Nephrology Quiz: Glomerular Diseases

Approach to the Patient with Kidney Disease

• Examination techniques for renal abnormalities:
  • Blood pressure measurements
  • Blood tests for creatinine and electrolytes
  • Urinalysis for protein, blood, nitrites and leucocytes
  • Abdominal examination for palpable kidneys
  • Percussing for tenderness in renal angle
  • Digital rectal examination for prostate enlargement
  • Checking sacrum and ankles for pitting oedema

The Kidneys

• Central role in excreting metabolic breakdown products (ammonia, urea, creatinine, uric acid, drugs, toxins).
• Produce large volumes of ultrafiltrate (120 mL/min, 170L/24h) at the glomerulus.
• Selectively reabsorb components of the ultrafiltrate along the nephron.
• Filtration and reabsorption rates are controlled by hormonal and haemodynamic signals to regulate fluid and electrolyte balance, BP, and calcium and phosphorus homeostasis.
• Activate Vitamin D and control red blood cell synthesis by producing EPO.

Functional Anatomy of the Kidney

• Composed of cortex and medulla.
• Contains nephrons:
  • Afferent arteriole
  • Efferent arteriole
  • Glomerulus
  • Bowman's capsule
  • Proximal convoluted tubule
  • Loop of Henle
  • Distal convoluted tubule
  • Collecting duct

Glomerular Architecture

• Filtration barrier:
  • Fenestration endothelium
  • Glomerular basement membrane
  • Podocytes (epithelial visceral cells)
  • Mesangial cells
• Blood vessels:
  • Afferent and efferent arterioles
• Bowman's space

Glomerular Diseases

• Most patients present asymptomatically until abnormalities are detected on routine screening.
• Various causes of injury:
  • Immunological
  • Inherited (eg, Alport's syndrome)
  • Metabolic (eg, diabetes)
  • Deposition of abnormal proteins (eg, amyloid)
• Glomerular cells are the target.
• Clinical features vary according to the insult type.

Nephritic and Nephrotic Syndromes

• Nephritic syndrome:
  • Haematuria
  • Hypertension
  • Oliguria
  • Fluid retention
• Nephrotic syndrome:
  • Heavy proteinuria (>3.5 g/24 hrs)
  • Hypoalbuminaemia
  • Oedema
• Many patients may not exhibit all features but some are typical of rapidly progressive glomerulonephritis.

Glomerular Diseases Mechanisms and Pathology

• Various mechanisms lead to glomerular injury.
• Mechanisms involve:
  • Deposition of immune complexes
  • Inflammation
  • Cell injury (e.g., podocyte injury)
• Different staining will reveal different characteristics of the diseases.

Renal Ultrasound

• Used to image the kidneys.
• Shows different components:
  • Normal kidney
  • Simple renal cyst
  • Hydronephrosis
  • Renal stone
  • Renal tumour

Imaging Techniques

• Various imaging techniques are available for kidney diagnosis. Including simple X-rays, ultrasound, CT scan (angio), MRI and myocardial perfusion.

Acute Kidney Injury (AKI)

• Sudden and often reversible loss of renal function (days or weeks).
• Associated with reduced urine volume.
• Significant complications, poor outcome (mortality = 50-70% in sepsis/multi-organ failure).
• Elderly patients at higher risk than non-elderly patients.
• Pre-renal, renal, and post-renal sub-types
• AKI can be classified using RIFLE criteria and AKIN criteria

Pathophysiology of AKI

• Pre-renal: decreased perfusion to kidney.
• Renal: damage to the kidney itself.
• Post-renal: obstruction to urine flow.
• Stages of damage include: initiation, extension, maintenance, and recovery.

Phases of AKI

• Initiation: ischemia, cell injury.
• Extension: microvascular injury, inflammation.
• Maintenance: dedifferentiation, proliferation.
• Recovery: redifferentiation/repolarization.

Renal Haemodynamics

• Afferent arteriole: prostaglandins cause vasodilation.
• Efferent arteriole: angiotensin II vasoconstricts.
• NSAIDs inhibit prostaglandins.
• ACE inhibitors / ARBs inhibit angiotensin II.

Acute Kidney Failure

• Tubule destruction, inflammation.
• Loss of function (decreased renal function).

Classification of AKI

• RIFLE (Risk, Injury, Failure, Loss, ESRD) and AKIN systems used to classify AKI based on
  • Creatinine levels
  • Urine output criteria

Management of AKI

• Assess fluid status (hypovolemia, fluid overload)
• Administer calcium and glucose/insulin to correct hyperkalemia
• Sodium bicarbonate to correct acidosis.
• Discontinue/reduce nephrotoxic drugs
• Ensure adequate nutritional support
• Screen for intercurrent infections
• Treat any urinary tract obstructions.

Acute Interstitial Nephritis

• Immune-mediated disorder.
• Primarily drug-induced (e.g., antibiotics, NSAIDs, diuretics)
• Can also be caused by infections (bacterial or viral), or toxins (e.g., heavy metals, certain fungi).
• Renal biopsy (Bx) usually required for diagnosis.
• Biopsy will show intense inflammation in the tubules and interstitium, with PMN and lymphocyte infiltrates.

Chronic Interstitial Nephritis

• Renal dysfunction with fibrosis and infiltration of the renal parenchyma by lymphocytes and plasma cells.
• Damage to tubules.
• Can lead to chronic kidney disease (CKD).

Chronic Kidney Disease (CKD)

• Irreversible deterioration in renal function over years
• Initially, only a biochemical abnormality.
• Eventually, loss of excretory, metabolic, and endocrine functions leads to clinical symptoms.
• CKD grade 5 = end-stage renal disease (ESRD).

Investigations of CKD

• Kidney function tests (GFR or Cr)
• Urine analysis (albumin/creatinine ratio)
• Other tests (electrolytes, blood counts, etc)
• Imaging studies

Management of CKD

• Monitor renal function
• Prevent or slow further renal damage
• Limit complications of renal failure
• Treat risk factors for cardiovascular disease
• Prepare for renal replacement therapy (RRT) if appropriate

End-Stage Renal Disease (ESRD)

• Complication of CKD
• Conservative management or dialysis/transplantation

Indications for Dialysis

• Fluid overload
• Hyperkalemia
• Metabolic acidosis
• Other relative indications (e.g., severe hypertension, intractable oedema)

Options for Renal Replacement Therapy

• Haemodialysis
• Haemofiltration
• Peritoneal dialysis
• Transplants

Haemodialysis Access

• Catheter
• Arteriovenous fistula
• Arteriovenous graft

Diagnostic Methods

• Non-invasive
  • X-ray
  • Ultrasound
  • CT scan
  • AngioCT
  • Myocardial perfusion
  • MRI
• Invasive
  • Angiography
  • IVUS
  • Angioscopy
• Functional
  • Tonometry
• Physical Exam

Physical Signs in Advanced CKD

• Possible physical findings include yellow complexion, pallor, raised jugular venous pressure, pulsations, pericardial friction rubs, etc.

The Progress of CKD

• Progression can be accelerated by various factors (disease, treatments).

Prevention of Early and Late CKD

• Early intervention and control of risk factors can slow the progression of CKD and reduce the risk of complications.

Cardiovascular and Renal Events Associated With Albuminuria

• Increased risk for cardiovascular and renal events with higher levels of albuminuria.

Biomarkers

• Early markers for progressive kidney disease include FGF-23, 1,25-dihydroxyvitamin D, parathyroid hormone, phosphorous.

Vascular Calcification in CKD

• Both intimal and medial calcification are noted.
• Specific factors, like Klotho and FGF-23, are involved.

Coronary Artery Calcification in CKD

• Atherosclerosis and Uremic arteriopathy frequently occur together.
• Uremic arteriopathy is associated with inflammation and oxidative stress

Calcifilaxis

• Skin condition, usually associated with chronic kidney disease.

Diagnostic Methods for CKD

• Non-invasive: simple X-rays, ultrasound, CT angio, myocardial perfusion, MRI
• Invasive: angiography, IVUS, angioscopy
• Functional tests: tonometry

Physical Signs in Advanced CKD

• Possible physical findings include yellow complexion, pallor, raised jugular venous pressure, pulsations, pericardial friction rubs, etc.

End-Stage Renal Disease (ESRD) Pathway

• Conservative or dialysis/transplantation are management options.

Indications for Dialysis

• Fluid overload, hyperkalemia, metabolic acidosis, and related clinical features can dictate the need for dialysis.

Options for Renal Replacement Therapy

• Haemodialysis involves filtering blood through a machine. Haemofiltration filters blood via a different process. Peritoneal dialysis involves using the peritoneum to filter waste. Renal transplant involves replacing the patient's diseased kidney with a healthy donor kidney.