Renal I

Question 1

raised urinary WCC and eosinophils, alongside impaired renal function indicates what pathology? [1]

Answer 1

Acute interstitial nephritis

Question 2

A patient reports haematuria following a TURP.

Describe what is occurring and how to fix x

Answer 2

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.

Question 3

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]

Answer 3

Cystine
- result from inherited recessive inborn errors of metabolism causing disruption in cystine transport and decreased absorption from the renal tubule.

Question 4

A patient has renal tubular acidosis. What is the most likely cause of their stone? [1]

Answer 4

Calcium phosphate stones

Question 5

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

Answer 5

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

Question 6

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]

Answer 6

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.

Question 7

Describe what is meant by Alport’s syndrome [1]

State a mneumonic for Alport’s syndrome features [3]

Answer 7

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

Question 8

Define the term ‘acute kidney injury’ [3]

Answer 8

• 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)

Question 9

What is diabetic kidney disease? [1]
How does it present:

urine findings? [2]
US? [1]

Answer 9

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

Question 10

Explain why each of the following may worsen AKIs: [3]

ACE inhibitors
NSAIDs;
Aminoglycoside antibiotics

Answer 10

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

Question 11

How can you manage hyperkalamia (if have AKI), if:

ECG changes [1]
If K > 6.5mmol/L [1]

Answer 11

ECG changes:
* Calcium gluconate (stabilises cardiac membrane)

If K > 6.5mmol/L:
* Insulin dextrose (causes intracellular movement of AKI)

Question 12

How do you treat AKI complicated pulmonary oedema [3]

Answer 12

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

Question 13

Describe three differential diagnoses for AKI [3]

Answer 13

: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.

Question 14

Define uraemia [1]

State 4 pathological consequences of uraemia [4]

Answer 14

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

Question 15

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]

Answer 15

Antineutrophil cytoplasmic antibodies (ANCAs) cause ANCA and ANA associated vasculitis

Question 16

Acute interstitial nephritis accounts for 25% of drug-induced acute kidney injury.
Name 5 drugs / classes that can cause this [5]

Answer 16

penicillin
rifampicin
NSAIDs
allopurinol
furosemide

Question 17

What are features of acute interstitial nephritis? [5]

Answer 17

Features:
* fever, rash, arthralgia
* eosinophilia
* mild renal impairment
* hypertension
* sterile pyuria
* white cell casts

Question 18

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]

Answer 18

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

Question 19

What mineral serum level would indicate chronic kidney diseae? [1]

Answer 19

Hypocalcaemia

Question 20

How can you distinguish between AKI and dehydration? [1]

Answer 20

Urea:Creatitine Ratio:

In dehydration: urea that is proportionally higher than the rise in creatinine

Question 21

Given the likely diagnosis of haemolytic uraemic syndrome, what are likely expected investigational findings? [3]

Answer 21

acute kidney injury
microangiopathic haemolytic anaemia
thrombocytopenia

Question 22

Define what the triad of nephrotic syndrome are [3]

Answer 22

A triad of the following:
1. Proteinuria (> 3g/24hr) causing
2. Hypoalbuminaemia (< 30g/L) and
3. Oedema

Question 23

Which are the diseases that cause glomerulonephritis? [5]

Answer 23

• Membranous nephropathy
• Post streptococcus nephropathy
• Focal segmental glomerulosclerosis
• IgA nephropathy
• Goodpasture’s disease

Question 24

What symptoms are usually seen in glomerulonephritis? [4]

Answer 24

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

Question 25

What level of proteinuria would indicate nephrotic syndrome? [1] What level of serum albumin would indicate nephrotic syndrome? [1]

Answer 25

Proteinuria: more than **3g per 24 hours** Low serum albumin: **less than 25g per litre**

Question 26

What is the difference between nephritic syndrome and nephrotic syndrome? [2] What are the classic signs of each? [4 x 2]

Answer 26

**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**

Question 27

What are the top causes of nephrotic syndrome in adults? [2]

Answer 27

Membranous nephropathy Focal segemental glomerulosclerosis

Question 28

The majority of cases of MCD are idiopathic, but in around 10-20% of cases, the cause is WHAT? [3]

Answer 28

· Drugs: **NSAIDs, rifampicin** · **Hodgkin**’s **lymphoma**, **thymoma** · **Infectious mononucleosis**

Question 29

Describe the features of MCD [3]

Answer 29

- **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

Question 30

Describe the management of MCD [2]

Answer 30

- Majority (80%) are steroid responsive: **prednisolone** - **Cyclophosphamide** next step for steroid resistant

Question 31

Describe the pathophysiology of primary and secondary FSGS [2]

Answer 31

**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.

Question 32

Describe the clinical features of FSGS [4]

Answer 32

Nephrotic syndrome Haematuria (microscopic) Hypertension Renal insufficiency

Question 33

State 4 underlying conditions that produce secondary FSGS: Viral [2] Drug [3] Other [2]

Answer 33

**Viral infection:** - HIV - CMV **Glomerular hyperfiltration:** - Due to reduced renal mass / solitary kidney etc **Drug induced:** - Heroin - Interferon alpha - Lithium **Obesity**

Question 34

What does renal biopsy depict in FSGS? [1]

Answer 34

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.

Question 35

Describe the management of FSGS [4]

Answer 35

Treat underlying cause **ACE inhibitor**: **enalapril** or **lisinopril** to reduce proteinuria Steroids; **prednisolone** (only in primary disease) **Furosemide** **simvastatin** / **atorvostatin** to control hyperlipidaemia

Question 36

Describe the pathophysiology of membranous nephropathy [3]

Answer 36

**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**.

Question 37

Describe the biospy freatures of MN [3]

Answer 37

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**

Question 38

Describe the management for membranous nephropathy? [6]

Answer 38

- 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**

Question 39

Describe the pathophysiology of IgA nephropathy [2]

Answer 39

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**

Question 40

How do you treat IgA nephropathy? [2]

Answer 40

1. **ACE inhibitors / ARBs** for proteinuria 2. **Oral prednisolone & Fish oil** if persistant proteinuria (> 1g for 3-6months): **prevents the immune** **reaction making defective IgA & IgG**

Question 41

Describe the pathophysiology of post-streptococcal glomerulonephritis [6]

Answer 41

**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

Question 42

Almost all cases of post-streptococcal glomerulonephritis have what type of infection?

Answer 42

**Pharyngitis or skin infection** (impetigo / tonsilittis)

Question 43

What does biopsy of kidneys of a patient with post-streptococcal glomerulonephritis depict? [2]

Answer 43

**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.

Question 44

The most commonly recognised clinical presentation among those diagnosed with PSGN is an acute nephritic syndrome How does this present? [4]

Answer 44

**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. }}

Question 45

Describe the investigations specific for post-streptococcal glomerulonephritis [3]

Answer 45

**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;

Question 46

Describe the pathophysiology of Goodpasture's syndrome [3]

Answer 46

**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.

Question 47

Acute managment for Goodpastures? [3] Long term management for Goodpastures? [2]:

Answer 47

**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**

Question 48

Describe what rapidly progressive glomerulonephritis is? [1] How does it appear histologically ? [1]

Answer 48

**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.**

Question 49

Explain 3 complications of nephrotic syndrome [3]

Answer 49

**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

Question 50

How do you diagnose DM nephropathy? [1]

Answer 50

**Microalbuminuria**: **A:CR 3-30mg/mmol**

Question 51

Treatment of DM nephropathy? [3]

Answer 51

**Glycaemic control** **BP < 130 / 80**: - ACEin / ARB **Na restriction to < 2 g/ day** **Statins to reduce CV risk**

Question 52

What test is used to confirm that patient is suffering / suffered from post-strep GN? [1]

Answer 52

**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

Question 53

Name three main complications of nephrotic syndrome [3]

Answer 53

Hyperlipidaemia Infection (loss of IgG) VTE | HIV