Renal I Flashcards
raised urinary WCC and eosinophils, alongside impaired renal function indicates what pathology? [1]
Acute interstitial nephritis
A patient reports haematuria following a TURP.
Describe what is occurring and how to fix x
This patient presents with clot retention after transurethral resection of prostate (TURP).
It is a common complication following the procedure, hence most patients are advised to refrain from walking and lifting heavy weights for at least one week post-surgery. In the event of clot retention, an emergency clot evacuation and diathermy to the bleeding point is the definitive management.
A patient is suffering from a kidney stone.
After taking a history from them you learn their mother also has a history of kidney stones.
What is the most likely type of kidney stone found and why? [2]
Cystine
- result from inherited recessive inborn errors of metabolism causing disruption in cystine transport and decreased absorption from the renal tubule.
A patient has renal tubular acidosis. What is the most likely cause of their stone? [1]
Calcium phosphate stones
A patient has a renal stone. As part of the work up you perform an urinalysis and obtain the pH. This is identified as being 7.5
What is the most likely cause of the stone?
Calcium phosphate
Calcium oxalate
Uric acid
Struvate
Cystine
A patient has a renal stone. As part of the work up you perform an urinalysis and obtain the pH. This is identified as being 7.5
What is the most likely cause of the stone?
Calcium phosphate
Calcium oxalate
Uric acid
Struvate
Cystine
Dialysis disequilibrium syndrome is a rare complication of dialysis.
How long after dialysis starting does it usually occur? [1]
What is the pathological consequence of this syndrome? [1]
Dialysis disequilibrium syndrome is a rare complication and usually affects those who have recently started renal replacement therapy. It is caused by cerebral oedema, but the exact mechanism is unclear.
Describe what is meant by Alport’s syndrome [1]
State a mneumonic for Alport’s syndrome features [3]
Alport’s syndrome:
- due to a defect in the gene which codes for type IV collagen resulting in an abnormal glomerular-basement membrane (GBM). The disease is more severe in males with females rarely developing renal failure.
- A favourite question is an Alport’s patient with a failing renal transplant. This may be caused by the presence of anti-GBM antibodies leading to a Goodpasture’s syndrome like picture.
Helpful mnemonic:
Can’t see - Lenticonus
Can’t pee - CKD, hematuria
Can’t hear a high C - sensorineural deafness
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)
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
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
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
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
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
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
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
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
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.
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
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
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.
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
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
