Renal Flashcards
1
Q
What are causes of HLA sensitisation prior to renal transplant?
A
- Previous transplant with poor HLA mathing
- pregnancies
- blood transfusions
2
Q
What influence does HLA antibodies have on renal transplant?
A
Reduces graft survival but still achieve better survival than dialysis
3
Q
What immunosuppression is used in renal transplantation?
A
Basiliximab induction = anti-CD25 (IL-2R)
Prednisolone
Tacrolimus = calcinuerin inhibitor
Mycophenylate = antimetabolite
4
Q
What is basiliximab?
A
Human/mouse chimeric mAb against IL-2R (CD25) present on activated T-cells to reduce rejection
5
Q
What is ATG? What is it’s role in renal transplant and risks?
A
Rabbit polyclonal Ab (thymoglobulin) that targets T-cells
Reduces acute rejection
Increased risk of infection and malignancy (esp PTLD in EBV donor+ recipient-)
6
Q
What are pros and cons of using Tacrolimus over cyclosporin for renal transplant?
A
Pros:
- less acute rejection
- less de novo Donor Specific Antibodies (chronic graft rejection and loss)
- less gum hypertrophy
- less hirsitism
- less drug interaction
Cons:
- more post transplant diabetes
- low magnesium/phosphate
- more neurotoxicity
- more hair loss
7
Q
Are tacrolimus and cyclosporin safe in pregnancy?
A
Yes
8
Q
What is the mechanism of action of mycophenylate?
A
Inhibits IMPDH involved in purine synthesis
9
Q
What interaction occurs with mycophenylate and ciclosporin?
A
Mycophenylate lower ciclosporin levels (but doesn’t affect tacrolimus)
10
Q
What are the pros and cons of mycophenylate compared to azathioprine?
A
Pros:
- less acute rejection
- no interaction with allopurinol
- no issue in TPMT deficiency
Cons:
- more diarrhoea
- not safe in pregnancy (need to use azathioprine pre conception)
11
Q
What is the mechanism of action of sirolimus and everolimus?
A
Bind FK binding protein and inhibit mTOR to inhibit IL-2 signalling
12
Q
Are mTORi (sirolimus, everolimus) safe in pregnancy?
A
No
13
Q
What is the most common cause of graft loss post renal transplant?
A
Death
14
Q
What are early and late causes of death with graft function?
A
Early:
- infection (33%)
- cardiovascular (29%)
- cancer (7%)
Late:
- cancer (29%)
- cardiovascular (22%)
- infection (13%)
15
Q
What are the early and late causes of renal graft loss (that are not death)?
A
Early (1st year):
- graft thrombosis/technical error (37%)
- rejection (17%)
- GN (3%)
Late:
- chronic allograft nephropathy (60%)
- GN (6%)
- Acute rejection and non-adherence (4%)
16
Q
What is chronic allograft nephropathy?
A
Multifactorial:
- chronic CNI toxicity
- chronic antibody mediated rejection (unresolved early rejection, non-adherence, donor specific antibodies)
17
Q
What is the most common cause of delayed graft function?
A
Post ischaemic ATN
18
Q
What are risk factor for post-ischaemic ATN as a cause for delayed graft function?
A
- deceased donor (uncommon in live)
- donor AKI
- donor age
- DCD
- cold ischaemia time
19
Q
What are causes of delayed graft function other than post-ischaemic ATN that need to eb excluded?
A
- Graft thrombosis (Day 1 USS)
- obstruction or urine leak
- rejection (needs biopsy)
- Early disease recurrence (FSGS, TMA, oxalosis)
20
Q
What are causes of early worsening graft function?
A
- acute rejection (biopsy)
- CNI toxicity
- renal artery stenosis
- obstruction/leak/collection post stent removal
- BK nephropathy
- recurrent disease (FSGS, aHUS)
21
Q
What are the two types of acute renal transplant rejection?
A
- T-cell mediated
- Antibody mediated
22
Q
What are risk factors for acute renal transplant rejection?
A
- previous HLA sensitisation
- pre-transplant antibodies against donor
- younger recipient with older donor
- prolonged ischaemia time
- delayed graft function
- HLA mismatches
23
Q
How is acute renal transplant rejection managed?
A
T-cell mediated:
- IV methylpred for 3 days
- optimise maintenance immunsuppression
- ATG if steroid resistance
Antibody mediated:
- plasma exchange
- IVIg
- consider rituximab
Need PJP prophylaxis
CMV prophylaxis or pre emptive monitoring
24
Q
What is the most important HLA matching in terms of long term outcomes and sensitisation for subsequent transplant?
A
DQ
25
What is BK and its relevance to renal transplant? How is it managed?
Polyoma virus that can cause nephropathy
Screened for with serum PCR in first 12 months
Reduce antimetabolite when viraemia detected
Biopsy if graft dysfunction to exclude concurrent rejection - see intranuclear viral staining + SV40 in medulla
No specific anti-viral, give IVIg or steroid
26
What CMV prophylaxis should be in renal transplant?
Depends on donor status:
D+R- = 6 months prophylaxis with valganciclovir
D-R+ = 3 months prophylaxis with valganciclovir OR pre emptive monitoring
D-R- = none unless ATG used
27
How is CMV infection treated in renal transplant?
PO double dose valganciclovir OR IV ganciclovir
Foscarnet or cidofovir if resistant
27
How can skin cancers be prevented post transplant?
- sun protection
- Switch CNI to mTORi
- avoid azathioprine
28
What COVID anti-virals interact with tacrolimus?
Paxlovid (remdesivir and molnupiravir do not)
29
What are the most common causes of renal artery stenosis?
- atherosclerotic disease (60-80%)
- fibromuscular dysplasia (10-20%)
30
What are the clinical features of fibromuscular dysplasia?
Affect F:M 3:1
60% involve renal artery (35% bilateral)
String of beads appearance in mid to distal renal artery
ischaemia rare
poor repsonse to intervention
31
What are clinical features of atherosclerotic renal artery stenosis?
Older age
M = F
Affects ostial/proximal portion of renal artery, can be bilateral
Can result in ischaemia
Less amenable to intervention
32
What is the pathophysiology of renovascualr hypertension?
Reduced renal blood flow results in activation of renin (needs 80% stenosis to see reduced blood flow)
Renin cleaves Angiotensinogen to angiotensinI, which is activated to angiotensinII by ACE
AngiotensinII results in:
- vasoconstriction
- renal sodium retention
- aldosterone secretion
- hypertrophy and remodelling of LV and vessels
- Sympathetic activation
33
What is pressure natriuresis?
Increased renal perfusion in contralateral kidney in unilateral renal artery stenosis results in increased sodium excretion
34
What is Pickering syndrome?
In bilateral renal artery stenosis or solitary kidney unable to do pressure natriuresis resulting in sodium and fluid retention, which results in pulmonary oedema
35
What features are suggestive of renal artery stenosis?
HTN age < 30 or > 50
Abrupt onset HTN
Acceleration of previously stable BP
Malignant HTN
Accelerated retinopathy
Flash pulmonary oedema
AKI with ACEi
36
What is the sensitivity and specificity of renin and aldosterone levels in renal artery stenosis?
Both are low!
37
What is the diagnostic tests can be used for renal artery stenosis?
Doppler ultrasound
CT with contrast
MRI with contrast
Nuclear scan
Gold standard = angiography
37
How is renal artery stenosis managed?
BP management with RAAS blockade
CV risk modification
Angioplasty for FMD, only considered in atherosclerotic if flash pulmonary oedema or progressive CKD
38
What s the definition of CKD?
eGFR < 60 AND evidence of kidney damage (proteinuria) on more than 2 occasions over at least 3 months
39
What are the different stages of kidney function?
1 = GFR > 90
2 = GFR 60-89
3a = GFR 45-59
3b = GFR 30-44
4 = GFR 15-29
5 = GFR < 15 or on dialysis
40
What is the role of each of these segments of the nephron?
Glomerulus
Juxtaglomerular apparatus
Tubules
Glomerulus = filtration
Juxtaglomerular apparatus = autoregulation
Tubules = sodium, water, potassium, acid/base and other electrolyte balances
41
How should proteinuria be treated?
RAAS blockade (ACEi or ARB)
SGLT2i
42
What are BP targets in CKD?
Aim < 140/90 if no albuminuria
Aim < 130/80 if albuminuria
43
What is the biggest cause of anaemia in CKD?
Iron deficiency (followed by EPO deficiency)
44
Through what mechanism does CKD result in acidosis?
Loss of ability to synthesize ammonia and secrete hydrogen
45
What is the role of sodium bicarbonate in CKD?
May slow progression in moderate CKD
46
What is the cause of hyperkalaemia in CKD?
Decreased clearance
Tubulointerstitial dysfunction
RAAS inhibitors
47
What factors increase phosphate excretion in the urine?
PTH
Klotho
FGF23
48
What is the function of FGF23?
Suppresses phosphate reabsorption
Increases phosphate excretion
Reduces 1,25 Vitamin D activation
49
What happens to levels of the following in CKD
FGF23
1,25 vitD
PTH
FGF23 increases
1,25 vitD decreases
PTH increases
50
What is the target phosphate level in CKD?
aim for normal range
51
How is AKI defined?
Using KDIGO:
- serum Cr increase by >26.5 umol/L in 48h
- increase serum Cr >1.5x normal in last 7 days
- urine volume < 0.5 mL/kg/h for 6 hours
52
What makes the kidney vulnerable to injury?
High metabolic demand marginal oxygenation to outer medulla (proximal tubule and loop of henle)
53
What are renal causes of AKI?
- glomerulonephritis
- acute tubular necrosis
- acute interstitial nephritis
- acute microvascular disease
54
What is the pathophysiology of acute tubular necrosis?
- ischaemic (extension of pre-renal AKI)
- toxic (myoglobin, aminoglycosides, IV contrast, chemotherapies)
55
What are biopsy features of acute interstitial nephritis?
Increased cellular infiltrate
56
What are causes of acute interstitial nephritis?
Drugs:
- beta lactams
- PPIs
- NSAIDs
- immunotherapy
Infection
Immune:
- Sjogren's
- sarcoidosis
- IgG4 disease
Idiopathic
57
What are aetiologies of acute miscrovascular AKI?
- thrombotic microangiopathy: HUS-TTP
- DIC
- catastrophic anti-phospholipid syndrome
- systemic sclerosis
- cholesterol emboli
58
How does urinary sodium help to demonstrate the cause of AKI?
- low urinary sodium = pre renal
- high urinary sodium = ATN
59
What do hyaline casts in urine indicate?
- reduced renal perfusion
- composed of uromodulin formed in loop of henle
- seen in exercise and dehydration
60
What doe renal tubular epithelial cells (RTEC) in urine indicate?
ischaemic or toxic tubular injury (ATN)
61
What do granular casts in urine indicate?
ATN
62
What do white cell casts in the urine indicate?
AIN
63
What do dysmoprhic red cells and red cell casts indicate in the urine?
Glomerular haemorrhage, especially in proliferative glomerular lesion
64
What are contraindications to kidney biopsy?
- kidney failure
- coagulopathy (antiplatelets, anticoagulation)
- bilateral cysts
- uncontrolled hypertension
- hydronephrosis
- UTI
65
What are the indications for RRT in AKI?
- acidaemia
- hyperkalaemia
- toxins
- overlaod
- uraemia (pericarditis, encephalopathy)
66
Where are the glomeruli in the kidney?
In the cortex
67
What are the 3 layers of the glomerulus?
- endothelial layer
- GBM (negatively charged)
- podocyte foot processes
68
What is the criteria to diagnose nephrotic syndrome?
Proteinuria > 3.5g/24 hours, hypoalbuminaemia, generalised oedema, hyperlipidaemia
69
What is the criteria of nephritic syndrome?
Haematuria with RBC casts and dysmorphic RBCs
Often seen with oliguria, hypertension and progressive reduction in GFR
70
Do you need proteinuria to diagnose nephritis?
No
71
What is the commonest glomerular disease worldwide?
IgA nephropathy
72
What is the size of albumin and filtration slits in the glomerulus?
- albumin: 7.2 nm
- smallest filtration slits: 8 nm
73
Where in the kidney is water actively reabsorbed independent of sodium?
Collecting duct via AQP2 channel stimulated by ADH
74
What proportion of sodium is reabsorbed in the collecting duct and what hormone influences this?
1-2%
Aldosterone
75
What proportion of sodium is reabsorbed in the following parts of the tubule:
- proximal convoluted tubule
- thick ascending loop
- distal convoluted tubule
- proximal convoluted tubule: 65-70%
- thick ascending loop: 25%
- distal convoluted tubule: 5%
76
Through what mechanism is sodium reabsorbed from the urine?
Na/K ATPase in tubular epithelial cells pushes 3Na out of the cell in exchange for pulling 2potassium in, creating intracellular Na deficiency which is then reclaimed from the urine
77
Where is the majority of water reabsorbed in the renal tubule?
PCT (follows sodium)
78
Where is potassium secreted in the renal tubule?
Collecting duct
79
What proportion of K+ is reabsorbed in the following parts of the renal tubule?
- PCT
- LOH
- DCT
-CD
- PCT: 45-50%
- LOH: 40-45%
- DCT: 0
-CD: 0 (actively secreted
80
Where in the renal tubule is the majority of the following reabsorbed?
-Ca
- Mg
- Phosphate
- HCO3
- Ca: PCT (70%)
- Mg: LOH (60-70%)
- Phosphate: PCT (70-80%)
- HCO3: PCT (85-90%)
81
How do diuretics cause secondary hyperaldosteronism?
Inhibit Na reabsorption causing vascular volume contraction, increasing aldosterone.
This leads to tubular K and H loss and results in hypokalaemia and metabolic alkalosis
82
How do potassium sparing diuretics cause hyperkalaemia and metabolic acidosis?
Antagonise aldosterone leading to K and H retention
83
How does the PCT reabsorb sodium?
Through apical Na-H exchange protein
Requires regeneration of HCO3 by carbonic anhydrase
84
What is the mechanism of action of acetozolamide?
Carbonic anhydrase inhibitor, prevents HCO3 regeneration resulting in less Na (and therefore water) reabsorption
Chance of metabolic acidosis
85
What is fanconi syndrome?
Fanconi syndrome is a defect of proximal tubule HCO3 regeneration resulting in proximal renal tubular acidosis, leading to malabsorption of various electrolytes and substances that are usually absorbed by the proximal tubule
86
What are causes of fanconi syndrome?
Inherited:
- cystinosis
- galactosemia
- herediatry fructose intolerance
- tyrosinemia
- Wilson disease
- lowe syndrome
- dent disease
- mitochondrial cytopathies
- glycogenosis
- idiopathic
Acquired:
- nucleoside reverse transcriptase inhibitors
- cisplatin
- azathioprine
- gentamicin
- monoclonal gammopathy
- lead poisoning
- AKI
- beestings
- Legionella pneumonia
87
What is the role of carbonic anhydrase in the PCT?
When Na is reabsorbed from urine in exchange for H, H combines in the urine with HCO3 to form H2CO3.
Carbonic anhydrase on the cell membrane cleaves this to H2O + CO2
The CO2 diffuses into the cell and carbonic anhydrase facilitates the formation of H2CO3
H2CO3 can then release H+ and HCO3-
This regenerates H+ and HCO3- for ongoing reabsorption and maintains pH
88
How does the thick ascending loop of henle reabsorb sodium?
Via N/K/Cl transporter (1Na, 1K, 2Cl)
Calcium is passively reabsorbed as K is returned to the urine
89
Why do thiazide diuretics result in hypercalcaemia?
Thiazides inhibit sodium reabsorption in DCT
Proximal parts of the tubule compensate for this, including thick ascending loop, to increase sodium reabsorption therefore increase calcium reabsroption
90
How does frusemide cause hypocalcaemia?
Blocks sodium reabsorption in loop of henle.
Calcium is passively reabsorbed along with sodium here, so reduces calcium reabsorption
91
What is mechanism of action of frusemide?
Loop diuretic = inhbits Na-K-2Cl cotransporter (NKCC2) in thick ascending lip
92
What is Bartter syndrome?
Defect in sodium reabsorption in thick ascending limb resulting in sodium wasting in urine
See metabolic acidosis, hypokalaemia and low/N BP
93
What are the 5 types of Bartter syndrome?
1: Na-K-2Cl mutation
2: ROMK mutation
3: CIC-kb mutation
4: Barttin mutation
5: upregulation of CaSR
94
Where in the body is CaSR found?
Parathyroid gland
Basolateral membrane of cells in TAL of LOH
95
What is the role of CaSR in renal tubule?
Calcium binding to CaSR inhibits K channel (luminal) and Na-K ATPase (basolateral) in TAL
Also reduces paracellular carrier proteins for calcium
Net effect is to reduce paracellular calcium and magnesium reabsorption
96
What is the pathological basis of familial hypocalciuric hypercalcaemia?
AD mutation in CaSR
97
How can hyperparathyroidism and FHH be distinguished?
Hyperparathyroidism should have high urinary calcium
98
What are clinical features of familial hypocalciuric hypercalcaemia?
- mild hypercalcaemia
- hypocalciuria
- inappropriately high/normal PTH
- high/normal serum magnesium
- hypophosphataemia
99
How is FHH managed?
Benign - no specific management
100
How is sodium reabsorbed in the DCT?
Via NaCl co-transporter (NCCT)
(site of thiazide action)
101
What is Gitelman syndrome?
Impaired NCCT function
Hypokalemia
Metabolic acidosis
Hypomagnesaemia (TRPM6 also inhibited)
Low BP
Hypocalciuria
102
How can Bartter and Gitelman syndrome be distinguished?
Bartter: high urine calcium
Gitelman: low urine calcium
103
What is Addison disease?
Cortisol insufficiency from impaired adrenal function results in inability to excrete K+ and H+, results in metabolic acidosis
104
What is diabetes insipidus?
ADH deficiency (central) or inability to respond to ADH (nephrogenic) resulting in polyuria
105
How does lithium cause diabetes insipidus?
Decreases expression of AQP2 genes
106
What is the role of JGA?
JGA = macula densa of distal tubule in close proximity to juxtaglomerualr cells of afferent and efferent arterioles + extraglomerular mesangial cells
When low BP sensed by JG cells or low Na in MD cells or beta-adrenergic stimualtion, JG cells secrete renin
107
What is the mechanism of action of each of the following:
- renin
- ACE
- Angiotensin II
- Aldosterone
- renin: cleaves angiotensinogen to angiotensin I
- ACE: cleave angiotensin I to angiotensin II
- Angiotensin II: stimulates aldosterone secretion AND constricts blood vessels
- Aldosterone: increases sodium and water retention
108
Which glomerular arteriole is greater affected to constrict in response to angiotensin II?
Efferent
109
What is the rationale for using ACEi/ARB in proteinuria?
Reduces intraglomerular pressure and filtration by decreasing efferent tone >afferent, thus reduces proteinuria
110
What is the mechanism of aldosterone?
Bonds to intracellular mineralocorticoid receptor in principle cells of collecting duct
Increases expression of Na/K ATPase to increase sodium reabsorption. This increases K+ lost in urine.
Also act on alpha intercalated cells to stimulate hydrogen ATPases which increase H+ excretion
111
What are clinical features of primary aldosteronism?
Hypertension
Mild hypokalaemia
Mild metabolic alkalosis
Polyuria
112
What is the most common cause of primary hyperaldosteronism?
Idiopathic bilateral adrenal hyperplasia
113
What are the 3 ways that hyperkalaemia can potentiate metabolic acidosis?
1. K+/H+ exchange across cell membranes
2. K+ competes with H+ for secretion in collecting duct
3. Hyperkalemia reduces renal ammonia production and inhibits H+ excretion
114
What is the primary urinary buffer H+?
Ammonia (NH3)
115
How does hypokalemia cause alkalosis?
Augments H-K-ATPase which secrete H+ to reabsorb K+ in type A intercalated cells of collecting duct
116
What is renal tubular acidosis?
Normal anion gap metabolic acidosis with preserved GFR
Either with hypokalaemia (1 or 2)
OR hyperkalaemia (4)
117
What are the different types of renal tubular acidosis?
Type 1: defect in distal tubule H+ secretion
Type 2: defect in proximal tubule HCO3 reabsorption
Type 4: decreased production of or reduced response to aldosterone
118
What is the most common type of renal tubule acidosis?
Type 4
119
How can type 1 and 2 renal tubular acidosis be distinguished?
Both are normal anion gap metabolic acidosis with hypokalaemia
Type 1 = distal
- urine pH > 5.5 (urinary alkalosis as no H in urine)
- renal stones due to citrate reabsoprtion in attempt to compensate by reabsorbing alkali
- no fanconi syndrome
- Associated with Sjogrens, SLE, PBC, autoimmune hepatitis
Type 2 = proximal
- urine pH < 5.5 (distal tubules secrete excess H)
- no renal stones
- fanconi syndrome (glycosuria, phosphaturia, uricaciduria, aminoaciduria)
- associated with myeloma, tenofovir, acetazolamide
120
How are type 1 and 2 renal tubular acidosis treated?
Alkali (bicarbonate or potassium citrate)
Potassium replacement
121
What are causes of type 4 renal tubular acidosis?
Diabetic nephropathy (most common)
NSAIDs
ACEi
Cyclosporin
Tacrolimus
High dose heparin
Spirinolactone
122
How is type 4 renal tubular acidosis treated?
Fludrocortisone if not overloaded or hypertensive
Thiazide or loop diuretic if hypertensive or overloaded
123
What event cause hyperparathyroidism in CKD?
- phosphate retention (initial trigger)
- decreased calcium concentration
- decreased calcitriol concentration
- increased FGF23 concentration
- reduced CaSR, FGF23R and klotho receptors
124
Where is glucose primarily reabsorbed in the kidney?
Proximal tubule, 97% by SGLT2i
125
What is the principle of convection with regard to dialysis?
The 'drag' of solutes across a semi-permeable membrane
Removes larger sized molecules and plays a bigger role in PD
126
What is the preferred access for haemodilation?
Arteriovenous fistula
127
What is the pathophysiology of dialysis disequilibrium syndrome?
Clearance of solutes (urea) extracellularly creates osmolar difference ICF vs ECF, water shifts into ICF and results in cerebral oedema
128
Where is most of the resistance for the movement of solutes in peritoneal dialysis?
Blood vessel wall
129
What is the optimal position for a PD catheter?
In pelvis below pelvic rim
130
What is the composition of PD fluid?
- glucose = key osmotic agent, can worsen diabetic control (icodextrin does not)
- physiologic Na, CCa, Cl, Mg
- lactate as a buffer
131
How is dialysis adequacy assessed?
PD: 24 hour urine and diasylate collection and calculate weekly Kt/V and CrCl + amount of fluid removed
HD: Kt/V or urea reduction ratio
132
What are the acute and chronic indications for dialysis?
Acute:
- fluid overload unmanageable with diuretic or fluid restriction
- refractory metabolic acidosis
- refractory hyperkalaemia
- Significant uraemic complications (encephalopathy, pericarditis)
Chronic:
- weight loss/ reduced appetite
- difficulty concentrating
- weakness
133
What is the typical eGFR when dialysis is commenced?
5-8 (not an indication)
134
What is the mechanism of the following:
- haematuria
- proteinuria
- haematuria: breaks in GBM
- proteinuria: podocyte injury
135
What is the definition of nephrotic syndrome?
- proteinuria > 3g/day
- hypoalbuminaemia
- oedema
136
What is the mechanism of thrombosis in nephrotic syndrome?
- urinary loss of anticoagulants
- hepatic overproduction of procoagulants (in response to low alb)
- platelet dysfunction
137
What serum albumin indicates prophylactic anticoagulation should be used?
< 20
138
What anticoagulant is the standard of care in the nephrotic syndrome?
Warfarin
139
What is the histopathological finding in membranous nephropathy?
Subepithelial spikes
140
What are the causes of membranous nephropathy?
- idiopathic (70%); often anti-PLA2R positive
- autoimmune (SLE, MCTD)
- infection (Hep B, C, malaria, syphilis)
- heavy metals
- cancer (lung, breast, colon)
141
What is the 1/3 rule of membranous nephropathy?
30% spontaneous complete remission
30% partial remission
30% progress to ESRF (if untreated)
142
What features are very high risk for membranous nephropathy?
- rapid eGFR decline
- severe nephrotic syndrome
- PLA2R > 150
143
How is membranous nephropathy treated?
1. Low risk
- normal eGFR< protein < 3.5g/day
- symptomatic support
2. moderate risk
- proteinuria >4g/day for > 6/12
- watch and wait OR rituximab OR Calcineurin inhibitor
3. High risk
- proteinuria >8, eGFR > 60, PLAR2R > 50
- rituximab +/- Calcineurin inhibitor OR cyclophosphamide/steroid
4. Very high risk
- rapid eGFR decline, severe nephrotic, PLA2R > 150
- cyclophosphamide/steroid
144
What are the two podocytopathies?
Minimal change disease
Focal segmental glomerulosclerosis
145
What are the LM and EM findings of minimal change disease?
LM = normal
EM = foot process effacement
146
What is the typical presentation of minimal change disease?
Sudden onset, severe nephrotic syndrome
Typically very steroid responsive
147
How is minimal change disease treated?
Initial = high dose prednisolone
Relapsing/steroid dependent = rituximab, CNI, MMF or cyclophosphamide
148
What are the features and treatment of primary FSGS?
- sudden onset severe nephrotic syndrome
- high risk for recurrence post transplant
Rx:
- prednisone (max 6/12)
- CNI if no response to pred (2nd line is MMF or rituximab or clinical trial)
149
What should be suspected in patients with FSGS who do not respond to immunosuppression?
Genetic cause
150
What is adaptive FSGS?
Hyperfiltration mediated segmental foot process effacement and proteinuria without nephrotic syndrome
common in diabetes, prematurity and indigenous
151
What is the most common primary glomerular disease?
IgA nephropathy
152
What is the pathophysiology of IgA nephropathy?
Autoantibodies against galactose deficient IgA1 form immune complexes and deposit in mesangium. This causes cellualr injury resulting in cellular proliferation and inflammation
153
What are the secondary causes of IgA nephropathy?
- liver disease
- infection
- IBD
- rheumatological conditions
- lymphoma
154
What is the MEST-C score for IgA nephropathy?
Mesangial hypercellularity
Endocapillary hypercellularity
Segemental glomerulosclerosis
Tubular atrophy
Crescent
155
What is the most common clinical presentation of IgA nephropathy?
Asymptomatic microscopic haematuria, proteinuria
(2nd in mucosal infection with macroscopic haematuria)
156
How is IgA nephropathy managed?
1. Supportive care
- RAS blockade
- BP control
- Na restriction
- lifestyle and CV risk mod
- SGLT2i
2. Clinical trial if proteinuria >1g/day
3. PO steroids (max 6/12)
157
What are histopathological features of infection-related GN?
- endocapillary proliferation
- IHC for C3 +/- IgG, IgA, IgM
- EM for hump shaped subepithelial deposits
158
What are clinical features of infection-related GN?
- haematuria
- hypertension
- AKI
- Low C3
- bacterial or viral infection
159
What features are associated with IgA- dominant infection related GN?
- elderly
- diabetics
- staph infection
160
How is infection related GN treated?
- treat underlying cause
- supportive care
- steroids only in severe cases due to risk of reactivating infection
161
What is the pathophysiology of anti-GBM?
Capillaritis in kidney and lung due to autoimmune reaction to NC1 domain of alpha3 chain of Type IV collagen
162
What are clinical features of anti-GBM disease?
- haematuria with rapidly progressive kidney injury
- pulmonary haemorrhage
- HLA-DR15
- relapse uncommon
163
How is anti-GBM disease treated?
- plasma exchange
- steroids
- cyclophosphamide
164
What self-antigens in pauci-immune GN are associated with the following ANCA patterns ?
pANCA
cANCA
pANCA = MPO
cANCA = PR3
165
What ANCA patterns are seen with the following vasculitides?
MPA
GPA
eGPA
MPA = pANCA = MPO
GPA = cANCA = PR3
eGPA = usually negative
166
What vasculitis more commonly affects the kidneys?
MPA
167
What ANCA vasculitis pattern is associated with higher risk of relapse?
PR3
168
How is ANCA-associated vasculitis treated?
Steroids is mainstay in induction and mainstay
1. Induction
- rituximab (better than cyclophosphamide for PR3)
2. Maintenance
- rituximab (> azathioprine> methotrexate>mycophenylate)
(plasma exchange only if anti-GBM positive)
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What is the classical pattern of lupus nephritis on kidney biopsy?
- immune deposits in subendothelial and subepithelial
- IgG, IgA, IgM, C3 and C1q positive
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How is lupus nephriitis treated?
- mesangial= treat extra-renal
- membranous = RAS blockade, BP control, hydroxychloroquine, immunosuppression if nephrotic
- proliferative = steroids + MMF or cyclophosphamide, MMF + CNI (voclosporin), OR Belimumab + MMF or CYC
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What is the mechanism of action of voclosporin?
- CNI
- no drug monitoring required
- less metabolic impact
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What is the mechanism of action and indication of belimumab?
- mAb against BAFF (B-cell activating factor)
- proliferative lupus nephritis
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What are histopathological features of MPGN?
- subendothelial deposits
- mesangial expansion
- GBM thickening with "tram track contour"
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What types of diseases demonstrate an MPGN pattern with positive Ig?
- monoclonal gammopathies
- infections
- autoimmune disease
- idiopathic
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What pattern of injury is seen with C3 glomerulopathy?
MPGN
- subendothelial deposits
- mesangial expansion
- GBM thickening with "tram track contour"
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What are mechanisms of C3 glomerulopathy?
- C3 convertase autoantibody (nephritic factors)
- Loss of factor H (genetic or autoantibodies)
- C3 mutations
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How are C3 glomerulopathy treated?
Mild-Mod: supportive
Mod-severe: steroids + MMF
Refractory: eculizumab (anti-C5)
