Outline of Session
• Physiology
• AKI
• CKD
• Glomerular
• RRT
• Aetiology
• Presentation
• Diagnosis
• Treatment
• Outcome
Core Medical Training Curriculum, updated August 2011
7extra Which is incorrect
concerning dipstick testing of
urine for protein?
• A A positive test can be found in patients with
normal kidneys
• B If positive only after several hours spent in
the upright posture, it may be of no significance
• C A positive test will result from lower urinary
tract infection
• D A positive test will result from increased light
chain excretion
• E 2+ proteinuria represents approximately
1gm/litre
7extra Which is incorrect
concerning dipstick testing of
urine for protein?
• A A positive test can be found in patients with
normal kidneys
• B If positive only after several hours spent in
the upright posture, it may be of no significance
• C A positive test will result from lower urinary
tract infection
• D A positive test will result from increased
light chain excretion
• E 2+ proteinuria represents approximately
1gm/litre
Dipstick urinalysis for protein
• Proteinuria can occur with urinary infection
and after exercise or fever in people who have
normal kidneys
• Orthostatic proteinuria (literally on standing)
disappears after lying in bed and is of no
significance
• Bence-Jones proteins don’t register on a
dipstix (which only detects albumin)
• Semiquantitative only eg 2 plus protein ~ 1g/l
Proteinuria Equivalents
ACR
PCR
mg/mmol mg/mmol
30
70
50
100
24hour
protein
0.5g
1.0g
Many labs do ACR first because more accurate at low levels
proteinuria but switch to PCR if ACR>30 because PCR cheaper
and as accurate at higher levels proteinuria
Classification of CKD
Stage
eGFR (ml/min)
1+2
60 plus other
evidence CKD
45-59
30-44
15-29
<15
3A
3B
4
5
Sometimes add suffix P to indicate PCR>100mg/mmol,
T to indicate transplant and D if on dialysis
21. Macroscopic haematuria is
commonly associated with
which of the following?
•
•
•
•
•
A
B
C
D
E
Reflux nephropathy
Diabetic glomerulosclerosis
Membranous glomerulonephritis
Light-chain nephropathy
Henoch Schönlein disease
21. Macroscopic haematuria is
commonly associated with
which of the following?
•
•
•
•
•
A
B
C
D
E
Reflux nephropathy
Diabetic glomerulosclerosis
Membranous glomerulonephritis
Light-chain nephropathy
Henoch Schönlein disease
Common causes Haematuria
Urological
•Cancers of kidney,
bladder or prostate
•Stones
•Urinary infection
•Benign tumours
eg bladder papilloma
•Trauma
Nephrological
•IgA nephropathy
•Henoch Schonlein Purpura
•Alports Syndrome
•Other glomerular disease
(usually with proteinuria)
•Polycystic kidney
•Medullary sponge
Microscopic haematuria
• Persistent microscopic haematuria +/- proteinuria
should prompt investigation for urinary tract
malignancy if >50 years
• Most common renal abnormality on biopsy is IgA
nephropathy though biopsy not usually necessary
• Persistent microscopic haematuria in absence of
proteinura should be followed annually with BP,
urine ACR, U&E for as long as haematuria
persists
NICE guideline on CKD, 2008
1 .Which of the following is most
accurate regarding tubular function?
• A 90% of sodium has been reabsorbed by
the start of the distal convoluted tubule
• B Over 25% of urinary creatinine derives
from proximal tubular secretion
• C Aldosterone acts on collecting duct cells
only
• D Distal tubular lesions lead to amino
aciduria
• E Tubular reabsorption of phosphate can be
increased by PTH
1 .Which of the following is most
accurate regarding tubular function?
• A 90% of sodium has been reabsorbed
by the start of the distal convoluted tubule
• B Over 25% of urinary creatinine derives
from proximal tubular secretion
• C Aldosterone acts on collecting duct cells
only
• D Distal tubular lesions lead to amino
aciduria
• E Tubular reabsorption of phosphate can be
increased by PTH
Sodium & the Kidney
100% Filtered
Na 5%
Na
60-65%
Nearly all filtered Na is reabsorbed
in PCT, TAL and DCT
Na
25-30%
Na 4%
Day to day control of
Na excretion takes
place in CCD by
aldo and ADH
Sodium & the Kidney
100% Filtered
Na 5%
Na
60-65%
Nearly all filtered Na is reabsorbed
in PCT, TAL and DCT
Na
25-30%
Na 4%
Day to day control of
Na excretion takes
place in CCD by
aldosterone
PCT - most aminoacids,
Ca and PO4 reabsorbed;
creatinine secreted (accounting
for up to 15%
urinary creatinine)
• proximal tubular secretion
of creatinine does not
account for more than 25%
urinary creatinine (except in
advanced renal failure)
• distal tubular lesions do not
lead to aminoaciduria
• tubular reabsorption PO4
not increased by PTH (PTH
acts to raise serum calcium
and to lower serum PO4)
• Aldosterone acts on
connecting segment and
CCD
3. With metabolic acidosis, a normal
anion gap would be most suggestive
of:
• A Alcohol excess
• B Lactic acidosis
• C Diarrhoea
• D Salicylate poisoning
• E Diabetic ketosis
3. With metabolic acidosis, a normal
anion gap would be most suggestive
of:
• A Alcohol excess
• B Lactic acidosis
• C Diarrhoea
• D Salicylate poisoning
• E Diabetic ketosis
How do you know
if acidosis is due to
diarrhoea or to some
other cause?
Measure anion gap
= [Na+ + K+] - [Cl- + HCO3-]
Normal 12 -18
Diarrhoea
RTA
Urinary diversion
Normal because when bicarb
is lost kidneys retain chloride
to maintain electroneutrality
Raised >18
DKA
Renal Failure
Salicylate
Methanol, ethylene
glycol
Raised due to presence
of unmeasured anions
Acidosis with raised
chloride suggests
diarrhoea, RTA or urinary
diversion
5 A 62-year-old man develops oliguria 48
hours after a laparotomy for bowel
obstruction. Which of the following
would be most suggestive of acute tubular
necrosis rather than pre-renal uraemia
•
•
•
•
A Urinary sodium less than 10mmol/L
B Blood pressure 95/60
C Red cell casts
D Urinary osmolality of less than 350
mosm/Kg
• E Increased skin pigmentation
5 A 62-year-old man develops oliguria 48
hours after a laparotomy for bowel
obstruction. Which of the following
would be most suggestive of acute tubular
necrosis rather than pre-renal uraemia
•
•
•
•
A Urinary sodium less than 10mmol/L
B Blood pressure 95/60
C Red cell casts
D Urinary osmolality of less than
350 mosm/Kg
• E Increased skin pigmentation
Incipient v established ATN
• Incipient (tubules
still function)
U/P osmolality • >1.5
Urine Na
• <20mmol/l
Urine Osm
• 350-1000mOsm/kg
• Established (tubules
don’t function)
• <1.1
• >40mmol/l
• <350mOsm/kg
NB - red cell casts are a feature of active GN not ATN
- BP 95/60mmHg reflects volume depletion or shock not
necessarily ATN
- skin pigmentation is a feature of CRF not ATN
Nephrologists don’t use these criteria at all!
10.A 44-year-old man has a serum
creatinine of 476 mol/l and urea 38 mmol/l.
Which of the following would be most
helpful in differentiating chronic from acute
renal failure?
• A Haemoglobin 9.8 g/dl
• B Blood pressure 165/100
• C Kidneys 7.8 cm bipolar length at
ultrasound scan
• D 1.2 gm proteinuria/24-hours
• E PTH 92 pg/ml(normal range 10-55)
10.A 44-year-old man has a serum
creatinine of 476 mol/l and urea 38 mmol/l.
Which of the following would be most
helpful in differentiating chronic from acute
renal failure?
• A Haemoglobin 9.8 g/dl
• B Blood pressure 165/100
• C Kidneys 7.8 cm bipolar length at
ultrasound scan
• D 1.2 gm proteinuria/24-hours
• E PTH 92 pg/ml(normal range 10-55)
Chronic v acute renal failure
Haemoglobin
Blood pressure
Renal size
Proteinuria
Calcium and PO4
PTH
• Chronic
• Acute
• usually anaemic
but not ADPKD
• HT if glomerular
• usually small*
• none to heavy if
glomerular
• usually low Ca
with high PO4
• variable - high in
2y hyperpara
• may become
anaemic quickly
• HT if RPGN
• normal
• none to heavy if
RPGN
• usually low Ca with
high PO4
• variable - can be
high
*Normal kidney length >10cms on sonar, borderline 9-10cms, small <9cms,
unequal if >1.5cms difference, but patients with CRF can have normal size kidneys
6.Which of following is not associated
with an increased risk of contrast
nephropathy?
• A Pre-existing renal failure
• B Hyperuricaemia
• C Non-insulin dependent diabetes
mellitus
• D Concomitant
therapy
with
theophyllines
• E Sodium depletion
6.Which of following is not associated
with an increased risk of contrast
nephropathy?
•
•
•
•
A Pre-existing renal failure
B Hyperuricaemia
C Non-insulin dependent diabetes mellitus
D Concomitant
therapy
with
theophyllines
• E Sodium depletion
Contrast Nephropathy
•
•
•
•
•
•
•
Risk increases with:
- high doses of contrast
- pre existing renal failure
- diabetes
- volume depletion
- hyperuricaemia
- advanced age
NB adenosine, a renal vasoconstrictor, is thought to be involved in pathogenesis
of CN, but trials of adenosine antagonists, theophylline and amitryptiline, have
given conflicting results. Current advice is to give 500ml saline before and after
procedure +/- N-acetyl cysteine.
7. Which of the following statements
concerning HUS is correct ?
• A Infective diarrhoea is invariably
associated
• B Platelet counts are usually higher
than in thrombotic thrombocytopaenic
purpura
• C It is usually fatal in children
• D Steroids are of proven benefit
• E Surviving patients are likely to
require long term dialysis
7. Which of the following statements
concerning HUS is correct ?
• A Infective
diarrhoea
is
invariably
associated
• B Platelet counts are usually higher
than in thrombotic thrombocytopenic
purpura
• C It is usually fatal in children
• D Steroids are of proven benefit
• E Surviving patients are likely to require
long term dialysis
Thrombotic Microangiopathy
MAHA with red cell fragments, raised LDH, low haptoglobin.
Thrombocytopenia (may be less severe in HUS)
AKI which may
require RRT
More likely
HUS
Neurological features eg confusion,
TIA, stroke, seizures, coma
More likely
TTP
HUS/TTP
• Aetiology
• D+ verotoxin producing strain of E coli 0157 esp in children
• D- sporadic form more commonly seen in adults. May be
idiopathic or assoc with drugs, HIV and malignancy (infective
diarrhoea not invariably associated)
• Pathogenesis
• ADAMTS13 is a metalloproteinase which cleaves VWF to
smaller subunits. Absence of or antibodies to this enzyme leads
to build up of VWF multimers which promote platelet
aggregation triggering MAHA
• Presentation
• Triad of ARF with MAHA and thrombocytopenia (HUS)
Healthy
Endothelial cells
Mature vWF molecules
Shear stress
Large unfolded vWF molecules
ADAMTS13
Cleaved plasma VWF which supports platelet adhesion
HUS/TTP
Endothelial cells
Mature vWF molecules
Shear stress
Large unfolded vWF molecules
Deficiency of
ADAMTS13
Platelet aggregation in microcirculation
HUS/TTP
• Differential diagnosis
• HUS, MHT, scleroderma renal crisis and DIC can all cause same
triad but clotting will be normal in first three and abnormal in DIC
• Treatment
• D+ supportive care only in children; PE with FFP in adults
• D- daily PE and FFP in adults until no further haemolysis
• Steroids may help idiopathic adult HUS/TTP if platelets do not
increase after several days PE (steroids not of proven value)
• Outcome
• D+ usually make complete recovery (not usually fatal in kids)
• D- up to 25% left with some renal impairment but long term
dialysis not usually necessary. MI and heart failure are common
6E Which of the following is correct
concerning hyperkalaemia?
•
•
•
•
A It may be caused by beta blockers
B It may be caused by paracetamol
C It may be caused by liquorice excess
D It can be corrected by IV calcium
gluconate
• E Causes ventricular tachycardia and
fibrillation
6E Which of the following is correct
concerning hyperkalaemia?
•
•
•
•
A It may be caused by beta blockers
B It may be caused by paracetamol
C It may be caused by liquorice excess
D It can be corrected by IV calcium
gluconate
• E Causes ventricular tachycardia and
fibrillation
Hyperkalaemia
• Aetiology
• Main causes begin with A - ARF, Addisons, Acidosis, Artefact,
ACEI, ARBs, Aldosterone antagonists, anti-inflammatories eg
NSAIDs, also beta blockers but not paracetamol (no effect) or
liquorice (hypokalaemic alkalosis)
• Presentation
• Peaked T waves followed by loss of P wave, broadening of QRS
complex (may mimic LBBB) then bradycardia leading to asystole
or VF (but not VT)
• Management
• Depends on level of K, likelihood it will rise further (always more
dangerous in ARF than CRF) and ECG changes
Treatment of hyperkalaemia
in acute renal failure
Reduce risk
of asystole
Calcium
Chloride/
Gluconate
Drive K+
into cells
Insulin/dextrose
Beta agonists
Sodium bicarbonate
Remove K+
from body
Dialysis
Resonium
14 Concerning diabetic nephropathy
• A It is unusual in patients with type 2
diabetes mellitus of < 5 years duration
• B It is unlikely to occur in a patient free of
proteinuria after 40 years of diabetes
• C It is usually associated with urinary ACR
3-30mg/mmol
• D Renal functional decline can be halted
by angiotensin receptor blockers
• E It can be reversed by meticulous control
of blood glucose
14 Concerning diabetic nephropathy:
• A It is unusual in patients with type 2
diabetes mellitus of < 5 years duration
• B It is unlikely to occur in a patient free
of proteinuria after 40 years of diabetes
• C It is usually associated with urinary ACR
3-30mg/mmol
• D Renal functional decline can be halted
by angiotensin receptor blockers
• E It can be reversed by meticulous control
of blood glucose
Diabetic nephropathy
• Aetiology
• - occurs after diabetic 15-20 years (rare in type 2 <5yrs)
• - risk to individual is greater in type 1 because have disease
for longer
• - increased incidence among asians, blacks and pima indians
• - unlikely if patient free of proteinuria for 40 years
• Presentation
• - DN present when Urine ACR >30mg/mmol
• Diagnosis
• - triad of diabetes + retinopathy + proteinuria = DN
• - most don’t need biopsy or arteriogram but consider other
diagnoses if no proteinuria (renovascular) or abnormal
serology (eg lupus)
Diabetic nephropathy
• Treatment
• - good evidence that tight BP control will slow but not halt rate of
progression, and that ACEI/ARB have benefits that extend beyond
their BP lowering effects. Optimal BP 130/80mmHg
• - likely that tight glucose control will prevent DN but no evidence
that this will reverse established disease
• - some evidence smoking and lipids influence renal outcome in DN
• - stop metformin when SC>200umol/l because risk of acidosis
• Outcome
- commonest cause of ESRD requiring dialysis - most patients
have type 2 because this accounts for 90% of all diabetes
- rate of decline of renal function is 10ml/min/year (untreated)
- death rate from vascular disease exceeds that from renal failure
13.Which of the following is most likely to
be true in a patient with autosomal
dominant
polycystic kidney disease?
• A The gene mutation is on chrome 16 or 4
• B Pancreatic cysts occur in > 25% of
patients
• C Mitral stenosis is a recognised
association
• D Liver failure may develop
• E End stage renal failure occurs in 90% of
patients by age 50 years
13.Which of the following is most likely to
be true in a patient with autosomal
dominant
polycystic kidney disease?
•
•
•
•
•
A The gene mutation is on chrome 16 or 4
B Pancreatic cysts occur in > 25% of patients
C Mitral stenosis is a recognised association
D Liver failure may develop
E End stage renal failure occurs in 90% of
patients by age 50 years
Polycystic kidneys
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Aetiology
- PKD1 gene on chrome 16 in 85%, PKD2 gene on chrome 4 in 15%
- Incidence is 1 in 1000 with “genetic anticipation”
Presentation
- often asymptomatic but also loin pain, haematuria, UTI, stones, HT or CRF
Diagnosis
- usually by ultrasound – but can’t definitely exclude till 30 years
Extrarenal manifestations
- liver cysts 40-90% but liver failure rare, pancreatic cysts 5-10% (not >25%)
- berry aneurysms 3-5%. Screening by MRA recommended if FH of SAH or has
unexplained headache, but not routinely. Intervene if aneurysm >10mm
- MVP, AR (not Mitral Stenosis) and colonic diverticulae
- erythrocytosis
Treatment
- tight control of BP may slow rate of decline of renal function
Outcome
- 50% PKD1 and 2 develop ESRD by 55 and 70 years accounting for ~10%
patients on RRT
29. A 68-year-old man has backache and hypercalcaemia,
plasma globulins are elevated at 52 g/l and he has a
normocytic anaemia. 24 hour urinary protein excretion is
0.5 grams. He develops diarrhoea and vomiting and
presents with acute renal failure. A renal biopsy is
performed. What is the most likely diagnosis?
•
•
•
•
•
A
B
C
D
E
Acute tubular necrosis
Amyloidosis
Interstitial nephritis
Intra-glomerular thrombi
Light chain nephropathy
29. A 68-year-old man has backache and hypercalcaemia,
plasma globulins are elevated at 52 g/l and he has a
normocytic anaemia. 24 hour urinary protein excretion is
0.5 grams. He develops diarrhoea and vomiting and
presents with acute renal failure. A renal biopsy is
performed. What is the most likely diagnosis?
•
•
•
•
•
A
B
C
D
E
Acute tubular necrosis
Amyloidosis
Interstitial nephritis
Intra-glomerular thrombi
Light chain nephropathy
Myeloma
• Aetiology of renal failure
• - nephrotoxicity due to free light chains
• - also dehydration, hypercalcaemia, infection, amyloid,
hyperuricaemia
• Presentation
• - AKI or CRF
• - Hypercalcaemia and low platelets are important clues to
diagnosis in renal failure
• Diagnosis
• - 10% clonal bone marrow plasma cells plus
• - Monoclonal protein in serum or urine plus/minus
• - Myeloma related organ dysfunction: hypercalcaemia, renal
insufficiency, anaemia, bone disease (lytic lesions)
• - renal biopsy not mandatory, usually shows light chain
nephropathy
Myeloma
•
•
•
•
•
•
•
•
•
Treatment
- clinical observation only if asymptomatic
- palliative only for frail elderly
- supportive eg DXT for bone pain, dialysis for renal failure
- disease suppression eg melphelan and prednisolone in
elderly,
- disease remission with thalidomide, dexamethasone and
bortezomib (a proteosome inhibitor, trade name velcade) in
younger patients
- cure by autologous stem cell transplant but only suitable for
a few
Prognosis
- median survival with myeloma now 5 years years but less
with renal failure
Palumbo and Anderson, Multiple Myeloma NEJM 2011;1046-60
12. Which of the following
statements is most accurate
concerning renal bone disease?
• A Hypercalcaemia associated with osteodystrophy
responds to high dose oral steroids
• B Serum calcium levels are usually high in secondary
hyperparathyroidism
• C Renal osteomalacia will respond to the 25
hydroxylated form of Vitamin D
• D A "brown tumour" of bone carries a malignant
potential
• E Serum phosphate should be maintained below 1.8
mmol/l
12. Which of the following
statements is most accurate
concerning renal bone disease?
• A Hypercalcaemia associated with osteodystrophy
responds to high dose oral steroids
• B Serum calcium levels are usually high in secondary
hyperparathyroidism
• C Renal osteomalacia will respond to the 25
hydroxylated form of Vitamin D
• D A "brown tumour" of bone carries a malignant
potential
• E Serum phosphate should be maintained below 1.8
mmol/l
 Hydroxylation
Vitamin D
GFR
Calcium
Aluminium
Osteomalacia
Phosphate
retention
PO4
PTH
2º hyper
para
3º hyperpara
Ca x PO4 >4.5
Soft tissue
calcification
Clinical features
• May be none
• Soft tissue calcification - itch, red eye,
calciphylaxis and (probably) increased risk CHD
due to coronary calcification
• 2y hyperpara - high PO4 with low Calcium,
may cause bone pain, fractures
• Osteomalacia - bone pain, rickets in childhood,
proximal myopathy, fractures
NB Osteitis fibrosa cystica is the term used to describe the appearance of bone in
2y hyperpara. In severe cases, proliferation of osteoclasts results in cyst
formation in bone called a “brown tumour” which is not premalignant
Treatment of renal bone disease
• Anything that keeps PO4 <1.8mmol/l!
• - low PO4 diet which means restricting dairy
products
• - calcium carbonate (calcichew) or acetate
(phosex) before food
• - aluminium hydroxide (alucaps) before food
• - sevelamer (renagel - non Ca non Al polymer)
before food
• - lanthanum (fosrenol) after food
• - dialysis - but not very efficient at removing
PO4
Treatment of renal bone disease
• Alfacalcidol or calcitriol (1:25DHCC) to keep
calcium normal and PTH 2-4 times ULN after
controlling PO4
• Cinacalcet (Mimpara) for severe 2y HPT
• Parathyroidectomy for 3y HPT, uncontrollable
itch with high Ca-PO4 product and calciphylaxis
(skin necrosis)
NB Hypercalcaemia assoc with renal bone disease does not
respond to oral steroids and renal osteomalacia does not
respond to 25OHD
Alfacalcidol
GFR
Phosphate
binders
PO4
Calcium
PTH
Aluminium
Ca x PO4 >4.5
Osteomalacia
2º hyper
para
Soft tissue
calcification
Cinacalcet
3º
hyperpara
Parathyroidectomy
15 A 45-year-old woman has a 10 week history of
oedema. Serum albumin is 22 g/l, creatinine 98
µmol/l and 24-hour urinary protein output 7.3 gm.
Which of the following is most applicable?
• A A trial of steroids is justified before
proceeding to renal biopsy
• B A history of rheumatoid arthritis would be
helpful for diagnosis
• C Renal vein thrombosis is likely if the
patient has diuretic-resistant oedema
• D There is a low risk of progressive renal
failure
15 A 45-year-old woman has a 10 week history of
oedema. Serum albumin is 22 g/l, creatinine 98
µmol/l and 24-hour urinary protein output 7.3 gm.
Which of the following is most applicable?
• A A trial of steroids is justified before
proceeding to renal biopsy
• B A history of rheumatoid arthritis would
be helpful for diagnosis
• C Renal vein thrombosis is likely if the
patient has diuretic-resistant oedema
• D There is a low risk of progressive renal
failure
Nephrotic syndrome
•
•
•
•
•
•
•
•
•
•
•
Aetiology
- primary GN, usually minimal change, membranous, FSGS
- drugs esp gold, penicillamine, captopril
- infections eg HIV, HBV, HCV, malaria
- malignancies esp lymphoma, carcinoma, myeloma
- systemic diseases incl diabetes, amyloid, lupus. NS in rheumatoid likely to
be due to DMARD, amyloid or less commonly RA related GN
Presentation
- quintad of oedema with PCR> 300mg/mmol, serum albumin <30g/l,
hyperlipidaemia and prothrombotic tendency
Diagnosis
- by renal biopsy except in children with highly selective proteinuria, and
most cases of diabetes and myeloma
- serological tests eg complement, vasculitis screen, myeloma screen,
hepatitis serology in selected cases
Nephrotic syndrome
• Treatment
- diuretics and salt restriction for oedema, ACEI/ARBs for HT and
antiproteinuric effects, statins for hyperlipidaemia and adequate
protein intake (1g/kg dry body wt plus 1g/g proteinuria)
• - steroids not justified before biopsy in an adult
• Complications and outcome
• - progressive renal failure not uncommon
• - infection, partly because of associated hypogammaglobulinaemia
• - DVT/PE because lose inhibitors of coagulation in urine
• - renal vein thrombosis may cause flank pain, macroscopic
haematuria or deterioration of renal function (not usually diuretic
resistant oedema)
16 Minimal change disease
• A Accounts for about 10% of all adult
nephrotic syndrome
• B May be associated with indomethacin
use
• C May be associated with amiodarone use
• D Is often accompanied by microscopic
haematuria
• E Is associated with the presence of C3
nephritic factor
16 Minimal change disease
• A Accounts for about 10% of all adult
nephrotic syndrome
• B May be associated with indomethacin
use
• C May be associated with amiodarone use
• D Is often accompanied by microscopic
haematuria
• E Is associated with the presence of C3
nephritic factor
Minimal change nephropathy
• Aetiology
• - usually idiopathic but can be 2y to lymphoma or assoc with NSAIDs, gold
or lithium (not amiodarone)
• Presentation
• - nephrotic syndrome accounting for 80-90% NS in children and 25% in adults
(not 10%). Micro haematuria is uncommon
• Diagnosis
• - biopsy in adults but not usually in children. Not associated with C3
nephritic factor
• Treatment
• - usually responds to steroids. Cyclophosphamide and cyclosporin can be used
if relapses
• Outcome
• - remission is common after steroids. CRF extremely unlikely. Often
complicated by pneumococcal peritonitis in past
17 IgA nephropathy
• A Is the commonest primary GN leading to
renal failure
• B Leads to end stage renal failure in 50%
of patients over 20 years
• C Occurs
more
commonly
among
Europeans than Japanese
• D Commonly presents with nephrotic
syndrome
• E May be histologically indistinguishable
from Haemolytic Uraemic syndrome
17 IgA nephropathy
• A Is the commonest primary GN leading
to renal failure
• B Leads to end stage renal failure in 50%
of patients over 20 years
• C Occurs
more
commonly
among
Europeans than Japanese
• D Commonly presents with nephrotic
syndrome
• E May be histologically indistinguishable
from Haemolytic Uraemic syndrome
IgA nephropathy
• Aetiology
• - commonest GN on renal biopsy, more common among japanese than
europeans and can also run in families though mode of inheritance unclear
• Presentation
• - usually with micro or macro haematuria esp following URTI, but also with
asymptomatic proteinuria, nephrotic syndrome (3%), CRF and occas as
RPGN with crescentic nephritis
• Diagnosis
• - biopsy shows mesangial proliferation with deposition of IgA. identical to
HSP (not HUS which shows intraglomerular thrombi)
• Treatment
• - control of HT, otherwise no specific therapy has been shown to alter
progression to ESRD. No evidence that tonsillectomy helps
• Outcome
• - 10-30% progress to ESRD over 20 years (the commonest primary GN
leading to renal failure)
4 extra Membranous nephropathy
• A Is caused by deposition of an
autoantibody to glomerular basement
membrane
• B Is associated with Familial lipodystrophy
• C Should be treated with plasma
exchange
• D Leads to progressive renal failure in the
majority of cases
• E May be the first manifestation of lung
cancer
4 extra Membranous nephropathy
• A Is caused by deposition of an
autoantibody to glomerular basement
membrane
• B Is associated with Familial lipodystrophy
• C Should be treated with plasma
exchange
• D Leads to progressive renal failure in the
majority of cases
• E May be the first manifestation of lung
cancer
Membranous nephropathy
• Aetiology
• - usually idiopathic but can be 2y to drugs, SLE and malignancy in up to 20%
cases. Should consider lung, colon and breast cancer in elderly patients
• Presentation
• - asymptomatic proteinuria or nephrotic syndrome. (MCGN type2 not
membranous is associated with partial lipodystrophy)
• Diagnosis
• - LM shows uniform thickening of GBM, EM subepithelial humps and IF
granular deposition of IgG along GBM. Humps are Ag/Ab complexes in the
GBM. Their origin is not known. The Ab is not directed at the GBM itself
• Treatment
• - supportive only unless progressive decline in function (MRC trial)
• - no evidence for plasma exchange
• Outcome
• - 33% stay the same, 33% get better and only 33% develop progressive
renal failure
23. Which of the following parameters
indicates the poorest prognosis in a
patient with acute Wegener’s
granulomatosis?
• A 100% active crescents on renal
biopsy
• B cANCA positivity
• C Extrarenal vasculitis
• D Female sex
• E Acute renal failure requiring dialysis
23. Which of the following parameters
indicates the poorest prognosis in a
patient with acute Wegener’s
granulomatosis?
• A 100% active crescents on renal
biopsy
• B cANCA positivity
• C Extrarenal vasculitis
• D Female sex
• E Acute renal failure requiring dialysis
Crescentic nephritis
• Aetiology
• - ANCA Associated Vasculitis (AASV) – WG (now known as
GPA), MPA, CS, idiopathic RPGN
• - SLE
• - anti GBM disease
• - Primary GN esp IgA
• Presentation
• - rapidly progressive renal failure plus
• - systemic eg fever, night sweats, weight loss, malaise (all)
• - ENT involvement with sinusitis and otitis media (WG)
• - asthma, eosinophilia (CS)
• - dyspnoea, cough, haemoptysis (WG, MPA, antiGBM)
• - photosensitivity, arthralgia, skin rash (SLE)
Crescentic nephritis
• Diagnosis
• - vasculitis screen with ANCA, antiGBM and ANF
• - cANCA (antiPR3) assoc with WG, pANCA
(antiMPO) assoc with MPA
• - urgent renal biopsy with IF staining
• Treatment
• - high dose steroid with cyclophosphamide
• - PE for AASV recently shown to be more effective
than methylprednisolone if SC >500umol/l
• - switch cyclophosphamide to azathioprine after
inducing remission (around 3 months)
Morgan et al JASN 2006;17:1224-34. Jayne et al. JASN 2007: 18; 2180-8
Crescentic nephritis
• Mortality
• - 75% 5 year survival if no ESRD, 25% 5YS if ESRD
• - main causes of death are complications from
underlying disease eg renal and lung failure and
complications from Rx eg infection and malignancy
• Renal Outcomes
• - renal prognosis determined by severity of renal
failure, need for dialysis, proportion of sclerosed
glomeruli and by degree of interstitial fibrosis on renal
biopsy
• - factors which do not influence outcome in WG are
gender, cANCA positivity, percentage crescents and
extrarenal vasculitis
22.
A 32-year-old woman complaining of painful hands
is found to have hypertension, proteinuria and dipstick
haematuria. Plasma creatinine is 147 µmol/l. Renal
biopsy shows proliferative glomerulonephritis with
occasional cellular crescents. Immuno-fluorescence
shows diffuse granular staining for IgA, IgG, IgM, C3 and
C4. What is the diagnosis?
•
•
•
•
•
A
B
C
D
E
IgA nephropathy
lupus
Membranous
Minimal change
Systemic vasculitis
22.
A 32-year-old woman complaining of painful hands
is found to have hypertension, proteinuria and dipstick
haematuria. Plasma creatinine is 147 µmol/l. Renal
biopsy shows proliferative glomerulonephritis with
occasional cellular crescents. Immuno-fluorescence
shows diffuse granular staining for IgA, IgG, IgM, C3 and
C4. What is the diagnosis?
•
•
•
•
•
A
B
C
D
E
IgA nephropathy
lupus
Membranous
Minimal change
Systemic vasculitis
Renal Immunofluorescence
and Electron Microscopy
• IgA nephropathy - mesangial deposition of IgA
• Lupus - full house IF of IgG, IgA, IgM, C3, C4
• Membranous - granular staining for IgG along GBM
with subepithelial immune complex deposits “spikes” on
silver staining
• Minimal change - foot process fusion on EM only
• AASV - no immunoglobulin deposition - described as
pauci immune to distinguish from lupus in patient with
crescentic nephritis
27 In suspected renovascular
disease, the most accurate
screening test is:
•
•
•
•
•
A
B
C
D
E
Captopril renogram
Intra-arterial renal angiography
Magnetic resonance angiography
Renal ultrasound scan
Renal vein renin estimation
27 .In suspected renovascular
disease, the most accurate
screening test is:
•
•
•
•
•
A
B
C
D
E
Captopril renogram
Intra-arterial renal angiography
Magnetic resonance angiography
Renal ultrasound scan
Renal vein renin estimation
Bilateral renovascular disease
• Aetiology
• - >90% atheromatous, <10% fibromuscular dysplasia
• - ARVD is a disease of the elderly, commonly assoc with
smoking, diabetes and vascular disease at other sites
• Presentation
• - may be asymptomatic
• - hypertension, commonly severe systolic HT
• - ARF esp if ACEI given to patient with BRVD
• - CRF: up to 15% patients on dialysis have BRVD
• - “Flash” pulmonary oedema due to fluid retention in BRVD
• Mechanism of renal failure
• - haemodynamic only if >60% stenosis
• - hypertensive nephrosclerosis (intrarenal artery stenoses)
•
•
•
•
•
•
•
•
•
•
•
Diagnosis
- suspect in arteriopath with difficult HT or ACEI renal failure
- renal sonar may show inequality of renal size (>1.5cms)
- captopril renogram is ok screening test if renal function normal
- MRA now considered best screening test
- intra arterial renal angio is still the gold standard for diagnosis
- renal vein renin ratio may predict response to revascularisation
Treatment
- control of HT avoiding ACEI/ARB if possible
- aspirin and statin for their anti ischaemic effect
- revascularisation by PTRA/stent if BRVD with >60% stenoses
and pulmonary oedema, difficult HT or need to use ACEI/ARB
• Outcome
• - high mortality from extra renal vascular disease and don’t
usually do well on dialysis
15extra Which is true regarding
renal organ donation?
• A Cadaveric renal transplants have a one year graft
survival rate of 50-60%
• B History of cerebral astrocytoma is a contraindication for
organ donation
• C The presence of decerebrate posturing is a
contraindication for organ donation
• D Patients who fulfil the criteria for brainstem death will
develop asystole in approximately 50% of cases if full
respiratory support is maintained for a further two weeks
• E Patients who are CMV seronegative should only
receive kidneys from CMV seronegative donors
15extra Which is true regarding
renal organ donation?
• A Cadaveric renal transplants have a one year graft
survival rate of 50-60%
• B History of cerebral astrocytoma is a contraindication for
organ donation
• C The presence of decerebrate posturing is a
contraindication for organ donation
• D Patients who fulfil the criteria for brainstem death will
develop asystole in approximately 50% of cases if full
respiratory support is maintained for a further two weeks
• E Patients who are CMV seronegative should only
receive kidneys from CMV seronegative donors
11. With regard to transplantation
• A Haplotype identical live-donor transplants do not
require any immunosuppression
• B Chronic pyelonephritic kidneys must be removed
prior to transplantation
• C Cadaveric graft survival rates of 90% should be
anticipated at one year
• D Post-transplant lymphoproliferative disease
(PTLD) always presents in the 1st year after
transplantation
• E The operation can be performed only twice
11. With regard to transplantation
• A Haplotype identical live-donor transplants do not
require any immunosuppression
• B Chronic pyelonephritic kidneys must be removed
prior to transplantation
• C Cadaveric graft survival rates of 90% should
be anticipated at one year
• D Post-transplant lymphoproliferative disease
(PTLD) always presents in the 1st year after
transplantation
• E The operation can be performed only twice
Transplant preparation
• Recipient work up
• - must be free of vascular disease, malignancy and infection
• - only indications for nephrectomy before transplant are
uncontrolled hypertension, pyonephrosis and significant recurrent
UTI (no indication to remove chronic pyelo kidneys per se)
• Donor work up
• - Cadaveric donors who fulfil criteria for brain stem death will
develop asystole within days of diagnosis. Decerebrate
posturing is a sign of neuronal activity ie does not fulfil criteria
• - must have no evidence of malignancy except 1y brain
tumours, or BCC/SCC with no recurrence 5 years after treatment
• - must be HBV, HCV, HIV negative. Can be CMV positive higher incidence of CMV disease if CMV+ kidney given to CMVdonor but this combination is not a contraindication to Tx
Post transplantation
•
•
•
•
•
•
•
•
•
•
Graft survival
- cadaveric graft survival rates >90% at one year now expected
- patient can have up to 3 further tx if graft fails
Anti rejection therapy
- all require immunosuppression except identical twins (haploidentical simply means they have inherited the same HLA and
DR antigens from parents, not that they are identical twins)
- most now start with prednisolone, tacrolimus and mycophenolate
Cancer risk
- skin cancers are most common malignancy. SCC>BCC which is
reverse of that seen in gen pop. Solar keratoses are premalignant
- post transplant lymphoproliferative disorder (PTLD) can
occur at any stage post transplant and is often assoc with EBV
- other cancers incl breast, cervix, colon - women should have
annual smear
17extra. In a patient whose
renal function deteriorates at 6
months post transplantation:
• A Transplant biopsy is unlikely to be helpful
• B A Cyclosporin level within the therapeutic
range excludes nephrotoxicity
• C Acute rather than chronic rejection is
most likely
• D CMV infection is a likely cause
• E Urinary obstruction should be excluded
in the transplant
17extra. In a patient whose
renal function deteriorates at 6
months post transplantation:
• A Transplant biopsy is unlikely to be helpful
• B A Cyclosporin level within the therapeutic
range excludes nephrotoxicity
• C Acute rather than chronic rejection is
most likely
• D CMV infection is a likely cause
• E Urinary
obstruction
should
be
excluded in the transplant
Graft Failure
•
•
•
CMV infection typically occurs between 6 and 16 weeks
Acute rejection usually occurs in first 3 months
Chronic allograft nephropathy (formerly chronic rejection)
from 6 months
• Calcineurin toxicity can occur despite therapeutic serum level
• Transplant artery stenosis
• Obstruction from ureteric stenosis or lymphocele – should be
excluded in every case
• Graft infection ie pyelonephritis
• Recurrence of original disease esp FSGS, IgA and diabetes
NB Transplant biopsy usually necessary in absence of infection or
obstruction
Carpe
Diem!
and
good
luck
4. A 29-year-old woman presents with weakness
and is found to have a serum potassium of 2.2
mmol/l and pH 7.1. Which of the following would
be most suggestive of proximal renal tubular
acidosis (RTA type 2)?
•
•
•
•
•
A
B
C
D
E
Renal calculi
Osteomalacia
Serum bicarbonate 8 mmol/l
Urinary pH 6.5
History of Sjogren’s syndrome
4. A 29-year-old woman presents with weakness
and is found to have a serum potassium of 2.2
mmol/l and pH 7.1. Which of the following would
be most suggestive of proximal renal tubular
acidosis (RTA type 2)?
•
•
•
•
•
A
B
C
D
E
Renal calculi
Osteomalacia
Serum bicarbonate 8 mmol/l
Urinary pH 6.5
History of Sjogren’s syndrome
How do kidneys
regulate acid base
balance?
Bicarbonate is
freely filtered by
glomerulus
Then nearly all
reabsorbed by
PCT
H+ excreted at
cortical
collecting duct
to maintain
normal pH
What can go wrong?
Type 2 - Proximal RTA
due to failure of
bicarbonate
reabsorption
(uncommon in adults)
Type 1 - Distal
RTA due to
failure of acid
secretion
(common)
Type 3 - Poorly characterised mix of types 1 and 2 (vanishingly rare)
Type 4 - Hyporeninaemic hypoaldosteronism causing acidosis and
hyperkalaemia (common)
Renal tubular acidosis
• Distal - type 1
• Proximal - type 2
• rare
Frequency • common
Mechanism • failure to excrete H+ • failure to reabsorb
bicarbonate
• 1y or 2y to cystinosis,
• 1y or 2y to SLE,
Causes
wilsons, myeloma,
sjogrens, PBC,
sjogrens - often assoc
CAH, urinary
with failure to reabsorb
obstruction,
PO4, AA, glucose, urate
medullary sponge,
(fanconi)
lithium
Renal tubular acidosis
• Distal - type 1
•
•
Serum bic
•
Serum K
Complications •
Urine pH
Therapy
pH > 5.5
often < 10mmol/l
usually low
nephrocalcinosis,
stones
• low dose bicarbonate,
K supps, citrate to stop
Ca-PO4 deposition if
stone former
Renal tubular acidosis
• Distal - type 1
•
•
Serum bic
•
Serum K
Complications •
Urine pH
Therapy
• Proximal - type 2
pH > 5.5
•
often < 10mmol/l
•
usually low
•
nephrocalcinosis,
•
stones
• low dose bicarbonate, •
K supps, citrate to stop
Ca-PO4 deposition if
stone former
Variable*
14-20 mmol/l*
normal or low
osteomalacia, rickets
(not calcinosis or stones)
high dose bicarbonate
*when serum bicarb drops below a threshold level in type 2 RTA, the tubules
start reabsorbing bicarbonate which means serum bic can be higher and
urine pH lower than in type 1 - known as the “threshold effect”
This is the IVP of a patient
whose U&E were:
Na+
136
K
3.5
Cl
112
Bic
14
Urea
7.6
Creatinine 127
Arterial pH was 7.24
What does the IVP show
and what is the explanation
for the blood results ?
1. The IVP shows an ileal conduit.
2. The blood results show evidence of a
normal anion gap acidosis. This is due to
direct loss of bicarbonate through the gut (eg
diarrhoea, urinary diversion) or through the
kidney (eg RTA). When bicarbonate is lost,
more chloride is retained by the renal tubules
to maintain electroneutrality.
25 .In a patient with reflux
nephropathy which of the following is
most accurate?
• A If reflux persists into adolescence ureteric reimplantation will become likely
• B Renal scarring rarely occurs beyond 8 years of
age
• C The patient has a > 50% chance of requiring
dialysis during his lifetime
• D There is a 5% chance of the patient’s offspring
suffering vesico-ureteric reflux
• E There is usually evidence of urinary infection
25 .In a patient with reflux
nephropathy which of the following is
most accurate?
• A If reflux persists into adolescence ureteric reimplantation will become likely
• B Renal scarring rarely occurs beyond 8
years of age
• C The patient has a > 50% chance of requiring
dialysis during his lifetime
• D There is a 5% chance of the patient’s offspring
suffering vesico-ureteric reflux
• E There is usually evidence of urinary infection
2extra Concerning chronic
pyelonephritis:
• A It is the most common cause of renal failure in
the UK
• B It is usually caused by recurrent acute
pyelonephritis
• C It may give rise to a salt losing nephropathy
• D Bilateral native nephrectomy is necessary prior
to renal transplantation
• E The IVU shows cortical scarring and a normal
calyceal pattern
2extra Concerning chronic
pyelonephritis:
• A It is the most common cause of renal failure in
the UK
• B It is usually caused by recurrent acute
pyelonephritis
• C It may give rise to a salt losing nephropathy
• D Bilateral native nephrectomy is necessary prior
to renal transplantation
• E The IVU shows cortical scarring and a normal
calyceal pattern
Reflux nephropathy
• Aetiology
• - Primary vesico ureteric reflux is inherited as AD with ~25% of
offspring developing reflux (not 5%)
• Presentation
• - as CRF in adult life
• - with UTI in childhood eg fever, unexplained vomiting or abdo
pain, failure to thrive in addition to dysuria
• - primarily a tubulo interstitial disorder, so may give rise to salt
wasting
• Investigations
• - DMSA scan in childhood will show cortical scars
• - Sonar in adults shows small scarred kidneys
• - IVU shows calyceal clubbing (not normal calyces) with cortical
scars
Reflux nephropathy
• Treatment
• - RCTs have shown equal efficacy of continuous antibiotics until puberty and
ureteric reimplantation in children with reflux and UTI - reimplantation now
less common than before
• - prophylactic antibiotics for asymptomatic infection now no longer
recommended after puberty
• - only patients with serious recurrent UTI or pyonephrosis require
nephrectomy before transplantation (bilateral nephrectomy not routine)
• Outcome
• - combination of reflux and UTI usually required to cause scarring and CRF
• - but new scars rarely develop after 8 yrs of age
• - progressive loss of renal function, invariably assoc with HT and proteinuria,
can occur in absence of both UTI and reflux if GFR<50ml/min
• - CRF not caused by recurrent acute pyelonephritis - UTI present in a
minority of adults
• - accounts for ~ 20% cases ESRD requiring dialysis (not 50%)
18 With regard to lupus nephritis:
• A It may present with a rapidly progressive
glomerulonephritis
• B It may present with histological changes
similar to diabetic nephropathy
• C It should be treated with oral steroids
alone when associated with a membranous
histology
• D It should only be treated with cytotoxic
agents when serum creatinine > 120 mol/l
• E Frequently complicates drug induced SLE
18 With regard to lupus nephritis:
• A It may present with a rapidly
progressive glomerulonephritis
• B It may present with histological changes
similar to diabetic nephropathy
• C It should be treated with oral steroids
alone when associated with a membranous
histology
• D It should only be treated with cytotoxic
agents when serum creatinine > 120 mol/l
• E Frequently complicates drug induced SLE
Lupus nephritis
• Aetiology
• - renal involvement occurs to some degree in most lupus patients, though
drug induced lupus is said to spare the kidney
• Presentation
• - can vary from asymptomatic urine abnormalities to HT, NS, ARF, CRF
• Diagnosis
• - all patients with lupus and urine abnormalities should have biopsy to guide
potentially toxic treatment regardless of serum creatinine. Histology can
change from one type to another in the same patient. Six distinct patterns are
recognised. Histology not similar to that of DN
• 1 - normal
• 2a - mesangial deposits 2b - mesangial hypercellularity
• 3 - focal and segmental proliferative GN
• 4 - diffuse proliferative (>50% glomeruli involved) causing RPGN
• 5 - membranous
• 6 - glomerulosclerosis
Lupus nephritis
•
•
•
•
•
•
•
•
•
•
•
Treatment
1 - no specific therapy
2 - steroids only
3 - steroids plus cytotoxic, may be cyclophosphamide
4 - steroids plus cytotoxic, usually cyclophosphamide
5 - controversial - likely to be steroids with azathioprine, mycophenolate or
cyclosporin but not cyclophosphamide and not steroids alone
6 - controversial
NB - cytotoxics indicated by histology and not simply by serum
creatinine
Outcome
- glomerular sclerosis is most important predictor of ESRD
- overall prognosis determined by presence or absence also of
neuropsychiatric, cardiac and pulmonary disease
20. Which of the following
infections is not associated
with glomerulonephritis?
•
•
•
•
•
A
B
C
D
E
Plasmodium malaria
HIV 1
Hantavirus
Schistosoma mansoni
Mycobacterium leprae
20. Which of the following
infections is not associated
with glomerulonephritis?
•
•
•
•
•
A
B
C
D
E
Plasmodium malaria
HIV 1
Hantavirus
Schistosoma mansoni
Mycobacterium leprae
Infections causing GN
•
•
•
•
•
•
•
Malaria
HBV
HCV
HIV
Schistosoma mansoni
Post streptococcal
Infective endocarditis
• NB Hantavirus and leptospirosis cause interstitial
nephritis
10extra. Which of the following
is a side-effect of Cyclosporin
A?
•
•
•
•
•
A
B
C
D
E
Hypokalaemia
Hirsutism
Pulmonary fibrosis
Hypothyroidism
Cardiomyopathy
10extra. Which of the following
is a side-effect of Cyclosporin
A?
•
•
•
•
•
A
B
C
D
E
Hypokalaemia
Hirsutism
Pulmonary fibrosis
Hypothyroidism
Cardiomyopathy
Side effects of transplant drugs
•
•
•
•
•
•
•
•
•
•
•
•
•
•
All immunosuppressives
- infection risk related to degree of immunosuppression, and cancer risk which is least
for steroids
Cyclosporin
- calcineurin inhibitor which blocks the T cell response
- nephrotoxicity, hypertension, dyslipidaemia, hirsutism, tremor, hyperkalaemia, gum
hypertrophy, seizures, abnormal LFTs (not hypokalaemia, pulmonary fibrosis,
hypothyroidism, cardiomyopathy)
Azathioprine
- inhibits purine metabolism
- neutropenia (important interaction with allopurinol), less commonly thrombocytopenia
and anaemia, also abnormal LFTs
Tacrolimus
- calcineurin inhibitor, more powerful than cyclosporin
- s/e as for cyclosporin except no hirsutism or gum hypertrophy
Mycophenolate
- inhibits purine metabolism but more specific for lymphocytes than aza
- abdo pain and diarrhoea are common, also neutropenia but ok with allopurinol
A 50 year old man with CRF
had 3 episodes of rejection
after a renal transplant. His
BP at 1 year was 210/118
mmHg with a loud bruit over
the transplant. What does the
angiogram show, how should
this be treated and what other
possible diagnosis should
have been considered before
the angiogram ?
1. Transplant artery stenosis which could be
secondary to rejection of donor artery, fibrosis at
site of anastomosis, clamping trauma or
atheroma of recipient’s iliac artery.
2. Angioplasty with or without stenting.
Surgical repair is associated with an increased
risk of graft loss.
3. Intrarenal AV fistula, most commonly a
complication of renal biopsy. 75% close
spontaneously, remainder require embolisation.
A 24 year old patient is admitted after falling
asleep in a toilet cubicle. BP is 130/70. There is
boggy tenderness of his right calf and both thigh
muscles. Bloods show urea 38mmol/l, creatinine
410umol/l, K 7.1mmol/l and CK 17000iu/l. What is
most appropriate form of treatment?
•
•
•
•
•
A - Continuous Ambulatory Peritoneal Dialysis
B - Dopamine
C - Forced alkaline diuresis
D - Haemodialysis
E - High dose diuretic therapy
A 24 year old patient is admitted after falling
asleep in a toilet cubicle. BP is 130/70. There is
boggy tenderness of his right calf and both thigh
muscles. Bloods show urea 38mmol/l, creatinine
410umol/l, K 7.1mmol/l and CK 17000iu/l. What is
most appropriate form of treatment?
•
•
•
•
•
A - Continuous Ambulatory Peritoneal Dialysis
B - Dopamine
C - Forced alkaline diuresis
D - Haemodialysis
E - High dose diuretic therapy
Rhabdomyolysis
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Aetiology
- following crush injury, drug overdose, status epilepsy
- renal failure due to toxic effects myoglobin on tubular cell
Presentation
- most commonly as ARF with abnormal LFTs
- may be boggy tenderness of affected muscles
Diagnosis
- CK usually >10000
- stix positive haematuria but no red cells due to urine myoglobin
Treatment
- may require fasciotomy
- forced alkaline diuresis to prevent ARF (not dopamine or iv diuretic)
- haemodialysis to treat ARF (not CAPD)
Outcome
- 50% mortality as for other causes of ARF requiring dialysis
26 Which of the following
statements about renal calculi is
most accurate?
• A The stone prevalence in the UK is 10%
• B Calcium oxalate stones account for 70%
of all calculi
• C Staghorn calculi are effectively removed
by lithotripsy
• D If cystinuria is the cause, progressive
renal failure should be anticipated
• E Primary hyperoxaluria is a sex-linked
recessive condition
26 Which of the following
statements about renal calculi is
most accurate?
• A The stone prevalence in the UK is 10%
• B Calcium oxalate stones account for 70%
of all calculi
• C Staghorn calculi are effectively removed
by lithotripsy
• D If cystinuria is the cause, progressive
renal failure should be anticipated
• E Primary hyperoxaluria is a sex-linked
recessive condition
19extra Jejuno-ileal bypass causes
renal calculi composed principally of
which of the following components?
•
•
•
•
•
A
B
C
D
E
Calcium
Cystine
Oxalate
Urate
Xanthine
19extra Jejuno-ileal bypass causes
renal calculi composed principally of
which of the following components?
•
•
•
•
•
A
B
C
D
E
Calcium
Cystine
Oxalate
Urate
Xanthine
5 types of renal stone
• Calcium oxalate 70%
• - assoc with hypercalciuria which can be idiopathic or 2y to primary hyperpara
or any other cause of hypercalcaemia eg sarcoid, excess vit D
• - assoc with hyperoxaluria which can be primary (a rare AR disorder) or 2y to
intestinal malabsorption eg jejuno-ileal bypass (Ca in gut binds fat instead of
oxalate leaving oxalate available for absorption)
• - ensure high fluid intake with adequate dietary calcium 1g/day ( not dietary
calcium restriction which leads to excess oxalate absorption as above)
• - thiazide to stimulate renal tubular Ca absorption
• - potassium citrate as citrate is an important inhibitor of Ca stone formation
• Calcium phosphate 10-20%
• - assoc with distal RTA as CaPO4 stones form in alkaline urine and urine is
always alkaline
• - ensure high fluid intake and correct RTA with sodabic
• - potassium citrate as above
5 types of renal stone
• Magnesium ammonium phosphate (Struvite) 5%
• - assoc with infection with urease producing organisms esp proteus
• - commonly staghorn requiring surgical removal (too big for lithotripsy)
• Urate 5%
• - assoc with hyperuricosuria and acid urine
• - causes radiolucent stones (all the others are radio-opaque), occas staghorn
• - treated by high fluid intake, allopurinol 100mg/day and by alkalinising urine
• Cystine 1%
• - assoc with cystinuria, an AR disorder causing failure of reabsorption of certain
amino acids by PCT. Occas staghorn. Does not cause progressive renal
failure. Not to be confused with cystinosis (an AR lysosomal storage disease)
which does.
• - Rx high fluid intake, penicillamine (chelates cystine) and by alkalinising urine
• Epidemiology
• - lifetime risk up to 10% men and 5% women (prevalence is less than 10%)
These two plain x-rays are before and after a medical
treatment. What abnormality is shown, what is the likely
cause and what was the medical treatment ?
1. The x-ray on the left shows a left sided
staghorn calculus.
2. The most likely cause is a cystine stone that
has been treated with increasing fluid intake,
alkalinisation and oral penacillamine. Cystine
stones are responsible for 1-2% of all urinary
calculi. Because the only calculi that can dissolve
with medical treatment are uric acid and cystine,
and since uric acid calculi are radiolucent, this
patient most likely had a cystine stone.
8 . Haemodialysis has a useful role in the
removal of which one of the following drugs
taken in overdose?
•
•
•
•
•
A
B
C
D
E
Digoxin
Amiodarone
Paraquat
Paracetamol
Salicylate
8 . Haemodialysis has a useful role in the
removal of which one of the following drugs
taken in overdose?
•
•
•
•
•
A
B
C
D
E
Digoxin
Amiodarone
Paraquat
Paracetamol
Salicylate
Drugs removed by haemodialysis*
•
•
•
•
•
•
•
Salicylates
Lithium
Barbiturates
Ethanol
Methanol
Ethylene glycol
Theophyllines (charcoal perfusion)
Not digoxin, amiodarone, paraquat or paracetamol
*have only had to dialyse once (for lithium) in 23 years in DGH setting
9 A 45-year-old man is admitted with end-stage renal
failure of undetermined aetiology. One hour into dialysis,
he begins to complain of nausea, headache, and blurred
vision. Shortly afterwards, he becomes confused and
disorientated. His blood pressure is 180/100 mmHg. What
is the most likely explanation?
• A Air embolism
• B Dysequilibrium syndrome
• C Intravascular volume contraction
resulting from rapid ultrafiltration
• D Pericardial tamponade
• E Reaction to hypotonic dialysate
9 .A 45-year-old man is admitted with end-stage renal
failure of undetermined aetiology. One hour into dialysis,
he begins to complain of nausea, headache, and blurred
vision. Shortly afterwards, he becomes confused and
disorientated. His blood pressure is 180/100 mmHg. What
is the most likely explanation?
• A Air embolism
• B Dysequilibrium syndrome
• C Intravascular volume contraction
resulting from rapid ultrafiltration
• D Pericardial tamponade
• E Reaction to hypotonic dialysate
Complications of haemodialysis
• Air embolism
• - extremely uncommon because air detector stops the machine if
air enters the system. Treat by head down left lateral position
• Dialysis dysequilibrium
• - Rapid removal of urea from blood and slower removal of
urea from brain causes cerebral oedema. Rapid ultrafiltration
• Rapid Ultrafiltration
- patient “crashes”. Easily recognised and treated
• Pericardial tamponade
• - extremely uncommon. Can occur in severe uraemia causing
pericarditis if given heparin. Causes dyspnoea and hypotension
• Hypotonic dialysate
• - extremely uncommon. Causes intravascular haemolysis with
lumbar pain, hyperkalaemia and cerebral oedema
19. Reduced complement levels
are consistent with which of the
following?
•
•
•
•
A Alport’s syndrome
B Amyloidosis
C SBE nephritis
D Anti GBM disease (Goodpasture's
syndrome)
• E Focal segmental glomerulosclerosis
(FSGS)
19. Reduced complement levels
are consistent with which of the
following?
•
•
•
•
A Alport’s syndrome
B Amyloidosis
C SBE nephritis
D Anti GBM disease (Goodpasture's
syndrome)
• E Focal segmental glomerulosclerosis
(FSGS)
Reduced serum complement
•
•
•
•
•
•
•
•
Occurs in:
- SLE
- infective endocarditis
- post strep nephritis
- shunt nephritis
- cholesterol embolism
- cryoglobulinaemia
- MCGN types 1 and 2
•
•
Complement normal in FSGS, amyloidosis, Alports, anti GBM disease
C3 nephritic factor is an IgG auto antibody to the C3 convertase of the the alternative
pathway of complement activation, found in both types of MCGN