IPFC 4 Midterm 1

Which of the following protects the kidney from trauma and helps maintain positioning as its main function?

- Renal fascia

- Renal pelvis

- Adipose capsule

- Renal capsule

Adipose capsule

Order the following layers from external to internal:

- Renal cortex

- Renal capsule

- Renal pelvis

- Renal medulla

Renal capsule (external kidney)

Renal cortex (internal kidney)

Renal medulla (internal kidney)

Renal pelvis (internal kidney)

Why is albuminuria seen in CKD?

Most proteins over 60 kDa such as albumin are too large to be filtered unless the glomerular membrane is damaged

What is the primary site of reabsorption in the kidney?

The proximal convoluted tubule

The PCT is the only region of the kidney that permits reabsorption of _______________

Glucose

Identify what region of the kidney each option fits with:

i. Primary site of sodium and chloride reabsorption as well as the site of action of aldosterone and ADH

ii. Site of urinary concentration due to the osmotic gradient

iii. 80% of filtered bicarbonate is reabsorbed here

i. Collecting duct

ii. Loop of Henle

iii. Proximal convoluted tubule

Which is not a function of the juxtaglomerular apparatus connecting the DCT and glomerulus?

- Houses macula densa cells that detect fluctuations in solute concentration

- Houses juxtaglomerular cells that secrete aldosterone into the collecting duct

- Regulates blood pressure via renin release

- None of the above

Houses juxtaglomerular cells that secrete aldosterone into the collecting duct

The JG cells are responsible for prorenin being converted to renin in response to a drop in BP

Vasopressin aka ADH is released from the hypothalamus in response to __________ (small/large) increases in blood osmolality and ________ (small/large) decreases in intravascular volume

Small; Large

ADH's primary function is to increase volume

ADH will increase the permeability of what part of the nephron to water?

The collecting duct

It increases the number of active water channels for reabsorption

Which is a function of the kidney?

- Clearance of drugs

- Activation of Vitamin D

- Erythropoiesis

- BP regulation

- All of the above

All of the above

Criteria for an AKI diagnosis

- Increase in SCr by 50% within 7 days OR

- Increase in SCr by 25 micromol/L within 48 hours OR

- Oliguria (urine volume under 0.5 mL/kg/hr for at least 6 hours)

True or false. AKI is a rare condition mostly associated with end stage renal disease

False.

AKI is quite common. Up to 20% of critically ill patients in hospital will have AKI, regardless of their baseline kidney function.

Which of the following conditions would NOT be associated with causing AKI?

- COPD

- Gastroenteritis

- Sepsis

- Heart failure

COPD

Which of the following is a risk factor for AKI?

- Amlodipine

- Diabetes

- White race

- All of the above

Diabetes

Which of the following is NOT a symptom of an AKI?

- Flank pain

- Urine discoloration

- Edema

- Polyuria

Polyuria

Identify if the following is a sign of fluid overload or fluid depletion:

- Decreased jugular venous pressure (JVP)

- Pitting

- Ascites

- Postural hypotension

- Decreased jugular venous pressure (JVP): depletion

- Pitting: overload

- Ascites: overload

- Postural hypotension: depletion

What is the most common anatomical classification of AKI?

Pre-renal

Which of the following is NOT a pre-renal cause of AKI?

- Glomerulonephritis

- NSAIDs

- Dehydration

- Burns

- Heart failure

Glomerulonephritis

This anatomical classification of AKI has to do with direct damage to the kidney

Intra-renal

Which of the following is typically more serious (i.e. a longer recovery time)?

- Pre-renal AKI

- Intra-renal AKI

- Post-renal AKI

Intra-renal (weeks to months)

Acute tubular necrosis (ATN) causes

Due to prolonged or severe pre-renal states or radiocontrast agents (common cause in hospitalized patients)

Acute interstitial nephritis (AIN) causes

Due to pyelonephritis, viral infections, and some antimicrobials (beta-lactams, sulfonamides, quinolones, vancomycin)

Glomerulonephritis causes

Due to diseases of the glomerulus (such as in lupus) or lithium and rarely NSAIDs

Which of the following is a cause of post-renal AKI?

- Kidney stone

- Amitriptyline

- High dose Vitamin C

- All of the above

All of the above

What is the treatment for most AKIs?

Treat the underlying cause and the AKI will resolve

eg. if dehydrated, give fluids. if septic, treat infection

Which of the following treatments is not appropriate in the supportive treatment of an AKI?

- SGLT2Is

- Furosemide

- Lokelma

- Enteral feeds

- Hemodialysis

SGLT2Is

What should dialysis patients who are sick (with potential dehydration) do to self-manage?

They should contact renal care team proactively when feeling dehydrated, try not to self-manage

What are the SADMANS drugs

Sulfonylureas

ACEIs

Diuretics

Metformin

ARBs

NSAIDs

SGLT2Is

Hold these in the setting of acute illness that affects fluid status

What is the leading cause of CKD?

Diabetes

Criteria for diagnosis of CKD

1. Decreased GFR (less than 60 mL/min/1.73m^2)

AND/OR

2. Markers of kidney damage (1 or more of the following)

- Albuminuria (ACR greater than 3 mg/mmol)

- Urine sediment abnormalities

- Electrolyte and other abnormalities due to tubular disorders

- Abnormalities detected by histology

- Structural abnormalities detected by imaging

- History of kidney transplantation

How do we classify CKD severity?

CGA.

- Cause

- GFR category (G1, G2, G3, G4, G5)

- Albuminuria category (A1, A2, A3)

Which of the following is a cause of CKD?

- Malignancy

- Hypertension

- Glomerular disease

- Cystic disease

- All of the above

All of the above

In young healthy adults, normal GFR is _____________________________

120 mL/min

Which of the following is the lab test used to measure kidney function most used in practice?

- mGFR

- eGFRCr

- eGFRcr-cys

- Timed urine clearance

Bonus: which is the most accurate

eGFRCr is used in practice

mGFR (i.e. true GFR with inulin) is the most accurate but is study only due to time/cost

Why can SCr not be used on its own to estimate renal function?

Lots of variation between individuals and over time in the same individual i.e. musculature, diet

Why is GFR indexed/standardized for BSA: mL/min/1.73m^2

Kidney function is proportional to kidney size and kidney size is proportional to the size of the person, represented by body surface area. BSA = 1.73m^2 was set as a normal mean value for young adults when indexing was proposed

Non-indexed eGFR: mL/min

-Used for ______________________

Indexed eGFR: mL/min/1.73m^2

- Used for ________________________

Drug dosing; CKD staging

A patient is 6'5, 280 lbs. If you are using non-indexed (BSA adjusted) eGFR to determine their kidney function, it will give you a ______________ (lower/higher) value than using indexed eGFR.

Higher

Non-indexed GFR reflects the actual BSA of the individual (which is significantly larger than 1.73m in this case) so the kidney function will be determined to be greater because it takes into account the patient's relatively larger kidneys, whereas indexed GFR does not.

When might 24 hour timed urine collection be preferred to eGFRCr?

- Unstable creatinine concentrations (i.e. AKI)

- Extremes in muscle mass and body types: amputees, bodybuilders, paraplegics, morbidly obese

Why does a 24 hour timed urine collection of creatinine tend to overestimate GFR?

Creatinine is both filtered and secreted. This causes more creatinine to appear in urine than was filtered — so the clearance overestimates the true GFR

Identify the eGFR (mL/min/1.73m) that corresponds to each GFR category

G1 ________

G2 ________

G3a _______

G3b ________

G4 _________

G5 _________

G1 >90

G2 60-89

G3a 45-59

G3b 30-44

G4 15-29

G5 <15

With the exception of G1 -> G2, it is increments of 15 mL/min/1.73m

For staging CKD, why do we measure albumin in the urine and not just total proteins?

Urine albumin is more accurate for early detection of CKD. It is more specific and sensitive than urinary total protein as total protein assays are insensitive and imprecise at low concentrations.

Identify the ACR (albumin to creatinine ratio) that corresponds to each albuminuria category for CKD

A1: ________________

A2: ________________

A3: ________________

A1: <3 mg/mmol

A2: 3-30 mg/mmol

A3: >30 mg/mmol

Which of the following does not meet the diagnostics for CKD?

- G4, A1

- G2, A1

- G1, A2

- G3, A3

G2, A1

eGFR between 60-90 and less than 3 mg/mmol albuminuria is not CKD

What GFR category is considered kidney failure/ESRD

G5 (under 15 mL/min/1.73m)

What is the main goal of therapy for managing CKD?

Avoid progression to End Stage Renal Disease (G5)

Kidney Failure Risk Equation (KFRE)

Complex modeling equation that estimates risk of ESRD at 2 years and 5 years

What is conservative renal care (CRC)?

Allowing kidney disease to run its natural course (no dialysis or transplant intervention)

When does KDIGO recommend initiation of dialysis?

- Acid-base or electrolyte abnormalities

- Intolerable pruritus (attributed to kidney failure)

- Inability to control volume status or BP

- Deterioration in nutritional status (refractory to dietary intervention)

- Cognitive impairment (attributed to kidney failure)

What eGFR is typically when dialysis will become necessary?

5-10 mL/min/1.73m

How does dialysis remove fluid?

Water moves from cells to blood to dialysate due to differences primarily in glucose concentration. Transmembrane pressure (TMP) also pushes water out of blood into dialysate

What is the preferred method of vascular access for dialysis?

Arteriovenous (AV) fistula

Which method of vascular access for dialysis is best for immediate use (i.e. no delay for maturity)

Central venous catheters (CVC)

Order the following methods of vascular access for dialysis by mortality (highest risk to least)

- Arteriovenous (AV) graft

- Arteriovenous (AV) fistula

- Central venous catheter (CVC)

1. Central venous catheter (CVC)

2. Arteriovenous (AV) graft

3. Arteriovenous (AV) fistula

Which is NOT a complication of dialysis?

- Thrombosis

- Catheter infections

- Hypertension

- Muscle cramps

- Bleed risk increase

Hypertension

Hypotension is associated with dialysis (fluid removal)

Intradialytic symptoms

Hypotension (20-30%)

Muscle cramps (5-20%)

N/V (5-15%)

Headache (5%)

Most patients go for dialysis ____ times a week which last _______ hours each

3; 3-4

Main benefit of at-home dialysis

Dialysis frequency and duration is more flexible

How does peritoneal dialysis work?

It requires surgical insertion into the patient's abdomen and the peritoneal membrane acts as a semipermeable membrane and the peritoneal cavity acts as the dialysate-filled compartment

How does continuous ambulatory peritoneal dialysis (CAPD) differ from continuous cycling peritoneal dialysis (CCPD)?

CAPD involves multiple exchanges throughout the day and CCPD is an automated cycler that performs multiple exchanges overnight

Which of the following is not a core recommended lifestyle intervention for prevention of CKD?

- Avoidance of alcohol

- Smoking cessation

- Physical activity: 150 min/week

- Optimal weight

- Reduced salt and protein intake

Avoidance of alcohol

KDIGO recommends protein intake of 0.8 g/kg/day in adults with CKD G3-G5. This is ___________ (more/less) than protein recommendations for the average adult

Less

High protein intake can worsen kidney disease

True or false. Recommended salt intake for patients with CKD is the same as for hypertension

True. 2000 mg a day

KDIGO recommended BP target in patients with CKD

<120 mmHg sBP

Consider less intensive BP-lowering therapy if frail, high risk of falls, limited life expectancy, symptomatic postural hypotension

True or false. A diabetic patient that gets CKD should still have the BP target of 130/80 mmHg based on KDIGO guidelines

False. <120 mmHg sBP in diabetic and non-diabetic patients with CKD

What is the target ACR in patients with CKD?

Ideally we target less than 3 mg/mmol. This target is more important for patients with diabetes. In non-diabetics with CKD, an ACR less than 30 mg/mol may be appropriate.

All CKD patients with SBP greater than _______ mmHg should be on an ACEI/ARB

120

All CKD patients with _____+ mg/mmol albuminuria regardless of BP (as long as patient can tolerate) should be on an ACEI/ARB

3

ACEI/ARB eligiblity in CKD

Patients with another ACEI/ARB indicated condition (HTN, HFrEf, ACS, DM)

OR patients who have a sBP over 120 mmHg

OR patients who have an ACR over 3 mg/mmol.

Practically speaking, just about anybody with CKD is going to get an ACEI/ARB if they do not have contraindications

When should you consider reducing dose/discontinuation of an ACEI or ARB in patients with CKD?

Symptomatic hypotension or uncontrolled hyperkalemia despite treatment

Recommendation for dosing ACEI/ARBs in CKD

Administer at the highest approved dose that is tolerated by the patient. Initiate therapy at the lowest dose recommended for the patient's renal function and titrate up past it to what was studied in trials for preventing CV events and CKD progression as tolerated

Which of ACEIs/ARBs is hepatically eliminated and does not typically require renal dose adjustments?

ARBs

True or false. ACEIs should be increased to doses shown to provide cardiovascular and renal protection, even if those doses are higher than what is traditionally considered "safe" from a renal function standpoint

True

True or false. There is no official dose equivalence between ACEI/ARBs so we try to avoid switching from ACEI to ARB

True.

Reasons to switch from an ACEI to an ARB include angioedema, intolerable cough, and renal impairment to the point that an ACEI must be dose adjusted for tolerability

What does KDIGO say about continuing an ACEI/ARB below a GFR of 30 mL/min?

Continue the ACEI/ARB as the STOP-ACEI trial studied stopping vs. continuing and showed no difference

True or false. You should never start an ACEI/ARB in patients with very poor renal function (i.e. eGFR under 30 mL/min)

False

It has not been studied, the approach depends on patient-specific factors but it definitely CAN be done.

In what acute CKD states should an ACEI/ARB be held and/or not be initiated in...

- Dehydration (SICK DAY)

- Acute heart failure

- Hyperkalemia

- AKI

Continue re-challenging the patient with a lower dose ACEI/ARB once the contributing factor has been resolved

Which of the following is an absolute contraindication to an ACEI/ARB?

- Renal artery stenosis

- History of hyperkalemia

- eGFR under 30 mL/min

- Dialysis

- History of AKI

Renal artery stenosis

Why are ACEI/ARB beneficial in CKD?

Increased BP within the glomerulus increases protein filtration through the glomerular membrane. This causes ongoing damage, worsening proteinuria.

ACEI/ARB reduce pressure in the glomerulus which reduces proteinuria and damage

Why can ACEI/ARBs sometimes worsen renal function to the point of AKI?

In settings of low renal perfusion, GFR is maintained by angiotensin II induced vasoconstriction of the efferent arteriole which is blocked by ACEI/ARBs

What did the ONTARGET trial show regarding combination of an ACEI + ARB?

Greater antiproteinuric effects than either agent alone but did not reduce risk of CV disease or death. It also increased hyperkalemia, hypotension, and caused a small increase in ESRD.

What patients with CKD should get SGLT2 inhibitors?

eGFR above 20 AND one or more of the following:

- T2DM

- Heart failure

- ACR > 20 mg/mmol

Which of the following is incorrect about SGLT2Is?

- Decrease glycouria

- Increase sodium delivery to macula densa

- Increase natriuresis

- Decrease weight

Decrease glycouria

SGLT2Is increase the excretion of glucose in the urine

True or false. SGLT2Is do a better job of lowering glucose and preventing cardiovascular outcomes as GFR increases

False.

SGLT2Is do provide the most glucose lowering when the kidneys work better (As eGFR decreases, there's less glucose to remove) but this relationship does not exist for the prevention of CV events

True or false. SGLT2Is are associated with significant increased risk of hypoglycemia in patients without diabetes

False

No hypoglycemia unless combined with insulin, SUs

Which is a potential adverse effect of SGLT2Is?

- Genital mycotic infection

- Urinary tract infection

- Increased risk of falls

- More than one of the above

- All of the above

All of the above

True or false. You should stop an SGLT2I in a patient who's baseline kidney function now falls below 20 mL/min

False.

Do not need to stop if eGFR drops below 20 but do not initiate

True or false. You should stop an SGLT2I in a patient starting dialysis

True.

No benefit reducing risk of ESRD at this point and little benefit in BG reduction for diabetics on dialysis

Finerenone is associated with ____________ (lower/higher) incidence of hyperkalemia compared with spironolactone and eplerenone

Lower

Which of the following is a steroidal mineralocorticoid receptor antagonist?

- Eplerenone

- Finerenone

- Spironolactone

- More than one of the above

- All of the above

More than one of the above (eplerenone and spironolactone)

When is finerenone indicated in CKD?

Add on to ACEI/ARB and SGLT2I in diabetic patients not meeting targets (albuminuria over 3 mg/mmol)

Which of the following is an indication for finerenone?

- Heart failure with reduced ejection fraction

- Add on to spironolactone

- eGFR > 25 mL/min

- Albuminuria under 3 mg/mmol

eGFR > 25 mL/min

True or false. FIGARIO-DKD and FIDELIO-DKD showed that finerenone improves both CV and renal outcomes

True

Under what potassium level are we comfortable initiating finerenone?

4.8 mmol/L

Under what potassium level are we comfortable continuing finerenone?

5.5 mmol/L

At what potassium level should finerenone be held?

5.5+ mmol/L

What finerenone doses were studied? At what eGFR do we initiate each one?

10 mg and 20 mg once daily

eGFR 25-60 mL/min -> finerenone 10 mg

eGFR 60+ mL/min -> finerenone 20 mg

Goal is to eventually titrate to 20 mg in all patients with eGFR over 25 mL/min (without going into hyperkalemia)

True or false. Non-DHP CCBs have more evidence as monotherapy for BP and proteinuria management in patients with CKD than DHP-CCBs

True (based on some older studies)

In practice, we use DHP CCBs more often in patients with CKD, but as an add-on to ACEI/ARBs

Why is a DHP-CCB like amlodipine considered the first add-on to an ACEI/ARB in patients with CKD and above target BP instead of a thiazide diuretic?

The ACCOMPLISH trial showed that ACEI + DHP-CCB was superior to ACEI + thiazide in reducing CV events

When is amlodipine indicated in CKD?

First add on to ACEI/ARB in diabetic CKD and nondiabetic CKD with proteinuria if BP targets not reached