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Renal Flashcards

1
Q

Gitelman, Gordon and Liddle Syndromes

  • Genetic defect
  • Triad of symptoms
A
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2
Q

Tubular sites of action of commonly-used diuretics

A
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3
Q

Viruses related to malignancy post transplant

A
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4
Q

Gene Mutations in atypical HUS

A

Mutations in CFH most common in sporadic and familial forms

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

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5
Q

Most common causes of primary glomerular diseases in nephrotic syndrome

A
  • *Children** - MCD - minimal change glomerulopathy
  • *Adults - Membranous GN**
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6
Q

Minimal Change Disease

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
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7
Q

Focal Segmental Glomerulosclerosis (FSGS)

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%
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8
Q

Membranous GN

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

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9
Q

Classification of Renal Tubular Acidosis

A
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10
Q

Treatment of IgA Nephropathy

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

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11
Q

Prevention of Recurrent Renal Calculi

A

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

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12
Q

Pathogenesis of ADPCKD

A
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13
Q

Management of ADPCKD

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
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14
Q

Types of Cryoglobulins

A
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15
Q

Pathogenesis of Vascular Calcification in ESRD

A
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16
Q

Pathogenesis of Renal Bone Disease

A

Contributing factors:

  • Biochemical Derangement –Ca, PO, PTH
  • Acidosis
  • Bone Turnover/Mineralisation
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17
Q

Causes of EPO resistance

A
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18
Q

Anaemia and CRF

  • Underlying mechanism
  • When to start EPO and target Hb
  • Iron study targets
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
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19
Q

Causes of ESRD
-most common cause

A

IgA GN MOST COMMON cause of ESKD due to GN

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20
Q

Fibromuscular Dysplasia

A
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21
Q

Atherosclerotic vs FMD renal artery stenosis

A
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22
Q

Unilateral vs Bilateral RAS

A

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

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23
Q

Doppler ultrasound in renal artery stenosisd

A

Good screening test!

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24
Q

Management of Renal Artery Stenosis

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
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25
Q

RTA
-focus on management

A
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26
Q

Hypertensive retinopathy

  • Mild changes (4)
  • Moderate changes (4)
  • Severe change (1)
A
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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
A
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28
Q

Anti-THSD7A antibody associated with…

A

Membranous Nephropathy (membranous GN)

  • low sensitivity
  • higher specificity
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29
Q

Most common urinalysis finding of AIN

A

Sterile pyuria

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30
Q

Indications for PD catheter removal post peritonitis (5)

A
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31
Q

PD Peritonitis

  • Most common cause
  • Most commo bug
  • Antibiotic therapy
A
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32
Q

Strongest predictor of mortality on dialysis

A

Hypoalbuminaemia

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33
Q

Most effective method to prevent interdialysis weight gain

A

Salt restriction

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34
Q

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

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

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35
Q

Why do patient’s on ACEI get an eGFR reduction

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

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36
Q

Ultrasound criteria for ADPCKD

A
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37
Q

Most common cause of GN leading to ESRF in Aus

A

IgA nephropathy!!!!!

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38
Q

Leading cause of death following renal transplant?

A

Cardiovascular disease

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39
Q

When should renal transplant be performed?

A
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40
Q

Causes of Renal Allograft Dysfunction <1 week post transplant

A
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41
Q

Causes of renal allograft dysfunction >1 week post transplant

A
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42
Q

Fanconi Syndrome

  • site of dysfunction
  • 4 lab findings
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.

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43
Q

Cause of Death in Renal Transplant Recipients

A
  • Early (1st year)
    • Cardiovascular (36%)
    • Infection (27%)
    • Cancer (3%)
  • Late (beyond 1st year)
    • Cancer (30%)
    • Cardiovascular (23%)
    • Infection (12%)
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44
Q

Top causes of graft loss/death

A

Early (1st year)

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

Late (beyond 1st year)

  • “Chronic allograft nephropathy” (CAN) (72%)
  • GN (7%)
  • Acute rejection (4%) & Non-adherence (4%) –overlap with CAN? (based on reporting)
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45
Q

Side effects of the transplant drugs

A

CNI = calcineurin inhibitor

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46
Q

Buzz word for CNI nephrotoxicity

A

(tacrolimus, cyclosporin)

  • *Isometric vacuolation** of tubular epithelial cells
  • *Striped** interstitial fibroiss
  • *Nodular arteriolar hyalinosis**
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47
Q

Major risk factors for renal calculi

A
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48
Q

Advantages and Disadvantages of Different Dialysis Modalities

A
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49
Q

Eculizumab in atypical HUS

A

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

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50
Q

Calciphylaxis

A
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51
Q

Acute Complications of Dialysis

A
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52
Q

Benefits of Bicarb Supplementation in CKD (3)

A

Slows progression of CKD
Prevention of Bone Buffering
Improved nutritional status

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53
Q

Principle cell of acute renal transplant rejection

A

T cell

54
Q

Absolute contraindications to renal transplantation

A
55
Q

SE of mTOR inhibitors

A

sirolimus and everolimus

56
Q

Buzz word for cellular mediated transplant rejection

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

57
Q

Management of Renal Bone Disease

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)
58
Q

Is there value in strict protein restriction in ESRD?

A

NO!

59
Q

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

A

It’s Galactose-deficient IgA1

60
Q

Definition of Delayed Graft Function post renal transplant

A

Requiring dialysis during the first week after transplantation

61
Q

What is the first change of CKD-MBD?

A

Raised FGF23

62
Q

Relationship between eGFR and urine output in early ESRD

A

i.e before they become oliguric/anuric

63
Q

What is the mechanism of renal failure in Gentamicin toxicity

A

Acute tubular necrosis

ATN, ATN, ATN!

64
Q

Strongest predictor of renal failure in GN

A

Proteinuria!

65
Q

Distinguishing Primary and Secondary FSGS

A
66
Q

Pathogenesis of renal artery stenosis

A
67
Q

In Which Part of the Kidney does Urine Acidification Occur?

A

Collecting Duct

68
Q

Benefits of PD - name at least 10

A
69
Q

Features of Cholesterol Emboli

A
  • urinary eosinophilia
  • livedo reticularis
  • vascular risk factors
  • old males
  • statins
  • “blue toe syndrome”
70
Q

4 Major Histological Changes in Diabetic Nephropathy

A
  1. Mesangial expansion
  2. Glomerular basement membrane thickening
  3. Podocyte injury
  4. Glomerular sclerosis
71
Q

Dialysis

  • Survival impact of BP
  • Survival impact of obesity
A
72
Q

Most common extra-renal manifestation of ADPCKD

A

Liver cysts in >80%

73
Q

Go through AKI by anatomical classification

A
74
Q

What are the commonest causes of ATN?

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
75
Q

Whatis the AKI GN screen? How should urinary sediment/cr:pr be interpreted?

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
76
Q

Is AKI associated with ESRF and mortality? Does its severity predict progression to CKD?

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
77
Q

What’s important about BK virus in renal transplant?

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
78
Q

What malignancies are associated with transplantation?

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

79
Q

What are the risks associated with the calcineurin inhibitors and mycophenolate?

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
80
Q

Describe the dynamics between renal flow and GFR as they relate to the afferent and efferent arteriolar resistance. Why do they not always share the same direction?

A
81
Q

In which circumstances do NSAIDs most affect renal function?

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

82
Q

Why does renal blood flow change after a high protein meal?

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

83
Q

With what degree of renal dysfunction do BUN and creatinine increase above the normal range?

A

~ 60% of kidney function lost

84
Q

What are the aims in the treatment of CKD-MBD? How do the various medications act?

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
85
Q

What is autosomal dominant polycystic kidney disease (ADPKD)? How does it present? What’s the difference between type 1 and 2? How is it diagnosed? What are the extra-renal manifestations?

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
86
Q

What is the classic presentation of nephrotic syndrome?

A

Heavy proteinuria
Minimal haematuria
Hypoalbuminaemia
Hypercholesterolaemia
Oedema
Hypertension

87
Q

Who gets minimal change disease? With what is it associated? What are the pathological findings? How does it present? Treatment?

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
88
Q

What is focal segmental glomerulosclerosis (FSGS)? Is it common? What are the causes? What are the adverse predictors? Treatment?

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
89
Q

What is membranous glomerulonephritis? Epidemiology? Causes? Pathologic findings? Course and prognostic factors? Treatment?

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
90
Q

What is Fabry’s disease? What’s the classic finding? How’s it treated?

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
91
Q

Go through the nephron, where the various substances are excreted/reabsorbed, and where the diuretics/hormones act

A

Distal tubule

  • Principal = Na and H2O. Affected by ADH
  • Intercalated = K and H
92
Q

What is acute interstitial nephritis? Causes? How does it present?

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
93
Q

What is the most common cause of primary glomerulonephritis? Presentation? Diagnostic findings? Prognosis/treatment?

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
94
Q

Is there a difference between calcium based and calcium free phosphate binders?

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
95
Q

What are the two best predictors of mortality in dialysis patients?

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
96
Q

How does angiotensin II act?

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
97
Q

Who’s at risk of contrast nephropathy? How can the risk be decreased?

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
98
Q

Which transplant immunosuppressive agents must be stopped with CMV infection?

A

Have to discontinue antimetabolite

  • - azathioprine or MMF
    • essential for virus eradication

Shouldn’t stop calcineurin inhibitor

99
Q

What is the best test for distinguishing ATN from pre-renal disease?

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
100
Q

What is the triad for rhabdomyolysis?

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
101
Q

Where does gentamicin accumulate in the kidneys?

A

Concentrates in the proximal tubular cells

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

102
Q

Is there a difference in mortality associated with early vs late initiation of dialysis? What are the indications for commencing dialysis?

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
103
Q

What are the iron aims in those on erythropoietin (EPO)? Is there a preferred route for dosage? What are the common side effects?

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
104
Q

What marker can indicate need for therapeutic intervention to lower phosphate (PO4) levels?

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

105
Q

What are the mean rates of renal transplant survival at 1, 5, and 10yrs? Does it differ between deceased and living? What about related vs unrelated?

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
106
Q

What’s the most common cause of secondary hypertension? Others?

A
  • *Renal disease**
  • >80% with CRF/CKD have hypertension
  • more severe in glomerular disease than interstitial
107
Q

What is renovascular hypertension?

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
108
Q

What are the most common causes of acute kidney injury (AKI)?

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
109
Q

What are the top 5 causes of CRF/CKD?

A

Below account for >90%

  • Diabetic nephropathy
  • Glomerulonephritis
  • HTN-associated CKD
  • Autosomal dominant polycystic kidney disease (ADPKD)
  • Other cystic and tubulointerstitial nephropathy
110
Q

What happens to ammonia in acidosis?

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)
111
Q

Go through the algorithm for approach to AKI with features of AIN

A

Glucocorticoids accelerate recovery but don’t impact survival

112
Q

Go through the categories of causes for AIN

A

therapeutic agents, infection, autoimmune + acute obstructive disorders

113
Q

Which medications classically cause obstructive AIN?

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
114
Q

What are the histologic and radiographic findings in chronic vesicoureteric reflux and reflux nephropathy?

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

115
Q

How does chronic lithium toxicity manifest?

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.
116
Q

What are the two radiological appearances of fibromuscular dysplasia? How do they correspond to the pathology?

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
117
Q

How is renal artery stenosis treated?

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%
118
Q

What is atheroembolic renal disease? Who gets it? Clinical presentation? Treatment?

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
119
Q

What is hypertensive nephrosclerosis?

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
120
Q

What is the causative mechanism behind sickle cell nephropathy?

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
121
Q

Go through the physiology, biochemistry, and causes of the types of renal tubular acidosis (RTA)

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
122
Q

What is used to measure efficacy of dialysis? What are its issues?

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
123
Q

Is high dose dialysis better than standard dose?

A

No.

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

124
Q

Does interdialysis interval matter?

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
125
Q

Does session length matter in haemodialysis? What about control of fluid balance?

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

126
Q

Does amount or rate of ultrafiltration affect mortality?

A

Inadequate ultrafiltration associated with increased mortality

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

127
Q

What performance measures could be used in dialysis patients to improve outcomes?

A

oAV fistula + Hb >=110 + goal albumin level

128
Q

What proportion of transplanted kidneys with delayed graft function never function? What are the risk factors for lower deceased donor allograft survival?

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)
129
Q

What are the main causes of immediate, early, and late post renal transplant graft dysfunction?

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
130
Q
A

Renal (3 decks)

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