Nephrology

Question 1

Measuring BP
What is the preferred method (and frequency)?
What are the various BP methods and according cut-offs for what is considered high?

Answer 1

• In office, automated office BP preferred
• Use ABPM for all adults to rule out white coat htn or masked htn
• Diabetic diagnostic threshold different ONLY for in office measurements.
• HBPM: Measure twice in AM and twice in PM for 7 days. Discard day 1 and take average other values
• ABPM: frequency should be at 20-30 minute intervals throughout the day and night
• If there is a >10mmHg difference in
  systolic between arms, use the higher arm

Question 2

AOBP Technique in Office - BONUS
How to do it?

Answer 2

• Use a HTN Canada validated device (same for home monitoring)
• BP taken between arms at least once, if >10mmHg difference, use
  the higher arm thereafter
• Cuff Bladder size: width 40% of arm circ, length 80-100% of arm circumference
  – If large arm circumference exceeds standard upper arm devices, can use validated wrist device w/ arm +
  wrist supported at heart level.
• Pt unattended in quiet room, feet flat on floor, not talking, back
  against chair, arm supported at level of heart
• 3-6 measurements used, at least 1-2 min between measurements

Question 3

HTN Diagnosis:
What is the diagnosis algorithm for HTN, in a patient where elevated BP is suspected?
[Algorithm updated in 2020]

Answer 3

Question 4

Non-Diabetics: Office visit 2 and beyond (same as 2018)
How do you dignose HTN after visit 1, depending on if there are office reading’s or if there aren’t?

Answer 4

Outpatient reading available
– High ABPM (preferred)/HBPM: diagnose HTN
– If NO nocturnal dip (sufficient dip >10% drop) - associated with increased risk of CV events

* Outpatient reading not available
– Visit 2: Dx if mean BP ≥140/90 WITH macrovascular disease, CKD, DM2
– Visit 3: Dx if mean BP (avg of all visits) ≥160/100
– Visit 5: Dx if mean BP (avg of all visits) ≥140/90

Question 5

HTN Work-up
What would you order?

Answer 5

• Routine Labs
  – Lytes (Na, K), Creatinine, Fasting Glucose and/or HbA1C, lipid profile (fasting or nonfasting), urinalysis
  – ACR if diabetic or renal disease
• ECG- 12 Lead
  – Echocardiogram not routinely recommended – perform if suspect LVH, systolic/diastolic dysfunction, CAD
  – HTN + evidence of heart failure – should assess LVEF (echo or nuclear test)
• All patients being treated for HTN should be monitored for new appearance of DM (as per CDA guidelines)
  – Also monitor lytes, creatinine and lipids – frequency determined by clinical picture

*Pregnancy
- Consider potential for pregnancy in women with HTN
- New in 2020 - consider pregnancy test if patient unsure of pregnancy status

• Assess global cardiac risk - often with a risk calculator
• To more accurately predict patient’s global cardiovascular risk
• To help engage individuals in conversations about health behaviour change to lower BP
• To use antihypertensive therapy more effectively
• Ex. Framingham risk score, myhealthcheckup.com supported in CHEP and by CMA

Question 6

HTN Follow-up
How do you follow-up if:
a) No HTN diagnosed
b) HTN Dx and using lifestyle changes
c) HTN Dx and treating with medical therapy

Answer 6

• If no HTN, no evidence of target organ damage – f/u yearly
• If HTN and using lifestyle and exercise to manage, follow up at 3-6 month intervals (1-2 month if higher BP)
• If treating HTN with medical therapy F/U every 1-2 months until 2 consecutive readings with BP < target, then F/U every 3-6 months

Question 7

Additional Recommendations - HTN
a) Pregnancy
b) Global Cardiac risk
c) ASA
d) Statin

Answer 7

a) Consider potential for pregnancy in women of child bearing age with HTN (*avoid RASi)

b) Assess global cardiac risk – a risk calculator
– Estimate CV risk to determine if patient is low, medium or high risk (will impact blood pressure targets)

c) Low dose ASA no longer recommended for primary prevention of cardiovascular disease

d) In Htn: Statin therapy is recommended with ≥3 risk factors of CVD or with established atherosclerotic disease, regardless of age 12

Question 8

Secondary HTN
In select patients, what secondary HTN disorders should be considered?

Answer 8

In select patients, consider
- Renovascular Hypertension (also CKD in general → HTN)
- Endocrine causes (Pheochromocytoma, thyroid disease)
- Primary hyperaldosteronism
- Obstructive Sleep Apnea
- Cushings
- Coarctation of Aorta

Diagnostic criteria in guidelines and BONUS AT END OF SLIDE DECK!

Question 9

Hyperaldosteronism
In patients with hyperaldosteronism, what must be performed before surgery?

Answer 9

• In patients with hyperaldosteronism, definite adrenal mass, and eligible for surgery, must first perform adrenal vein sampling to assess lateralization of aldosterone hypersecretion prior to
  ordering adrenalectomy
• For patients with established primary aldosteronism and in whom surgery is an option: selective adrenal venous sampling to differentiate unilateral from bilateral overproduction of aldosterone

Question 10

HTN 2020 - Renovascular HTN
Who to screen?
How to screen?

Answer 10

* Who to screen
– Patients presenting with 2 or more of the following (GRADE D)
* Sudden onset or worsening HTN age >55 or <30
* Abdominal bruit
* HTN resistant to ≥ 3 drugs
* Increase in Cr ≥ 30% with ACEi or ARB
* Other atherosclerotic vascular disease, particularly in smokers or dyslipidemia
* Recurrent pulm edema associated w/ Hypertension surges

* How to Screen
– Any of: Doppler US, captopril renogram, MRA, CTA
* Avoid captopril and CTA if renal GFR <60 ml/min/1.73m2

Question 11

FMD (fibromuscular dysplasia) related renal artery stnosis
When do you work-up for FMD?
What is the work-up?
Once FMD is confirmed, what do you order?

Answer 11

• Work up for FMD if HTN and one or more: (CHEP 2020)
  – Kidneys asymmetrical (>1.5cm difference)
  – Abdominal bruit but no atherosclerosis risk factors
  – Confirmed FMD in another vascular bed
  – Family hx of FMD
• How to workup for FMD:
  – **CTA or MRA **(similar specificity and sensitivity, GRADE D)
• Once FMD is confirmed:
  – Screen vasculature from head to pelvis with either CTA or MRA (cervicocephalic lesions, intracranial aneurysms, lesions in other vascular beds)

Question 12

Hypertension Goals:
When do you start pharmacologic therapy and what is the BP target for…
a) Diabetic
b) High risk patient
c) Moderate-high risk
d) Low risk

Answer 12

Question 13

Hypertension Goals: For…
a) Acute post ischemic stroke with thrombolysis
b) Acute post ischemic stroke without thrombolysis
c) Ischemic stroke - chronic management
d) Hemorrhagic stroke - acute management
e) Hemorrhagic stroke - chronic management
f) CKD
g) PKD
h) Post renal transplant
i) Pregnancy (see OB Med Lecture

Answer 13

Question 14

High risk patient (“Sprint” trial candidates)
a) Who is considered a Hypertension Canada High-risk patient?
b) What should be their BP target?
c) Who is excluded?

Answer 14

• Hypertension Canada High-risk patient
  – >50 age AND SBP 130-180 AND one or more of the following:
• Clinical or subclinical cardiovascular disease
• CKD (non diabetic, proteinuria < 1g/day, gfr 20-60 ml/min)
• Estimated 10 year global cardiovascular risk ≥15%
• Age ≥ 75
• Should be considered for intensive bp management with target SBP
  < 120 mmhg
• Excluded
  – Diabetes, history of stroke, gfr < 20, proteinuria > 1g/day, GN, PKD
  – Contraindications: non-adherent, secondary htn, life limiting disease, standing
  SBP < 110

Question 15

BP Targets - CKD
Hypertension Canada 2020 & KDIGO CKD+HTN Guideline 2021
a) What is the CKD BP target based on HTN Canada 2020 and C-CHANGE 2022?
b) And what about the KDIGO CKD and HTN guideline recommendations?

Answer 15

CKD Target: Hypertension Canada 2020, C-CHANGE 2022
“Individualize BP targets in patients with CKD.”
* CKD patients who meet high risk (SPRINT) criteria, target SBP< 120, in Diabetics: <130/80
* In Polycystic Kidney Disease target SBP <110 if meets certain criteria – more in bonus slides

KDIGO 2021 CKD and HTN guideline:
– Target SBP <120, up titrate ACE/ARB as high as tolerated [Gr2B]
* In all CKD = Diabetic and non-Diabetic (*not dialysis/post transplant)
– SBP <120 is recommended with greater certainty among patients at higher risk for CV disease (AKA SPRINT CANDIDATES)
– With less certainty among patients with diabetes, stage 4 or 5 CKD, severe albuminuria (ACR
>300 mg/g), prior stroke, very low diastolic BP, and severe hypertension
» BASICALLY THE PTS EXCLUDED FROM SPRINT
– Post transplant: long term <130/80, use DHP-CCB or ARB first line

Which guideline to follow on exam?
“Individualize BP Target” based upon the patient’s hx, but be aware that <120 if safe is a reasonable goal for all pts with CKD, especially if meeting HIGH RISK/ SPRINT criteria.

Question 16

HTN Treatment: Lifestyle
What are the recommendations?

Answer 16

* Exercise: 30-60 minutes, moderate intensity, “dynamic” (walk/jog/cycle/swim), 4-7 days/week
* Weight: BMI 18.5-24.9; waist circumference <102 cm(M), <88(F) to PREVENT HTN
* Alcohol: abstaining from alcohol or to prevent HTN (no safe limit); [updated in 2020]
* In adults with HTN who drink 6+ drinks per day, reduction to <2 can reduce
* BP Diet: DASH diet
– Consider increasing potassium intake if not at risk of hyperK (no specific dose)
* Risk factors: ACEi/ARB/MRA therapy, other Rx that predispose to hyperK (septra, amiloride, triamterene), eGFR <60, baseline K > 4.5
* Salt: ≤5g/day (≤2g sodium, i.e. <87mmol Na)
* Stress reduction: including cognitive-behavioural interventions and relaxation techniques
* Smoking Cessation – offer advice in combination with pharmacotherapy
* No need to supplement with calcium or magnesium to prevent or treat HTN

Question 17

HTN - First-Line Therapy
What is it?

Answer 17

In the general population: monotherapy or single pill combo (SPC)

• Long-acting thiazide (chlorthalidone) /thiazide-like diuretics preferred >over hydrochlorothiazide HCTZ
  – Avoid hypoK if using thiazide monotherapy
• ACEi monotherapy
  – Do not use in Black patients without other indications
  - Not first line in isolated systolic HTN
• ARB
• Long-acting CCB
• β-blockers can be considered first line only if <60 years old
• Do not use α-blockers as first-line

Question 18

HTN - Second-line Therapy
What is it?

Answer 18

• In general population, add on drugs from 1st line choices:
  – Thiazide + DHP-CCB
  – ACEi + DHP-CCB

🛎Use Single Pill Combos where available (Gr B)
(eg) ACE or ARB + DHP – CCB
(eg) ACE or ARB + TZD

AVOID
– ACE + ARB
– Non-DHP CCB + beta-blocker (risk of bradycardia)

• R/A patients with uncontrolled BP at least every 1-2 months

Q: Should I maximize the first drug or add a second agent if pt is uncontrolled?
A: Depends on the clinical scenario!

Question 19

Diabetes and HTN
a) BP target?
b) 1st line therapy?
c) If needed, recommended combination therapy?

Answer 19

• BP target <130/80
• ACEi or ARB 1st line for CV disease or risk factors, CKD/ microalbuminuria
• Otherwise ACEi/ARBs, DHP CCB, thiazide all 1st line

* If combination therapy with ACEi is needed, DHP CCB preferred over thiazide
– Not in guideline but if hyperK, long-acting thiazide-like diuretic would be more appropriate

• SGLT-2 inhibitors can also reduce BP in hypertensive patients (more later!), but not yet on guidelines for this indication of lowering BP

Question 20

HTN - Post-Stoke Management
a) Ischemic stoke - thrombolysis and no thrombolysis
- acutely, subacutely and chronically
b) Hemorrhagic Stoke - acutely and long-term

Answer 20

• Within 72 hours of ischemic stroke
  – Thrombolysis: treat if >185/110*
  
  • <185/110 prior to giving tPA and keep below 180/105 for next 24hr
    – No thrombolysis: treat if >220/120, aim for 15-25% reduction gradually over 24 hours
• Ischemic Stroke: If neurologically stable, can start lowering after 24-48 hours
  – Target <140/90 within a few days to 1 week
  – Combination ACEi and thiazide preferred 1st line (Grade B)

* Hemorrhagic Stroke - NEW TARGETS –strokebestpractices.ca Nov. 2020
* Acute Stroke Management: A SBP threshold at an individual target of <140-160mmHg for
first 24-48h may be reasonable.
– Use IV agents to reduce BP acutely, check BP q 15min until you achieve target and monitor closely first 24-48h
* Long term target for patients with history of spontaneous ICH : <130/80

Question 21

Renovascular HTN
a) Pharmacotherapy to use
b) When angioplasty and stenting is indicated

Answer 21

• ACEi or ARB not contraindicated with bilateral renal artery stenosis
  – But caution in initiating, close K, Cr follow up
• Atherosclerotic RAS is managed medically
  – no benefit to stenting over medical therapy in most
• Angioplasty and stenting could be considered if any of the following present: (REVISED in 2020 guidelines)
  1. uncontrolled HTN resistant to maximally tolerated pharmacotherapy
  2. progressive renal function decline
  3. Acute pulmonary edema
• Refer to HTN specialist
• OF NOTE– angioplasty **without **stenting is often done in Fibromuscular Dysplasia cases (risk of periprocedural dissection)

Question 22

HTN Management - in other Special Populations (1)
a) Isolated systolic HTN
b) Diastolic HTN (+/- systolic HTN)
c) LVH
d) Non-diabetic CKD with proteinuria

Answer 22

Long acting DHP CCB include amlodipine, felodipine

Question 23

HTN Management - Other Special Populations (2)
a) CAD (in general)
b) Stbale angina
c) Recent MI

Answer 23

Question 24

HTN Management - Other Special Populations (3)
a) LV systolic dysfunction (EF <40%)

Answer 24

LV systolic dysfunction (EF <40%):
* 1st line: Both β-blocker AND ACEi (ARB if ACEi intolerant)
* MRA can be added if recent CHF exacerbation/MI, ↑BNP, NYHA II-IV
– Watch out for hyperkalemia!
* Hydralazine + ISDN, if can’t use ACEi/ARBs
* Other agents: DHP-CCB, thiazides

• Angiotensin Receptor-Neprilysin Inhibitor combination in place of ACEi/ARB in patients with HFrEF (EF <40%) – can be used first line even - More in cardio lecture!
• SGLT2i also indicated for all patients with HFreF but not specifically to reduce BP (reduces symptoms, risk of hospitalization, CV death)

Question 25

Response to Therapy:
If response to therapy is not as good as expected, what should you rule out?

Answer 25

• If response to therapy is not as good as expected, rule out:
  – Non-adherence
  
  • Action: simplify to daily dosing; use SPC if possible; multidisciplinary team approach
    – White coat HTN: use ABPM or HBPM
    – Inaccurate measurements
    – Interfering drugs or substances, e.g. NSAIDs, corticosteroids, cocaine
    – Secondary HTN
    – Encourage more patient responsibility/autonomy
  • Monitor BP, adjust dose, educate!!

Question 26

Interpreting urine microscopy
Based on ATN, AIN or pyelonephritis, and glomerular disease

Answer 26

Question 27

Glomerulonephritis - Nephritis Syndrome / Proliferative
What are the 3 main categories and diseases within each category?

Answer 27

Question 28

Anti-GBM Disease
What does it effect and how do you treat?

Answer 28

• Fulminant disease, limited to lung and kidney
  – Called Goodpasture’s if RPGN is accompanied by pulmonary hemorrhage
• Treatment:
  – Pulse corticosteroids
  – Cyclophosphamide
  – Plasma exchange (ustil titers are no longer detectable)
  EXCEPTIONS: consider conservative treatment if 85-100% crescents, no pulm hemorrhage, treated w/dialysis at presentation [where risk of immunosuppression potentially outweigh benefits as pt has
  ESRD already]
• Steroids usually at least 4-6 months/ Cyclophosphamide 2-3 months
• No maintenance therapy!

Question 29

Pauci-immune / ANCA Vasculitis
a) What are the 3 types and how do you differentiate between p-ANCA/anti-MPO and c-ANCA/anti-PR3?
b) Clinical features
c) Diagnosis and Treatment Pathway

Answer 29

Clinical features:
– Constitutional symptoms
– Arthralgias, rash
– Sinusitis, asthma, pulm hemorrhage
– Nephritis
– Mononeuritis multiplex

Question 30

Pauci-immune / ANCA Vasculitis
a) Induction Treatment
b) When to consider Ritux over Cyclophosphamide?
c) Maintenance Therapy
d) When to use plasma exchange (PLEX)?

Answer 30

INDUCTION: Methylprednisolone up to 1g x 3 days + Cyclophosphamide or Rituximab
RPGN, Creat > 354 → Cyclophosphamide preferred (KDIGO 2021 – less data for Ritux)
*When to consider Ritux over Cyclophosphamide:
– Pre-menopausal women, men interested in preserving fertility
– Frail older adults
– Relapsed disease
– ACR (Rheum) 2021 guidelines: Rituximab preferred (if no evidence of RPGN)

Maintenance therapy
- Azathioprine OR continue Rituximab if used as induction agent
- Taper glucocorticoids (usually 1mg/kg/d first week then taper)
No maintenance therapy in dialysis dependent pts x 3 months with no extra-renal manifestations

When to use plasma exchange (PLEX): Anti-GBM+ (“double positive”/overlap)
KDIGO: Consider if vital organ / life threatening, Creat > 500
ACR: No PLEX with active GN but can be considered for patients at ↑ risk of progression to ESRD who accept a potential increased risk of infection.

Question 31

Immune complex: Low C3
a) What disease is this?
b) Presentation
c) Diagnosis
d) Management

Answer 31

*** Low C3: **Post-streptococcal/infectious GN
– 2–3 weeks post-infection (strep throat/strep cellulitis, chronic abscess, endocarditis, etc)
Presentation varies from
* Microscopic hematuria to
* Proliferative GN: red/ brown urine, proteinuria, edema, Htn, AKI

– Diagnosis: low C3, normal C4, +ASOT (70%), +anti-DNase B (90%)

– Management: supportive care (this can include diuresis if edema); treat infection if still active (e.g., cultured from any site)
– Resolves in 3 – 4 weeks
– Biopsy only undertaken if considering other glomerular disorders, or course varies from typical trajectory i.e. severe AKI requiring dialysis: this
is uncommon with PSGN

Question 32

Immune comples: Low C4
a) Etiologies
b) Diagnosis
c) Management

Answer 32

* Low C4: MPGN (new pathologic classification based upon immunofluorescence, beyond scope of GIM)
Multiple etiologies:
– Associated with **HCV **(>HBV), HIV, cryos, other infection (endocarditis, Syphilis, endemic parasites – malaria, schistosoma), complement dysregulation (there is genetic testing for this, beyond scope of GIM), monoclonal gammopathies,
autoimmune disorders, TMA/ HUS, APLAS, Sickle Cell anemia, Polycythemia
– Nephritic syndrome with low C4, normal C3 (*but can be low too)

– Dx on biopsy

– Management: treat the underlying cause
– – see next slide for new HCV GN guidelines (KDIGO Nov 2022)

Question 33

Hepatitis C and CKD
- new KDIGO guideline (2022)
a) what CKD patients should be screened for Hep C
b) which CKD patient’s should be referred for Hep C therapy
c) What is the pathway from presentation, to diagnosis

Answer 33

• All patients with CKD should be screened for Hep C at diagnosis of CKD, and at time of initiation of renal replacement therapy
• All patients should be evaluated for HCV Therapy (if transplant candidate, coordinate timing w transplant centre)
  – Both pangenotypic regimens in your GI lecture can be even in CKD 5
• HCV + GN workup →
  – Note management nuances outside of scope of GIM… but FYI if RPGN or cryoglobulinemic flare
  KDIGO suggests Antiviral AND immunosuppression (Ritux) +/- PLEX
  
  • Or if patient has progressive GN or cryoglobulinemic kidney disease not responding to antivirals
    “I would consult my colleagues in nephrology / hepatology
    / infectious diseases / heme…”

Question 34

Immune complex: Low C3/C4
a) What disease is most common?
b) How to diagnose?
c) Treatment principles

Answer 34

* Low C3 and low C4: SLE most common (more in Rheum lecture)
– Presents as nephritic and/or nephrotic. Elevated dsDNA. Dx. requires biopsy

Treatment Principles: Hydroxychloroquine for all
Often young women – remember pregnancy test and counseling before starting immunosuppression (particularly MMF/cyclophosphamide!)

Class III/IV: induction with steroids and 1 of cyclophosphamide (CYC) or Mycophenolate (MMF),
Prefer MMF if at risk of infertility, or of Asian/African/Hispanic ancestry
[can consider adding if refractory a Calcineurin inhibitor (CnI ex tacrolimus), B-lymphocyte target biologic (ex ritux, belimumab)]

Class V: ACEi/ARB for proteinuria and good BP control, statin
– If nephrotic range proteinuria – add Glucocorticoid + 1 of MMF, AZA, CYC, CnI, Ritux, AZA.
– If progressive renal dysfunction (i) Renal US to R/O renal vein thrombus (ii) Consider repeating renal biopsy (possible concurrent class III/IV) (iii) May need additional immunosuppression

Question 35

Immune Complex: Normal C3/C4
a) What is the disease, how does it present and what conditions is it associated with?
b) Diagnosis
c) Prognosis

Answer 35

IgA Nephropathy (great oral scenario question)
– Most common cause of GN worldwide (esp Asians > Caucasians, rare if African descent)
– Associated with celiac disease, autoimmune disease, hepatitis, HIV, cirrhosis (and others)
– Various presentations: microscopic hematuria, gross hematuria, proteinuria, RPGN or
nephrotic syndrome
– can mimic nephrolithiasis presentation
– Flares with ANY infection (“syn-pharyngitic”)
– HSP: **systemic ** IgA vasculitis with arthritis, purpura, GI symptoms

• Diagnosis: clinical (rarely need kidney biopsy – unless to confirm clinical diagnosis), + look for 2o causes above!)
• Prognosis dependent on degree of proteinuria and HTN control
  – <0.5g/ day: low risk of progression
  – Overt proteinuria and/or high Cr: Progression to ESRD = 15-25% at 10 years

Question 36

IgA Nephropathy: Treatment

Answer 36

* Treatment:
– ACEi or ARB if proteinuria >0.5g/day; titrate to proteinuria <500 mg-1g/day
– Adequate BP control (SBP<120)
– Fish oil not clearly established, not recommended in guidelines
– KDIGO Glomerulonephritis Guideline 2021
– Consider steroids x 6 months if high risk of progressive CKD
– High risk of progression= refractory proteinuria >0.75-1g despite optimal medical therapy with RAAS blockade x 90d
– Counsel about risks of treatment toxicity (infections etc)
– These patients should be under nephrologist care – not for GIM to manage primarily!

Question 37

Nephrotic Syndrome
a) 4 overarching symptoms/signs
b) 4 main categories of nephroptic syndrome and diseases within each

Answer 37

acronym (PALE)

Question 38

Management of Nephrotic Syndrome
a) Diagnosis
b) General Care
c) Definitive management

Answer 38

Diagnosis → usually requires biopsy
*unless PLA2R antibody + normal renal function– can forego biopsy, but still do screening for 2o causes

General Care
– Edema: Na restriction + loop diuretics (1st line, can add other diuretics as needed)
– Hypercholesterolemia: Statins, heart healthy diet
– Proteinuria: ACEi, BP control
– Thrombosis: CONSIDER “Prophylactic” full-dose anticoagulation with warfarin if – albumin <20-25 AND any of: BMI>35 | Inherited thrombophilia (ex FVL) | NYHA 3-4 | Prolonged immobilization | Proteinuria >10g/day | Recent
orthopedic or abdominal surgery
– If high bleeding risk, KDIGO suggests ASA 81mg daily instead
– DOACs = not studied in NS, highly –protein bound in blood so not ideal in this situation w hypoalbuminemia!

Definitive management
– Immunosuppression in most 1o Cases
– Minimal Change, FSGS : Steroids
– Membranous: Risk evaluation for progression to renal failure – low risk (wait and see) → Higher risk - immunosuppressants
– Treat underlying cause if 2o Cause

Question 39

GIM PEARLS from KDIGO 2021 for Nephritic/Nephrotic Disorders:
What are they?

Answer 39

1. SMOKING CESSATION FOR ALL
2. DIET: NA <2g, heart healthy, adequate protein if Nephrotic range proteinuria (0.8-1g/kg/d)
3. HTN: Target <120 if possible / safe
   (e.g no orthostasis, not frail… they comment “In practicality 120-130 in most pts w GN disease”)
4. VACCINATE: pneumococcal, influenza, SHINGRIX, COVID-19 mRNA vaccines, Hep B if not immune
5. PRE-IMMUNOSUPPRESSION: TBST, Hep serologies, HIV, Strongyloides if endemic risk.
6. ON TREATMENT:
   Contraception, Gonadal protection
   Bone health [see endo lecture]
   TMP-SMX on high dose steroids, Ritux or Cyclophos

Question 40

Proteinuria:
What are the Proteinuria Categories (6), level of proteinuria associated, and examples of each category?

Answer 40

Question 41

Common causes of AKI
What are they?

Answer 41

* Pre-renal
– Hypovolemia (dehydration, hemorhhage, vomiting, rhabdomyolysis, tumor lysis syndrome) – Cardiorenal/heart failure
– Sepsis, anaphylaxis
– NSAIDS, contrast, ACEi

* Intra renal
– AIN
– Nephrotoxic drugs
– GN, autoimmune disease, vasculitis
– Thrombosis
– Sickle cell
– Abdominal compartment syndrome
– Rhabdomyolysis (pigment nephropathy)

* Post renal
– Obstructive uropathy

Question 42

Acute intersitial nephritis (AIN)
a) Causes
b) Presentation
c) Culprit drugs
d) Treatment
(great oral scenario)

Answer 42

• Causes
  – Drugs (#1 cause)
  – Infections
  – Systemic illnesses: “The S’s”: SLE, sarcoid, Sjogren’s, IgG4 disease
• Presentation
  – Timing: 1 week to weeks/ months following. If previous exposure to drug, can occur sooner
  – Acute renal failure, sometimes with fever and/or rash
  – Hematuria, non-nephrotic range proteinuria
  – Pyuria (WBC in urine) and WBC casts (not always)
  – Eosinophils may be increased in blood and/or present in urine (not always)
• Common drugs (not a dose-dependent effect):
  – Anti-inflammatory: NSAIDs, COX-2 inhibitors
  – Anti-biotics: penicillins, cephalosporins, sulphonamides, rifampin, cipro, septra
  – Anti-gout: allopurinol
  – Anti-acid: PPI’s
  – Anti-edema: loop diuretics, thiazides
• Treatment
  – Remove offending agent.
  – If severe renal failure, often biopsy – especially if requiring dialysis!
  – In select cases, glucocorticoids – empiric if severe renal failure unless contraindicated

Question 43

Contrast Induced Nephropathy and Cholesterol emboli syndrome / atheroembolic disease
(great oral scenario)

Answer 43

Contrast-induced nephropathy (CiN)
– PREVENTION: None
* Hold metformin, RAS , diuretics, SGLT 2, avoid NSAIDS prior to the study
* Ensure euvolemia (3 ml/hg/hr 1 hour before procedure, 1ml/kg/hr 6 hours after procedure for CKD)
– TIMING: 1 – 3 days post contrast load
– COURSE: nonoliguric, most self resolve in 1 – 2 weeks
– Treatment: supportive

Cholesterol emboli syndrome/ atheroembolic disease
– PREVENTION: none
– TIMING: subacute, step-wise decline – takes weeks
– COURSE: early on: urine eosinophils, elevated ESR, peripheral eosinophilia, decreased C3/C4
* Urine R+M otherwise unremarkable
* Cutaneous manifestations: livedo reticularis, blue toes

Question 44

Rhabdomyolysis
a) symptoms
b) signs on exam
c) lab findings
d) and treatment

Answer 44

* Symptoms: Muscle pain, weakness, cola coloured urine
– Malaise, fever, tachycardia, nausea, vomiting in some

* Physical exam: muscle tenderness and swelling

* Lab findings: high CK, + RBC on dipstick, - blood on microscopy
– AKI from hypovolemia and third spacing
– Hyperkalemia and hyperphosphatemia from damaged muscle cell rupture
– Hypocalcemia from deposition of calcium salts in damaged muscle
– Uricemia from rupture of damaged muscle cells
– Metabolic acidosis

* Treatment:
– IV fluids
– Management of electrolytes
– Do not treat hypocalcemia

Question 45

Cardiorenal syndrome:
How do you manage?

Answer 45

• Management
  – Improve cardiac function (LVAD and cardiac resynchronization therapy)
  **– Volume control **(aggressive fluid removal - diuresis with furosemide)
  **– RAS blockade **(*not associated with improvement of gfr)
  – SGLT 2 inhibitors
  **– Ultrafiltration **(removal of isotonic fluid from venous compartment via
  semipermeable membrane)

Question 46

Heptorenal syndrome
a) clinical presentation
b) Type 1 HRS
c) Type 2 HRS
d) Diagnosis
e) Treatment

Answer 46

* Clinical presentation:
– Rise in serum creatinine with normal urine sediment – Tubular function is preserved (no/minimal hematuria or proteinuria!)
– Urine sodium < 10

* Type 1 HRS:
– Two fold increase in serum creatinine to a level greater than 221 umol/L over less than 2 weeks

* Type 2 HRS:
– Gradual kidney decline with ascites refractory to diuretics

* Diagnosis: discontinue diuretics + antihypertensives, give IV albumin 1g/kg and you will not see
an improvement

* Treatment: stop diuretics, restrict sodium and water
– Treatment with albumin + vasoconstrictor (terlipressin is not available here, thus we give midodrine + octreotide)
– Liver transplant or TIPS

Question 47

Causes of AKI in transplant
What are they?

Answer 47

• ACUTE REJECTION! (always suspect this)
  – Often varying degree of proteinuria, hematuria
  – Requires biopsy to diagnose
• Medication (Cyclosporine, Tacrolimus)
  – Reversible, bland sediment, no blood or protein
• Infection (bacterial - anytime, BK virus – later complication)
  – WBC in urine, mild proteinuria/hematuria, tenderness over graft if pyelo
• Renal artery/vein thrombosis,
• Usually early post-operatively. Requires urgent ultrasound
• Hydronephrosis
• Recurrence of primary disease
• PTLD (post-transplant lymphoproliferative disorder - later complication)
• (Causes of AKI in native kidneys)

Question 48

Classification of CKD - KDIGO 2012
a) KDIGO CKD Definition
b) Grades dependent on eGFR and ACR

Answer 48

KDIGO CKD Definition: abnormalities in either kidney structure or function for >3 months:
-Albuminuria ACR >3 mg/mmol]
-Urine sediment abnormalities
-Electrolyte abnormalities due to tubular disorders
-Structural abnormalities detected by imaging
-Kidney Transplant hx.
-eGFR< 60mL/min/1.73m2

Question 49

Prevent progression: CKD Targets
What are the 6 areas you should think about and targets for each?

Answer 49

New: SGLT2i for all CKD (+/- diabetes, eGFR ≧ 20*, ACR > 20 mg/mmol)
→ prevent **composite **of decline in eGFR, progression to ESRD, kidney death, all cause mortality, nonfatal MI, hosp for HF (CCS 2022)
→ continue until dialysis or transplant (KDIGO 2022)

Blood Pressure: recall changes from Hypertension 2020 guidelines:
– ACEi or ARB first line
– Diuretics if evidence of increased salt/water retention

Dyslipidemia:
* CCS → Age ≥ 50 years and non dialysis eGFR <60 or ACR >3 mg/mmol → STATIN, add ezetimibe 2nd line, bile acid sequestrant as 3rd /alternate
* KDIGO → In adults aged ≥ 50 years with GFR categories G3a-G5 but not treated with chronic dialysis: statin or statin/ezetimibe
→ In adults aged ≥50 years with CKD and GFR categories G1-G2: statin or statin/ezetimibe

Glycemic control optimization if diabetic (SGLT2i, GLP1RA)

Smoking Cessation

Proteinuria: <500 mg – 1 g/d (ACEi/ARB). DM2: proteinuria as low as possible

Question 50

Statins in ESRD:
What are the recommendations?

Answer 50

• Evidence differs for dialysis pts and non-dialysis CKD
• SHARP trial demonstrated benefit on CV outcomes in non-dialysis CKD
  – 2021 CCS lipid guidelines
  
  • statin therapy for primary CV risk reduction in pts age 50+, eGFR ≤ 60 ml/min or ACR ≥3mg/mmol, except for pts on dialysis
  • target treatment to LDL-C < 2 mmol/L or apoB <0.8 g/L or non HDL-C <2.6 mmol/L
• In dialysis pts, benefits (in both 1° and 2° prevention) are uncertain:
  – 2016 CCS lipid guidelines (same in 2021 guideline), KDIGO:
  
  • don’t initiate statin/ezetimibe in patients on dialysis
  • may continue statins/ezetimibe if already taken prior to dialysis

Question 51

CKD - Sick Day Management
What medications should be held?

Answer 51

• Medications that may result in a decline in renal function when patient has a threat to their volume status OR may have decreased clearance
  – Instruct patients to hold these medications on days when they are feeling unwell, and re-initiate when they are feeling better/ volume status restored
• SADMANS medications
  – S-Sulfonylurea
  – A-ACEi
  – D-Diuretics
  – M-Metformin
  – A-ARBs
  – N-NSAIDS
  – S-SGLT2i

Question 52

Management of Complications:
List the targets in CKD

Answer 52

• Summary of targets in CKD :
  – K <5
  – HCO3 > 22
  – PO4 and Ca toward normal range
  – PTH target unknown for pre-dialysis CKD
  – PTH target for dialysis patients is 2-9x ULN
  – Hb 95-115, Tsat >30%, ferritin >500
  – Other:
• BP targets (see earlier HTN slides)
• SGLT2
• Fracture Risk
• Euvolemia (salt, fluid restrict)
• Optimize CV risk (Smoking, DM2, lipids)

Question 53

Management of Complications: Anemia
If HGB <100, what is the 1st and 2nd step?

Answer 53

• Anemia: Rule out other causes of anemia, e.g. blood loss

If Hgb < 100:
**– 1st step: **Iron studies
* Ferritin ≤ 500, Tsat ≤30%: Oral or IV iron (prefer IV if feasible & no Contraindications)
* Monoferric (ferric derisomaltose) or Venofer (iron sucrose)

– 2nd step: Hb <100 and iron replete or after trial
– Erythropoietin-stimulating agent (ESA)*: Eprex or Aranesp

– Target Hb while on ESA: no higher than 115
* Hb >115 with ESA associated with stroke, CAD, HTN

*Caution in pts with: active cancer, previous stroke, uncontrolled BP

Question 54

Management of Complications:
What is CKD-MBD? And why does it matter?

Answer 54

• What is CKD-MBD?
  – Disorder of mineral metabolism manifested by:
• Hyperphosphatemia
• Hypocalcemia
• Low vitamin D
• HyperPTH

– Why does it matter?
* Vascular calcification
* Excess fracture risk
* Excess risk of CV death
* Excess risk of all-cause mortality

Question 55

Management of Complications: What are the targets and management of each?
a) Hyperkalemia
b) Metabolic acidosis
c) Hypocalcemia

Answer 55

* Hyperkalemia: target K <5
– Potassium-restricted diet
– Diuretics may help
– K binders
– Avoid NSAIDs, look at other medications
→ High K foods to watch out for:
-Fruits- ORANGES, tropical fruit (mango, papaya, pomegranate, kiwi, melons)
-Veg- Avocado, tomatoes, potatoes,
beans, green leafy vegetables
-Other-Nuts/seeds, milk

* Metabolic acidosis: target normal HCO3
– Sodium bicarb tabs to keep HCO3 >22
– RCT evidence to slow decline in GFR!

* Hypocalcemia: target normal Ca
–Decreased 1-α-hydroxylase activity
–Rx: calcium carbonate and calcitriol
** (1,25 Vit. D)
**Can’t use if hyperphosphatemic

Question 56

Management of Complications:
How to we manage? What are the KDIGO recommendations?

Answer 56

* Hyperphosphatemia: target normal PO4
– Decreased renal PO4 excretion due to low GFR
– Low PO4 diet
– Oral phosphate binders with meals
* calcium-containing: e.g. calcium carb (TUMS) – TYPICALLY FIRST LINE sec to cost
– But avoid if hypercalcemia, adynamic bone disease, vascular calcification
* Non-calcium containing: e.g. sevelamer or lanthanum
– look into non calcium containing binders

– 2017 KDIGO MBD:
* “Restrict dose of calcium-based phosphate binders”
* HOWEVER in real life, still use TUMS first as cannot easily access non-calcium binders ($$$)

High PO4 foods to watch out for:
-Dairy- CHEESE, milk
Protein- shellfish, liver, deli meats

Question 57

Management of Complications: 2017 CKD-MBD Guidelines
a) What are the targets for phosphate, calcium and PTH?
b) What to do if PTH is above target?

Answer 57

2017 CKD-MBD Guidelines
* Managing biochemical CKD-MBD
– Bring phosphate toward normal range
– Bring calcium toward normal range
– Target PTH 2-9x ULN in dialysis patients

• What if PTH is >9x ULN?
  – Calcitriol (1,25 Vit. D) but only if PO4 and Ca are not high
  – Cinecalcet (a calcimimetic): activates Ca-sensing receptor to shut off PTH
  secretion
  – Surgical parathyroidectomy in selected patients

Question 58

Management of Complications: CKD-MBD
What are the recommendations for osteoporosis / fracture risk?

Answer 58

2017 CKD-MBD Guidelines
* CKD 1-2: with osteoporosis and/or high risk of fracture, manage as per
general population
* CKD 3 +: PTH in the normal range and OP / high risk of fracture, manage as per general population (2B)

• CKD 3+: with biochemical abnormalities of CKD-MBD and OP or fragility fractures: “tx takes into account the magnitude and reversibility of the biochemical abnormalities and the progression of CKD, with consideration of a bone biopsy (2D)”… see next slide

Routine BMD reasonable in patients with CKD3-5d if it will impact reatment decisions (2017 KDIGO update)

Question 59

Management of Complications: MBD
Managing osteoporosis in clinical practice
What is recommended and what treatment complications should you watch for?

Answer 59

In Clinical Practice:

CKD NON dialysis patients:
optimize MBD as per previous slide
* Can consider anti-OP medications if eGFR permits and optimized MBD parameters
* Most Bisphosphonates acceptable down to eGFR 30-35

• Beware of the risk of severe hypocalcemia with bisphosphonates or denosumab use in CKD
• Anti-osteoporosis drugs being studied presently in dialysis population (would not pick this choice on exam!)

Question 60

Uremic symptoms on history:
What do you look for?

Answer 60

• Anorexia, N/V, weight loss, appetite loss
• Metallic taste in mouth
• Pericarditis: doesn’t usually show classic diffuse ST elevation
• Peripheral neuropathy
• Bleeding, i.e. platelet dysfunction
• CNS: mental status changes, seizures, mood disorder
• Amenorrhea, decreased libido, erectile dysfunction
• Nocturia, restless legs (related to iron deficiency)
• Pruritus

Question 61

Indications for Dialysis:
What are the urgent and non-urgent indications?

Answer 61

* Urgent: AEIOU:
– Acidosis (severe)
– Electrolyte problems, i.e. hyperkalemia
– Intoxication: methanol, ethylene glycol, Li, ASA
– Overload, volume
– Uremia: pericarditis, encephalopathy/seizures

Dialyze if REFRACTORY to medical management

• Non-urgent : severe QOL issues due to uremia (e.g. pruritis, weight loss)

Question 62

CKD and Diabetes
[New 2022 KDIGO Guidelines
C-CHANGE 2022 Guidelines
CCS 2022 Guidelines for Cardiorenal Risk Reduction]
a) For T1DM and T2DM, when to screen for CKD?
b) Non-pharmacologic treatment

Answer 62

a) * Screen individuals w/ T1DM 5 years after diagnosis
* Screen T2DM at time of diagnosis then annually for CKD (ACR, serum
Cr).
– eGFR < 60 OR ACR > 2 in 2 of 3 samples over 3 months = CKD

Non Pharmacologic Treatment:
1. Comprehensive care (diet, exercise etc)
– Na < 2g
– Exercise moderate intensity 150 min/week
– Protein intake 0.8g/kg
2. A1c goal ranging 6.5-8% not on dialysis

Question 63

Diabetes and CKD:
Pharacotherapy in 2022/2023 that is recommended to manage DM

Answer 63

First line for diabetes with CKD
– metformin (gfr >30)
* eGFR 30-44 – initiate at ½ dose and titrate upwards to half of max
recommended dose
* Monitor b12 annually (once on met 4+ yrs)
* Monitor renal function q3-6mos

– SGLT 2i (eGFR >20-30*) ↓ MACE [major adverse cardiac events] (w empa, cana), Hospitalization for HF, Progression of nephropathy

Add On:
- GLP 1 agonists - ↓ MACE (liraglutide, semaglutide)

eGFR >20 for EMPAgliflozin (EMPA_KIDNEY) – empagliflozin 10 mg daily; note even non-diabetics enrolled!
eGFR >25 for DAPAgliflozin (DAPA CKD) – dapagliflozin 10 mg daily, note even non-diabetics enrolled!
eGFR >30 for CANAgliflozin (CREDENCE) – canagliflozin 100 mg daily, inc to 300 mg at week 13, note only had T2DM with CKD eGFR 30-90 enrolled.

Question 64

KDIGO DM/CKD 2022 phamacotherapy guidelines
What medications are recommended for patients with DM/CKD?

Answer 64

* Treatment with ACE or ARB for DM2 with HTN + albuminuria
– Consider for albuminuria without hypertension
– Repeat Cr, BP, K in 2-4 weeks
– Accept up to 30% rise of creatinine within 4 weeks
* Above 30%? Think volume depletion, NSAIDs, AKI, RAS…
– Advise contraception
– Hyperkalemia: dietary change, consider K binder before altering RASi dose

* Treatment with SGLT 2i
– Gfr > 20 ml/min, and can continue if gfr falls below 20 unless starting dialysis
– Does not apply to transplant patients
– Hold SGLT2 in fasting, surgery, critical medical illness

• Treatment with non steroidal MRA (finerenone – not in Canada yet!)
  – For DM2, gfr >25 ml/min, normal K, albuminuria 30mg/g despite max RASi

Question 65

Summarize the Lifestyle and Pharmacotherapy Guidelines for patients with
1) CKD
2) CKD + DM

Answer 65

Question 66

CKD in the CDA guidelines
What are the stages of diabetic nephropathy by level of urinary albumin level?
[bonus]

Answer 66

• Note the different diagnostic level for albuminuria in diabetes