Glomerular Disease Flashcards
Glomerular disease may be primary (glomerular injury due to a primary renal pathology) or secondary (glomerular injury occurring as part of a systemic process).
Primary: IgA nephropathy, minimal change disease, focal segmental glomerulosclerosis
Secondary : Vasculitis (e.g. ANCA-associated vasculitis), amyloidosis, diabetes mellitus
Isolated haematuria
This refers to the recurrent presentation of haematuria.
Haematuria refers to blood in the urine that may be visible or non-visible. Isolated haematuria is broadly defined as persistent haematuria in the absence of proteinuria and normal renal function. This requires reassessment over 1-4 weeks to determine whether haematuria is persistent.
Typical causes include:(3)
IgA nephropathy
Alport syndrome
Thin basement membrane disease: diffuse thinning of the basement membrane on electron microscopy. May be familial in up to 50% of cases
Importantly, blood may occur from any location along the urinary tract. Therefore, it is important exclude other causes before confirming isolated haematuria (e.g. imaging, cystoscopy). Features that are suggestive of blood from glomerular origin include:
Dysmorphic red blood cells: red cell structure appears abnormal under the microscope
Red blood cell casts: identification of red bloods cells within urinary casts seen under the microscope. A cast is a microscopic cluster of particles wrapped in uromodulin (Tamm-Horsfall protein). Uromodulin is secreted by epithelial cells lining the loop of Henle, distal tubule & collecting duct.
Isolated proteinuria
The refers to the persistent presence of protein in the urine.
Proteinuria refers to the presence of protein in the urine that may be glomerular, tubular, overflow (i.e. myeloma) or post-renal in origin. Isolated proteinuria is broadly defined as persistent proteinuria in the absence of other urinary abnormality (e.g. haematuria), co-morbidities (hypertension & diabetes) and in the presence of normal renal function.
The degree of proteinuria is non-nephrotic range (i.e. < 3.5 g/day) and can be detected with urine dipstick, spot urinary protein:creatinine ratio or a 24-hour urinary collection. Persistent isolated non-nephrotic range proteinuria usually indicates underlying renal disease or a systemic disorder that needs further investigation.
It is important to exclude more benign causes of proteinuria including:
Transient proteinuria: common in young individuals. Absent on repeat testing and exercise is a common precipitant.
Orthostatic proteinuria: presence of proteinuria only in the upright position
Nephrotic syndrome
Nephrotic syndrome is broadly defined as a triad of heavy (nephrotic range) proteinuria > 3.5 g/day, hypoalbuminaemia (< 35 g/L) and peripheral oedema. The condition may also be accompanied by hyperlipidaemia and thrombotic disease (venous and arterial blood clots).
Nephrotic syndrome
Nephrotic syndrome is broadly defined as a triad of heavy (nephrotic range) proteinuria > 3.5 g/day, hypoalbuminaemia (< 35 g/L) and peripheral oedema. The condition may also be accompanied by hyperlipidaemia and thrombotic disease (venous and arterial blood clots).
The causes of nephrotic syndrome can be broadly divided into primary renal disorders and secondary systemic conditions.
Primary: minimal change disease, focal segmental glomerulosclerosis (FSGS), membranous nephropathy.
Secondary: diabetes mellitus, amyloidosis, systemic lupus erythematosus, HIV infection
Nephritic syndrome (i.e. glomerulonephritis)
Nephritic syndrome is classically described as the presence haematuria, variable proteinuria (may be nephrotic range), oliguria (i.e. acute kidney injury) and hypertension. The term ‘nephritic syndrome’ is often used interchangeably with nephritis or glomerulonephritis simply referring to inflammation within the glomeruli.
Nephrotic syndrome vs nephritic syndrome
Nephrotic syndrome is broadly defined as a triad of heavy (nephrotic range) proteinuria > 3.5 g/day, hypoalbuminaemia (< 35 g/L) and peripheral oedema. The condition may also be accompanied by hyperlipidaemia and thrombotic disease (venous and arterial blood clots).
Nephritic syndrome is classically described as the presence haematuria, variable proteinuria (may be nephrotic range), oliguria (i.e. acute kidney injury) and hypertension. The term ‘nephritic syndrome’ is often used interchangeably with nephritis or glomerulonephritis simply referring to inflammation within the glomeruli.
Glomerulonephritis has quite a variable clinical presentation.
Mild: presentation with minimal haematuria and proteinuria only
Severe: typically presents with the classical ‘nephritic syndrome’
Self-limiting: development of an acute glomerulonephritis that gets better without treatment
RPGN: severe glomerulonephritis that has a fulminant course with rapid deterioration in renal function over days to weeks to a few months.
Chronic: slowly progressive renal disease presenting with features of CKD
There are three major causes of nephritic syndrome:
Immune complex deposition: Poststreptococcal glomerulonephritis, autoimmune (e.g. lupus), IgA nephropathy
Anti-GBM deposition: anti-glomerular basement membrane disease
Small-vessel vasculitis: eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, polyangiitis with granulomatosis
The principal investigation for a suspected glomerular disease is …
The principal investigation for a suspected glomerular disease is a renal biopsy.
Basic urinary tests are important to provide objective measurement of blood and/or protein in the urine
Urine dipstick: most sensitive for detection of albumin
Urinary protein:creatine ratio: a spot sample is collected to determine the protein content (level of protein divided by level of creatinine). Normal is < 30 mg/mmol
24 hour urinary collection: urine is collected over 24 hours to determine the protein content. Normal is < 0.2 g
A series of basic blood tests are required in any patient with suspected glomerular disease.
Full blood count Urea & electrolytes Bone profile HbA1c Blood gas Lipid profile: hyperlipidaemia seen in nephrotic syndrome
Renal screen
This refers to a series of specialist blood tests that are completed to look for the possible causes of acute renal impairment and glomerular disease. It is a broad screen that can test for specific causes of glomerular disease, or at least provide important clues to the possible underlying cause.
Complement: typically low in vasculitis
Anti-nuclear antibody (ANA)
Anti-neutrophil cytoplasmic antibody (ANCA)
Anti-glomerular basement membrane antibody (GBM)
Anti-dsDNA: raised in systemic lupus erythematosus
Myeloma screen: serum free lights chains, protein electrophoresis
Anti-PLA2R autoantibody: raised in membranous nephropathy
Virology: Hepatitis B, Hepatitis C and Human immunodeficiency virus
Cryoglobulins: immunoglobulins that precipitate at low temperatures
Creatine kinase: may be raised in rhabdomyolysis
Imaging - renal
Imaging using a renal ultrasound or CT kidney, urinary, and bladder (CT KUB) is essential in the work up of acute kidney injury and chronic kidney disease to exclude an obstructive pathology and assess the overall structure of the kidneys (e.g. any features of polycystic).
