07.1 Haematuria, nephrotic and nephritic syndromes

Haematuria, Nephrotic and Nephritic Syndromes

• Haematuria is the presence of red blood cells (RBCs) in the urine, often indicating renal or urogenital issues.
• Microhaematuria is when at least 3 RBCs are present per high-power field, only visible under a microscope. It's common in glomerular diseases like IgA nephropathy.
• Macrohaematuria is blood visible to the naked eye in the urine. Differentiate from pseudohaematuria via microscopy.
• Pseudohaematuria is discoloured urine without RBCs, caused by things like foods (e.g., beetroot), drugs (e.g., rifampicin), or conditions like myoglobinuria or haemoglobinuria.

Learning Objectives

• Define and classify haematuria, differentiating true from pseudohaematuria, and identifying sources (e.g., glomerular vs. non-glomerular).
• Define and classify proteinuria, including glomerular, tubular, and overflow proteinuria.
• Differentiate between nephrotic and nephritic syndromes, focusing on clinical presentation, pathophysiology, and diagnostic implications.

Key Concepts and Definitions

• Proteinuria: Elevated protein levels in urine, a key sign of kidney disease.
• Glomerular Proteinuria: Damage to the glomerular barrier leads to excessive albumin leakage.
• Tubular Proteinuria: Tubular dysfunction results in failure to reabsorb small proteins.
• Overflow Proteinuria: Excess low-molecular-weight proteins overwhelm tubular reabsorption.
• Functional Proteinuria: Benign, temporary proteinuria due to factors like fever or exercise.
• Nephrotic Syndrome: Marked by significant proteinuria (over 3.5g/day), hypoalbuminemia, edema, and hyperlipidemia. Indicates glomerular filtration barrier damage.
• Nephritic Syndrome: Characterised by haematuria, reduced glomerular filtration rate (GFR), and non-nephrotic proteinuria.

Pathophysiology

• Haematuria Mechanisms:
  • Glomerular origin: Blood leaks from damaged glomeruli, often indicated by dark urine and dysmorphic RBCs; a proteinuria of over 500mg/day frequently accompanies it.
  • Non-glomerular origin: Blood originates outside the glomeruli (e.g., urinary tract infection, stones). Often does not show dysmorphic RBCs, and proteinuria is usually under 500mg/day.
• Nephrotic Syndrome Pathophysiology:
  • Hypoalbuminemia and Oedema:
    • Underfilling mechanism: Low albumin results in lower oncotic pressure, shifting fluid to extracellular spaces and causing edema.
    • Overfilling mechanism: Sodium retention and RAAS (Renin-Angiotensin-Aldosterone System) activation lead to enhanced water retention and oedema formation.
• Nephritic Syndrome Pathophysiology:
  • Inflammation in the glomeruli leads to increased capillary permeability and a reduced GFR, marked by oliguria, dysmorphic red blood cells (RBCs), and RBC casts.
  • RAAS activation contributes to volume expansion and hypertension.

Clinical Applications

• Case Study: A male patient (45) presents with dark urine, facial swelling, and high blood pressure suggesting potential nephritic syndrome.
• Diagnostic Approach: Dipstick urinalysis, microscopic examination (to identify RBC morphology), urine protein/creatinine ratio, and other tests (e.g., kidney function tests, urine culture) assess proteinuria.

Pharmacology

• ACE Inhibitors/ARBs: Reduce proteinuria, manage hypertension, and protect kidneys. Particularly in nephrotic and nephritic syndromes with concurrent hypertension.

Differential Diagnosis

• Haematuria: Differentiate pseudohaematuria (non-RBC causes) from glomerular (e.g., IgA nephropathy, thin basement membrane disease, glomerulonephritis) and non-glomerular sources.
• Proteinuria: Characterise as overflow, tubular, or glomerular. Note protein levels and any specific symptoms.

Investigations

• Urine dipstick: Initial assessment of haematuria and proteinuria; needs microscopy and examination.
• Microscopic Urinalysis: Identifies RBC morphology (dysmorphic vs isomorphic) and presence of casts.
• Urine Protein/Creatinine Ratio (PCR): Quantifies proteinuria from a spot urine sample.
• Urine culture: Checks for urinary tract infections.

Summary and Key Takeaways

• Dysmorphic RBCs and RBC casts strongly suggest a glomerular origin for haematuria.
• Nephrotic syndrome is characterized by heavy proteinuria, hypoalbuminemia, and hyperlipidaemia; it requires treatment focused on managing these factors.
• Nephritic syndrome presents with haematuria, hypertension, and moderate proteinuria, requiring early blood pressure control and immunosuppression if autoimmune.