Renals 101121

Question 1

normal glomerular filtration rate

Answer 1

120ml/hr

Question 2

How is AKI classified

Answer 2

Pre-renal, intrinsic renal, post-renal

Question 3

Causes of pre-renal AKI

Answer 3

o True volume depletion (e.g. haemorrhage) Hypotension
o Oedematous state Selective renal ischaemia (e.g. renal artery stenosis)
o Drugs affecting renal blood flow
 ACE inhibitors or ARBs – reduce efferent constriction
• ACEi are very contraindicated in RAS
 NSAIDs or Calcineurin inhibitors – decrease afferent dilatation
 Diuretics – affect tubular function, decrease preload

Question 4

AKI vs tubular necrosis

Answer 4

o Pre-Renal AKI is NOT associated with structural renal damage
 Responds immediately to restoration of circulating volume
 However, a prolonged AKI insult  ischaemic injury (ATN)
o ATN does NOT respond to restoration of circulating volume
o Epithelial cell casts would be seen in the urine on microscopy

Question 5

causes of postrenal AKI

Answer 5

• Hallmark is physical obstruction (at any level) to urine outflow
o (Intra-renal obstruction) Ureteric obstruction (bilateral)
o Prostatic / urethral obstruction Blocked urinary catheter
o Retroperitoneal fibrosis / Ormond’s disease

Question 6

Pathophysiology of post renal AKI

Answer 6

o GFR is dependent on the hydraulic pressure gradient
o Obstruction results in increased tubular pressure
o This results in an immediate decline in GFR

Question 7

causes of renal aki

Answer 7

• Pathophysiology is more diverse (abnormality could be anywhere in the nephron):
o Vascular disease (e.g. vasculitis)
o Glomerular disease (e.g. glomerulonephritis)
o Tubular disease (e.g. ATN) = MOST COMMON
o Interstitial disease (e.g. analgesic nephropathy – long-term excessive use of analgesics)

Question 8

causes of direct tubular injury

Answer 8

 Most commonly ischaemic
 Endogenous toxins  myoglobin (i.e. rhabdomyolysis from muscle injury), immunoglobulins
 Exogenous toxins  contrast medium > aminoglycosides, amphotericin, aciclovir

Question 9

infiltrative causes of renal AKI

Answer 9

 Amyloidosis (causes nephrotic syndrome)
 Lymphoma
 Multiple Myeloma

Question 10

Define severity of AKI

Answer 10

o Serum creatinine

o Urine output

Question 11

How is AKI staged

Answer 11

stage 1 (1.5-1.9x baseline serum creatinine , <0.5ml/kg/h 6-12 hours urine output)
stage 2 (2-2.9 x creatine, <0.5ml/kg/h for 12 hours)
stage 3 (3x creatinine, anuria for 12 hours)

Question 12

Consequences of CKD

Answer 12

o (1) Progressive failure of homeostatic function
 (1a) Acidosis
 (1b) Hyperkalaemia
o (2) Progressive failure of hormonal function
 (2a) Anaemia
 (2b) Renal bone disease
o (3) Cardiovascular disease
 Vascular calcification (renal osteodystrophy)
 Uraemic cardiomyopathy
o (4) Uraemia and death

Question 13

Anaemia of CKD

Answer 13

o Progressive decline in EPO-producing cells
o Usually occurs when GFR <30 ml/min
o Causes normochromic, normocytic anaemia
 This helps distinguish it from other causes of anaemia (e.g. iron deficiency, B12 deficiency)
o TREATMENT: use artificial erythropoiesis-stimulating agents (ESAs)
 Erythropoietin alfa (Eprex)
 Erythropoietin beta (NeoRecormon)
 Darbopoietin (Aranesp)
o NOTE: reasons for CKD not responding to an erythropoiesis-stimulating agent:
 Iron deficiency, TB, malignancy, B12 and folate deficiency, hyper-parathyroidism

Question 14

Hyperkalaemia of CKD

Answer 14

o Hyperkalaemia causes membrane depolarisation
o This impacts on:
 Cardiac function
 Muscle function
o Medications that cause hyperkalaemia:
 ACE inhibitor
 Spironolactone (potassium-sparing diuretics)

Question 15

Reasons for CKD not responding to EPO

Answer 15

 Iron deficiency, TB, malignancy, B12 and folate deficiency, hyper-parathyroidism

Question 16

Renal bone disease types

Answer 16

o	Complex entity resulting in reduced bone density, bone pain and fractures:
	Osteitis fibrosa cystica	
	Osteomalacia
	Adynamic bone disease	
	Renal osteodystrophy

Question 17

Cardiovascular disease in CKD

Answer 17

Cardiovascular disease (vascular calcification, uraemic cardiomyopathy):
o This is the MOST IMPORTANT consequence of CKD (it is most likely thing to kill them)
o The risk of a cardiac event seems to be directly related to GFR

o Atherosclerosis:
 Traditional risk factors such as cholesterol and hypertension contribute towards the risk
 Renal vascular lesions are characterised by heavily calcified plaques (rather than lipid-rich atheromas)

o Uraemic Cardiomyopathy (THREE phases):
 LV hypertrophy  LV dilatation  LV dysfunction

Question 18

Indications for dialysis

Answer 18

o	Refractory hyperkalaemia 
o	Refractory fluid overload
o	Metabolic acidosis
o	Uraemic symptoms (encephalopathy, nausea, pruritis, malaise, pericarditis)
o	CKD stage 5 (GFR <15mL/min)

Question 19

What is the best measure of kidney function

Answer 19

GFR (normally = 120mL/minute; 7.2L/hour)

o There is an age-related decline of around 1 mL/min per year

Question 20

Clearance

Answer 20

o Clearance can be used to calculate GFR
o There are THREE criteria* that need to be fulfilled for a marker to be used to measure GFR:
 Marker is NOT bound to serum proteins
 Freely filtered by the glomerulus
 NOT secreted or reabsorbed by tubular cells
o If these conditions are fulfilled, then clearance = GFR; at any one point:
 C = (U x V)/P

Question 21

perfect GFR marker in research

Answer 21

insulin

Question 22

CKD-EPI

Answer 22

CKD-Epidemiology Collaboration (CKD-EPI)
• The equation is based on the same four variables as MDRD but models the relationship between GFR and serum creatinine, age, sex and race differently
• It is an improvement on MDRD, but it is still imprecise at higher GFRs
o Reduces bias at GFRs >60mL/min (but imprecise at higher GFRs)
o I.E. Accurate at LOW GFRs and less accurate at HIGH GFRs

Question 23

cYSTATIN c

Answer 23

 This is an alternative endogenous marker
 This is constitutively produced by all nucleated cells at a constant rate and is freely filtered
 Almost completely reabsorbed and catabolised by tubular cells
 NOTE: CKD NICE guidelines have included cystatin C, however, it is not used that frequently

Question 24

Urine protein: creatinine ratio

Answer 24

o This is a quantitative assessment of the amount of proteinuria
o Measurement of creatinine corrects for urinary concentration
o Two methods to do PCR:
 24hr urine collection (cumbersome and messy; highly inaccurate without patient education)
 Spot urine measurement

Question 25

Renal imaging

Answer 25

o 1st line: CT KUB
o 2nd line: Ultrasound KUB
 This can differentiate AKI and hydronephrosis

o Plain KUB films (can show ‘staghorn calculi’)
o IV urogram (done more in paediatrics to look for anatomical defects)
o MRI KUB
o Functional imaging (static and dynamic renograms)
 IV radiolabelled nuclei are injected, and kidney uptake is measured
 Any kidney not showing up on scans signifies a non-functional kidney
o Renal biopsy is often necessary for various diagnoses (ultrasound or CT guided)