Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

RACP > Renal > Flashcards

Renal Flashcards

1
Q

I /Causes of renal artery stenosis

A

Atherosclerotic disease 60-80%
Fibromuscular dysplasia 10-20%

Other:

  • Renal artery embolism
  • Dissection/Thrombosis
  • Post traumatic injury
  • Occlusion from aortic stent graft
  • External compression
  • Systemic vasculitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Fibromuscular dysplasia (FMD)

A

Non-atheromatous, non-inflammatory vascular condition
- F>M 3:1
- Age 30-50
-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Factors affecting renin level

A

Oestrogen, pregnancy, cortisol excess, intra-renal parenchymal dx
Postural changes, sympathetic tone, sodium intake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Most common cause of overall graft loss in Australia

A

Early (1st year):

  • Cardiovascular (36%)
  • Infection (27%)
  • Cancer (3%)

Later (>1yr)

  • Cancer
  • CVD
  • infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Death-censored graft loss: most common cause?

A

Early: Graft thormbosis (38%)
Rejection 24%
GN (4%)

Late:
Chronic allograft nephropathy (72%)
GN (7%)
Acute rejection 4%, non adherence 4%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which chromosome is PKD1 located

A

16

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which chromosome is PKD2 located

A

chromosome 4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Extra-renal manifestation of ADPKD?

A

pancreatic/hepatic cysts, mitral valve prolapse, aortic regurgitation and intracranial aneurysms (a cause of haemorrhagic stroke)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Cystinuria

A

Cystinuria is an autosomal recessive disorder characterised by the formation of recurrent renal stones. It is due to a defect in the membrane transport of cystine, ornithine, lysine, arginine (mnemonic = COLA)

Genetics
chromosome 2: SLC3A1 gene, chromosome 19: SLC7A9

Features
recurrent renal stones
are classically yellow and crystalline, appearing semi-opaque on x-ray

Diagnosis
cyanide-nitroprusside test

Management
hydration
D-penicillamine
urinary alkalinization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What one of the following is the most common type of SLE associated renal disease?

A

Diffuse proliferative glomerulonephritis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Inheritance pattern of Alport sx

A

X-linked dominant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is a nephrotic range proteinuria in a 24hr collection?

A

> 3/5g/24h

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is partial lipodystrophy associated with?

A

membranoproliferative glomerulonephritis type II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does crescent formation signify?

A

Parietal epithelial cell proliferation and mononuclear cell infiltration form crescent-shape in Bowman’s space - hallmark of inflammatory GN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

RPGN Type 1

A

Anti GBM mediated
LINEAR immunofluorescence pattern due to IgG and C3 deposition along capillary loops

If there is lung haemorrhage - Goodpasture’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

RPGN Type 2

A

Immune complex mediated
GRANULAR pattern due to subendothelial or subepithelial deposition of IgG and C3

C3 Normal:

  • IgA Nephropathy
  • HSP

Decreased C3:

  • Membroproliferative GN
  • SLE
  • IE
  • Post-infectious GN
  • Cryoglobulinemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

RPGN Type 3

A

Non-immune mediated
No immune staining

ANCA +ve
c-ANCA: GPA
p-ANCA: EGPA, Microscopic polyangiitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

alport syndrome

A
  • X-linked dominant
  • defect in the gene which codes for type IV collagen
    Alport’s syndrome usually presents in childhood. The following features may be seen:
  • microscopic haematuria
  • progressive renal failure
  • bilateral sensorineural deafness
  • enticonus: protrusion of the lens surface into the anterior chamber
  • retinitis pigmentosa
  • renal biopsy: splitting of lamina densa seen on electron microscopy.
    electron microscopy: characteristic finding is of the longitudinal splitting of the lamina densa of the glomerular basement membrane, resulting in a ‘basket-weave’ appearance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Which renal disease is
associated with partial
Lipodystrophy

A

Mesangioglomerulonephritis with C3 nephritic factor
low C3 and normal C4
PResents as nephrotic syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What causes hypokalaemia
hypertension with low renin
and aldosterone?

A

cushings, liddle’s, 11 beta hydroxylase deficiency, 17 alpha hydroxylase deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Aminoglycoside inducd nephrotoxicity

A
    • 5-7 days
  • ATN (distal tubular damage)
  • inability to concentrate urine
  • Can see hypo of elements

RF:
- duration of therapy
- age
- comorbid disease
- reduced affective arterial vol
- Sepsis
- frequency of dosing

Mild proteinuria
hyaline and granular cast
FeNa >1%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

ATN

A

FeNA >1%
Urine Na >40mmol/L
Urine osmolality <350mOsm/kg
Urea:creatinine ratio normal
FeUrea >35%
Brown granular cast

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

In ADPKD, what predicts progression to ESKD?

A

Size of cyst

htTKV as a prognostic biomarker in ADPKD.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

AIN

A

Features
* fever, rash, arthralgia
* eosinophilia
* mild renal impairment
* hypertension

Pathophysiology
histology: marked interstitial oedema and interstitial infiltrate in the connective tissue between renal tubules

Causes
drugs: the most common cause, particularly antibiotics
penicillins and cephalosporins, rifampicin, antimicrobial sulfonamides, ciprofloxacin and other quinolones
NSAIDs
allopurinol
furosemide
PPI
systemic disease: SLE, sarcoidosis, and Sjögren’s syndrome
infection: Hanta virus , staphylococci

Urine:
- sterile pyuria
- White cell cast

Acute interstitial nephritis, most commonly:
Drug induced (NSAIDs, COX-2i, antibiotics+++, PPI) 70-75% - also not dose dependent.
Autoimmune (SLE, sjorgrens, sarcoid) 10-20%
Infections (eg legionella, CMV, streptococcus)
Presentation non-specific – nausea, vomiting, malaise, rash, fever, eosinophilia. But many are asymptomatic. May be oliguric.
Labs:
↑creatinine, eosinophilia, eosinophiluria (25-35%).
Urine sediment typically shows white cells and white cell casts.
May have red cells, gross haematuria only in ~5%.
Variable proteinuria but usually not significant and nephrotic syndrome in <1%.
Definitive diagnosis only on biopsy/histology.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

RTA

A

Type 1 (distal), defect in H+ secretion in DT
Urine pH >5.5
Hypokalaemia
Urine: calcium is high
Causes:
Hereditary
Collagen vascular dx
Cirrhosis
Nephrocalcinosis
MM

Type 2: Proximal, defect in HCO3 reabsorption in PCT
urine pH <5.5
Hypokalaemia

Causes:
Sulfanomides
Acetazolamide (Carbonic anhydrase inhibitors)
Fanconi sx
MM

Type IV, Inadequate aldosterone –> reduced sodium reabsorption and K secretion
Urine ph<5.5
Hyperkalaemia, hyperchloraemia

Causes:
- hyporeninemic hypoaldosteronism
- HTN
- DM
- Chronic interstitial nephritis
- Aldosterone resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

FMD

A
  • non atheromatous, non-inflammatory vascular condition
  • Women, 30-50
  • Renal arteries in 60%, bilateral in 35%
  • mid to distal artery, string of beads appearance
  • RF: smoking, pregnancy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Common dx to recur post transplant

A

MPGN, aHUS
FSGS and IgA

least likely: anti-GBM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

BK virus nephropathy

A

Histologically is similar to graft rejection
Serum PCR is a specific and sensitive test for diagnosis
Clinical outcome is good if detected earlier

Presents as **patchy interstitial (plasma cells and Lt) nephritis
presence of viral inclusions +SV40 **
BK lives in the medulla

Decoy cells in urine (characteristic, but not patho)

RF:
- degree of immunosuppression, donor age, ureteral stent, viral co-infection

Tx: is reduction of immunosuppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

IgA nephropathy

A

§ Most common cause of primary GN
§ Peak 20s/30s
Male:F 2:1

		§ Presentation:
			□ 40-50% Macroscopic haematuria +/- flank pain, low grade fever
			□ 30-40%: microscopic haematuria + mild proteinuria 
			□ 10%: NS or RPGN
				® Nephrotic sx is suggestive of advanced dx RARE: malignant HTN or AKI
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

IgA nephropathy

Associated disease

A

HIV
Cirrhosis/CLD - etoh, HBV, HCV
Coeliac (1/3 of pts)
GPA in remission

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

IgA nephropathy

Biopsy indication

A

Proteinuria >1g/day *The need for dialysis and death increased in those presenting with protein excretion >1g/day *

New onset HTN
Elevated serum creatinine

Degree of renal injury and HTN at presentation correlates with progression of dx to ESRD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

IgA nephropathy

Treatment

A

Goal: reduce rate of decline
BP control
RAAS blockade
SGLT2i

> 1g/day –> consider immunosuppression

IS or dialysis: □ IS should NOT be considered in those with severe irreversible kidney damage
eGFR <30 for >3mo , small echogenic kidneys, any evidence of severe interstitial fibrosis, tubular atrophy or glonerularsclerosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

IgA nephropathy

prognostic factors

A

HTN
Proteinuria (rather than microalbuminuria)

Poor prognostic factors:
- MALE
- Proteinuria >1-2g/day
- HTN
- Smoking
- Hyperlipidemia
- ACE genotype DD

25% will develop ESRF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

dialysis disequilibrium syndrome (DDS)

A

neurologic symptoms related to cerebral edema. New patients who are just being started on intermittent hemodialysis are at greatest risk for DDS, particularly if the BUN is markedly elevated (>175 mg/dL or 60 mmol/L).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Clinical utility of PLA2R antibodies

A

80% association with primary membranous nephropathy
- specificity 99%, sensitivity 78%
- good response to rituximab

No correlation to secondary MN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is another antibody that specific to podocyte mb antigen?

A

IgG4 ab for THSD7A
Smaller number of primary MN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Membranous GN

A

Nephrotic sx
Antibody and complement induced cytotoxicity on podocytes –> non exudative, non-proliferative capillary wall lesion
(granular deposits of IgG and C3 at the basement mb Thickened basement mb
Spike and dome

  • Subepithelial immune complex:
    > IgG ab binding tp foot processes on podocytes ( PLA2R, THSDA antigens)
    >** correlates with disease activity ** in primary MN
  • Complement activation via lectin pathway
    > syblytic effect
    > stimulates GEC-GBM degrading protease and TGF-beta > matrix production
    > **no inflammatory cells **

Associated with:
Solid tumour malignancies: prostate, lung, lymphoma, leukaemia
HBV, malaria, syphilis
SLE (Class V), thyroiditis, RA
NSAIDs/gold

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

When do you start immunosuppresive therapy in Primary Mb GN

A

PLA2R or TSHD7A positive in serum and proteinuria >3.5g/day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What are the treatment options for PMN?

A

ACEi/ARB - improve proteinuria and improve prognosis

Severe cases need IST:
- - Rituximab
- Cyclophosphamide + steroid
- CNI +/- pred

1/3 will develop ESRF
Steroids alone won’t be effective
consider anticoagulation for high-risk patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What does low urinary chloride indicate in the context of hypokalaemia/metabolic alkalosis?

A

GI losses/dehydration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Risk with EPO use

A
  • HTN
  • VTE
  • Seizures
  • Pure red cell aplasia

Side-effects of erythropoietin
- accelerated hypertension potentially leading to - encephalopathy and seizures (blood pressure increases in 25% of patients)
-bone aches
-flu-like symptoms
-skin rashes, urticaria
-pure red cell aplasia* (due to antibodies against erythropoietin)
raised PCV increases risk of thrombosis (e.g. Fistula)*
- iron deficiency 2nd to increased erythropoiesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Membranoproliferative GN

MPGN/MCGN

A

Can be** nephritic or nephrotic**
Poor prognosis

3 types:
- type 1 (90%):
> Hep C, cryoglobulinemia **
> > other: SLE, Hep B, Subacute endocarditis
> Renal biopsy:
EM: “tram tracks**” due to subendothelial and mesangial immune deposits
> Low C3 and C4

Type 2: dense deposit disease (DDD)
- causes: **partial lipodystrophy **(patients classically have a loss of subcutaneous tissue from their face), factor H deficiency
- caused by persistent activation of the alternative complement pathway
- LOW serum C3
- C3b nephritic factor is found in 70%
> an antibody to alternative-pathway C3 convertase (C3bBb)
> stabilizes C3 convertase
> renal biopsy
electron microscopy: intramembranous immune complex deposits with ‘dense deposit

LM:
- thickening of BM due to C3 deposition
- mesangial cytoplasm between GBM and endothelial cells
- Hypercellularity (mesangial cells and monocytes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Membranous nephropathy

Good prognostic factors

A

Female
Young
Asymp. proteinuria (modest)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Risk factors for urothelial (transitional cell) carcinoma of the bladder

A

Smoking
- most important risk factor in western countries
- hazard ratio is around 4
Exposure to aniline dyes
- for example working in the printing and textile industry
-examples are 2-naphthylamine and benzidine
Rubber manufacture
Cyclophosphamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Risk factors for squamous cell carcinoma of the bladder include

A

Schistosomiasis
Smoking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Anti-glomerular basement membrane (GBM) disease (Goodpasture’s syndrome)

A
  • rare type of small-vessel vasculitis associated with both pulmonary haemorrhage and rapidly progressive glomerulonephritis
  • Ab againt Type 4 collagen
  • M 2x >F
  • Bimodal distribution (20s, 60s)
  • HLA DR2

renal biopsy: linear IgG deposits along the basement membrane
raised transfer factor secondary to pulmonary haemorrhages ( rasied DLCO)

Tx:
- PLEX
- Steroids
- Cyclophosphamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Time course difference between infection induced IgA nephropathy and PSGN?

A

IgA is days and PSGN is weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

PSGN

A

Nephritic syndrome
Associated with GA beta haemolytic strep
Usually infection 2-6 weeks prior

Oliguria, oedema, HTN, tea/cola coloured urine

Lab: low C3 (norm 6-8 wks after presentation), increased ASO and Anti DNase titre
EM: Hump-shaped subepithelial deposits
Endocapillary diffuse proliferation and exudative glomerulonephritis on light microscopy
**immunofluorescence: **granular or ‘starry sky’ appearanc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What level of stenosis in the renal artery causes symptomatic HTN?

A

> 80%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Acyclovir and AKI? mechanism

A

Acute kidney injury (AKI) due to intratubular crystal precipitation is observed in association with many medications. Patients are generally asymptomatic, although occasionally present with flank pain. Urinalysis may show hematuria, pyuria, and crystals with a characteristic morphology
—** Acyclovir is rapidly excreted in the urine (being both filtered and secreted) and has a relatively low solubility**. Thus, bolus intravenous (IV) therapy, especially if the patient is volume depleted, may lead to the deposition of acyclovir crystals in the tubules, resulting in intratubular obstruction and foci of interstitial inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Membranous nephropathy

Risk of progression

A

This patient has membranous nephropathy - depending on certain risk factors, patients with this disease are stratified to either low, moderate or high risk
Low risk of progression – Protein excretion remains less than 4 g/day and creatinine clearance remains normal for a six-month follow-up period.
●Moderate risk of progression – Protein excretion is between 4 and 8 g/day and persists for more than six months, and creatinine clearance is normal or near normal and remains stable over 6 to 12 months of observation.

●High risk of progression – Protein excretion is greater** than 8 g/day** and persists for three months and/or creatinine clearance is reduced (and considered due to MN) or declines over three months of observation

All patients with proteinuria are commenced on an ACE/ARB. For patients that are low risk, observation is recommended. For patients that are moderate and high risk - immunosupression is recommended, of which cyclophosphamide + corticosteroid combination is recommended

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Urine anion gap

A

GI cause: negative
Renal cause: positive (i.e. in RTA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Renal cell cancer

basics

A
  • RCC accounts for 85% of primary renal neoplasm
  • arises from proximal renal tubular epithelium
  • most common: clear cell
  • Men
  • middle age
  • vHL sx
  • TS
  • slight increase with ADPKD

fx:
- haematuria, loin pain, abdominal mass
- PUO
- Endocrine: EPO, PTHrp, renin, ACTH

  • 25% will have mets at presentation
  • paraneoplastic hepatic dysfunction sx
  • Veriocele

Stauffer syndrome
a paraneoplastic disorder associated with renal cell cancer
typically presents as cholestasis/hepatosplenomegaly
it is thought to be secondary to increased levels of IL-6

Management:
- for confined disease a partial or total nephrectomy depending on the tumour size
patients with a T1 tumour (i.e. < 7cm in size) are typically offered a partial nephrectomy
- alpha-interferon and interleukin-2 have been used to reduce tumour size and also treat patients with metatases
- receptor tyrosine kinase inhibitors (e.g. sorafenib, sunitinib) have been shown to have superior efficacy compared to interferon-alpha

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Crescenteric/RPGN

A
  • a rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli.

Causes
- Goodpasture’s syndrome (linear glomerular IF staining)
- Wegener’s granulomatosis (pauci immune)
- others: SLE, microscopic polyarteritis

Features
-nephritic syndrome: haematuria with red cell casts, proteinuria, hypertension, oliguria
- features specific to underlying cause (e.g. haemoptysis with Goodpasture’s, vasculitic rash or sinusitis with Wegener’s)

  • Anti-GBM/ANCA GN: fibrinoid necrosis and little/no endocapillary hypercellularity in the non-necrotic area. more disruption to Bowman’s capsule
  • Immune complex crescenteric GN: more glomerular endocapillary hypercellularity, thickening of capillary wall, more diffuse process, less crescents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Most common cause of HTN

A

Essential HTN (80-95%)
RF:
- salt
- obesity
- Alcohol
- angiotensin excess
- sympathetic excess
- FHx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

HTN

A

DBP >95mmHg, steep increase in cardiovascular mortality

Increase IHD and stroke risk with both increasing systolic and diastolic BP

Clinical evidence showes treating HTN –> reduces stroke (35-40%), MI (20-25%), HF (50%)

There is evidence for intensive BP control to <120mmHg systolic
**Half dose drug combination is better than full dose monotherapy **
Night time dosing improves mortality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Causes of secondary HTN

A

Common:
- intrinsic renal disease
- renovascular disease
- Mineralocorticoid excess
- OSA
- Meds: OCP, NSAIDS

Uncommon:
- Pheochromocytoma
- Glucocorticoid excess/cushing’s
- Coarctation of Aorta
- Hyper/Hypothyroidism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Primary aldosteronism

A

Morning PAC and PRA
- PAC >416, PRA <1.0
- AND: PAC/PRA >555 per hour (increases)
- then investigate for primary aldosteron excess

Confirmatory tests:
1. oral salt loading
2. IV salt loading
3. Fludrocortisone suppression

Tx:
Adrenal CT
- unilateral hypodense nodule >1cm <2cm
> under 40 - consider APA or PAH
> over 40: Adrenal venous sampling - if lateralisation -> APA or PAH
otherwise: bilateral idiopathic hyperplasia - medical tx

59
Q

Renal artery stenosis

A
  • Angiogram is gold standard
  • CT angio: most sensitive
  • resistive indices >0.8: predicts poor outcome with angioplasty
  • treatment with stent doesn’t work

Tx:
Unilateral RAS:
- ACEi/ARB +/- thiazide
- Angioplasty for FMD

Bilateral
- Avoid ACEi/ARB
- no evidence for stenting

60
Q

Creatinine

A
  • metabolism of creatine in muscle and meat
  • Variable based on age, body size, and sex
  • Freely filtered, not reabsorbed, but secreted by PT
  • GFR 125ml/min
61
Q

Osmolality

A

2 x NA + gluc + urea

62
Q

ADH production

A
  • osmoreceptors in the hypothalamus sense osmolality
  • ParaVN and SON express gen coding for VP
  • posterior pituitary
  • V2 receptors in thick ascending LoH, DCT, and CD
  • cAMP pathway –> increases AQP2 gene transcription and phosphorylates already made AQP2 vesicles –> fusion to mb –> increases AQP2
  • water entry into cell

Tolvaptan: blocks V2 receptors in distal nephrons and CD. Reduces cyst formation in PCKD

V2 is released if there is a fall in arterial blood **volume **

  • V1 receptor increase vascular resistance
63
Q

Regulators of effective arterial blood volume

A

RAAS
Carotid sinus and aortic arch: baroreceptors –> medulla oblongata –> increase sympathetic activity
Cardiac receptors: regular release of ANP and BNP

64
Q

Stimuli for renin release

A
  1. sympathetic nerve activation (acting through β1-adrenoceptors)
  2. reduced Na delivery to distal tubules
  3. renal artery hypotension (caused by systemic hypotension or renal artery stenosis)
65
Q

Euvolemic hypotonic hyponatraemia

A

SIADH, psychogenic, renal failure (adv), Thiazide
Low serum Na, low serum osmolality, high urine osmolality >100

High urine Na, normal serum K and pH

66
Q

Causes of SIADH

A
  • ADH secreation from Small CLC
  • CNS disorder
  • Drugs: SSRI, carbamazepine, cipro, amiodarone, immunosuppression
    -** Recent surgery - mediated by pain afferents**
  • Pulm. disease
  • Hormone def: hypopituitarism and low TSH
  • Idopathic: occult tumour or GCA
66
Q

Causes of SIADH

A
  • ADH secreation from Small CLC
  • CNS disorder
  • Drugs: SSRI, carbamazepine, cipro, amiodarone, immunosuppression
    -** Recent surgery - mediated by pain afferents**
  • Pulm. disease
  • Hormone def: hypopituitarism and low TSH
  • Idopathic: occult tumour or GCA
67
Q

Hypovol. hyponatraemia

A
  • Renal fluid loss: high urine Na and chloride
  • GI loss:
    > diarrhoea or sequ in 3rd space -> low urine Na
    > vomiting: high urine Na , due to metabolic alkalosis –> Na excretion with loss of urinary bicarb, and low urine chloride
68
Q

Hypervolemic hyponatraemia

A

HFrEF, reduced tissue perfusion, arterial vasodilatation

69
Q

Hypertonic hyponatraemia (serum osmolality is high)

A

HYperglycaemia
IVIG infusion
Sorbitol or mannitol irrigation in uro or gynae procedures

70
Q

which diuretic causes hypercalcaemia?

A

thiazide

71
Q

AR syndromes that resemble actions fo diuretics

A

Bartter = loop diuretic
- high levels of prostaglandin production –> stimulates renin
- hypokalaemia and metabolic alkalosis
- will also have low Ca and Mg level in serum

Gitelman: thiazide
- high serum Ca, and low serum Mg
cramps in limbs, polyuria and fatigue

Tx:
- electrolytes
- NSAIDS to block PGE2

72
Q

What do the macula densa sense?

A

stimulated by decrease in chloride

73
Q

What happens to renin with ACEi/ARB?

A

Renin level increase

74
Q

RAAS

A
  • angiotensinogen produced by the liver (others)
  • ACE: vascular endothelial cells in the lung (others)
    >Converts AT1 to AT2
    > breaks down bradykinin
  • AT2:
    > arterial vasoconstriction –> increase BP (early)
    > Hypothalamys: increase thirst, increase ADH –> increase CO
    > Renal: low levels: vasoconstrict efferent (increase GFR). High levels: vasoconstrict afferent and efferent: dec. GFR
    > Adrenal (late) via AT1R: zona glomerulosa to increase aldosterone –> R. on CD principal cells of CD–> cGMP –> N/K atpase and increase ENaC –> Na retension

AT2 receptor 1: vasoconstricts, inflammatory mediator, proliferation of vascular smooth muscle
recep 2: opposite, but less in the kidneys

Intrarenal RAS:
- AT2 in renal interstitial fluid is 1000x more than systemic system
- very sensitive to sodium intake

ACE2: produced by endothelium of coronary and intrarenal vessels have opposing action to ACE1

75
Q

Affect of aldosterone outside of the kidneys

A
  • activation of inflammatory cascade and production of proinflammatory cytokines
  • insulin resistance
  • ## promates cardiac fibrosis
76
Q

what increases potassium uptake into the cells?

A

Insulin
Aldosterone
Catecholamines, GH
Alkalosis

Increased potassium secretion during daylight hours

77
Q

K+ and acidosis

A

Hyperkalaemia –> increase K+ into cells, thus H+ out of cells –> acidosis in plasma

78
Q

Bicarbonate and kidneys

A
  • No bicarb in the urine
  • 90% reabsorbed in PCT
  • 10% in distal nephrons
79
Q

Normal anion gap

A

Loss of bicarb
compensated by increase in Cl-
- Severe diarrhoea
- Renal failure
- Proximal Type 2 RTA

Impaired acid secretion:
- mod renal impairment
- RTA - Typw 1 and 4

80
Q

High Anion gap acidosis

A

Methanol
Ureamia
DKA
Paraldehyde
Isoniazid/iron
Lactic acidosis
Ethylene glycol, ethanol
Salicylates

CAT
Carbon monoxide
Aminoglycoside
Theopyllines

81
Q

type 1 RTA

A

Distal defect in H-ATPase
Normal anion gap/metabolic acidosis
urine pH increased >5.5

Causes:
- autoimmune disease
- Sjogrens, RA
-* Hypercalciuria as a primary defect*

Urine:
- increased calcium
- reduced citrates
- high urine pH
= increased risk of nephrolithiasis

Hypokalaemia:
- lack of H+ excretion for Na, means K+ has to exchange for Na+
- Metabolic acidosis at PCT –> reduced Na reabsorption –> aldosterone activation –> increased Na reabsorption in CD exchange for K+

Hypokalaemia reversed with Nabicarb (alkali) therapy

82
Q

Type 2 RTA

A

Proximal
Loss of bicarb reabsorption secondary to Na/H+ pump in PCT
- increased bicarb distally, overwhelms pump
- increased excretion of bicarb
- fall in serum bicarb 12-20
- metabolic acidosiss

Causes:
Myeloma
Fanconi
- global PCT dysfunction (so you lose phosphate, glucose, AA, Na, bicarb). Genetic: associated with wilson’s. Acquired: cisplatin, heavy metals
Drugs

Urine pH <5.5, rapid rise in pH when serum bicarb is corrected

Urine calcium is low
Hypercalcaemia
Hypokalaemia

Treatment with bicarb requires higher dose cf type 1. increased bicrb diuresis stimulates potassium secretion –> hypokalaemia

83
Q

Type 4 RTA

A

Hyperkalaemia
Mild normal anion gap metabolic acidosis

Causes:
- hyporeninemic hypoaldosteronism
>NSAIDs, CNI, chronic interstitial nephritis, DM, acute GN
>ARBs or K+ sparing diuretics
>Heparin (toxin to zona glomerulosa cells)
>Primary adrenal insufficiency (addison’s)

84
Q

Polycystic kidney diseae

A

ADPKD (commonest inherited renal disease)
PKD1 on Chr16, PKD2 (Chr 4)
OTher: GANB, DNAJB11

PKD1/PKD2: polycystin 1/2 –> ciliopathy
100% penetrance
mostly monoallelic, most mutations are point mutations. nontruncating mutations (33%)

15% don’t have family history - de novo, mosaicism, mild disease

PKD1 is more severe thatn PKD2
Kidney function is usually intact till 4th decade
50% reach ESKD by 60 (ESKD is 55 for PKD1 and 75 for PKD2)

85
Q

PCKD

RF for progressive renal disease

A
  • PKD1, truncting mutation
  • MALE
  • Early onset of sx
  • FHx of early ESKD
  • Kidney size
  • HTN
  • Proteinuria (usually absent in PCKD)
86
Q

PCKD

Clinical presentation

A

PKD1 have more cysts than PKD2
Cysts can occur in other organs
not associated with RCC

HTN
Haematuria
Proteinuria (less common)
Renal failure
Flank pain:
>cyst haemorrhage
>Cyst infection (quinolone are good for cyst penetration
>Calculi
>UTI
Chronic pain sx

87
Q

PCKD

Extra-renal manifestation

A

Cerebral aneurysm 5% in young 20% in >60
- usually have MCA involved
- Avoid smoking and BP control is important
- Screen high risk pt: MRI without gad or CTA

Hepatic cysts:
- mod- sev PLD in 15% of ADPKD
- More severe in post-menopausal females (avoid estrogen replacement)
- hepatomegaly –> early satiety, reflux, abdo bloating/pain, dypnoea,backpain, ascites, oedema
- IVC obstruction/ cholangitis

Pancreatic cysts (a/w IPMN)
Seminal vesicle cysts

Cardiac:
-MVP and AR
- less frequent MR/TR
- CM, LVH, diastolic dysfucntion, AF, coronary aneurysm/dissection, asymptomatic pericardial effusion
- consider beta blockers

Aortic aneurysm/dissection
Colonic and duodenal diverticulae
Abdominal wall/inguinal hernia

88
Q

PCKD

Diagnosis

A
  • enlarged kidneys and bilateral diffuse cysts
  • MRI is more sensitive
  • if no FHx:
    > more than 10 cysts and bilateral enlargement
    no Cyst on MRI by 18 excludes dx

If Fhx positive:
- <40: >3 cysts total involving both kidneys
-if <5 cysts on MRI by 40 = exclude dx
- 40-59: 2 cyst in each kidney on USS
- >60: >4 cysts in each kidneys

89
Q

PCKD

DDx

A
  • multiple benign simple cysts
  • Acquired renal cystic dx: dialysis pt
  • ADTKD (dilation of Med. CD, prog fibrosis, not enlarged, cortex spared, bland urine sediment
  • ARPKD (PKHD1 gene mutation), more severe disease
  • TS: can coexist (PKD1 + TSC2 = early ESKD)
    > angiomyolipoma, skin angiofibromoas, cortical tubers, astrocytoma, seizrues, LAM (lymphangioleiomyomatosis), cardiac rhambo, sclerotic bone disease
90
Q

PCKD

Treatment

A
  1. HTN: contributes to GFR decline and CV morbidity.
    - BP control reduced TKV and GFR decline
    - improves CV mortality cf non-PCKD CKD
    - ACEi/ARB
  2. Reduce salt intake (2.3-3 g/day)
  3. Increase fluid intake >3L/day
    - maintain urine osmolality <280
    - hypotonic urine: helps reduce cyst growth and GFR decline
  4. Lipid control

Drugs:
1. Tolvaptan: V2-R antagonist
- earlier tx is more beneficial
- reduce rate of TKV growth, GFR decline, kidney pain
- Effects of eGFR is sustained and cumulative
4 yrs of tx delays dialysis by 1 year

indication: eGFR <90, and deciline >5ml/min/year or 2.5 for 5 years or more
Dose: 45mg mane, then 15mg 8hrs later
Max: 90mg mane, 30mg afternoon

if hypernatraemic: hydrate or reduce dose
if hyponatraemia: reduce hydration or increase dose
low osmolar diet

Often need to drink 5L/day
ADR:
- 6-8% decline in eGFR (is ok)
- polydipsia, polyuria, nocturia
- abnormal LFTs
- Hypernatraemia

Contraindication for Tolvaptan:
- baseline hypernatraemia
- inability to sense or respond to thirst
- Hypovolemia
- Concomitant diuretic use
- interacts with CYP3A4

91
Q

Amyloidosis and brief info on tx

A

AL: Daratumumab (CD38), CyBorDex or BMD
AA: TNF alpha blocker
Hereditary ATTR: Liver transplant
WT ATTR: tafamidis - prevents misfolding

92
Q

BK nephropathy

A

Polyomavirus
DNA
Decoy cells in urine is characteristic

Biopsy:
- interstitial nephritis, and tubular injury
- Viral inclusions in epithelial cells
- DCT and CD mostly involved

Occurs 2-60 month post transplant
present with progressive graft dysfunction with no symptoms
Graft failure in 45% of affected pts

RISK
Tac or MMF
Recccurent episode of rejection
HLA mismatch
Men

Tx:
reduce IS

93
Q

Management of acute rejection

A
  • tissue
  • Methylpred for 3 days
  • Failure to respond:
    > OKT3 or Antithymocyte depleting ab
  • +/- increase CNI
  • PLEX/IVIG/Ritux if antibody mediated
  • REfractory or recurrent: High dose Tac or MMF
94
Q

What renal tx immunosuppression is ok in Pregnancy?

A

cyclosporin or azathiopurine

95
Q

Benefits of renal transplant

A

Improves QoL
Increases life expectancy
Return to employment
Ability to travel
Improves fertility and pregnanct outcome

Where as, dialysis has reduced life expectancy, reduced QoL

96
Q

Renal transplant

Random facts

A
  • For deceased donor transplant: high mortality in the first 100 days
    - Live donor is better: graft survival and pt survival; attenuates early mortality risk in elderly pts
  • younger pt, greater mortality cf. to gen popn
  • pre-empttive transplant is associated with best long term outcomes
  • HLA sensitised patients are difficult to match

-CDC>flow>virtual XM (risk of rejection/graft loss)

  • Single kidney: probable increase in BP, increased risk of ESKD but absolute risk ~0.5%

ABO incompatible donors:
- higher AR and AMR
- comparable outcomes to matched living donors in the long term.

Duration of dialysis pre-tx –> reduced survival post

  • ## death with graft function is the most common cause of graft loss in older people
97
Q

Renal Transplant

Criteria for living donors

A
  • low perioperative risk
  • Acceptable lifetime risk of ESKD (rememeber that accumulative risk for young people are greater)
  • pre donation risk –> post donation risk
    > age, HTN, DM (absolute contraindication), BMI, GFR, albuminuria, smoking
98
Q

Renal transplant

Treatment overview

A

Belatacept: Target CD80/86 ligand (preventing signal two) - it’s a CTLA4 attached to IgG Fc)

Induction with Basiliximab or ATG:
Basiliximab - Anti CD 25 (IL-2R ab): inhibit T-cell proliferation

Maintenance:
Prednisone
CNI: TAC/cyclosporin
Mycophenolate (95%) vs Aza (anti metabolite)

99
Q

Renal Transplant

Low dose tac + MMF + Pred + Anti CD25

A

Better survival, GFR at 3yrs, low rate of rejection

100
Q

Renal Transplant

Basiliximab vs ATG

A
  • B has less acute rejection and minimal SE
  • ATG: less acute rejection high immunological risk group
  • Increased risk of infection and malignancty
    > EBV D+/R- has high risk of PTLD
    > can use in steroid resistance rejection
101
Q

Renal Transplant

What do you use for maintenance IS?

A
  • Steroids
  • CNI
  • Antimetabolite
102
Q

Renal Transplant

CNI

A
  • rate limiting enzyme in T-cell proliferation
  • Inhibit IL2 mediated T-cell proliferation
  • inherently nephrotoxic with long term use
  • Causes HTN, lipids, Thrombotic microangiopathy
  • (without CNI –> high rate of rejection and poor graft survival

Remembers ther is NO bone marrow suppression
- can use in pregnancy

103
Q

Renal Transplant

CNI

A

TAC is stronger so less rejection and de novo DSA (results is chronic rejection)

If they have risk of T2DM –> use cyclosporin
If they have immunological risk –> tacrolimus

Tac: More hypomg/phos, more neurotoxic and tremor
Cyclo: more hum hypertrophy, more hirsutism, interaction with drugs ie statin

104
Q

Renal Transplant

Antimetabolites

A

Inhibits T-cell proliferation in the cell cycle (G1-S)
- MMF results in less early rejection

MMF/MPA:
- inhibits IMPDH involved in purine synthesis
- levels lowered by cyclosporin (not Tac)
- AE: Bone marrow suppression
* worsened with the use of valgangciclovir +/- bactrim

Myco vs Aza:
- less rejection
- more diarrhoea
-** MMF CI in pregnancy **–> switch to AZA

105
Q

What’s beneficial about mTORi?

A

Less viral infection
Less renal toxicity
Less malignancy
Less neutropenia and diarrhoea

More rejection and discontinuation rate

106
Q

Renal transplant

Graft loss - death with graft function

What are early and late causes?

A

Early: CVD, Infection, Cancer
Late: Cancer, CVD, infection

107
Q

Renal transplant

Death censored graft loss

Early and late causes

A

Early (<1yr): graft thrombosis, rejection, GN
Late:
Chronic allograft nephropathy
> Chronic antibody mediated rejection
- Early unresolved rejection
- Non adherence
- De novo DSA (esp class 2 DQ)

GN

108
Q

Renal transplant

Immediate allograft dysfunction

DGF

A
  • delayed graft function
  • mostly due to ischaemic ATN
    >RF: deceased donor, donor AKI, Donor age, DCD, cold ischaemia time >24h, mode of dialysis

Other causes other than ATN:
- Thrombosis - not salvageable, USS /MAG-3 scan
- Obstruction/urine leak
- Rejection (biopsy 1 week after)
- Early recurrence

109
Q

Causes of immediate graft loss

A

DGF
Rejection
Vascular- thrombosis
Obstruction

110
Q

Causes of graft loss 1-12 weeks

A

Rejection
Drugs (CNI toxicity)
Obstruction
Infection
Recurrence of underlying GN

111
Q

Acute graft loss >3months

A

Volume depletion
Drugs
Rejection
Obstruction
Recurrence
- earluy: FSGS, aHUS, MPGN, ANCA
- Late: IgAN, MbN, MPGN
RAS
De novo

112
Q

Acute rejection

A
  • either cell mediated (T-cell) or Ab mediated or mixed
  • Rising creatinine - rejection until proven otherwise (BIOPSY)

RF:
Prev. HLA sensitisation
Pre-tx ab against donor
- ABO, HLA, non-HLA
- Younger pt, older donor
- Ischaemia time, DGF
- HLA mismatch (More MM, the worse graft survival, DQ MM is important)

Treatment:
1. TCMR:
- methylpred
- ATG if steroid resistant

  1. AbMR
    - PLEX
    - IVIG
    - +/- Rituximab

Prophylaxis:
PJP
CMV

Rejection without return baseline –> affects survival

113
Q

CMV

A

most common opportunistic infection
- associated with increased mortality
- increased risk with D+, R- status and degree of IS

Proph vs pre-emptive:
- D+/R-: prophylaxis for 6 months
- D-/R+ or D+/R+: 3 months
- D-/R-: no proph unless ATG used for induction

Tx:
- Valgang is good for both prophylaxis and tx (2x)
- Gang for severe or poor GI absorption
- if resistant: UL97 mutation
- –> Foscarnet or cidofovir
foscarnet inhibits viral specific DNA polymerase

114
Q

Common cancers in IS renal transplant

A

NHL, Kidney, Melanoma
Cancer death in tx pt:
NHL, lung, colorectal

115
Q

Skin cancers are very common in tx patients

A

Met. SCC - common cancer related death in post tx
Avoid AZA

116
Q

HLA importance in renal tx

A

HLA is coded on chr 6
DR>B>A

117
Q

Post tx complication: random facts

A
  • RR of kaposi sarcoma is very high (400-500)
  • post tx lymphoproliferative dx - Bcell monoclonal, EBV associated, relflects over IS.
  • **diabetes **: 10-15% at 1 year
    > increased graft failure and increased mortality
    > infrequently develops nephropathy
    > More potent pred. of graft failure than AR

Smoking 2x risk of graft loss and 50% overall survival
BP affects graft survival
Obesity: surgical complication, DGF, increased mortality and poor graft survival

common cause of early graft loss is non-adherence

118
Q

Post-transplant erythrocytosis

A

it’s angiotension mediated
so tx with ACEi or ARBs

119
Q

Electrolyte disturbance post tx

A
  • hypomagnesemia: CNI renal wasting
  • hypophosphataemia: diuresis, increased PTH or FGF 23, which increases phosphate excretion
120
Q

MAG3 scan

A
  • ATN: normal perfusion, slow wash out and persistent isotope accumulation
  • Hyperacute rejection: no perfusion
  • Cyclosporin toxicity: prolonged clearance
121
Q

RF for renal stones

A

Urinary factors:
High urine calcium
High urine oxalate
Low urine citrate
Low pH – e.g. chronic diarrhoea with HCO3 loss

Dietary:
Low calcium intake
High oxalate intake
High animal protein intake
Low potassium intake
High sodium intake
Lower fluid intake

Other: previous hx of stones, FHx, those with increased enteric oxalate absorption (malabsorption post-bariatric surgery), drugs (acyclovir), diabetes/obesity/gout/HTN

122
Q

Lupus nephritis

A

Renal involvement is common
Proteinuria>haematuria
Female and black people

WHO classification
class I: normal kidney
class II: mesangial glomerulonephritis
class III: focal (and segmental) proliferative glomerulonephritis
class IV: diffuse proliferative glomerulonephritis
class V: diffuse membranous glomerulonephritis
class VI: sclerosing glomerulonephritis

Class IV (diffuse proliferative glomerulonephritis) is the most common and severe form. Renal biopsy characteristically shows the following findings:
- glomeruli shows endothelial and mesangial proliferation, ‘wire-loop’ appearance
- if severe, the capillary wall may be thickened secondary to immune complex deposition
- electron microscopy shows subendothelial immune complex deposits
- granular appearance on immunofluorescence

123
Q

Lupus nephritis

Treatmentt

A

Everyone should be on HCQ

IS for active III/IV
- Steroid + MMF or CYC
- Maintenance: MMF or AZA

V:
- RAAS blockade, HCQ, BP optimise
- IS if nephrotic range proteinuria

123
Q

Lupus nephritis

Treatmentt

A

Everyone should be on HCQ

IS for active III/IV
- Steroid + MMF or CYC
- Maintenance: MMF or AZA

V:
- RAAS blockade, HCQ, BP optimise
- IS if nephrotic range proteinuria

124
Q

aHUS

A
  1. Mutation in factor H predom. C-terminal
  2. autoantibody bind to C terminal epitope
  3. C3 mutation prevents factor H binding

> 50% have an underlying mutation, then get an environmental second hit

Tx:
Eculizumab - high risk of meningococcal infection
thus vax and abx for first 2 weeks of treatment
PLEX

Avacopan is a complement** 5a receptor (C5aR) antagonist** that blocks C5a-induced upregulation of C11b (integrin alpha M) on neutrophils and inhibits C5a-mediated neutrophil activation and migration. - used in ANCA +ve vasculitis

125
Q

REnal bone disease

A

abnormality in Ca, PO4, PTH, FGF23, Klotho and Vit d metabolism
Ab bone turnover, mineralisation and linear growth or strength

Each biochemial abnormality is associated with high mortality rate due to CVS

MBD develops as early as Stage 2 CKD
Klotho is lost, FGF23 is raised (associated with mortality) bone formation is reduced and vascular calcification develops

Phosphate:
- doesn’t rise til later on as FGF23 and PTH maintain PO4 excretion
**
Pattern of Bone dx:**
- Osteitis fibrosa cystica - high turnover mediated by PTH
- Adynamic bone disease - low turnover
- higher # risk and ectopic calcification cf high turnover dx
- Osteomalacia: low turnover with abnormal mineralisation
- Mixed

treatment:
- Control phosphate
- Maintain calcium
- lower PTH (once >2x ULN):
> - Calcitriol usually given when PTH >50, aiming to turn off the PTH production. no effect on outcome
> Calcimimetics (cinacalcit) - once started need to continue forever. Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH secretion. The reduction in PTH is associated with a concomitant decrease in serum calcium levels.
> Surgery:
- complication post op: hungry bone: hypocalcemia, hypophosphataemia, hypomg,
- K+ may go up

126
Q

CKD

A
  • increases all cause mortality
  • lower GFR and albuminuria are independent RF for **CVD and mortality **
  • non-traditional RF for CVD in CKD:
    > Vascular calficification due to bone mineral metabolism abnormality
    > Uraemia
    > Inflammation

RF:
age, DM, HTN, ethinicity, F - CKD, M- ESKD, FHx, obesity, episodes of AKI

127
Q

SGLT2:

CKD

A

improvement in decline in RF, ESKD and renal or CV death
Improvement in all cause mortality and CVD and hosp. from HF

Independent of DM status

128
Q

What should we not use alpha blockers early on for BP control

A

Excess mortality

129
Q

Proteinuria

A

Most potent predictor of ESKD
*not in PCKD

ACEi/ARB similar affect
MRA added to RAS blockade improves proteinuria

Reduction in proteinuria slow GFR decline

Independent RF for CVD

130
Q

Dialysis

A

Wouldn’t start statin on pt on HD - no change in mortality

  • high PO4, low calcium, high PTH and high FGF23 are all independently associated with increased mortality
131
Q

Diet

A

Salt intake <2.5g, 100mmol/day

132
Q

What is the action of PTH?

A
  • reduce renal reabsorption of PO4, increase bone turnover, increase FGF23, increase 1,25 Vit-D
133
Q

VitD and PO4

A

increases renal reabsorption of PO4 and gut absorption, increase FGF23 production, and reduced PTH release

134
Q

FGF23 and phosphate

A

reduce renal reabsorption, reduce 1,25 VitD, reduce PTH

135
Q

FGF23

A

produced by osteoclast and osteoblasts in response to increase PO4, increase PTH, increase Vit D

less in response to high calcium

FGFR/Kloth co-receptor: in PCT and, DCT, PTH gland
- In the PCT: inhibits Na/Phosphate –> phosphaturia
- inhibit 1,25 Vit D by inibiting alpha 1 hydroxylase and stimulating 24 hydroxylase (catabolic)
- directly inhibits PTH secretion

Klotho is produced in the kidney, this in CKD, FGF23 is unable to inhibit PTH production due t lack of klotho

136
Q

Osteoporosis and CKD

A
  • DEXA not validated
  • difficult to diagnose
  • Treat CKD-MBD first
  • anti-resorptive therapy may increase risk of # (in animal model)
137
Q

FSGS

A

Causes
* idiopathic
* secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
* HIV
* heroin
* Alport’s syndrome
* sickle-cell

renal biopsy:
focal and segmental sclerosis and hyalinosis on light microscopy
effacement of foot processes on electron microscopy

138
Q

Which CD4 T cell is most implicated in the pathogenesis of GN?

A

Th17

139
Q

Congential nephrotic syndrome

A

NPHS1 – nephrin

140
Q

Familial FSGS

A

NPHS2 – podocin
TRPC6

Do not respond to steroids

141
Q

Whst’s the difference between primary and secondary FSGS on EM?

A

Primary shows diffuse foot process effacement, where as secondary shows focal/segmental

142
Q

serum soluble urokinase‐type plasminogen activator receptor
(suPAR).

A

Up to two thirds patients with **FSGS **have elevated levels of

Renal disease only occurs when sufficient circulating suPAR
activates podocyte β3 integrin causing foot process
effacement, proteinuria and FSGS like glomerulopathy

Immature myeloid cells produce suPAR

RACP (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions