Nephrology Flashcards
What is glomerulonephritis?
Glomerulonephritis refers to a large and clinical significant group of renal diseases that result in inflammation/damage of glomeruli. Typically due to immunologically-mediated inflammation of the renal glomeruli. It is the third commonest cause of ESRD (End-Stage Renal Disease)after diabetes mellitus and hypertension.
Depending on the cause, glomerular disease can result in:
- Nephrotic syndrome
- Nephritic syndrome
- Acute Kidney Injury
- Chronic Kidney Disease
- Asymptomatic proteinuria
- Asymptomatic haematuria
How can glomerulonephritis be classified?
There are many different types and subtypes of glomerulonephritis. Most occur due to deposition of immune complexes in the glomerulus (either basement membrane, subendothelium or subepithelium), causing inflammation of the glomerulus.
One of the ways to classify glomerulonephritis is the primary/secondary classification. Primary glomerulonephritis occurs when the glomerular injury is not part of a systemic disease, such as anti-GBM or IgA nephropathy. Secondary glomerulonephritis occurs when the renal injury is a result of systemic disease such as SLE or Wegner’s granulomatosis.
Can also be classified based on whether it causes proliferation of the basement membrane or not. Those that do cause proliferation of cells in the glomerulus lead to nephritic syndrome. Diseases which are classed as non-proliferative tend to cause nephrotic syndrome.
How is glomerulonephritis investigated?
Bloods:
- FBC to detect normocytic normochromic anaemia.
- Comprehensive metabolic profile - elevated creatinine indicates severe or late disease, hypoalbuminaemia in patients with nephrotic syndrome. Elevated liver enzymes if post-viral hepatitis.
- eGFR may be normal or reduced.
- Lipid profile may show hyperlipidaemia
24-h urine collection is used to quantify proteinuria. Urine may also show lipduria seen as oval fat bodies.
A renal ultrasound is used to differentiate from other causes of acute renal failure such as obstructive uropathy.
Antibody testing for:
- Rheumatoid factor
- ANCA
- Anti-GBM (Goodpasture Syndrome)
- Anti-dsDNA (SLE)
- ANA (SLE)
- HIV or Hepatitis virology.
What is nephrotic syndrome?
Nephrotic syndrome is characterised by breakdown of filtration barrier and massive protein leak:
- Hypoalbuminaemia
- Proteinuria (>3g/24h) seen as “frothy” urine.
- Hyperlipidaemia
- Oedema seen as swelling or puffy appearance in EMQs.
What are the causes of nephrotic syndrome?
Nephrotic syndrome tends to be caused by non-proliferative causes of glomerulonephritis. Can be classified as primary glomerular disease (disease that interferes with podocyte function), and systemic causes. Primary causes all result in loss of podocyte foot processes, but can be differentiated by light microscopy.
What are the clinical features of nephrotic syndrome?
Patients usually present with increasing peripheral oedema. However, up to 4l of fluid can be retained before it becomes clinically visible. The oedema often starts peri-orbitally and can become very severe with lower leg and genital oedema. Can also cause ascites as well as pleural and pericardial effusions.
It is important to note that hypertension and raised JVP/pulmonary oedema are not features of nephrotic syndrome. If those are present, it could be nephritic syndrome or significant cardiac or renal failure.
How is nephrotic syndrome investigated?
Nephrotic syndrome is diagnosed on the basis of clinical and laboratory findings:
-
Urine analysis must show proteinuria and lipiduria. It is important to measure the amount of protein excreted. Can be done by a 24h-urine collection.
- Protein:creatinine ratio is almost as accurate, and less error prone than 24h-urine collection.
- Blood analysis must show hypoalbuminaemia and can show hyperlipidaemia.
Assess renal function through measurement of serum urea and creatinine and an eGFR.
The urine should be assessed for the presence of haematuria (suggesting glomerulonephritis).
A renal ultrasound gives assessment of renal size and morphology, and should be performed early.
Nephrotic syndrome in adults requires renal biopsy to identify the cause, prior to definitive treatment.
Describe the management of nephrotic syndrome
The general management principles for nephrotic syndrome include:
- Salt and fluid restriction. May require diuretics to control fluid.
- Reduction of proteinuria. Proteinuria will itself aggravate tubulointerstitial inflammation. Use ACE-I or ARBfor their anti-proteinuric effect.
- Hypercoagulability- prophylactic anticoagulation with SC heparin.
- Infection
- Dyslipidaemia
What is nephritic syndrome?
Nephritic syndrome is a manifestation of glomerular inflammation and is characterised by PHAROH:
- Proteinuria(<3g/24h - less than nephrotic syndrome)
- Haematuria- may be seen as ‘coke-coloured’ urine.
- Azotaemia- presence of nitrogen-containing compounds in blood, notably creatinine and urea
- Red Cell Casts
- Oliguria
- Hypertension
What are the causes of nephritic syndrome?
Like most causes of glomerulonephritis, nephritic syndrome is a result of immune-complex mediated damage. Nephritic syndrome is caused by proliferative glomerular disease - causes of glomerulonephritis where there is proliferation of cells within the glomerulus. These causes include:
-
Acute post-infectious (post-streptococal) Glomerulonephritis
- This occurs 1-3 weeks after streptococcal throat infection or impetigo, usually after Group A alpha-haemolytic streptococci (strep pyogenes).
- Bloods: ASOT (anti streptolysin-O) titre increased,decreased complement
- Biopsy: Increased cellularity of glomeruli and granular deposits of IgG and C3 in GBM. Electron microscope shows subendothelial humps.
-
IgA nephropathy - Berger disease is thecommonest glomerulonephritis (GN) worldwide
- Caused by deposition of IgA immune complexes in glomeruli.
- Presents 1-2 days after an URTI with frank haematuria or asymptomatic/microscopic haematuria
- Can progress to ESRF
- Biopsy: shows granular deposition of IgA and complementin mesangium
-
Rapidly Progressive Crescentic Glomerulonephritis causes nephritis syndrome as well as AKI (see notes specifically on rapidly progressive GN). Caused by anti-GBM, immune-complexes or pauci-immune causes. Examples include:
- Wegener’s granulomatosis
- Microscopic polyangiitis
- SLE
- Goodpasture syndrome
-
Hereditary nephritis - Alport’s syndrome is a hereditary glomerular disease caused by mutation in type IV collagenalpha 5 chain
- X linked
- Causes nephritic syndrome as well as sensorineural deafness and eye disorders (lens dislocation, cataracts)
- Presents at 5-20 years with nephritic syndrome progressing to ESRF
- Thin basement membrane disease (benign familial haematuria) is quite common (5% prevalence). It is due to a hereditary defect in type IV collagen alpha 4 chain, inherited autosomal dominant, causing glomerular basement membrane thinning. In most cases microscopic haematuria is the only consequence. Renal function usually normal.
What are the clinical features of nephritic syndrome?
- Intermittent macroscopic haematuria (red or brown urine “cola-coloured urine”)
- Hypertension
- Pitting oedema
- If ↓GFR: oliguria and uremic symptoms (see uraemia)
Describe the investigations for nephritic syndrome
Urine:
- Dipstick urine for haematuria, proteinuria.
- Urine microscopy for red morphology ± casts/
- Urinalysis will show proteinuria. The amount of proteinuria is variable (often <1g/day, but may be nephrotic range).
Blood:
- SCr, eGFR, U&E, FBC, bone profile, LFT.
- Acute phase markers (CRP, ESR).
- Immunological and serological (‘nephritic’) screen
Imaging and Histology
- USS kidneys.
- Renal biopsy
Describe the management of nephritic syndrome
Management is supportive, while trying to establish (and perhaps treat) the cause.
Salt and water restriction is necessary to establish fluid status. Treat accordingly.
Blood pressure control should be aimed at <130/80
Adequate nutrition
Prompt treatment of infection
Renal replacement therapy
What are the types and causes of rapidly progressive glomerulonephritis?
What is rhabdomyolysis?
Rhabdomyolysis is the development of AKI due to extensive muscle damage and resulting muscle cell death and the release of myoglobin; ~7% of all cases of AKI.
