MET3 Revision: Renal I Flashcards
Define the term ‘acute kidney injury’ [3]
- Rise in serum creatinine of > or equal to 26 μmol/L within 48 hours
- or 1.5x increase in serum creatinine known or presumed to have occurred in the last 7 days
- or 6 hours oliguria (urine output < 0.5ml/kg/hour)
Which populations are at risk of AKI? [6]
- · Elderly
- · CKD patients (eGFR < 60ml/min/1.73m2)
- · Cardiac failure
- · Liver disease
- · Vascular disease
- · Taking potentially nephrotoxic medications (ARBS, ACEIs, NSAIDs)
What is diabetic kidney disease? [1]
How does it present:
urine findings? [2]
US? [1]
This typically presents with:
- proteinuria and albuminuria
- reduced estimated glomerular filtration rate (eGFR) in the absence of signs or symptoms of other primary causes of kidney damage.
On ultrasound, the kidneys may be enlarged if diabetes is poorly controlled
Describe how you manage AKIs
IV fluids for dehydration and hypovolaemia
- If hypovolameic: give bolus fluids (250-500mls)
- (Assess BP (lying/standard), JVP, HR, Cap. refill, Conscious level, Lactate, Weight (important if on dialysis))
- If >2 L given & remains hypoperfused: give further circulatory support (+ve inotropes)
- If euvolaemic & passing urine: give maintenence fluids (est. daily output + 500ml)
Withhold medications that may worsen the condition
- NSAIDs
- ACE inhibitors
Withhold/adjust medications that may accumulate with reduced renal function:
- metformin
- opiates
Relieve the obstruction in a post-renal AKI:
- insert a catheter in a patient with prostatic hyperplasia
Dialysis may be required in severe cases
How do you monitor patients with AKI? [5]
- Urine catheter: monitor hourly input/output
- U&Es, bone profile, venous bicarbonate at least once a day whilst creatitine rising
- Blood gases & lactate: if septic & underperfused
- Daily weights (measurement of daily body weight change can provide a more accurate method of monitoring body fluid status)
- Regular fluid management
Describe how you would investigate AKI [3]
Urine dipstick:
- UTI (leukocytes & nitrates)
- Glomerulonephritis (haematuria & leuocytes)
- Acute interstitial nephritis (leucocytes by themselves)
- Glucose suggests diabetes
Bloods:
- U&E: important to ID hyperkalaemia
- FBC, CRP & bone profile
- ANA & ANCA: ID vasculitis
- anti-GBM (formation of anti-GBM antibodiescan be directed against collagen in the kidneys and lungs)
- complement levels (C3, C4)
- RF
- immuglobulins
- creatine kinase (evidence of rhabdomyolysis)
- LFTs
- HIV, HCV, IgG and Hep B Surface antigen
Ultrasound (within 24hrs; within 6hrs if due to sepsis obstruction)
- should be performed in new cases of AKI
Explain why each of the following may worsen AKIs: [3]
ACE inhibitors
NSAIDs;
Aminoglycoside antibiotics
ACE Inhibitors:
- depress A-II and thus inhibit A-II-mediated vasoconstriction of the efferent arteriole (efferent arteriole dilates)
- This lowers glomerular filtration pressure and decreases the glomerular filtration rate
NSAIDS:
- Reduced renal plasma flow caused by a decrease in prostaglandins, which regulate vasodilation at the glomerular level.
Aminoglycosides:
- have a preferential accumulation in the kidney cortex
How can you manage hyperkalamia (if have AKI), if:
ECG changes [1]
If K > 6.5mmol/L [1]
ECG changes:
* Calcium gluconate (stabilises cardiac membrane)
If K > 6.5mmol/L:
* Insulin dextrose (causes intracellular movement of AKI)
How do you treat AKI complicated pulmonary oedema [3]
GTN infusion
Furosemide > 80 mg bolus
Recovery requires functioning renal system
Refer adults, children and young people immediately for renal replacement therapy if any of the following are not responding to medical management
Describe three differential diagnoses for AKI [3]
:Chronic kidney disease:
- Reduced kidney function with elevation of creatinine is chronic (>3 months), although there may be acute on chronic kidney disease.
Increased muscle mass:
- Any elevation of creatinine is minor and typically non-acute.
Drug AEs
- Certain medicines such as cimetidine or trimethoprim may lead to an elevation of creatinine that is minor and non-acute.
Define uraemia [1]
State 4 pathological consequences of uraemia [4]
Uraemia: build up of urea in your blood. It occurs when the kidneys stop filtering toxins out through your urine.
Causes:
- nausea and vomiting
- altered mental state & confusion by causing encephalopathy
- acute pericardititis
- asterixis
How can microscopy be used to help distinguish between causes of AKI [3]
It is not widely used in the UK but is more commonly performed in other countries (e.g., USA, China). * It may reveal:
- Granular casts in acute tubular injury
- Red cell casts in glomerulonephritis/vasculitis
- Oxalate crystals - suggestive of ethylene glycol poisoning}}
What is the difference between crystalloid & colloid fluids for resuscitation of AKI? [2]
Crystalloids have small molecules, are cheap, easy to use, and provide immediate fluid resuscitation, but may increase oedema
Colloids have larger molecules, cost more, and may provide swifter volume expansion in the intravascular space, but may induce allergic reactions, blood clotting disorders, and kidney failure.
Cyrstalloids are preffered in AKI
A patient is suspected to have AKI and after testing their bloods, is found positive for ANA and ANCA. What is their likely cause of AKI? [1]
Antineutrophil cytoplasmic antibodies (ANCAs) cause ANCA and ANA associated vasculitis
Acute interstitial nephritis accounts for 25% of drug-induced acute kidney injury.
Name 5 drugs / classes that can cause this [5]
penicillin
rifampicin
NSAIDs
allopurinol
furosemide
Name 3 systemic diseases and 2 infections that cause acute interstitial nephritis [5]
systemic disease: SLE, sarcoidosis, and Sjögren’s syndrome
infection: Hanta virus , staphylococci
What are features of acute interstitial nephritis? [5]
Features:
* fever, rash, arthralgia
* eosinophilia
* mild renal impairment
* hypertension
* sterile pyuria
* white cell casts
One of the best ways to differentiate between acute kidney injury (AKI) and chronic kidney disease (CKD) is what type of imaging? [1]
Explain your answer [4]
One of the best ways to differentiate between acute kidney injury (AKI) and chronic kidney disease (CKD) is renal ultrasound
most patients with CKD have bilateral small kidneys. Exceptions to this rule include:
* autosomal dominant polycystic kidney disease
* diabetic nephropathy (early stages)
* amyloidosis
* HIV-associated nephropathy
What mineral serum level would indicate chronic kidney diseae? [1]
Hypocalcaemia
How can you distinguish between AKI and dehydration? [1]
Urea:Creatitine Ratio:
In dehydration: urea that is proportionally higher than the rise in creatinine
Given the likely diagnosis of haemolytic uraemic syndrome, what are likely expected investigational findings? [3]
acute kidney injury
microangiopathic haemolytic anaemia
thrombocytopenia
Which form of GN has an overlap with IgA nephropathy? [1]
How does this commonly present? [3]
Henoch-Schonlein purpura: IgA mediated samlled vessel vasculitis
- palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of arms and legs
- abdominal pain
- polyarthritis
Which drugs should be stopped in cases of AKI? [5]
DIANA:
D: diuretics
I: Ionated contrasts
A: ace inhibitors / ARBs
N: NSAIDs
A: aminoglycosides
Define what the triad of nephrotic syndrome are [3]
A triad of the following:
1. Proteinuria (> 3g/24hr) causing
2. Hypoalbuminaemia (< 30g/L) and
3. Oedema
Which are the diseases that cause glomerulonephritis? [5]
- Membranous nephropathy
- Post streptococcus nephropathy
- Focal segmental glomerulosclerosis
- IgA nephropathy
- Goodpasture’s disease
What symptoms are usually seen in glomerulonephritis? [4]
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
What level of proteinuria would indicate nephrotic syndrome? [1]
What level of serum albumin would indicate nephrotic syndrome? [1]
Proteinuria: more than 3g per 24 hours
Low serum albumin: less than 25g per litre
Describe the clinical presentation of a patient with nephrotic syndrome [10]
- Oedema (peripheral and facial)
- Proteinuria (>3g/24hrs)
- Hypercholesterolaemia
- Hypoalbiminaemia
- Hypertension (caused by reduced eGFR and salt & water retention)
- Haematuria
- Frothy urine
- Fatigue
- Recurrent infections (immune dysfunction)
- A / V thrombosis (hypercoagulability)
- Xanthelasma (cholesterol deposit near eyelid)
- Leukonychia
Describe risk factors for GN [6]
- Group A Streptococcus pyogenes
- Respiratory infections
- GI infections
- Hep B
- Hep C
- Infective endocarditis
- HIV
- SLE
- Lung & Colorectal cancer
What is the difference between nephritic syndrome and nephrotic syndrome? [2]
What are the classic signs of each? [4 x 2]
Both are clinical syndromes that are at opposite ends of a spectrum of clinical presentations
Nephrotic syndrome (GN):
* When the basement membrane in the glomerulus becomes highly permeable resulting in proteinuria & involves
* Proteinuria (more than 3g per 24 hours)
* Hypoalbuminaemia / low serum albumin (less than 25g per litre)
* Peripheral oedema
* Hypercholesterolaemia
Nephritic syndrome:
is a clinical presentation, and patients with nephritic syndrome may be diagnosed with renal diseases such as glomerulonephritis (a pathological diagnosis made after biopsy), and maybe rapidly progressive glomerulonephritis (RPGN) in which a patient has rapid fall in renal function (RPGN is a subset of glomerulonephritis).
A nephritic syndrome is a constellation of symptoms:
* 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
Describe the investigations would conduct for nephrotic syndrome? [7]
- Urinalysis: haematuria, proteinuria, dysmorphic rbc, leukocytes
- Protein:Creatinine ratio (PCR): >300mg/mmol
- Microscopy: investigate infections
- FBC: normocytic normochromic anemia is a feature of several systemic diseases with GN
- Lipid profile: hyperlipidaemia
- U&Es
- LFTs: hypoalbuminaemia; normal/elevated creatinine; elevated liver enzymes
- Ultrasound of kidneys
What are the top causes of nephrotic syndrome in adults? [2]
Membranous nephropathy
Focal segemental glomerulosclerosis
The majority of cases of MCD are idiopathic, but in around 10-20% of cases, the cause is WHAT? [3]
· Drugs: NSAIDs, rifampicin
· Hodgkin’s lymphoma, thymoma
· Infectious mononucleosis
Describe the features of MCD [3]
- Features of nephrotic syndrome
- Normotension (HTN is rare)
- Highly selective proteinuria (i.e. only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus
Describe the management of MCD [2]
- Majority (80%) are steroid responsive: prednisolone
- Cyclophosphamide next step for steroid resistant
focal segmental glomerulosclerosis is the most common cause of nephrotic syndrome in which populations? [1]
African-Americans & Hispanics
Describe the pathophysiology of primary and secondary FSGS [2]
Primary FSGS: Idiopathic
- A circulating factor that damages podocytes in the glomeruli leading to foot process effacement
- Proteins and lipids pass through BUT ALSO get stuck inside th glomerulus causing hyalinosis and eventually sclerosis.
Secondary FSGS: SCA, post- HIV / Herion / Lithium
- represents an adaptive response to renal injury that is usually associated with less significant proteinuria and renal impairment.
Describe the clinical features of FSGS [4]
Nephrotic syndrome
Haematuria (microscopic)
Hypertension
Renal insufficiency
State 4 underlying conditions that produce secondary FSGS:
Viral [2]
Drug [3]
Other [2]
Viral infection:
- HIV
- CMV
Glomerular hyperfiltration:
- Due to reduced renal mass / solitary kidney etc
Drug induced:
- Heroin
- Interferon alpha
- Lithium
Obesity
What does renal biopsy depict in FSGS? [1]
Renal biopsy shows focal and segmental sclerosis and hyalinosis on light microscopy, and effacement of foot processes on electron microscopy. Sclerosis is seen in this light microscopy image next to the bowmans capsule.
Describe the management of FSGS [4]
Treat underlying cause
ACE inhibitor: enalapril or lisinopril to reduce proteinuria
Steroids; prednisolone (only in primary disease)
Furosemide
simvastatin / atorvostatin to control hyperlipidaemia
Define membranous nephropathy [1]
Membranous nephropathy (MN) is an immunologically mediated disease characterised by glomerular basement membrane thickening in the absence of significant cellular proliferation on histology
Describe the pathophysiology of membranous nephropathy [3]
Autoimmune reaction against important antigens in the filtration barrier.
This causes development of autoantibodies: directed against the phospholipase A2 receptor (PLA2R) that are highly expressed on podocytes are a major cause of primary MN seen in up to 80% of case
Causes the formation of immune deposits and subsequent thickening of the glomerular basement membrane.
Histology shows IgA deposits and mesangial proliferation.
What is the primary [1] cause of membranous nephropathy [1]
What are the secondary causes of membranous nephropathy membranous nephropathy:
- Infection: [3]
- Malignancy:[3]
- Drugs: [3]
- Other autoimmune: [3]
Primary: Autoimmune
Secondary:
- Infection: Hep B, malaria, syphilis
- Malignancy: lung cancer, lymphoma, leukemia
- Drugs: gold, penicillamine, NSAIDs
- Other autoimmune: SLE (class V disease), thyroiditis, rheumatoid
- Sarcoidosis
Which HLA is associated with membranous nephropathy? [1]
HLA-DR3
Describe the biospy freatures of MN [3]
A thickened GBM with subepithelial electron-dense droplets.
This creates a ‘spike and dome’ appearance.
It is thought these subepithelial deposits are immunoglobulins, as it is primarily an autoimmune disease.
There will also be thickened capillary loops
Describe the management for membranous nephropathy? [6]
- Low salt and protein diet
- ACEin (enalapril or lisinopril) & ARB (losartan) to reduce proteinuria
- Statin (simvastatin or atorvostatin) to reduce lipid levels
- Furosemide / hydrchlorothiazide to treat oedema
- Corticosteroids: Prednisilone or cyclophosphamide
- Immunosuppressant: Rituximab
What is the prognosis of membranous nephropathy? [3]
- one third have spontaneous remission
- one third remain proteinuric
- one third develop end-stage renal failure
Describe the pathophysiology of IgA nephropathy [2]
Mesengial deposits of IgA immune complexes
Often accompanied by C3 and IgG (in association with a mesangial proliferative glomerulonephritis of varying severity)
Causes mesengial hypercellularity and proliferation
Investigations for IgA nephropathy:
A diagnosis of IgAN can only be made by WHAT investigation? [1]
What are the results for this investigation? [1]
Kidney biopsy:
* Mesangial IgA deposition either by immunofluorescence or immunoperoxidase studies.
How do you treat IgA nephropathy? [2]
- ACE inhibitors / ARBs for proteinuria
- Oral prednisolone & Fish oil if persistant proteinuria (> 1g for 3-6months): prevents the immune reaction making defective IgA & IgG
Describe the pathophysiology of post-streptococcal glomerulonephritis [6]
Pathophysiology:
1. Throat or skin GAS infection
2. Production of antibodies against streptococcal antigens
3. Nephritogenic streptococcal antigens become lodged in glomerular membrane
4. Anti-streptococcal antibodies bind to form immune complexes
5. Activation of complement and inflammation
6 Damage to glomerulus → clinical features of PSGN
Almost all cases of post-streptococcal glomerulonephritis have what type of infection?
Pharyngitis or skin infection (impetigo / tonsilittis)
What does biopsy of kidneys of a patient with post-streptococcal glomerulonephritis depict? [2]
Subendothelial deposits activate complement, leading to the infiltration of inflammatory cells: neutrophils! and proliferative glomerulonephritits
Subepithelial ‘humps’ of deposits trigger inflammation, leading to epithelial cell damage, which allows the protein to filter more freely into the urine.
The most commonly recognised clinical presentation among those diagnosed with PSGN is an acute nephritic syndrome
How does this present? [4]
Generalised oedema
Due to salt and water retention due to renal insufficiency
Can progress to respiratory distress due to pulmonary oedema
Hypertension
Due to salt and water retention due to renal insufficiency
Gross haematuria (40%)
Oliguria
NB: PSGN can be asymptomatic(unknown proportion), diagnosed incidentally with microscopic haematuria. }}
Describe the investigations specific for post-streptococcal glomerulonephritis [3]
Evidence of strep infection:
- Antistreptolysin O titer (ASOT) increases
- anti DNAse
- low C3
Culture
- Throat or skin swab for culture to confirm GAS (although only positive in 25% of cases because of the delay from initial GAS infection to the clinical presentation of PSGN (usually 1-3 weeks depending on the site of infection)
Renal biospy:
- Light microscope: shows diffuse glomerular cellular infiltration and endocapillary proliferation
- Immunofluorescence: shows diffuse granular deposits of complement (C3) and immunoglobulin G (IgG)
- Electron microscope: shows immune complexes characteristically localised to subepithelial deposits, commonly called dome-shaped ‘humps’ and subendothelial deposits.
Serology:
- The Streptozyme test is a combined test measuring the levels of the following 5 antibodies that can be produced in response to a recent GAS infection;
Describe the pathophysiology of Goodpasture’s syndrome [3]
Autoimmunity against the alpha-3 chain of type IV collagen in basement membranes. Type IV collagen is in all basement membranes but the alpha-3 chain is found primarily in the basement membranes of alveoli and glomeruli.
There are three main mechanisms:
Anti-GBM antibodies
These attack the basement membranes of alveoli and glomeruli by binding to them and activating the complement cascade, leading to their death.
Auto-reactive T cells
These contribute to anti-GBM disease. Circulating T cells that are specific to epitopes in the alpha-3 chain of type IV collagen contribute to the formation of crescent formation.
Genetic component
There have also been rare cases of familial anti-GBM disease where patients with HLA-DR15 and -DR4 are at increased risk.
Acute managment for Goodpastures? [3]
Long term management for Goodpastures? [2]:
Acute:
* Intensive plasmapheresis (Plasma exchange 4 L daily for 10 to 14 days)
Removes the pathogenic antibody and inflammatory mediators
4 litres per day for 10-14 days, or until anti-GBM is undetectable
* Prednisone
The dose is tapered over the course of 3 months
- Cyclophosphamide
Long term:
- Less toxic drugs such as azathioprine and low dose prednisolone
Describe what rapidly progressive glomerulonephritis is? [1]
How does it appear histologically ? [1]
Any aggressive GN, rapidly progressing to renal failure over days or weeks.
presents with an acute severe illness but tends to respond well to treatment.Histology shows glomerular crescents.
Describe what rapidly progressive glomerulonephritis is? [1]
How does it appear histologically ? [1]
Explain 3 complications of nephrotic syndrome [3]
Thromboembolism:
* Increase in clotting factors
* Decrease in anti-thrombin III
* Platelet abnormalities
* Treat w/ heparin & warfarin
Infection:
- urine losses of immunoglobulins and immune mediators: increase risk of UTIs, respiratory and CNS infections
Hyperlipidaemia:
- Increase cholesterol, LDLs and triglycerides
- Decreased HDLs
- Hepatic synthesis in response to decrease in oncotic pressure and defective lipid breakdown
What is the most common cause of end-stage renal failure? [1]
DM nephropathy
What are the pathophysiological effects of hyperglycaemia in DM nephropathy? [4]
What effect does this have in the nephron? [
Hyperglycaemia leads to increase growth factors, RAAS activation, AGE products and oxidative stress
Causes:
- Increase in glomerular capillary pressure
- podocyte damage
- endothelial dysfunction
- Glomerulosclerosis
- Nodule formation (Kimmelstein-Wilson)
- Fibrosis - leads to loss of renal function
How do you diagnose DM nephropathy? [1]
Microalbuminuria: A:CR 3-30mg/mmol
Treatment of DM nephropathy? [3]
Glycaemic control
BP < 130 / 80:
- ACEin / ARB
Na restriction to < 2 g/ day
Statins to reduce CV risk
What test is used to confirm that patient is suffering / suffered from post-strep GN? [1]
raised anti-streptolysin O titres are used to confirm the diagnosis of a recent streptococcal infection
This measures antibodies against streptolysin O, a substance produced by group A streptococcus bacteria
Name three main complications of nephrotic syndrome [3]
Hyperlipidaemia
Infection (loss of IgG)
VTE
HIV
