Renal Flashcards

Question 1

Q

Gitelman, Gordon and Liddle Syndromes

Genetic defect
Triad of symptoms

Question 2

Q

Tubular sites of action of commonly-used diuretics

Question 3

Q

Viruses related to malignancy post transplant

Question 4

Q

Gene Mutations in atypical HUS

Answer

A

Mutations in CFH most common in sporadic and familial forms

antibodies to CFH - complement factor H likely cause in atypical HUS

Question 5

Q

Most common causes of primary glomerular diseases in nephrotic syndrome

Answer

A

*Children** - MCD - minimal change glomerulopathy
*Adults - Membranous GN**

Question 6

Q

Minimal Change Disease

Answer

A

*Population - Children** (90% of idiopathic nephrotic syndrome)
*Histopathology -** LM normal, IFM no complement/Ig deposits, EM diffuse effacement of epithelial (podocyte) foot processes
*Associations**
Drugs - NSAIDS (most common cause of secondary MCD), ABx, lithium, vaccines, gamma interferon
Neoplasms - esp haematologic such as Hodgkin, non-Hodgkin and leukaemia > solid organ
Infections (rare) - syphilis, TB, Hep C, HIV
Allergy (tenuous connection)

Other glomerular diseases - IgA, SLE, T1DM, PCKD, HIV nephropathy

Treatment

-Corticosteroids, children response more regularly and quicker than adults. Then try other immunosuppressives
Low Na diet, diuretics and ACEI/ARBs in adults
-High relapse rate but progression to ESRD is rare

Question 7

Q

Focal Segmental Glomerulosclerosis (FSGS)

Answer

A

*Population** - Children and adults, older children > young
*Histopathology - LM FSGS,** EM diffuse foot process effacement (primary), segmental effacement (secondary)
*Presentation**
-Primary = acute/subacute nephrotic syndrome with high proteinuria
-Secondary = gradual onset (weeks to months), lower protein, less oedema
-Genetic = positive FHx, early onset

Most reliable prognostic factor of renal survival is response to treatment

*Primary** - 50% respond to corticosteroids
*Secondary -** aim lower intraglomerular pressure = ACEI
5 year renal survival rates 60 - 90 %
10 year renal survival rates 30 - 55%

Question 8

Q

Membranous GN

Answer

A

*Population - Adults** >> Children
*Histopathology**
-LM = GBM thickening with spikes on silver staining
-IFM = diffuse granular pattern of Ig G and C3 staining along GBM
-EM = subepithelial electron-dense deposits on outer aspect of the GBM, effacement of foot processes, GBM expansion by deposition (spikes) of new extracellular matrix between deposits
Primary 75%
Secondary - SLE, drugs (penicillamine, NSAIDs, gold salts, anti-TNF), Hep B, C, malignancy, haemopoetic cell transplant, CVHD, post renal transplant, sarcoid)

Diagnosis
-Anti PLA2R antibiodies and biospy if Ab negative
-Anti THSD7A testing - new not mainstream
Treatment - a lot will remit without treatment, only immuneRx those who will progress
Everyone: ACEI - Slows progression and low salt diet
Moderate/High risk of progression - cytotoxic-based (cyclophosphamide) or calcineurin inhibitor-based regimen, each combined with glucocorticoids
Should also screen these patients for malignancy
ESRF 14% at 5 years, 35% at 10 years

Question 9

Q

Classification of Renal Tubular Acidosis

Question 10

Q

Treatment of IgA Nephropathy

Answer

A

IgAN most common cause of ESKD due to GN in ANZ, so worth knowing about it

Treatment for IgAN–ACEi/ARB for proteinuria >0.5-1 g/d with RAS blockade all others controversial, no proven benefit

Question 11

Q

Prevention of Recurrent Renal Calculi

Answer

A

First line - hydration (aim UO >2L)
Then can try dietary changes
Thiazides, Potassium Alkali and Allopurinol if meets criteria

Question 12

Q

Pathogenesis of ADPCKD

Question 13

Q

Management of ADPCKD

Answer

A

Conservative measures:

HTN contributes to CV morbidity and GFR decline
BP control - aim < 130/80reduces the increase in TKV + eGFR decline AND improves CV mortality more than non-PCKD causes of CKD
ACE or ARB is first-line
Reduction in sodium intake
- 2.3 –3g / day (lower may be harmful)
Increase fluid intake
- >3L / day -maintain urine osmolality <280 mOsm/kg attempting to make hypotonic volume
Lipid control
Caloric restriction is protective in animal models
- Thoughts that obesity may be detrimental in this condition

Tolvaptan

Vasopressin V2-receptor antagonist
Earlier Rx is started = more benefit
for every 4 years on the Rx, delay dialysis by ~1 year,
reduce the speed of which of which cysts develop. reduces rate of eGFR decline and TKV

Cerebral aneurysms

5% in young adults, up to 20% in pts >60 yrs.
Usually MCA involved (can have multiple sites)
Screen high-risk pts only (MRA without gadolinium or CTA if MRI C/I):
- Previous rupture
- Positive family Hx of ICH / aneurysm
- Neurological Sx
- High-risk job e.g. flying
- Prior to major surgery

Question 14

Q

Types of Cryoglobulins

Question 15

Q

Pathogenesis of Vascular Calcification in ESRD

Question 16

Q

Pathogenesis of Renal Bone Disease

Answer

A

Contributing factors:

Biochemical Derangement –Ca, PO, PTH
Acidosis
Bone Turnover/Mineralisation

Question 17

Q

Causes of EPO resistance

Question 18

Q

Anaemia and CRF

Underlying mechanism
When to start EPO and target Hb
Iron study targets

Answer

A

Variety of factors

- loss of EPO efficacy, lower levels relative to the degree of anaemia
loss of production
substrate deficiency
elevate dhepcidin
shortened RBC lifespan

Assoc with reduced QoL, increased CVD, cognitive impairment, hospitalisation

Managemet

rule out other cause
Fe replacement!!
ESA –> target Hb 100-115, increased mortality if Hb >120

Question 19

Q

Causes of ESRD
-most common cause

Answer

A

IgA GN MOST COMMON cause of ESKD due to GN

Question 20

Q

Fibromuscular Dysplasia

Question 21

Q

Atherosclerotic vs FMD renal artery stenosis

Question 22

Q

Unilateral vs Bilateral RAS

Answer

A

Unilateral Renal Artery Stenosis –> Elevated RAS system with a normal volume state due to the contralateral kidney promoting a pressure natriuresis

Question 23

Q

Doppler ultrasound in renal artery stenosisd

Answer

A

Good screening test!

Question 24

Q

Management of Renal Artery Stenosis

Answer

A

Increasing stenosis leads to hypertension and potentially high-risk syndromes and impacts CVS risk
In those with FMD, angioplasty is the treatment of choice
Aggressive CVS risk factor control, including use of ACEI/ARB, is the bedrock of management
In mild-moderate atherosclerotic disease, high quality evidences exists to show that medical intervention offers no added benefit to medical therapy alone
Low quality data to suggest that high-risk subsets may benefit with intervention

Question 25

Q

RTA
-focus on management

Question 26

Q

Hypertensive retinopathy

Mild changes (4)
Moderate changes (4)
Severe change (1)

Question 27

Q

IgA Nephropathy

Epi fact
Key pathogenesis/histology feature
Treatment - mild/mod and severe
Prognosis - recurrence post transplant?
Key difference between IgA and HSP

Question 28

Q

Anti-THSD7A antibody associated with…

Answer

A

Membranous Nephropathy (membranous GN)

low sensitivity
higher specificity

Question 29

Q

Most common urinalysis finding of AIN

Answer

A

Sterile pyuria

Question 30

Q

Indications for PD catheter removal post peritonitis (5)

Question 31

Q

PD Peritonitis

Most common cause
Most commo bug
Antibiotic therapy

Question 32

Q

Strongest predictor of mortality on dialysis

Answer

A

Hypoalbuminaemia

Question 33

Q

Most effective method to prevent interdialysis weight gain

Answer

A

Salt restriction

Question 34

Q

What type of amyloid is desposited in renal disease
-What might they present with?

Answer

A

_B2 microglobulin
Carpal tunnel_

Dialysis-related amyloidosis is due to deposition of fibrils derived from beta-2 microglobulin, which accumulate in patients with end-stage kidney disease who are being maintained for prolonged periods of time by dialysis.

Patients with dialysis-related amyloidosis most commonly complain of shoulder pain related to scapulohumeral periarthritis and rotator cuff infiltration by amyloid, and of symptoms of carpal tunnel syndrome

Question 35

Q

Why do patient’s on ACEI get an eGFR reduction

Answer

A

Change in efferent arteriolar tone
Up to 30% is to be expected and does not require medication cessation
May actually predict those who are likely to respond

Question 36

Q

Ultrasound criteria for ADPCKD

Question 37

Q

Most common cause of GN leading to ESRF in Aus

Answer

A

IgA nephropathy!!!!!

Question 38

Q

Leading cause of death following renal transplant?

Answer

A

Cardiovascular disease

Question 39

Q

When should renal transplant be performed?

Question 40

Q

Causes of Renal Allograft Dysfunction <1 week post transplant

Question 41

Q

Causes of renal allograft dysfunction >1 week post transplant

Question 42

Q

Fanconi Syndrome

site of dysfunction
4 lab findings

Answer

A

Fanconi syndrome — Generalized proximal tubular dysfunction, referred to as Fanconi syndrome, is characterized by phosphaturia, renal glucosuria (glucosuria with a normal plasma glucose concentration), aminoaciduria, tubular proteinuria, and proximal RTA.

Question 43

Q

Cause of Death in Renal Transplant Recipients

Answer

A

Early (1^st year)
- Cardiovascular (36%)
- Infection (27%)
- Cancer (3%)
Late (beyond 1^st year)
- Cancer (30%)
- Cardiovascular (23%)
- Infection (12%)

Question 44

Q

Top causes of graft loss/death

Answer

A

Early (1^st year)

Graft thrombosis/ technical (38%)
Rejection (24%)
GN (4%)

Late (beyond 1^st year)

“Chronic allograft nephropathy” (CAN) (72%)
GN (7%)
Acute rejection (4%) & Non-adherence (4%) –overlap with CAN? (based on reporting)

Question 45

Q

Side effects of the transplant drugs

Answer

A

CNI = calcineurin inhibitor

Question 46

Q

Buzz word for CNI nephrotoxicity

Answer

A

(tacrolimus, cyclosporin)

*Isometric vacuolation** of tubular epithelial cells
*Striped** interstitial fibroiss
*Nodular arteriolar hyalinosis**

Question 47

Q

Major risk factors for renal calculi

Question 48

Q

Advantages and Disadvantages of Different Dialysis Modalities

Question 49

Q

Eculizumab in atypical HUS

Answer

A

Humanised anti-C5 monoclonal antibody
Improves: Platelet count (statisically significant), eGFR and quality of life

Question 50

Q

Calciphylaxis

Question 51

Q

Acute Complications of Dialysis

Question 52

Q

Benefits of Bicarb Supplementation in CKD (3)

Answer

A

Slows progression of CKD
Prevention of Bone Buffering
Improved nutritional status

Question 53

Q

Principle cell of acute renal transplant rejection

Question 54

Q

Absolute contraindications to renal transplantation

Question 55

Q

SE of mTOR inhibitors

Answer

A

sirolimus and everolimus

Question 56

Q

Buzz word for cellular mediated transplant rejection

Answer

A

Tubulitis

(inflammatory cells in the tubualr wall)

However, it may occur in other renal diseases as well, e.g., glomerulonephritis and acute tubular necrosis

Question 57

Q

Management of Renal Bone Disease

Answer

A

NO evidence that correcting Ca and PO4 levels BUT no evidence that correcting this imbalnce corrects the risk of mortality

velphoro (sucroferric oxyhydroxide) - PBS approved, expensive, cant be on other non-Ca PO4 binders, not as constipatign very minimal to no absorption of Fe
Calcitriol (ifPTH > 45)

Cinacalcet

Calcium mimetic (next step after phosphate binders)

Question 58

Q

Is there value in strict protein restriction in ESRD?

Question 59

Q

In IgA nephropathy how is the IgA the body makes different from normal

Answer

A

It’s Galactose-deficient IgA1

Question 60

Q

Definition of Delayed Graft Function post renal transplant

Answer

A

Requiring dialysis during the first week after transplantation

Question 61

Q

What is the first change of CKD-MBD?

Answer

A

Raised FGF23

Question 62

Q

Relationship between eGFR and urine output in early ESRD

Answer

A

i.e before they become oliguric/anuric

Question 63

Q

What is the mechanism of renal failure in Gentamicin toxicity

Answer

A

Acute tubular necrosis

ATN, ATN, ATN!

Question 64

Q

Strongest predictor of renal failure in GN

Answer

A

Proteinuria!

Answer 39

A

Collecting Duct

Answer 40

A

urinary eosinophilia
livedo reticularis
vascular risk factors
old males
statins
“blue toe syndrome”

Answer 41

A

Mesangial expansion
Glomerular basement membrane thickening
Podocyte injury
Glomerular sclerosis

Answer 42

A

Liver cysts in >80%

Answer 43

A

progression of pre-renal causes
- ischaemia for a period of time that leads to tubular cell death
Toxins
- drugs (vancomycin/gentamicin/amphoteracin)
- IV contrast (CT scans/angiography)
- Myeloma/immunoglobulins/paraproteins

Answer 44

A

Bloods

UEC
ANA/ENA/dsDNA/c3 and c4/ANCA (MPO/Pr3)/anti-GBM Ab
ASOT/anti-DNase B
sPEP/serum free light chains

Urine

Urine MCS
- bland urine sediment
  - no glomerular red cells, favours pre-renal /ATN/myeloma/interstitial renal disease
- active urine sediment - glomerular red cells
  - seen in acute GN
- hyaline/granular/tubular/epithelial casts
  - suggestive of ATN
Pr/Cr
- proteinuria >1g/day suggestive of glomerula/intrinsic renal disease
uBJP - immunoglobinopathy

Answer 45

A

AKI is associated with adverse outcomes
- AKI associated with increased mortality, even when adjusted for comorbidities and severity of illness
- Severe AKI requiring RRT in ICU patients is risk factor for death
- However the association with mortality is present even for small changes in serum creatinine
Pooled mortality rate for adults with AKI is 23.9%
Mortality rate increased with AKI stage

CKD following AKI

Some patients with severe AKI do not recover kidney function and remain dialysis dependent
- Rate of dialysis dependence at hospital discharge 13-29%
Risk of de novo CKD following reversible, hospital associated AKI in patients with normal pre-hospital kidney function

Answer 46

A

*Levels in urine and blood are predictive of pathology**
*- timely** detection and reduction in immunosuppression reduces graft loss from 90% to 10-30%
which specific agent is reduced depends on the clinical scenario
*BK DNA in blood t**ends to be used (vriaemia = 50% PPV for BK nephropathy)
urine is very sensitive so has a high false positive rate with regard to infection causing pathology

Answer 47

A

All virus associated malignancies increased

EBV/HHV-8
HPV in women causing cervical/vulvar carcinomas

Skin

40% of malignancies in organ transplant recipients, ~50% of those in whites
SCC and BCC account for >90%. SCC much more common
2.7x risk of melanoma (highest in renal), and increased mortality associated

SCC

low risk = small, well differentiated, low risk site = excise and assess margins
high risk = large, poorly differentiated, high risk site = intraoperative frozen section to ensure margins
Counsel about sun protection and warning signs of malignancy
Regular skin checks dictated by history

Solid organ malignancy HR ~2x
Haematological malignancy HR ~7x

Note that hormone associated malignancy rates aren’t increased in transplant patients
- breast and prostate cancer specifically

Answer 48

A

Calcineurin inhibitors (AEs are all increases)

Cyclosporine and tacrolimus
Nephrotoxicity most common and dose dependent
Hypertension, hyperlipidaemia, hyperkalaemia, tremor, hirsutism (tac causes alopecia), glucose intolerance, gingival hyperplasia (tac less everything except more hyperglycaemia)
Tacrolimus 10-100x more potent with more predictable oral absorption. Cleared by CYPIIIA so need to watch for inducers and inhibitors
Both associated with increased risk of lymphoproliferative malignancies (like azathioprine)

Mycophenolate

Non-nucleotide purine metabolism inhibitor
Superior to azathioprine in preventing rejection after renal transplant. Also adopted in liver transplant
Bone marrow suppression and GI the most common

Answer 49

A

*Prostaglandins and bradykinin** appear to play an important role in dampening the renal vasoconstrictor effects of the sympathetic nerves or angiotensin II
Especially their efferent arteriolar constriction

In stressful conditions they help prevent excessive reduction in GFR and renal flow
- NSAIDs inhibit prostaglandins and so can cause significant reductions in GFR in such circumstances

Answer 50

A

Amino acids are co-transported with sodium to be reabsorbed in the proximal tubule.

Increased delivery to the proximal tubule = increased reabsorption of sodium = decreased delivery of sodium to the macula densa = autoregulatory mechanisms to increase sodium delivery to macula densa to maintain steady state = increased renal blood flow

Similar mechanism may explain the marked increase in flow in uncontrolled hyperglycaemic states

Answer 51

A

~ 60% of kidney function lost

Answer 52

A

Prevention
Low phosphate diet
Phosphate binders
- - calcium. Can result in total body calcium accumulation
- - sevalamer and lanthanum. Don’t predispose to hypercalcaemia
Calcitriol
- - direct suppression of PTH secretion
- - indirect suppression of PTH secretion by raising ionized calcium concentration
- - can result in hypercalcaemia/hyperphosphataemia through GIT absorption
Calcimimetics
- - cinacalcet
- - enhance sensitivity of parathyroid cells to suppressive effects of calcium
- - reduce PTH and plasma calcium

Answer 53

A

Systemic disorder resulting from mutations in PKD-1/2 genes

both transmembrane proteins in all segments of the nephron
1:400-1000, accounting for 4% of ESRF
90% inherited, remainder spontaneous
PKD-1 85% and worse prognosis

Presentation

significant phenotypic heterogeneity
often asymptomatic until 4th-5th decade, with slow decline in function over 10-20yrs
abdo pain, haematuria, UTI, hypertension, masses, renal impairment, imaging
rupture can result in gross haematuria or acute pain with signs of peritonitis
increased frequency of UTIs and cyst infection can occur

Diagnosis

Family history or imaging studies
genetic analysis for PKD-1/2 in equivocal or considering family donor
Screening for aneurysms only in FHx, intervene for >10mm

Extra-renal manifestations

Cerebral aneurysm: 2-4x increased risk of SAH from rupture. Highest risk in FHx of aneurysm
Hepatic cysts: 50-70% by age 60, weakly correlated with extent of renal disease
Pancreatic cysts: 7-10%
Cardiac disease: valvular disease in 25-30%, most commonly MVP/AR
Diverticulae and hernias: increased frequency and incidence of colonic perforation

Answer 54

A

Heavy proteinuria
Minimal haematuria
Hypoalbuminaemia
Hypercholesterolaemia
Oedema
Hypertension

Answer 55

A

Makes up 70-90% of nephrotic syndrome in childhood

only 10-15% in adulthood
can be a misdiagnosis of early FSGS (if you miss the sclerosed glomeruli on your biopsy), consider in those non-responsive to steroids or frequently relapsing

Associations

hodgkins
allergies
NSAIDs
URTI

Pathology

- Nothing on light microscopy and nothing on immunoflourescence
- Effacement of foot processes on electron microscopy

Presentation

Abrupt onset of oedema and nephrotic syndrome with acellular sediment
Hypertension in 50%, atopy/allergies in 30%
Decreased GFR in 30%, predictors: low serum albumin and intrarenal oedema. Responds to IV albumin and diuretics
Can get ATN and interstitial inflammation

Treatment

Prednisolone first line. Not resistant until after 4 months
80-85% CR by 20-24 weeks. Increased relapse with rapid taper
Cyclosporine can induce remission
Cyclophosphamide, chlorambucil, MMF in relapsers, steroid dependent, steroid resistant

Prognosis (in those who are steroid responsive)

50-75% have a relapse
10-25% have frequent relapses
25-30%steroid dependent

Answer 56

A

Segmental glomerular scars involving some but not all glomeruli

most prominent in glomeruli at the corticomedullary junction (superficial biopsy can miss it)
4 histological variants

Epidemiology

~1/3 of adult nephrotic syndrome
1/2 of African Americans

Causes

Primary FSGS
Secondary FSGS - viruses, hypertensive nephropathy
reflux nephorpathy
cholesterol emboli
drugs
sickle cell disease, lymphoma, radiation nephritis

Adverse predictors

Nephrotic range proteinuria
African American
Renal insufficiency
fibrosis on biopsy

Treatment

Primary: steroids work but less often than in MCD. Remission in 20-45% on steroids for 6-9 months
Cyclophosphamide in steroid non-responsive (30-50% respond)
- cyclosporine works but is itself nephrotoxic and they relapse when it’s stopped
Secondary: no evidence for immunosuppression, just treat the cause
Recurs in 25-40% of transplants for ESRF with graft loss in 50% of those

Answer 57

A

Accounts for ~30% of nephrotic syndrome in adults

- Most common cause in the elderly and in Australia
- Peak 30-50; M:F 2:1

Aetiology

most commonly idiopathic
25-30% associated with: malignancy, infection, rheumatologic conditions
Need to distinguish from diabetes and amyloidosis

Pathology

strongly associated with IgG4 subtype deposition
M-type phospholipase A2 receptor antibody ( associated with idiopathic, titre of antibody correlates with disease severity
Positive in 70-80% of idiopathic membranous nephropathy, primarily IgG4 subclass
antibody response to treatment correlates with disease response
‘Spikes’ on silver staining (membrane growing around immune deposits)
anti THSD7a present also

Subendothelial deposits or tubuloreticular inclusions points strongly toward membranous lupus nephritis

Prognosis

1/3 spontaneously remit, but not necessarily quickly
1/3 have relapsing nephrotic syndrome with normal renal function
1/3 develop renal failure or die due to complications of nephrotic syndrome
has the highest incidence of thrombosis of the nephrotic syndromes
- warfarin if serum albumin <20mg/day
  - adverse predictors: male, >50yrs, hypertension, proteinuria

Treatment (steroids alone don’t work)

Cyclosporin effective in inducing remission but relapse common after cessation
- Risk of long-term continuation at low dose unclear
Rituximab (MENTOR) –as effective as cyclosporin in inducing remission and remaining relapse-free; increasing evidence;
- not on PBS for membranous nephropathy
What we don’t know how rituximab compares with cyclophosphamide require further studies
Generally a period of non-immunosuppressive period for spontaneous remission
Don’t forget:
- Anticoagulation (higher VTE risk for same level of hypoalbuminaemia);
- Statin; Diuretics & salt/fluid restriction

Answer 58

A

*X-linked inborn error of globotriaosylceramide metabolism** (lysosomal storage disorder)
lysosomal alpha-galactosidease A activity

Present in 3rd decade with

mild-mod proteinuria -> progression to ESRF
skin lesions (angiokeratomas)
neurologic: acroparasthesia due to small-fibre neuropathy
cardiac: LV enlargement, conduction abnormalities
*Maltese cross fat globules under polarized light in the urine**
due to accumulation of non-broken down stuff

Treatment

- RAAS
- recombinant alpha-galactosidase A clears the deposits

Answer 59

A

Distal tubule

Principal = Na and H2O. Affected by ADH
Intercalated = K and H

Answer 60

A

Acute kidney injury characterised by inflammatory infiltrate in the renal interstitium

Causes

Drugs: 70-75%; abx 30-49%; NSAIDs; others
Infections: 4-10%
Systemic diseases: 10-20%. Sarcoid, sjogren’s, SLE, MM
Tubulointerstitial nephritis and uveitis syndrome: 5-10%

Presentation

Nonspecific symptoms
Usually without proteinuria, more common in NSAID induced
Rash, fever, eosinophilia (triad in10%)

Ix

- Temporal relationship to cause
- Inflammatory sediment: RBC, WCC, WCcasts
- no single investigation is diagnostic, it’s a clinical diagnosis with supportive investigations

Answer 61

A

IgA nephropathy

Peak 20-30yrs, M:F 2:1, highest in Asians/Caucasians
also the commonest GN causing ESRF or transplant

Pathology

Unclear aetiology (thought that it it’s due to IgG antibodies against glycosylated region of IgA -> IgA-IgG ab complex deposition)
Mesangial deposition of IgA (plus others)-> reaction -> injury

Presentation

40-50% >=1 macroscopic haematuria, during or immediately post URTI
30-40% microscopic haematuria during or immediately post URTI
<10% nephrotic syndrome or RPGN

Associations

CLD, especially alcohoic cirrhosis: most common secondary IgA nephropathy

Diagnosis

Renal biopsy: Prominent, globular deposits of IgA, often with C3 and IgG in the mesangium
Indistinguishable from HSP; SLE has more IgG

Prognosis

50% slowly progress to ESRF over 20-25yrs
Predictors of progressive: serum creatinine, new HTN (5x higher progression c/w normotensive), persistent >1g/day protein (5x higher progression c/w <1g/day), smoking, hyperlipidaemia, ACE genotype DD
In IgAN, even > 1 g/day proteinuria associated with poor renal prognosis
Asians (Chinese) – increased risk of more rapid progression
Frank haematuria = good prognosis

Treatment

BP control, RAAS if proteinuria (essential first line treatment), statin if lipids
Isolated haematuria with no/minimal proteinuria = don’t treat, don’t biopsy. Monitor 6/12
Persistent proteinuria = RAAS
Severe/RPGN with nephrotic range proteinuria or severe findings on biopsy = immunosuppress
no evidence it’s of benefit and some that it’s of harm but feel like something should be done
- steroids + cyclophosphamide followed by azathioprine

Answer 62

A

Calcium free associated with a 22% reduction in all cause mortality.

sevalamer has more safety data than lanthanum

Should only use calcium based in

hypocalcaemic/normocalcaemic without vascular calcification or adynamic bone disease

Answer 63

A

Phosphate (high = bad)

HR ~2 for >2.0mmol/L

Serum albumin (low = bad)

HR 3.4 for 30-34
HR 7 for 25-29
HR 13 for <25

Answer 64

A

Stimulates aldosterone secretion -> Na reabsorption in distal tubules
Constricts efferent arterioles -> Increased Na reabsorption
- Efferent artiorole constriction reduces peritubular capillary hydrostatic pressure, favouring reabsorption
- Efferent arteriole constriction increases peritubular capillary colloid osmotic pressure, favouring reabsorption
Direct stimulation of Na reabsorption
- In proximal, loops, distal, collecting
Alters the pressure-natriuresis curve (see attached)
- Normal curve is very steep, meaning minor changes in BP increase Na excretion
- HTN with impaired ability to decrease renin excretion lose curve steepness, requiring much higher BP to increase Na excretion
- Angiotensin II blockade shifts the curve to the left, allowing for lower BPs to excrete Na

Answer 65

A

Angiography higher risk than contrast CT

Risk factors

- CKD
- Diabetic nephropathy higher risk than other CKD
- Heart failure, due to renal hypoperfusion
- MM
- hypoosmolar contrast (not used in Aus)

<1% go on to require dialysis

Risk management

- Don’t use contrast
- Use a lower dose and avoid repetitive studies
- Avoid volume depletion and NSAIDs
- Hydrate: 8hourly bag NaCl 0.9% running 8hr pre until 8hrs post
- NAC carries risk of anaphylaxis and has conflicting data
- Prophylactic haemofiltration works but not done outside of those already being dialysed

Answer 66

A

Have to discontinue antimetabolite

- azathioprine or MMF
- essential for virus eradication

Shouldn’t stop calcineurin inhibitor

Answer 67

A

*Fractional sodium excretion**
Urine sodium is low (<20mEq/L) in pre-renal disease due to conservation of Na and water
Urine sodium is high (>40-50mEq/L) in ATN due to impaired tubular reabsorption

Limitations

Can be low in ATN superimposed on chronic pre-renal disease
Low fractional excretion of sodium not unique to pre-renal disease
Diuretics make it a free for all

Other

Fluid responsiveness: If back to normal within 24-72 hrs post repletion then pre-renal, otherwise ATN
BUN/Cr ratio: normal (10-15:1) in ATN; >20:1 in pre-renal

Answer 68

A

Pigmented granular casts in the urine
Red/brown colour of urine
Marked increase in CK

Can be differentiated from haemolysis by

haptoglobin
peripheral blood smear

Answer 69

A

Concentrates in the proximal tubular cells

Preferentially accumulates in the renal cortex
- concentration can greatly exceed that of serum

Answer 70

A

No difference in survival or CV events/infections/dialysis complications

828pts assigned to dialysis at eGFR 10-14 vs 5-7

Absolute indications

Uraemic pericarditis/pleuritis/encephalopathy
No correlation between urea level and manifestations, has more to do with rate of accumulation

Common

Declining nutritional state
Refractory acidosis, hyperkalaemia, hyperphosphataemia
Persistent or difficult to treat volume overload

eGFR of 5-15 is the grey zone

>15 generally don’t
<5 generally unable to be treated medically
5-15 judge based on symptoms

Answer 71

A

Aim Tsat >20% and ferritin >200-300

- IV superior to oral in dialysis patients

In HDx IV is preferred with dialysis
In PD or pre-dialysis subcut is preferred weekly/fortnightly

Most common side effect is hypertension

- 20-50% will develop DBP >=10mmHg

Many others, but headache, rash and flu like syndrome common

Pure red cell aplasia is rare

- Due to antibodies against EPO molecule
- Consider in those with significant anaemia in EPO >=3-4/52 that’s previously responded

Answer 72

A

*FGF-23** can indicate need for intervention even in normal phosphate levels
secreted by osteocytes
increases early in the course of CKD
results in internalisation of the sodium phosphate cotransporter in the proximal tubule -> phosphaturia

Increases renal phosphate excretion
Stimulates PTH which also increases phosphate excretion
Suppresses formation of 1,25OHD, leading to diminished phosphate absorption in the GIT

Answer 73

A

Living donor trumps deceased donors

ABO incompatible tranbsplant simjjilar longterm outcome incontemporary era - increased death-censored graft loss and rejection in first month
*3/6 HLA matched family donor** beats randomly selected cadaveric donor
*0/6 HLA match in both living and deceased** confers poor outcomes

Living unrelated as high as 6/6 HLA match deceased and comparable to living related

*Increased survival with decreased age of deceased donor**
No absolute upper limit for donation
Survival of allografts from >70yrs is lower than from younger

Answer 74

A

*Renal disease**
>80% with CRF/CKD have hypertension
more severe in glomerular disease than interstitial

Answer 75

A

Due to an occlusive ledion of a renal artery –> underlying mechanism is activation of RAAS

Groups

Older arteriosclerotic patients with an obstructing plaque
Fibromuscular dysplasia: more common in young, white women. Often bilateral and more distal

Consider

Other evidence of atherosclerotic vascular disease
Recent loss of hypertensive control, unexplained deterioration in renal function or decline with ACEI
50% have an abdominal/flank bruit

Ix

DTPA can look at flow. Not useful in bilateral or eGFR <20
Doppler U/S provides good estimates of flow
Angiography the gold standard

Answer 76

A

Pre-renal

Most common form of AKI
Usually due to decreased CO; autoregulatory mechanisms fail at SBP <80

Intrinsic

Sepsis: complicates >50% sepsis; can occur without hypotension
Ischaemia
Nephrotoxins: contrast, abx (ATN vs AIN), chemotherapy, endogenous

Post-renal

Manifold

Answer 77

A

Below account for >90%

Diabetic nephropathy
Glomerulonephritis
HTN-associated CKD
Autosomal dominant polycystic kidney disease (ADPKD)
Other cystic and tubulointerstitial nephropathy

Answer 78

A

Renal PCTs increase production of NH3 from breaking down glutamine

Then secreted into the urine where it buffers H and allows for net excretion of acid
(NH4+ can’t cross back across into the tubular cells)

Answer 79

A

Glucocorticoids accelerate recovery but don’t impact survival

Answer 80

A

therapeutic agents, infection, autoimmune + acute obstructive disorders

Answer 81

A

Due to crystal deposition in tubular cells and interstitium

Sulfadiazine for toxoplasmosis
Indinavir or atazanavir for HIV
IV aciclovir

Findings

‘sheaf of wheat’ sulfonamide crystal
reg-green birefringent needly shaped crystals of aciclovir

Answer 82

A

Recurrent UTIs

with subsequent patchy interstitial scarring and tubular atrophy
loss of functioning nephrons with hypertrophy of the remnant glomeruli
eventual secondary FSGS

U/S

asymmetric, small, irregular kidneys with thin cortices

Surgical reimplantation not of help in adults after damage is already done

Answer 83

A

Slowly progressive kidney disease

Accumulates in the principal cells of DCT by entering through epithelial Na channel
Inhibits glycogen synthase kinase and downregulates vasopressing-regulated aquaporins
Can get chronic tubulointerstitial nephritis after 10-20yrs. More in those with repeated toxicity

Treatment

amiloride inhibits entry into the principal cells
Frequent monitoring. Discontinuing can be difficult.

Answer 84

A

*Multifocal FMD i**s more common
String of beads on angiography
Corresponds to medial fibroplasia
*Focal FMD**
Circumferential or tubular stenosis on angiography
Corresponds to intima fibroplasia

Answer 85

A

Fibromuscular dysplasia

responds well to percutaneous renal artery angioplasty

Atherosclerotic renal artery stenosis

if BP controlled and renal function stable can be medical managed and followed up

Medical

RAASI, cease smoking, statins, aspirin

Revascularisation

Reserved for failing medical therapy or developing complications
Complications: dissection, capsular perforation, haemorrhage, atheroembolic disease
Flow restored in 25%, no change in 50%

Answer 86

A

Cholesterol crystals breaking free from atherosclerotic plaque lodging in downstream microvessels

mostly after angiographic procedures of coronary vessels

Other causes

vascular surgery
anticoagulation with heparin
thrombolysis
trauma

Risk factors

diabetes, HTN, IHD

Clinical

1-14/7 after event, can continue for weeks after
fever, abdo pain, weight loss, cutaneous manifestations (livedo reticularis, localised gangrene)
transient eosinophilia common, increased ESR, decreased complement
biopsy shows microvascular occlusion with cholesterol crystals

Treatment

nothing effective once developed
withdraw anticoagulation
statins might help

Answer 87

A

The name given to those with ESRF without a specific aetiology

afferent arteriolar thickening
homogenous eosinophilic deposition
narrowing of vascular lamina

Clinical

LVH
HTN
retinal hypertensive changes

Management

antihypertensives help CV outcomes but not course of kidney dysfunction

Answer 88

A

Occlusion of the vasa recta in the renal medulla

relative hypoxia predisposes to HbS polymerization and erythrocyte sickling

Sequelae

hyposthenuria (low specific gravity)
haematuria
papillary necrosis

Proteinuria in 20-30%

treat with ACEI

Answer 89

A

Type 1

- Defect in DCT intercalated hydrogen excretion. Antiporter with K explains hypokalaemia.
- Can get very acidotic
- Stones due to multiple mechanisms:
- - Increased bone release of calcium/phosphate to buffer acidosis
- - Direct reduction in tubular reabsorption of calcium/phosphate
- - High urine pH favour calcium phosphate precipitation (but not calcium oxalate)
- - Decreased citrate excretion (usually a potent inhibitor of calcium stone formation)

Causes

- Autoimmune: Sjogren’s, AIH/PBC, SLE, RA
- Drugs: Amphoteracin B, lithium, ibuprofen
- Hypercalciuria
- Other: Wilson’s, obstructive nephropathy, renal allograft rejection

Treatment

- Underlying cause and bicarbonate - alkali therapy
- Reduced hypokalaemia and nephrocalcinosis/stones/OP

Type 2

- Defect in proximal bicarbonate resorption; once serum matches resporptive capacity the urine become bicarb free
- Classic Fanconi: generalised proximal tubular resorptive defect
- Acidosis stabilises due to residual resorptive capacity of tubules
- Hypokalaemia due to mild hypovolaemia resulting in hyperaldosteronaemia
- Treatment can worsen due to increasing sodium and water delivered to distal tubule. Overcome by replacing alkali with potassium citrate

Causes

acetazolomide
monoclonal gammopathies

Treatment

Underlying cause
Much higher bicarb doses - note that hypokalemia WORSENS with therapy
Thiazide (induces mild hypovolaemia -> proximal sodium and thus bicarb resorption)

Type 4

- Hypoaldosteronism or aldosterone resistance -> impaired H and K secretion
- Hyperkalaemia -> intracellular alkalosis due to exchange of K with H -> reduced NH3 secretion in the proximal tubule -> decreased urine buffering and acid excretion
- Low urinary pH due to inadequate NH3 for buffering. Different to type 1 where the H that gets through in the urine can be buffered by NH3 and allows for alkalotic urine

Causes

Reduced aldoserone production
aldosterone resistance

Answer 90

A

Kt/V

Clearance of urea multiplied by duration of dialysis divided by volume of distribution of urea in the body

Issues

- Need to wait for urea to equilibrate due to recirculation
- Urea clearance may not reflect other toxin clearance
- Presumes a single session represents all sessions

Answer 91

A

No.

HEMO showed no difference in haemodialysis, ADEMEX showed no difference in peritoneal dialysis

Answer 92

A

*Yes.** ESRDCPM showed that mortality was increased on the day following the long interval on 3x weekly haemodialysis
22.1 vs 18.0 deaths per 100 person years

Answer 93

A

Sessions >240mins associated with increased survival

Fluid balance

Being >2kg over or >2kg under dry weight consistently is associated with increased mortality compared to hitting dry weight

Dry weight = the minimum sodium and volume that can be tolerated without inducing hypotension

Answer 94

A

Inadequate ultrafiltration associated with increased mortality

Ultrafiltration >12mL/hr/kg associated with increase CV mortality

Answer 95

A

oAV fistula + Hb >=110 + goal albumin level

Answer 96

A

<5%

Risk factors

Prior sensitisation with >50% panel reactivity
Presence of delayed graft function (DGF)
- Requirement for dialysis within the first week after transplantation
Number and severity of rejection episodes
2nd/3rd transplant
Donor <5yrs or >60yrs
Greater degrees of HLA mismatching
Allograft disfunction at discharge (>176mmol/L)

Answer 97

A

Immediate

Pre-renal: hypotensiona and volume depletion
Renal: Post-ischaemic ATN most common. Hyperacute/acute rejection less so (acute = >24hrs post)
Post-renal: Obstruction: ureteral necrosis + leak/haematoma

Early (1-12 weeks)

Pre-renal is same
Renal: Rejection most common, cellular or antibody mediated, 20% get it, usually <6 months and often early. Hypertension common, creatinine rise late.
Calcineurin inhibitor toxicity: acute = arterioles and responds to reduction. chronic = endothelial damage and doesn’t respond
Post-renal: obstruction

Late (>3 months)

Pre-renal: volume and renal artery stenosis
Renal: Rejection, calcineurins, recurrence of primary disease, de-novo disease
Post-renal: Obstruction

Late chronic

Chronic allograft nephropathy, acute rejection is a major predictor
Calcineurins
Hypertensive nephrosclerosis
Viral
Recurrent or de-novo disease