105. Acute kidney injury Flashcards
what symptoms may ppl have with aki
reduced urine output
pulmonary and peripheral oedema (secondary to fluid overload)
arrhythmias (secondary to changes in potassium and acid-base balance)
features of uraemia (for example, pericarditis or encephalopathy)
Nausea
Lethargy
what signs should you look for aki
Hypertension
Fluid status:
- Fluid overload with raised jugular venous pressure (JVP), pulmonary oedema and peripheral oedema.
- Hypovolemic if hypovolemic cause eg GI losses
Pericardial rub
why do ppl with aki get pericarditis
Uremic pericarditis is thought to result from inflammation of the visceral and parietal layers of the pericardium by metabolic toxins that accumulate in the body owing to kidney failure.
define aki
Rise in creatinine of more than 25 micromol/L in 48 hours
Rise in creatinine of more than 50% in 7 days
Urine output of less than 0.5 ml/kg/hour over at least 6 hours and more than eight hours in children and young people.
A 25% or greater fall in eGFR in children and young people within the previous 7 days.
risk factors aki
Older age (e.g., above 65 years)
Sepsis
Chronic kidney disease
Heart failure
Diabetes
Liver disease
Cognitive impairment (leading to reduced fluid intake)
Medications (e.g., NSAIDs, gentamicin, diuretics and ACE inhibitors)
Radiocontrast agents (e.g., used during CT scans)
General investigations aki
Bloods:
U&Es
albumin
lipid profile
VBG for acute ?hyperkalaemia
Urine:
Urine output
Urine dip
Urinalysis
Brown/black casts → ATN
Red casts → glomerulonephritis
White casts → acute interstitial nephritis
Urinary electrolytes, urea and creatinine (albumin:creatinine) ratio
Imaging:
ECG
USS for obstructive uropathy
CT
Biopsy for intrinsic cause
General management aki
- IV fluid resuscitation to promote renal perfusion (unless fluid overloaded)
- Hold nephrotic medications (DAMN) /risk vs benefit
Diuretics
ACEi/ARB/Antibiotics
Metformin
NSAIDs - Correct electrolyte imbalances
Hyperkalaemia (1. Calcium gluconate, 2. Insulin + dextrose) - If obstructed → catheter if bladder outlet obstruction - monitor urine output and weight
- Renal replacement therapy if indicated eg
Severe acidosis/hyperkalemia
Drug intoxications
Refractory
complications of aki
Fluid overload, heart failure and pulmonary oedema
Hyperkalaemia
Metabolic acidosis
Uraemia (high urea), which can lead to encephalopathy and pericarditis
what is aki (characterised by)
It is characterised by a decline in renal excretory function over hours or days that can result in failure to maintain fluid, electrolyte, and acid-base homeostasis
causes of pre-renal aki
hypovolemia
hypotension/shock
renal artery stenosis
aortic dissection
hf
what in the history and exam is suggestive of pre-renal aki
History:
vomiting/diarrhoea/burns
Heart failure
Examination
Hypovolemic status
Fluid overloaded if heart failure
what invetsigation finding is indicative of pre-renal aki
High urea>creatinine ratio
where is the pathology in renal aki
Involves damage at the level of the nephron
what is the normal pressure gradient across the nephron maintained by?
relative Afferent vasodilAtion and efferent vasoconstriction
Causes of renal aki
Change in pressure gradient
- NSAIDs
- ACEi/ARBs
Necrosis of tubule causing obstruction (acute tubular necrosis
- pre-renal injury
- rhabdomyolysis
- haemolysis
- drugs (AVRG)
Inflammation of glomerulus (glomerulonephritis)
nephrotic
- minimal change
- focal segmental glomerulosclerosis
- membraneous GN
nephritic
- post-strep GN
- IgA nephropathy (inc HSP)
- Lupus nephritis
nephritic rapidly progressing
- anti-GBM
- polyarteritis nodosum
- granulomatosis with polyangitis
Haemolytic uraemic syndrome
Acute interstitial nephritis
- Drugs PPN
causes of post-renal aki
External
- Benign prostatic hyperplasia (benign enlarged prostate)
- Tumours (e.g., retroperitoneal, bladder or prostate)
Internal
- Kidney stones
- Neurogenic bladder
- Strictures of the ureters or urethra
features of renal artery stenosis
hypertension
Renal hypoperfusion leads to hyperactivation of the renin-angiotensin-aldosterone axis, causing hypertension.
chronic kidney disease
‘flash pulmonary oedema’
causes of renal artery stenosis
acute (usually due to thromboembolism)
or chronic (usually due to atherosclerosis or fibromuscular dysplasia).
what drugs affect the haemodynamics and therefore can cause renal aki
NSAIDs cause afferent vasoconstriction
ACEi and ARBs cause efferent vasodilation
These reduce the pressure gradient and therefore reduce eGFR
what drugs are nephrotoxic
Acute tubular necrosis causing drugs: (AVRG)
Aminoglycosides
Vancomycin
Radio contrast
Gentamicin
Acute interstitial nephritis causing drugs: (PPN)
PPI
Penicillin
NSAID
what drugs should you hold during aki
DAMN
Diuretics
ACEi/ARB/Antibiotics esp aminoglycosides
Metformin, lithium, digoxin, opiates (narrow TW) (may have to be stopped)
NSAIDs
why do you soemtimes stop metformin in aki
increased risk of toxicity (but doesn’t usually worsen AKI itself)
causes of acute tubular necrosis
Ischaemia due to hypoperfusion (e.g., dehydration, shock or heart failure)
Nephrotoxins (e.g., gentamicin, radiocontrast agents or cisplatin) (eg, aminoglycosides, radiocontrast media, myoglobin, cisplatin, heavy metals, light chains in myeloma kidney).
Myoglobin : rhabdomyolysis, haemolysis
what invetsigation confirms ATN
Muddy brown casts on urinalysis confirm acute tubular necrosis
prognosis ATN
The epithelial cells can regenerate, making acute tubular necrosis reversible. Recovery usually takes 1-3 weeks.
what is nephrotic syndrome
Nephrotic syndrome occurs when the basement membrane in the glomerulus becomes highly permeable, resulting in significant proteinuria. It refers to a group of features without specifying the underlying cause.
It involves:
Proteinuria (more than 3g per 24 hours)
Low serum albumin (less than 25g per litre)
Peripheral oedema
Hypercholesterolaemia
what is the most common cause of nephrotic syndrome in children
Minimal change disease
what is the most common cause of nephrotic syndrome in adults
Membranous nephropathy
presentation nephrotic syndrome
Frothy urine due to excess protein in the urine
Generalised oedema due to a combination of a decrease in oncotic pressure from hypoalbuminemia, as well as a primary renal sodium retention
complications of nephrotic syndrome
thrombosis, hypertension and high cholesterol
relapse
how does nephrotic syndrome cause thrombosis
due to loss of proteins that normally prevent blood clotting, and because the liver responds to the low albumin by producing pro-thrombotic proteins.
how does nephrotic syndrome cause infection
due to loss of immunoglobulins, complement, and other compounds in the urine. Immunotherapy may exacerbate the infection risk.
how does nephrotic syndrome increase the pts risk of cvs disease
Patients become hypoalbuminemic due to the urinary loss of albumin. The liver tries to compensate for this protein loss by increasing the synthesis of albumin, as well as other molecules including lipids. These lipid abnormalities increase the patient’s risk of cardiovascular disease.
triad of minimal change disease? with values
oedema
proteinuria
proteinuria > 3.5 grams/24 hours OR urine ACR > 300 mg/mmol* or PCR > 300g/mol*
hypoalbuminaemia
serum albumin <2.5 g/dL
gold standard invetsigation for proteinuria
24-hour urine collection to quantify proteinuria (gold standard)
nephrotic range proteinuria is?
proteinuria > 3.5 grams/24 hours
OR urine ACR > 300 mg/mmol*
OR PCR > 300g/mol*
what blood tests would you do ?minimal change
U&Es
albumin
lipid profile
defintive diagnosis of minimal change?
Renal biopsy
Definitive diagnosis of MCD relies on renal biopsy in adults, with light microscopy typically showing normal glomeruli, and electron microscopy revealing diffuse podocyte foot process effacement. In children, renal biopsy is generally avoided.
indications for renal biopsy ?minimal change
Aged < 12 months >10 years
Steroid resistant
Low serum C3
Clinical evidence of systemic disease e.g. HSP, SLE
Concern regarding ciclosporin nephrotoxicity
Persistent renal impairment, persistent hypertension or family history of FSGS
Management minimal change disease
High dose steroids (i.e. prednisolone) for 4 weeks (60mg/m2/day) and then gradually weaned over the next 8 weeks
Low salt diet
Diuretics may be used to treat oedema
Albumin infusions may be required in severe hypoalbuminaemia
Antibiotic prophylaxis may be given in severe cases
biopsy results membraneous nephropathy
the basement membrane is thickened with subepithelial electron dense deposits. This creates a ‘spike and dome’ appearance
M looks like spike and dome
causes of membraneous nephropathy
idiopathic: due to anti-phospholipase A2 antibodies
infections: hepatitis B, malaria, syphilis
malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia
drugs: gold, penicillamine, NSAIDs
autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid
Management membraenous nephropathy
- ACEi or ARB (to reduce proteinuria)
+ ONLY IF SEVERE…immunosuppression
biopsy reuslts focal segmental glomeruloscleorsis
focal and segmental sclerosis and hyalinosis on light microscopy
effacement of foot processes on electron microscopy
management of focal segmental glomerulosclerosis
steroids +/- immunosuppressants
causes of focal segmental glomeruloscleoris
idiopathic
secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
HIV
heroin
Alport’s syndrome
sickle-cell
what is nephritic syndrome
Nephritic syndrome refers to a group of features that occur with nephritis:
Haematuria (blood in the urine), which can be microscopic (not visible) or macroscopic (visible)
Oliguria (significantly reduced urine output)
Proteinuria (protein in the urine), but less than 3g per 24 hours (higher protein suggests nephrotic syndrome)
Fluid retention
epidemiology post strep glomerulonephritis
The most commonly affected age group are children between the ages 5-12years, with an increased risk also present for older adults >60years.
Boys appear to be affected twice as commonly as girls.
pathophysiology post strep glomerulonephritis
nephritogenic streptococcal antigens become lodged in glomerular membrane → anti-streptococcal antibodies bind to form immune complexes → activation of complement and inflammation → damage to glomerulus
type 3 hypersensitivity
3 year old frothy urine, generalised oedema and pallor
minimal change disease
nephritis developing 1-3 weeks after URTI/tonsilitis
Post-streptococcal glomerulonephritis
management of post strep glomerulonephritis
self limiting
supportive
- monitor BP –> diuretics
- monitor oedema –> diuretics
Antibiotic therapy should be given if there is any evidence of a persistent streptococcal infection. Early antibiotics reduce the incidence and severity of PSGN.
what tests should you get to support a diagnosis of post strep glomerulonephritis
evidence of infection!
- A throat or skin swab for culture should be taken to help confirm the presence of GAS.
- Streptozyme test (includes ASO titre)
complement
- low C3 levels duirng first 2 weeks (as it has been deposited)
Renal biopsy features of strep glomerulonephritis
subepithelial ‘humps’
Immunofluorescence: diffuse granular deposits of complement (C3) and immunoglobulin G (IgG).
young male, recurrent episodes of macroscopic haematuria
typically associated with a very recent respiratory tract infection
IgA nephritis (bergers disease)
Management IgA nephroathy/bergers disease
isolated hematuria, no or minimal proteinuria and normal eGFR
- no treatment needed
persistent proteinuria above 500 to 1000 mg/day, a normal or only slightly reduced eGFR
+ ACE inhibitors
falling eGFR or not responding to ACEi:
+ corticosteroids
how to differentiate strep glomer from IgA neph
Age: SG young, IgA teenage
Timing of URTI: SG 1-3 weeks ago, IgA days ago
Complement levels: SG low
Proteinuria: SG has worse
Haematuria: IgA has worse
Histology IgA nephropathy
mesangial hypercellularity, positive immunofluorescence for IgA & C3
markers of prognosis iga nephroapthy
markers of good prognosis: frank haematuria
markers of poor prognosis: male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidaemia, ACE genotype DD
causes of rapidly progressing glmerulnpehritis
Goodpasture’s disease
Polyarteritis nodosum
Wegener’s granulomatosis (granulomatosis with polyangitis)
Microscopic polyangitis
invetsigations ?vasculitis causing glomerulonephritis
cxr
renal biopsy
antibodies (c-ANCA, p-ANCA, anti-GBM)
angiography
what is goodpastures disease
antibodies attack the alpha-3 subunit of type IV collagen found in the basement membrane of the lungs and kidneys.
This anti-glomerular basement membrane (anti-GBM) disease leads to small vessel vasculitis in the kidneys and lungs causing bleeding in the lungs and renal failure.
investigations goodpastures
anti-GBM antibody titre
renal biopsy (cresenteric glomerulonephritis)
management of goodpastures
- intensive plasmapherisis
+immunosupression:
- prednisolone
- cyclophosphamide
classic presentation goodpastures
patient with no history of lung or renal dysfunction who presents after noticing an abrupt onset of haemoptysis, cough, shortness of breath, peripheral oedema, dark urine and oliguria.
features microscopic polyangitis
purpura
p-anca
alveolar haemorrhage
mononeuritis
glomerulonephritis
investigations microscopic polyangitis
p-ANCA antibodies
renal biopsy
cxr
management of microscopic polyangitis
cyclophospahmide with high dose steroids
features granulomatosis with polyangitis
saddle nose
haemoptysis
epistaxis
c-anca
wegners
mononeutiits
mononeuritis
glomerulonephritis
autoantibodies in graulomatosis with polyangitis
c-ANCA
cxr granulomatosis with polyangitis
many diff but
cavitating lesions are common
renal biopsy granulomatosis with polyangitis
epithelial crescents in bowmans capsule
management granulomatosis with polyangitis
steroids
cyclophosphamide
plasma exhcnage
features of polyarteritis nodosa
skin - livedo reticularis
neuro
renal
other - ass w hep B, CVS events, HTN
features of eosinophilic granulomatosis with polyangiitis
resp inc asthma
ENT
NO bleeding
NO RENAL
urianlysis interpretation of ‘casts’
Brown/black casts → ATN
Red casts → glomerulonephritis
White casts → acute interstitial nephritis
features acute interstitial nephritis
fever, rash, arthralgia
eosinophilia
mild renal impairment
hypertension
investigation findings acute interstitial nephritis
bloods:
eosinophilia
urinalysis:
sterile pyuria
white cell casts
complcation of AIN
Tubulointerstitial nephritis with uveitis
Tubulointerstitial nephritis with uveitis (TINU) usually occurs in young females. Symptoms include fever, weight loss and painful, red eyes. Urinalysis is positive for leukocytes and protein.
which cause of aki is associated with malignancy
Membranous nephropathy is frequently associated with malignancy making this the most likely diagnosis.
what is rhabdomyolysis
Rhabdomyolysis is caused by skeletal muscle breakdown.
This causes the release of intracellular contents such as myoglobin and potassium into the blood stream.
Excess myoglobin can precipitate in the glomerulus causing renal obstruction, direct nephrotoxicity and acute kidney injury.
triad rhabdomyolysis - symptoms
dark urine, generalised weakness and myalgia.
features of rhabdomyolysis blood tests etc.
acute kidney injury with disproportionately raised creatinine
elevated creatine kinase (CK)
myoglobinuria
hypocalcaemia (myoglobin binds calcium)
elevated phosphate (released from myocytes)
hyperkalaemia (may develop before renal failure)
metabolic acidosis
causes of rhabdomyolysis
seizure
collapse/coma (e.g. elderly patients collapses at home, found 8 hours later)
Ischaemia: embolism, surgery
ecstasy
crush injury
McArdle’s syndrome
drugs: statins (especially if co-prescribed with clarithromycin)
diagnosis of rhabdomyolysis
A creatine kinase >5x the normal range is typically diagnostic.
management rhabdomyolysis
IV fluids to maintain good urine output
Correction of electrolyte disturbances
urinary alkalinization is sometimes used
electrolytes in rhabdomyolysis
Hyperkalaemia (liberated from the damaged muscle)
Hyperphosphatemia (liberated from the damaged muscle)
Hyperuricaemia (liberated from damaged muscle)
Hypocalcaemia (calcium is taken into the damaged muscle by several mechanisms).
What is the pathophsyiology of SLE?
SLE is characterised by anti-nuclear antibodies (ANA). These are autoantibodies against proteins within the cell nucleus. These antibodies generate a chronic inflammatory response, leading to the condition’s features.
Presentation SLE?
Hair loss
Mouth ulcers
Fatigue
Fever
Photosensitive malar rash
Lymphadenopathy
Shortness of breath
Pleuritic chest pain
Weight loss
Splenomegaly
Arthralgia (joint pain)
Non-erosive arthritis
Myalgia (muscle pain)
Raynaud’s phenomenon
Oedema (due to nephritis)
what makes malar rash in SLE worse?
triggered or worsened by sunlight.
Invetsigation findings SLE
Autoantibodies
ANA - 85% will have positive - other things can make it positive
Anti-dsDNA - 50% will have positive - specific
Full blood count may show anaemia of chronic disease, low white cell count and low platelets
CRP and ESR may be raised with active inflammation
C3 and C4 levels may be decreased in active disease
Urinalysis and urine protein:creatinine ratio shows proteinuria in lupus nephritis
Renal biopsy may be used to investigate for lupus nephritis
Complications of lupus?
- CVS disease
- Infection (from disease and immunosupp drugs)
- Anaemia of chronic disease
- pericarditis
- pleuritis
- lupus nephritis
- neuropsychiatiric (optic neuritis, transverse myelitis, psychosis)
- recurrent miscarriage
- VTE - due to antiphospholipid secondary to SLE
Management SLE
First-line options include:
Hydroxychloroquine
NSAIDs
Steroids (e.g., prednisolone)
Treatment options for resistant or more severe SLE include:
DMARDs (e.g., methotrexate, mycophenolate mofetil or cyclophosphamide)
Biologic therapies
Biological therapies include:
Rituximab (a monoclonal antibody that targets the CD20 protein on the surface of B cells)
Belimumab (a monoclonal antibody that targets B-cell activating factor)
Presentation HSP
Purpura (100%)
Joint pain (75%) usually knees and ankles
Abdominal pain (50%)
Renal involvement (50%) - microscopic or macroscopic haematuria and proteinuria, oedema
most common trigger HSP
URTI 1-3 weeks prior, streptococcus
what type of hypersensitivity is HSP
type 3 - immune complex mediated
Invetsiagtions HSP
To rule out other things:
- Sepsis : blood culture, CRP
- Thromboytopaenia (inc leukaemia) : coagulation studies
- Other vasculidities: Autoantibody screen: antinuclear antibodies, antineutrophil cytoplasmic antibodies, and complement levels
To help support HSP diagnosis
- ESR raised in 75% of patients
- Serum IgA may be high
To test for complications:
- urinalysis : haematuria, proteinuria
- Serum creatinine and electrolyte levels
Elevated creatinine indicates renal impairment or renal failure
Electrolyte abnormalities may occur in patients with severe gastrointestinal symptoms.
- blood pressure
If non-typical presentation :
- skin/renal biopsy for confirmation of diagnosis
If severe abdo pain:
- abdo USS
Management HSP
Supportive (fluid, rest, symptomatic relief)
- paracetamol (avoid ibruprofen if abdo pain)
- steroids may be used in severe cases
Monitoring
- 6 months periodic urinalysis and BP monitoring
- abnormlaity on urinalysis –> test serum cretainine
- if persistent - refer to nephrologist
monitoring post HSP
- 6 months periodic urinalysis and BP monitoring
- abnormlaity on urinalysis –> test serum cretainine
- if persistent - refer to nephrologist
cause HUS? exacerbating factors?
The most common cause is a toxin produced by the e. coli 0157 bacteria, called the shiga toxin. Shigella also produces this toxin.
The use of antibiotics and anti-motility medications such as loperamide to treat gastroenteritis caused by these pathogens increases the risk of developing HUS.
features HUS
Reduced urine output
Haematuria or dark brown urine
Abdominal pain
Lethargy and irritability
Confusion
Oedema
Hypertension
Bruising
management HUS
supportive
- antihypertensive
- blood transfusion
- dialysis
HUS is a medical emergency and has a 10% mortality. It needs to be managed by experienced paediatricians under the guidance of a renal specialist. The condition is self limiting and supportive management is the mainstay of treatment:
Urgent referral to the paediatric renal unit for renal dialysis if required
Antihypertensives if required
Careful maintenance of fluid balance
Blood transfusions if required
70 to 80% of patients make a full recovery.
