Case 9: Nancy Jones

GFR

Fluid filtration rate through kidneys (glomerulus → Bowman’s capsule

Normal: 120 mL/min/1.73m²

GFR: Measurement

Glomerular marker clearance

Markers

• Inulin: Gold standard

• Urine creatinine: Creatine (in muscles) metabolism byproduct

  • Small secretion in tubules = Over-estimate GFR = eGFR

• BUN and Serum creatinine: Increased = Low GFR

GFR: Determinants

Control renal blood flow (RBF)

• Myogenic response

• Tubuloglomerular feedback

• RAAS

GFR Determinants: Myogenic Response

Increase RBF = Afferent arteriole stretch = Reflexive vasoconstriction = Increase resistance = Constant RBF + GFR

GFR Determinants: Tubuloglomerular Feedback

Increased afferent arteriole pressure = High RBF + GFR = Increase Na+ and Cl- delivery to early DCT = Detected by macula densa cells

Macula densa cells release adenosine = Stimulate afferent arteriole constriction = Decrease RBF + GFR

GFR Determinants: RAAS

Decreased afferent arteriole pressure = Low RBF + GFR = Detected by JG cells

JG cells release renin = Activate RAAS = Stimulate efferent arteriole constriction + Increase Na+/water reabsorption = Increase RBF + GFR

Renal Clearance

2 mechanisms:

1. Glomerular Filtration: Passive clearance

• Small and unbound molecules filtered

2. Tubular Secretion: Active clearance

• In PCT

• Large and protein-bound molecules eliminated by transporters (antibiotics, diuretics)

AKI: Description

Sudden renal function loss with increased creatinine and BUN

• Prerenal: Low perfusion (most common)

• Renal: Kidney damage

• Postrenal: Inadequate urine drainage

AKI: Epidemiology

Risk factors:

• Older age

• Infections

  • Pneumonia

• CKD

• HTN

• Meds

  • NSAIDs

  • Nephrotoxic antibiotics

AKI Etiology: Prerenal

Decreased renal perfusion

• Hypovolemia

  • Hemorrhage

  • Vomiting

  • Diarrhea

  • Diuretics

• Hypotension

• Decreased circulation/arterial volume

  • CHF

  • Liver failure

  • Pancreatitis

• Renal artery stenosis

• Drugs

  • NSAIDs

  • ACE inhibitors

AKI Etiology: Renal

Direct kidney injury

Acute Tubular Necrosis: Tubule damage from ischemia or toxicities

• Most common cause

• Ischemia: Hypoxia, hypotension

• Toxicity: Contrast

Acute Interstitial Nephritis: Renal interstitium inflammation

• Drug hypersensitivity

Glomerulonephritis: Glomerular inflammation

Vascular diseases

AKI Etiology: Postrenal

Bilateral urine flow obstruction from renal pelvis to urethra

• Acquired obstructions

  • Benign prostatic hyperplasia

  • Tumours

  • Stones

  • Iatrogenic (catheter injuries)

• Neurogenic bladder: Disrupted detrusor/sphincter innervation → Urinary retention

• Congenital malformations

AKI Pathogenesis: Prerenal

Decreased blood to kidneys (perfusion) = Low GFR (kidney function loss)

JG cells secrete renin = RAAS activation = Aldosterone increase Na+/water reabsorption = Increase urine osmolality (high solutes)

***High Na+ in blood = ADH secretion = Increase urea and water reabsorption

• High blood BUN:creatinine ratio

AKI Pathogenesis: Renal

Ischemia + toxin exposure = Tubular cell necrosis/apoptosis = Decreased reabsorption capacity (kidney function loss)

Increased Na+/water in urine = Decreased urine osmolality (low solutes)

AKI Pathogenesis: Postrenal

Bilateral urinary flow obstruction = Retrograde urine flow to kidneys = Increase hydrostatic pressure in tubules = Decrease GFR (kidney function loss)

AKI: Clinical Presentation

4 phases

1. Initiating event (kidney injury)

2. Maintenance (oliguric/anuric) phase 

3. Polyuric/diuretic phase

4. Recovery phase

AKI Clinical Pres: Initiating Event

Asymptomatic

Symptoms of underlying cause

AKI Clinical Pres: Maintenance Phase

Oliguria

Anuria

Fluid retention (pulmonary edema)

Hyperkalemia

Met acidosis

Uremia

AKI Clinical Pres: Polyuric/Diuretic

Polyuria: Increased urine output (glomerular filtration returns to normal)

Abnormal tubular reabsorption

• Electrolyte and water loss

• Dehydration

• Hyponatremia and hypokalemia

AKI Clinical Pres: Recovery Phase

Kidney function and urine production normalize

AKI: Investigations

Blood test

Urinalysis

Imaging

AKI: Blood Test

Prerenal:

• High serum creatinine

• High BUN:creatinine

Renal:

• High serum creatinine

• High BUN:creatinine

Postrenal:

• High serum creatinine

• Normal BUN:creatinine

AKI: Urinalysis

Prerenal:

• Low Na+ and urea

• High osmolality and specific gravity

• Microscopy:

  • Hyaline casts (clear tube-shaped proteins)

Renal:

• High Na+ and urea

• Low osmolality

• Microscopy:

  • Granular, brown, pigmented casts

    • Cellular debris and renal tubular epithelial cells → Tubular injury/necrosis

  • RBC cast

    • Glomerulonephritis

Postrenal:

• Oliguria

• Neurogenic Bladder: Normal

• Stones, Malignancy: Hematuria, crystals

AKI: Imaging

Ultrasound and noncontrast CT

Mostly for postrenal AKI:

• Confirm cause

• Bladder distension

• Stones

• Bilateral hydronephrosis (collecting system distension)

AKI: Treatment/Management

Treat underlying cause

**Dialysis

**Supportive care

• Discontinue nephrotoxic substances

• Manage volume status

AKI: Complications

Oliguric/Anuric Phase:

• Hypoxia

  • From pulmonary edema

• Hyperkalemia

  • Low urine K+ excretion

• Met acidosis

  • Low urine NH4+ excretion

  • Low bicarb reabsorption

Polyuric/Diuretic Phase:

• Electrolyte and water loss

  • Normal filtration + impaired reabsorption

Renal Replacement Therapy (RRT)

Support or replace kidney function

• Dialysis

• Kidney transplantation

RRT: Indications

A: Acidosis (severe met)

E: Electrolyte abnormalities

I: Ingestion

• Toxins

• Meds

O: Overload of fluid (refractory)

U: Uremia

• Pericarditis

• Encephalopathy

• Bleeding

RRT: Dialysis

Remove solutes and water from blood through diffusion (bypass kidneys)

• Hemodialysis:

  • Diffusion across semipermeable membrane = Remove solutes

  • Ultrafiltration = Hydrostatic pressure gradient = Remove excess water

• Peritoneal Dialysis:

  • Diffusion across peritoneum (semipermeable membrane)

RRT: Kidney Transplantation

Kidney donation from living or deceased donor

• Prefer left kidney from living (longer renal vein)

• Placed in iliac fossa (mostly right)

  • Extraperitoneal position

  • Increase vascularization + decrease complications

• Indication: Severe/end-stage renal disease

Indigenous Health Practice: Smudging

Traditional ceremony to purify/cleanse soul of negative thoughts

Process:

• Plants ignited to create smoke

• Waft smoke over person + inhale

• Dispose ashes outside (soil)

Hospitals Can:

• Modify policies to accommodate smudging

• Create smudging areas

Other Indigenous Health Practices

Sweat Lodge Ceremonies:

• Purification

• Involve steam in room and prayer

Pipe Ceremonies:

• Passing pipe with blessed tobacco in circle

• For spiritual and physical cleansing