Crash course: Renal Flashcards
What is AKI? What is it measured by?
acute decline in renal function, leading to fall in urine output
Measured by rise in creatinine + urea
What is CKD? How is it measured?
Decline in renal function due to progressive damage present for >3 months
Measured via decline in eGFR
What are the stages of CKD based on eGFR?
1: >90
2: 60-89
3a: 45-59
3b: 30-44
4: 15-29
5: <15 = end stage, dialysis
What are the caveats of stage 1 and 2 CKD grades?
If stage 1/2 based on eGFR but NO Sx, NOT CKD
What are the 2 most common causes of CKD?
Diabetes
HTN
Give 2 less common causes of CKD
Autosomal dominant polycystic kidney disease
Untreated AKI (Pyelonephritis, ATN, obstruction)
What are the 3 broad causes of AKI?
PRE-renal: decrease in flow to the kidneys.
RENAL: direct damage to nephrons
POST-renal: ‘Surgical causes”- physical outflow obstruction
From most to least common, what are the broad causes of AKI
Pre-renal
Post-renal
Renal
Give 5 causes of pre-renal AKI
Hypovolaemia
Sepsis
CCF
Renal artery stenosis
ACE inhibitors
Give 6 causes of renal AKI
Ischaemia
Nephrotoxins
Glomerulonephritis
Interstitial nephritis
Hepatorenal syndrome
HUS / TTP
Give 4 causes of post-renal AKI
Stone
Tumour
Prostate
Blocked catheter
Which 3 structures can be damaged to result in renal causes of AKI?
Glomerulus: Nephrotic + Nephritic syndrome
Blood vessels: HUS + TTP
Tubules: ATN + acute interstitial nephritis
Give 4 causes of nephrotic syndrome
Minimal change
Membranous
FSGS
Secondary causes
What triad characterises Nephrotic syndrome?
Peripheral oedema
Proteinuria (3g/day or PCR >300mg)
Low serum albumin
Give 2 other features of nephrotic syndrome
Increased cholesterol
Increased clotting tendency- Antithrombin III is lost
What is the pathophysiology in all causes of nephrotic syndrome?
Breakdown of PODOCYTES (filtration barrier)
Large molecules e.g. Protein not filtered out - lost in urine
What is the broad management of nephrotic syndrome?
Steroids
What is the most common cause of nephrotic syndrome in kids?
Minimal change disease
What is seen on histology in minimal change disease?
Light microscopy: Nothing
Electron microscopy: Loss of podocyte foot processes
Immunofluorescence: Nothing
What is the prognosis for minimal change disease?
Majority respond to Prednisolone ~(90%)
In which population is membranous glomerulonephropathy seen?
Adults
What do immunofluorescence microscopes detect?
Immune complexes
What is seen on histology in membranous glomerulonephropathy?
Light microscopy: Diffuse basement membrane thickening
Electron microscopy: Spikey immune complex deposits
Immunofluorescence: Immune complexes across all of basement membrane
How does membranous glomerulonephropathy respond to steroids?
Poor response
Give 2 associations to Membranous glomerulonephropathy
SLE
Anti-phospholipase A2 antibodies
What is focal segmental glomerulonephritis? (FSGS)
Focal = Only some glomeruli are damaged (vs diffuse)
Segmental = Only some regions of each individual glomerulus damaged
Which population is affected by focal segmental glomerulonephritis?
Adults
What is seen on histology in Focal segmental glomerulonephritis?
Light microscopy: Focal + segmental scarring
Electron microscopy: Loss of foot processes
Immunofluorescence: Nothing
How does focal segmental glomerulonephritis respond to steroids?
Not great (better than membranous glomerulonephropathy)
Give 2 secondary causes of nephrotic syndrome. What is seen on histology?
Diabetes: Kimmelstiel Wilson nodules
Amyloidosis: apple green birefringence on Congo red stain
What are the 2 types of amyloidosis? What causes each?
AA: chronic inflammation (e.g RA, SLE)
AL: Light chains (MM): plasma cells produce Abs, Abs clog up kidneys + cause damage
Give 5 causes of nephritic syndrome
IgA
Post streptococcal
Rapidly progressive (crescentic)
Alport’s syndrome (hereditary)
Benign familial
What triad characterises nephritic syndrome?
HTN
Haematuria
Peripheral oedema
What is seen in the urine in nephritic syndrome?
Red cell casts- “Cola-coloured”
What is seen on bloods in nephritic syndrome?
Deranged U+Es
What is the pathophysiology of nephritic syndrome?
Big proteins + complexes damage delicate blood vessels + cause inflammation
Give 3 features of IgA nephropathy?
Commonest cause of nephritic syndrome worldwide
After group A Streptococcal infection (1-2 days remember: IgA = Acute)
Deposition of IgA immune complexes within glomeruli
What is seen on immunofluorescence in IgA nephropathy?
IgA immune deposits in mesangium
What is the prognosis for IgA nephropathy?
1/3 get better
1/3 get CKD
1/3 need dialysis
Give 2 features of post-streptococcal glomerulonephritis
After group A strep infection (1-3w)
Thought to be due to antigen mimicry + immune complex deposition
What is seen on bloods in post-streptococcal glomerulonephritis?
Raised Anti-streptolysin-O titre
Reduced C3 (as immune complex mediated)
What is seen on immunofluorescence in post-streptococcal glomerulonephritis?
Granular IgG deposits in basement membrane
What is management in post-streptococcal glomerulonephritis?
Supportive
What is Rapid progressive nephritic syndrome? (crescentic)
Most aggressive type of glomerulonephritis causing renal failure in weeks.
Characterised by severity + presence of crescents (macrophages in Bowman’s space)
Name 3 causes of rapidly progressive nephritic syndrome
Goodpasture’s
Immune complex mediated
Pauci-immune (ANCA associated)
What is Goodpasture’s characterised by?
Presence of Anti-glomerular basement membrane antibodies
Causes glomerulonephritis + pulmonary haemorrhages
What is the antigen targeted in goodpastures disease?
Alpha-3 subunit of type IV collagen found in the basement membrane of the lungs + kidneys.
What is seen on histology in Goodpasture’s?
Light microscopy: Crescents
Immunofluorescence: LINEAR deposition of IgG in GBM
Give 4 causes of immune complex mediated rapidly progressive nephritic syndrome
SLE
IgA nephropathy
Post-infectious
HSP
Describe histology in immune complex mediated rapidly progressive nephritic syndrome
Light microscopy: Crescents
Immunofluorescence: BUMPY deposition of immune complexes in GBM or mesangium
What are the subtypes of Pauci-immune rapidly progressive nephritic syndrome?
cANCA: granulomatosis with polyangiitis (GPA)
pANCA: microscopic polyangitis (MPA), eosinophilic granulomatosis with polyangiitis (eGPA)
What is seen on histology in Pauci-immune rapidly progressive nephritic syndrome?
Light microscopy: Crescents
Immunofluorescence: No/ scanty immune complexes
What other features may be seen in Pauci-immune rapidly progressive nephritic syndrome?
Vasculitis: Skin rash, pulmonary haemorrhage
What causes Alport’s syndrome?
X-linked abnormalities in type IV collagen
What triad is seen in Alport’s syndrome?
Nephritic syndrome
Bilateral sensorineural deafness
Lens dislocation
What is the prognosis of Alport’s syndrome?
Progressive, causes end stage renal failure in early adulthood
What causes benign familial haematuria?
Autosomal dominant abnormality in type IV collagen
aka. thin basement membrane disease
What are the symptoms of benign familial haematuria?
Asymptomatic haematuria
No other issues generally
What is the most common renal cause of AKI?
Acute tubular necrosis
What is acute tubular necrosis?
Damage to tubules
Tubule cells die + shed leading to presence of brown casts in urine
Give 2 causes of acute tubular necrosis
Hypovolaemia
Toxins:
* Aminoglycoside abx: gentamicin
* Myoglobin (rhabdomyolysis)
* IV contrast
What should you think of in acute interstitial nephritis? What occurs?
Think of allergic reaction to medications
Interstitial infiltrate + eosinophils excreted as white cell casts or white cells in urine with no infection (sterile pyuria)
+/- rash
+/- fever
Give 3 drugs that may precipitate acute interstitial nephritis?
Penicillins
Allopurinol
NSAIDs
What causes chronic interstitial nephritis?
Long term paracetamol/ NSAID use
What is haemolytic uraemia syndrome?
Microangiopathy characterised by:
* Progressive renal failure (AKI)
* Microangiopathic haemolytic anaemia (MAHA)
* Thrombocytopenia
What is the most common cause of HUS?
E. coli O157:H7
(shiga toxin-producing E. coli or STEC)
Describe the pathophysiology of HUS
- Gastroenteritis (E.coli 90%) → toxin
- Endothelial damage
- Thrombosis, platelet consumption + fibrin strand deposition → ↓ Platelets
- Destruction of RBCs: schistocytes, ↓ Hb
Where are micro thrombi in HUS?
Microthrombi confined to kidneys
What pentad of features characterises Thrombotic thrombocytopenic purpura?
Haemolytic anaemia
Uraemia
Thrombocytopenia
Fever
Neurological Sx: seizures, hemiparesis, impaired consciousness, impaired vision
What is the mortality in TTP if untreated?
90%
Give 6 causes of TTP
Post-infection e.g. UTI, GI
Pregnancy
Drugs: ciclosporin, OCP, penicillin, clopidogrel, aciclovir
Tumours
SLE
HIV
What is the pathophysiology of TTP?
- Deficiency in protease ADAMTS13 that cleaves vWF
- Large vWF multimers form
- Platelet aggregation + fibrin deposition
- Microthrombi
Where do microthrombi occur in TTP?
Everywhere, esp. CNS
What is the aetiology of polycystic kidney disease? What does this cause?
Autosomal Dominant
Due to mutation in PKD gene encoding polycystin
Causes haematuria + kidney failure
Give 2 extra renal manifestations of PKD
Liver cysts (common)
Berry aneurysms (leading to SAH)
What is the aetiology of lupus nephritis? What is seen?
Damage due to immune complex deposition,
See wire loop capillaries + lumpy immune complex deposition
What are the 2 extremes of lupus nephritis?
Early stage (stage 1): only mesangial disease- not affecting kidney function
Advanced (stage 6): >90% sclerosis = end stage
A 25M is involved in an RTA. On arrival his BP is 65/40 mmHg but he is quickly resuscitated and stabilised in ITU.
2 days later the SHO notices that over the past 6h, his catheter urine output has only been 50ml. What is the cause of his renal dysfunction?
Acute tubular necrosis
Often get a pre-renal AKI, rehydrate them, become stable, but then renal function continues to decline- because you cant reverse necrosis
(he has progressed from pre-renal to ATN)
