Renal disease

Question 1

Pre-renal disease

Clinical markers?

Answer 1

Reduced blood supply.
Very common cause of AKI
Leads to reduction in GFR
Creatinine and Urea increase in concentration
Doesn’t cause kidney damage unless iscahemia is severe

Question 2

Causes of pre-renal disease

Answer 2

Shock: hypovolaemic, cardiogenic, distributive
Renovascular: embolus, aortic dissection, renal artery stenosis and thrombosis, or ACE-Is given in bilateral RAS

Question 3

post-renal disease?

Answer 3

Normal blood supply, but increased intratubular pressure and decreased GFR.
=hydronephrosis
Affects medulla: LoH and CT

Question 4

causes of post-renal disease?

Answer 4

catheterisation, stones, strictures, clots, external/internal malignancy
Bladder outlet obstruction can also cause post-renal AKI, e.g. prostatic enlargement, urethral strictures or phimosis / paraphimosis.
bladder extension a strong indicator

Question 5

Intrinsic kidney disease

Answer 5

normal blood supply
disease of
1.glomerulus (glomerulitis) (5%)
2. tubules (acute tubular necrosis caused by ischaemia, or nephrotoxicity) (85%)
3. interstitial area (inflammatory reactions)/ interstitial nephritis (10%)

Question 6

How can pre-renal lead to renal disease?

Answer 6

prolonged interruption of blood supply could cause ischaemia and Acute Tubular Necrosis, where cells lining tubules necrose, leading to porous/leaky tubule membranes and blockage due to necrosed cells.

Question 7

Most common cause of AKI?

Answer 7

pre-renal disease

Question 8

How could Acute Tubular Necrosis be identified with U&E analysis?

Answer 8

In initial pre-renal AKI, urine osmolality is high {>S00mosmol/kg), and urine sodium is low, as concentrating powers are retained.
If ATN develops, urine is isotonic with plasma {<400mosmol/kg) and has high sodium, as concentrating powers are lost.

Question 9

Drugs causing ATN? Toxins?

Answer 9

aminoglycosides, nephalosporins, radiological contrast
mediums, NSAIDs
Toxins: heavy metal poisoning, myoglobinuria or haemolytic uraemic syndrome {HUS).

Question 10

What is myoglobinuria?

Answer 10

rhabdomyolysis: when in excess, myoglobin is released

but too much to be efficiently filtered, and some precipitates into tubules to cause damage

Question 11

What is haemolytic uraemic syndrome?

Answer 11

Occurs in children following a diarrhoeal illness caused by verotoxin- producing E.coli 0157, or following an URTI in adults.
It leads to thrombocytopenia (can cause purpura), haemolysis and ATN. Children usually recover within a few weeks, but prognosis is poor in adults. Treatment is supportive, including dialysis.

Question 12

What is interstitial nephritis?

Answer 12

Most commonly caused by drugs, however the damage is not limited to tubular cells (such as in ATN), and bypasses the basement membrane to cause damage to the interstitium.
Antibiotics are the most common cause of interstitial nephritis, with other agents including diuretics, allopurinol and proton pump inhibitors.
It normally responds to withdrawal of the drugs and a short course of oral steroids.

Question 13

What are normal protein levels?

What about in proteinuria?

Answer 13

Normally 150mg day-1 max

30mg-300mg day-1

Question 14

Are urine dipsticks sensitive to all protein?

Answer 14

Just albumin, less so for globulin, haem, or light chain

Question 15

Risk factors for diabetic nepropathy?

Answer 15

Men
T1DM before 20 years
South Asian or Afro-Carribean
Diabetic retinopathy
HT
Genetic: FMX

Question 16

Stage 1 DN?

Answer 16

hyperfiltration stage:
GFR increases
there is increased circulating volume
-glucose cotransport means sodium absorption in proximal tubule, but low delivery to distal, where more is taken in!
-glucose also inhibits the renin-angiotensinogen system: afferent vasodilation and loss of auto-regulation

no protein in urine

Question 17

Stage 2 DN

Answer 17

Latent phase:
GFR normalises
sub-clinical amounts of protein in the urine
podocyte failure or loss: glomerular hypertrophy leading to leakage of protein, and podocyte apoptosis because more ROS from heightened glucose metabolism

Question 18

Stage 3 DN?

Answer 18

Microalbuminaemia: stage II progresses to stage III if there is poor diabetic control, hypertension (loss of nocturnal BP dip), smoking, increased protein intake or obesity.

Question 19

Stage 4 DN?

Answer 19

Proteinuria

Leads to renal damage, because high protein not tolerated by kidney and causes scarring and damage

Question 20

How do you treat stage II DN?

Answer 20

identify risk factors and address them if possible
ACEI-I for HT
glucose control 
cholesterol
smoking
diet and exercise

Question 21

Treating stage III and IV DN?

Answer 21

manage HT with ACE-I or ARBs
diuretics
beta blockers to address sympathetic hyperactivity in DM
SDLT2
glucose control won’t help renal pathology much any longer, but there is likely to be other complications where this would be important, so should be parrt of the overall treatment strategy

Question 22

How might Uss identify DN?

Answer 22

Would show increased size of kidney

Question 23

Describe the assessment o f CKD using estimated glomerular filtration rate and the 5 stages of CKD

What is eGFR?

Answer 23

CKD is diagnosed when any two tests three months apart show reduced eGFR, and can be staged 1-5 depending on the level of reduction.
Stage 1 has no reduction in eGFR, yet there is other long-term evidence of kidney disease, e.g. proteinuria/haematuria, a genetic diagnosis of kidney disease, or evidence of structuraly abnormal kidneys
Stage 2: evidence of structural damage
GFR 60-89
Stage 3:
GFR 30-59
Stage 4: 15-29
Stage 5: ESRF <15

eGFRis just an estimate of GFR based on a plasma level of creatinine. This can be inaccurate in certain situations, so a 24hour urinary creatinine may be collected to calculate true creatinine clearance.

Question 24

Aetiology of CKD

Answer 24

Diabetes Mellitus (20-40%).
Hypertension.
Chronic Glomerulonephritis
. Chronic pyelonephritis. 
Obstructive uropathy. 
Renovascular disease.
Drugs (long-term NSAIDs). 
Polycystic kidney disease.

Question 25

How does CKD appear on Uss?

Answer 25

reduction in size

reduced cortical thickness

Question 26

Symptoms of CKD

Answer 26

Often symptomless until very advanced.
o There may be vague fatigue and anorexia. Polyuria / nocturia.
Restless legs syndrome.
Sexual dysfunction.
Nausea & pruritis (early uraemia).
Yellow pigmentation, encephalopathy and pericarditis (severe uraemia). Pedal oedema & pulmonary oedema.
o Due to hypertension, can be both a cause and a symptom.

Question 27

signs of CKD?

Answer 27

Pallor due to anaemia, or rarely a yellow tinge. Excoriations due to pruritis.
Hypertension/ fluid overload signs.
Pericardia! rub (rare).

Question 28

What bloods would you order to investigate CKD?

Answer 28

FBC: anaemia

U and E, calcium, phosphate, PTH and glucose

Question 29

Other than bloods what other investigations would you order for CKD?

Answer 29

Urine dip: protein levels, infection or any casts?
24 hour urinary protein/creatinine clearance
CXR if you suspect pulmonary edema
Renal Uss: any obstructive causes suspected

Question 30

How do you manage a CKD?

Answer 30

1. Treat any reversible causes: toxicity , obstruction
2. Blood pressure- < 130/80
   If proteinuria: < 125/75
   CV prevention w statins and low dose aspirin
3. o Recombinant EPO for those with evidence of anaemia.
   o Calcium/ Vitamin D supplementation for those with bone disease.
   o K+restriction if any suggestion of hyperkalaemia.

4Renal replacement therapy is indicated in those with ESRD.
o Guidelines suggest this should be for any symptomatic CKD 5 patient,
however many consultants will delay starting dialysis.

Question 31

Are NSAIDs and ACE-Is useful in AKIs? Why or why not?

Answer 31

No- they might be useful in CKD for their ability to relieve efferent and afferent vasoconstriction (ACE-I and NSAIDs, respectively), but in AKI they can exacerbate disease

Question 32

How might you manage an AKI?

Answer 32

-A-E assessment, correct any hypoxia
-Halt any NSAIDs or ACE-I
-restrict potassium (hyperkalaemia risk -ECG)
-pre-renal cause (treat shock); post-renal (urology referral); renal cause (fluid status, replace, CVP measurement, if there is urine output after fluid replacement, continue large
quantities of fluid +/-diuretics {furosemide stress test)).
If there is no urine output or complications, nephrologist input is necessary.
Emergency management of life threatening complications;
o Pulmonary oedema :
o Acute hyperkalaemia:
Indications for acute dialysis are refractory hyperkalaemia, pulmonary oedema, acidosis, uraemic pericarditis / encephalopathy, complete anuria or drug OD.

Question 33

Hyperkalaemia on an ECG

Answer 33

Tall, peaked T-waves.
Widened QRS complex.
Flattened P Waves/ Prolonged PR interval.