible to ischemia? Give 3 reasons why

The medulla.

• Low oxygen tension

• High metabolic activity

• Countercurrent blood supply

What is acute kidney injury (AKI)?

A rapid decline in glomerular filtration rate (GFR) leading to retention of nitrogenous waste products (urea and creatinine).

What are the three major pathophysiological categories of AKI?

• Pre-renal

• Intrinsic renal

• Post-renal

What is the basic pathophysiology of pre-renal AKI? Give 5 causes

Renal hypoperfusion due to

• hypotension

• Heart failure (Decreased CO)

• Volume depletion (blood loss, vomiting)

• Liver failure

• Sepsis

What 4 hormonal systems are activated during renal hypoperfusion in pre-renal AKI? What is the purpose of these responses?

• Noradrenaline

• Angiotensin II

• Endothelin

• ADH

Reduce renal blood flow and preserve salt and water.

9 Clinical Features of Pre-renal AKI

• Dry mouth

• Dizziness

• Hypotension (low BP)

• Tachycardia

• Slack skin (Reduced skin turgor)

• Thirst

• Weight loss

• Reduced urine output (oliguria)

• The patient also may have symptoms/signs of heart or

  liver disease

What causes intrinsic renal AKI?

Structural damage to kidney tissue

What are 5 major causes of intrinsic renal AKI?

• Glomerulonephritis

• Atheroembolic disease

• Acute interstitial nephritis's

• Acute glomerulonephritis

• Acute tubular necrosis

What pathological feature characterizes crescentic glomerulonephritis?

Crescent formation in Bowman’s space

What type of process causes acute interstitial nephritis?

Inflammatory reaction in renal interstitium.

What is the 4 classic features of AIN?

• Fever

• Rash

• Eosinophiluria

• Leukocyturia

What is AIN caused by?

• Usually drug related

  • Antibiotics (especially penicillin)

  • Proton pump inhibitors

• Spontaneous

• Hereditary

What are the 2 treatments of AIN?

• Withdrawal of offending drug & observation

• Occasionally corticosteroids

What causes renal atheroembolic disease?

Acute or Chronic Deterioration due to underlying atherosclerotic disease due to cholesterol emboli from atherosclerotic plaques.

What 2 patient groups are at risk of renal atheroembolic disease?

• Peripheral vascular disease

• Coronary artery disease

What 2 clinical findings suggest Atheroembolic Disease?

• Livedo reticularis (skin)

• Eosinophiluria (Eosinophiluria)

What is the most common cause of intrinsic AKI?

Acute tubular necrosis.

What are the 3 main pathological processes in ATN?

• Medullary Ischaemia

• Tubular damage

• Tubular Obstruction secondary to

sloughing of tubular cells and debris

What are common causes of ATN? (%)

• Sepsis (48%)

• Hemodynamic causes (32%)

• Toxic causes (20%)

What are 6 toxic causes of ATN?

– ACE inhibitor

– NSAID

– Contrast Dye (perhaps less of a concern than originally thought)

– Antibiotics (gentamicin, amphotericin)

– Pigment Nephropathy (caused by rhabdomyolysis)

– DIC

CAPDAN

What is the mechanism of post-renal AKI?

Urinary outflow obstruction.

What 2 imaging findings suggest post renal AKI?

1. hydronephrosis → Dilatation of the renal pelvis due to obstruction.

2. hydroureter → Dilatation of the ureter due to distal obstruction.

What are 6 common causes of post-renal AKI?

• Benign prostatic hyperplasia (BPH)

• Urinary Retention (Drugs or Neurological Condition)

• Pelvic malignancy

• Nephrolithiasis (rare)

• Retroperitoneal fibrosis

• Urethral stricture

BURNUP

What 10 exposures may precipitate AKI?

1. Sepsis

2. Critical illness

3. Circulatory shock

4. Burns

5. Trauma

6. Cardiac surgery (especially with cardiopulmonary bypass)

7. Major non-cardiac surgery

8. Nephrotoxic drugs

9. Radiocontrast agents

10. Poisonous plants and animals

BCCCMNPRST

What 9 patient factors increase susceptibility to AKI?

1. Dehydration or volume depletion

2. Advanced age

3. Female gender

4. Black race

5. Chronic kidney disease (CKD)

6. Chronic diseases (heart, lung, liver)

7. Diabetes mellitus

8. Cancer

9. Anemia

BAD FAD CCC

What is the continuum of acute kidney injury?

Pre-renal state (renal hypoperfusion)→ AKI → Recovery/ repair phase.

What are the two classification systems for AKI severity?

1. RIFLE classification

• Risk

• Injury

• Failure

• Loss

• End-stage kidney disease

2. AKIN classification (Acute Kidney Injury Network)

According to KDIGO guidelines (2012), how is AKI assessed?

By staging severity based on creatinine rise and urine output - The cause of AKI should always be determined whenever possible

What 9 investigations are used to diagnose AKI?

• History

• Physical examination

• Urine microscopy

• Serum chemistry

• Urine sodium

• Chest X-ray (CXR)

• Renal ultrasound

• Renal biopsy (in selected cases)

• Additional laboratory tests

What 4 examination findings help assess AKI?

• Pulse volume - Low-volume pulse

• Blood pressure- lying and standing.

• Neck veins- Volume status.

• Skin rash

  • Drug reactions

  • Vasculitis

Is AKI usually symptomatic early?

No — it is often asymptomatic initially

What urine output change occurs in about half of AKI patients?

Oliguria (Urine output <400 mL in 24 hours)

What laboratory changes occur in AKI?

• Rising urea

• Rising creatinine

What 3 complications may develop in AKI?

• Volume overload

• Metabolic acidosis

• Hyperkalemia

4 criteria in diagnosis of pre-renal AKI

• Hx of volume loss

• Elevated urea and creatinine

• Altered urea/creatinine ratio

ie. disproportionate elevation of urea

• Bland urinary sedimen

6 criteria for Diagnosis of Intrinsic Renal Disease

– Hx of volume loss/hypotension (anaesthetic note)

– Elevated urea and creatinine

– Ratio maintained

– Muddy brown casts - ATN

– Rbc, WBC, casts (red or white) on urinalysis

– Proteinuria – glomerular disease

What 3 conditions cause a bland urine dipstick?

• Acute interstitial nephritis

• Acute tubular necrosis

• Some forms of myeloma

What 3 conditions cause blood only on dipstick?

• IgA nephropathy

• Post-infectious GN

• Lupus nephritis

What 4 conditions cause protein only on dipstick?

• Minimal change disease

• Membranous nephropathy

• Focal segmental glomerulosclerosis (FSGS)

• Amyloidosis

What 5 conditions cause both blood and protein on dipstick?

• Rapidly progressive GN

• ANCA-associated vasculitis

• Anti-GBM disease

• IgA nephropathy

• Lupus nephritis

What 8 symptoms suggest obstructive (post-renal) AKI?

• Poor urinary stream

• Frequency

• Nocturia

• Dribbling

• Dysuria

• Pain

• Weight loss

• Anorexia

What urine sodium level suggests pre-renal AKI vs intrinsic renal disease?

• pre-renal AKI <20 mEq/L

• intrinsic renal disease >40 mEq/L

What urine osmolarity suggests pre-renal AKI vs ATN?

• pre-renal AKI >500 mOsm/kg (kidneys conserve water).

• ATN <450 mOsm/kg (loss of concentrating capacity)

Why should previous laboratory tests be reviewed in AKI evaluation?

To identify previous chronic kidney disease.

What 3 lab abnormalities suggest chronic kidney disease?

• Elevated phosphorus

• Hypocalcemia

• Anemia

What are the 2 key principles in AKI management?

• Maintain intravascular volume.

• Perfusion

What should be given when pre-renal AKI is suspected?

• Trial of Fluids If suspect a pre-renal

element.

• 5-10mls/kg bolus of Isotonic Fluid (saline or ringers lactate)

• Monitor for evidence of volume overload

What 3 drugs should be avoided in AKI?

• NSAIDs

• ACE inhibitors

• SGLT2 inhibitors.

How do ACE inhibitors affect glomerular hemodynamics?

Efferent arteriole vasodilation.

How do SGLT2 inhibitors affect glomerular hemodynamics?

Afferent arteriole vasoconstriction → Reduce intraglomerular pressure and protect nephrons.

Is the kidney protective effect of SGLT2 inhibitors dependent on glucose lowering (T2D)?

No.

What 4 investigations are required for severe hyperkalemia?

• ECG

• Cardiac monitoring

• Venous blood gas

• Lab potassium measurement

Hyperkalemia Management- 5 steps

– Stabilise myocardium-30ml of 10%calcium gluconate IV, repeat ECG if changes

– 5-10 units iv insulin with 50ml of 50%

dextrose

– Salbutamol nebs

– +/- IV bicarbonate- may need renal input

– +/- Dialysis

3 steps when managing acidosis in AKI

1. Do an ABG

   • Confirm acidosis

   • Check respiratory compensation

   • Exclude mixed disorders

2. Determine if metabolic or respiratory

3. Calculate the anion gap

   • Identify cause of metabolic acidosis

Causes of Normal Anion Gap Acidosis

• Hyperalimentation

• Acetazolamide / Amphotericin B

• Renal tubular acidosis

• Diarrhea

• Uretero-sigmoidostomy

• Pancreatic fistula / post-hypercapnic state

(HARDUP)

Causes of High Anion Gap Acidosis

• Glycols

• Oxoproline

• L-lactate

• D-lactate

• Methanol

• Aspirin

• Renal failure

• Ketones

(GOLDMARK)

What are the 5 major indications for dialysis in AKI (Kidney Replacement Therapy-KRT)?

1. Refractory volume overload

2. Hyperkalemia (>6.5 mEq/L or rapidly rising)

3. Severe metabolic acidosis (pH <7.1)

4. Uremic complications (pericarditis, neuropathy, altered mental status)

5. Poisoning

Name 2 types (modalities) of KRT.

• IHD (Intermittent Haemodialysis)

• CRRT (Continuous Renal Replacement Therapy)- may improve patient outcomes

What is the duration of AKI recovery?

Variable

What usually happens to kidney function after recovery?

Often returns to baseline.

Which type of AKI has a better prognosis, oliguric or non-oliguric?

Non-oliguric

What long-term risk occurs after AKI?

Increased post-hospital mortality.

What is the overall mortality of AKI?

20–70%.

What is the mortality in ICU patients requiring dialysis? Why might modern outcomes appear better?

79% - modern outcomes appear better as dialysis started earlier due to lower thresholds.

A 56-year-old man with hypertension, type 2 diabetes, hypercholesterolemia, and osteoarthritis undergoes an elective laparoscopic cholecystectomy for cholelithiasis. His medications include diclofenac, ramipril, dapagliflozin, amlodipine, atorvastatin, and metformin.

Pre-operative labs show creatinine 121 µmol/L and eGFR 56 mL/min.

During surgery there is a bile leak requiring conversion to open surgery and severe hypotension (60/40 mmHg for ~15 minutes).

Post-operatively he develops fever (39°C), leukocytosis (WCC 20,000), and abdominal pain, and is transferred to the ICU. A contrast CT abdomen reveals a fluid collection which is drained. He receives gentamicin, metronidazole, and cefotaxime.

His urine output falls to 10 mL/hr then becomes anuric, with 210 mL total urine in 24 hours. Over the next few days creatinine rises from 257 → 321 → 467 → 550 µmol/L.

On day 4 he has:

• pH 7.05

• Potassium 6.9 mEq/L

• Anion gap 25

• Urine sodium 60 mEq/L

• Chest X-ray: volume overload

• O₂ saturation 85% on 100% FiO₂

• What type of AKI is most likely?

Intrinsic AKI → Acute tubular necrosis

How can diclofenac cause renal failure?

NSAIDs inhibit prostaglandins → afferent arteriole vasoconstriction → reduced renal perfusion.

A 56-year-old man with hypertension, type 2 diabetes, hypercholesterolemia, and osteoarthritis undergoes an elective laparoscopic cholecystectomy for cholelithiasis. His medications include diclofenac, ramipril, dapagliflozin, amlodipine, atorvastatin, and metformin.

Pre-operative labs show creatinine 121 µmol/L and eGFR 56 mL/min.

During surgery there is a bile leak requiring conversion to open surgery and severe hypotension (60/40 mmHg for ~15 minutes).

Post-operatively he develops fever (39°C), leukocytosis (WCC 20,000), and abdominal pain, and is transferred to the ICU. A contrast CT abdomen reveals a fluid collection which is drained. He receives gentamicin, metronidazole, and cefotaxime.

His urine output falls to 10 mL/hr then becomes anuric, with 210 mL total urine in 24 hours. Over the next few days creatinine rises from 257 → 321 → 467 → 550 µmol/L.

On day 4 he has:

• pH 7.05

• Potassium 6.9 mEq/L

• Anion gap 25

• Urine sodium 60 mEq/L

• Chest X-ray: volume overload

• O₂ saturation 85% on 100% FiO₂

• What 6 factors contributed to this patient’s AKI?

• Intraoperative hypotension

• Sepsis

• Nephrotoxic drugs

• Contrast CT

• ACE inhibitor

• NSAID use

• Diabetes

A 56-year-old man with hypertension, type 2 diabetes, hypercholesterolemia, and osteoarthritis undergoes an elective laparoscopic cholecystectomy for cholelithiasis. His medications include diclofenac, ramipril, dapagliflozin, amlodipine, atorvastatin, and metformin.

Pre-operative labs show creatinine 121 µmol/L and eGFR 56 mL/min.

During surgery there is a bile leak requiring conversion to open surgery and severe hypotension (60/40 mmHg for ~15 minutes).

Post-operatively he develops fever (39°C), leukocytosis (WCC 20,000), and abdominal pain, and is transferred to the ICU. A contrast CT abdomen reveals a fluid collection which is drained. He receives gentamicin, metronidazole, and cefotaxime.

His urine output falls to 10 mL/hr then becomes anuric, with 210 mL total urine in 24 hours. Over the next few days creatinine rises from 257 → 321 → 467 → 550 µmol/L.

On day 4 he has:

• pH 7.05

• Potassium 6.9 mEq/L

• Anion gap 25

• Urine sodium 60 mEq/L

• Chest X-ray: volume overload

• O₂ saturation 85% on 100% FiO₂

• What dialysis indications are present in this patient?

• Severe hyperkalemia

• Severe metabolic acidosis

• Volume overload

• Oliguria