Kidney Disorders 2 Flashcards
CKD
Briefly describe the epidemiology of CKD.
1/10 Canadians live with CKD
diabetes is the leading cause of CKD
ESRD increased 35% since 2009
95% of patients managed in primary care
What is chronic kidney disease?
progressive loss of function occurring over several months to years
characterized by gradual replacement of normal kidney architecture with fibrosis
can progress to the need for dialysis or transplant
Why is CKD one of the leading causes of morbidity and mortality in North America?
progressive loss of kidney function leads to:
-complications
-may require RRT
cardiovascular disease
-leading cause of mortality*
What are the two main causes of CKD?
diabetes and HTN
diabetes being the leading cause
Which populations are at higher risk for CKD?
hypertension
diabetes
cardiovascular disease
first degree relative with CKD
Indigenous
What are the two definitions of CKD?
kidney function:
-GFR < 60ml/min/1.73m2 for 3 months or more with or without kidney damage
kidney structure:
-kidney damage for > 3 months, with or without decreased GFR, as evidence by pathological abnormalities, abnormalities in blood or urine or as seen by imaging
What are the markers for kidney damage?
albuminuria (ACR > 3mg/mmol)
urine sediment abnormalities (ex: RBC casts)
electrolyte abnormalities
abnormalities detected by histology
structural abnormalities
history of kidney transplant
Describe the screening process for CKD.
measure eGFR and ACR
-if eGFR < 60ml/min re-measure in 3 months or sooner
-if ACR > 3 re-measure 1-2 times over next 3 months
confirm CKD diagnosis after 3 months
-eGFR > 60ml/min and ACR < 3=person doesnt have CKD
-eGFR 30-59ml/min and/or ACR 3-60=person has CKD but can be managed in primary care
-eGFR < 30ml/min and/or ACR > 60=person has CKD but refer to nephrologist
Describe the decline in GFR due to age.
GFR decreases by ~ 1ml/min/1.73m2/year beginning in the 4th decade of life
GFR will decrease to < 60ml/min in 5-25% of otherwise healthy adults due to aging alone
What is the concern with reduced GFR due to age alone?
there are still risks associated:
-higher risk of AKI
-medication accumulation with reduced GFR
-reduced reserves in the event other comorbidities develop over time
Describe the staging of CKD based on GFR.
G1 (normal or high): > 90ml/min
G2 (mildly decreased): 60-89ml/min
G3a (mild-moderately decreased): 45-59ml/min
G3b (moderate-severely decreased): 30-44ml/min
G4 (severely decreased): 15-29ml/min
G5 (kidney failure): < 15ml/min
G3a and lower can be classified as CKD
Describe the staging of CKD based on albuminuria.
note: using ACR
A1 (normal-mildly increased): < 3mg/mmol
A2 (moderately increased): 3-30mg/mmol
A3 (severely increased): > 30mg/mmol
To determine GFR category, what equation would you use to estimate the GFR?
CKD-EPI
Are albuminuria and GFR dependent on each other in the context of CKD?
no, they are independent
-GFR could be fine but ACR could be high leading to a poor prognosis and vice versa
-worst possibility is a combo of both being bad
What is the clinical presentation of CKD?
often asymptomatic
-symptoms minimal in stages 1-2
higher incidence of symptoms in stages 3-4
-low energy, fatigue, confusion
-foaming, tea-coloured, bloody or cloudy urine
-edema
-shortness of breath
-pruritis
Provide a very brief overview of care for CKD based on GFR.
eGFR 30-59ml/min (3a-3b): usually managed in primary care
eGFR < 30ml/min (4-5): usually with nephrologist
delay progression
reduce CV risk
treat complications
Describe the progression of CKD.
once CKD develops, it generally progresses over time
-autoimmune CKD may undergo remission
rate of GFR decline highly variable between individuals
-lower GFR and greater albuminuria=faster progression
rate of progression is related to etiology
-quick: diabetic nephropathy, glomerular dx, polycystic kidney disease, transplant
-slow: hypertensive, tubulointerstitial disease
What are the non-modifiable factors associated with faster progression of CKD?
African American
male
advanced age
family history
What are the modifiable factors associated with faster progression of CKD?
uncontrolled HTN
poor blood glucose control
proteinuria
smoking
obesity
What are the interventions to delay the progression of CKD?
blood pressure control
RAAS blockade
-ACEI/ARB
-non steroidal MRAs
blood glucose control in people with DM
-SGLT2 inhibitors
-GLP 1 agonists?
smoking cessation
avoidance of nephrotoxins
Describe blood pressure control in the context of CKD.
HTN can be both a cause and a consequence of CKD
associated with faster progression of CKD and CVD
strict bp control delays progression of CKD
What are the blood pressure targets according to Hypertension Canada?
<130/80 for patient with diabetic CKD
SBP < 110 for adults with polycystic kidney disease
SBP < 120 for “high risk” patients
SBP < 140 for “all other patients”
What are the blood pressure targets according to KDIGO?
SBP < 120 for patients with high bp and CKD when tolerated
<130/80 for kidney transplant recipients
What are the indications defining high-risk patients for intensive blood pressure management?
AARF
age > 75
atherosclerosis
renal (eGFR < 60ml/min/1.73m2 or proteinuria < 1g/d)
Framingham risk score > 15%
What are cautions and contraindications for pushing SBP to < 120?
heart failure
institutionalized elderly individuals
diabetes
previous stroke
eGFR < 20 (includes dialysis and transplant)
patient unwilling/unable to adhere to multiple meds
standing SBP < 110
inability to measure SBP accurately
What are the results from the SPRINT trial in regards to SBP <120 and CKD progression?
did not slow CKD progression
Describe proper BP measurement.
sitting position
back supported
arm bare and supported
middle of cuff at heart level
do not talk or move before or during
legs uncrossed
feet flat on floor
What are the lifestyle recommendations from Hypertension Canada for blood pressure control?
salt restriction
-reduce sodium intake towards < 2000mg (5g of salt)/day
exercise
-30 to 60 minutes moderate intensity 4-7 days/week
weight reduction in overweight/obese patients
-BMI 18.5-25kg/m2
limit alcohol consumption
-1 to 2 drinks/day
How many drugs are often required to control blood pressure with CKD?
3-4
What are the first-line options for blood pressure control and CKD?
ACEI/ARB
diuretics
long acting CCB
consider comorbidities, stage of CKD, degree of albuminuria, type of CKD
What is the first line treatment for HTN if a patient has proteinuria?
ACEI/ARB
-diabetic kidney disease: ACR > 3mg/mmol
-nondiabetic proteinuric CKD: ACR > 30mg/mmol
What is the benefit of ACEI/ARBs in the context of CKD?
reduce BP and glomerular capillary pressure
-by selectively vasodilating the efferent arteriole
reduce proteinuria
improvement in kidney outcomes (failure, doubling of SCr, GFR decline, progression of albuminuria) and CV outcomes
Which antihypertensive reduces proteinuria more than any other?
ACEI/ARB
Which ACEI/ARB is used for RAAS blockade in CKD?
used interchangeably
What are the contraindications to ACEI/ARBs?
pregnancy
angioedema
bilateral renal artery stenosis
What are the precautions to ACEI/ARBs?
intravascular fluid depletion
-reduce/hold dose if severe vomiting, diarrhea, fluid loss
eGFR < 30ml/min/m2
hypotension (caution if BP < 110/70)
hyperkalemia (K+ > 5.5mmol/L)
What are the monitoring parameters for ACEI/ARB therapy?
2-4 weeks following initiation or any dose increase
-SCr (increase > 30% from baseline may warrant dc)
-K+ (if high: restrict dietary K+, add diuretic)
-blood pressure
-urinary ACR
What are the strategies that can be done to reduce potassium if hyperkalemia occurs to a patient with CKD on an ACEI/ARB?
moderate potassium intake
review concurrent drugs
consider:
-diuretics
-sodium bicarbonate
-potassium binders
ACEI/ARB are so important that we want to do as much as we can to keep them on board
What is the dosing of ACEI/ARBs for CKD?
start at a low dose and titrate to maximum tolerated dose (or highest approved dose)
-dose dependent reduction in albuminuria lowering effect
What was the old recommendation for combo ACEI+ARB therapy?
CKD with refractive proteinuria
What is the recommendation today for combo ACEI/ARB therapy?
avoid ACEI/ARB combination
-superior for reducing proteinuria and BP but actually worsened renal outcomes
Which drug is a direct renin inhibitor?
aliskiren
What is the use of aliskiren for CKD?
no longer used
-does more harm than good
What did the Cochrane review from 2014 find regarding MRAs and CKD?
reduced proteinuria 30-40%
improved bp
possible slowing of CKD progression
no CV/ESRD outcomes
doubled risk of hyperkalemia
5 fold risk of gynecomastia
What are the steroidal aldosterone antagonists?
spironolactone and eplerenone
non-selective
What is the non-steroidal aldosterone antagonist?
finerenone
higher specificity for MR vs glucocorticoid/androgen receptor
What is the benefit of finerenone?
reduction in albuminuria while having less side effects
What are the KDIGO recommendations regarding finerenone in CKD with diabetes?
use with proven kidney or CV benefit for patients with T2DM, an eGFR > 25ml/min, normal K+ levels (<4.8), and albuminuria (ACR > 3) despite maximum tolerated dose of a RAASi
What are the KDIGO guidelines regarding MRAs for hypertension?
possible use in refractory HTN (uncontrolled on 3 other drugs including a diuretic) with GFR > 45ml/min
steroidal or non-steroidal MRA
What are the limitations of finerenone?
not currently covered by SK formulary or NIHB
less evidence available in patients also taking a SGLT2i
not to use in combo with steroidal MRAs in patients with HF
Why are diuretics frequently used for hypertension in CKD?
fluid retention is an important contributor to HTN in CKD
most patients require diuretic therapy
Which diuretic should you initiate with for hypertension treatment in CKD?
thiazide
-may switch to or combine with loops for volume control or if BP becomes resistant to therapy
-may prefer combo with metolazone, chlorthalidone, or indapamide (effective diuresis at GFR < 30ml/min)
Which diuretics should be avoided in stage 3-5 CKD?
potassium sparing diuretics
Describe DHP CCBs for hypertension control in CKD.
preferred to thiazides in combo with ACEI/ARB in patients with diabetes (CV benefits)
no evidence for slowing CKD progression
may cause fluid retention and edema (nuisance effect in CKD)
Describe non-DHP CCBs for hypertension control in CKD.
shown to decrease proteinuria but not same extent as ACEIs
not preferentially used for reducing proteinuria but may provide benefit when added to ACEI/ARB
-no evidence for slowing CKD progression
tolerability and safety:
-constipation and bradyarrhythmia
-lots of drug interactions and contraindications
Which beta-blockers are renally eliminated and require dosage adjustment once CrCl approaches 30ml/min?
atenolol
bisoprolol
What is the use of beta-blockers for hypertension control in CKD?
only used if compelling indications (not used as stand alone)
-ex: HF, post-MI, angina
-inconsistent evidence for CV benefits in CKD
What are the common side effects of beta-blockers?
fatigue
limited exercise tolerance
What is the use of alpha-2 agonists for hypertension control in CKD?
adjunctive therapy for HTN because no drug interactions with commonly used bp meds
What are the side effects of alpha-2 agonists?
CNS (caution in the elderly)
rebound HTN if abruptly stopped
What is the use of alpha-1 blockers for hypertension control in CKD?
adjunctive treatment for elevated bp
-might consider in patients with BPH
What are the common side effects of alpha-1 blockers?
dizziness
orthostatic hypotension
What is the use of direct vasodilators for hypertension control in CKD?
adjunct treatment
-use is limited by side effects (headache, fluid retention)
-hydralazine has no renal dose adjustment=positive
What is the role of SGLT2 inhibitors for hypertension control in CKD?
bp reduction is a side advantage
-not the main reason they are used
Describe proteinuria.
linked with progression of diabetic and non-diabetic CKD
high risk of progressing to kidney failure
indicator of subclinical CVD
>150 mg protein lost in urine per day (albumin or others)
What is microalbuminuria a predictor of?
loss of kidney function
Why do we want to identify microalbuminuria early?
so that we can institute appropriate therapy (ACEI/ARB) to slow progression
Differentiate between mild proteinuria, moderate proteinuria, and nephrotic range.
mild: 150-500mg (A2)
moderate: > 500mg (A3)
nephrotic range: more than 3g or albumin excretion > 2200mg/24h
What are the symptoms of nephrotic syndrome?
hyperlipidemia
hypoalbuminemia
edema
thromboembolic risk
foamy urine
Why do we treat patients with CKD that have no hypertension with an ACEI/ARB?
reduce glomerular capillary pressure and volume
possible direct effect on podocytes to decrease proteinuria
What is the first line therapy for kidney diseases with proteinuria?
ACEI/ARB (CV and kidney benefits)
-diabetic or hypertensive kidney disease with A2 or A3 albuminuria
-other kidney diseases with proteinuria
What is the benefit of SGLT2 inhibitors for CKD?
renal and CV benefits
-reduces decline in GFR, progression to ESRD, death due kidney disease, all-cause and CV mortality
-regardless of diabetes or not
What is the recommendation from CCS for SGLT2 inhibitors in CKD?
recommended for adults with CKD (ACR > 20mg/mmol or GFR > 25ml/min/1.73m2)
-even without diabetes
How often should diabetics be screened for CKD?
at least annually in stable patients
-random urine ACR, SCr, and eGFR
What is the importance of blood glucose control in CKD?
prevents and delays progression of diabetic nephropathy
What is the target A1C in CKD?
< 7.0 for most patients
-< 6.5 may be appropriate in some to decrease CKD risk
In which patients might A1C measurements be less accurate?
advanced CKD (G4-G5)
-particularly with dialysis
What is the benefit of metformin for blood glucose control in CKD?
CV benefit
-lack of evidence for kidney protective effects
True or false: metformin does not require renal dose adjustments
false
renal dose adjustments due to the concern of lactic acidosis
What are KDIGOs recommendations regarding SGLT2 inhibitors for diabetics with CKD?
1st line for patients with T2DM, CKD, and eGFR > 20ml/min
What are the complimentary actions of SGLT2 inhibitors with ACEI/ARBs?
ACEI/ARBs dilate the efferent arteriole to reduce glomerular pressure, SGLT2 inhibitors constrict the afferent arteriole to further reduce glomerular pressure and long-term renal protection
What is the key point regarding SGLT2 inhibitors and CKD?
guidelines recommend them to improve renal and CV outcomes regardless of the patients A1C (even if targets are met)
What are the guidelines for SGLT2 inhibitors and dialysis?
not to be initiated if eGFR < 20ml/min but may be continued until dialysis
What is the early decline in eGFR with SGLT2 inhibitors that we are willing to accept and continue with?
< 30%
What are the adverse effects of SGLT2 inhibitors?
thirst
urinary frequency (take in AM)
genital mycotic infections
hypovolemia
dizziness/orthostatic hypotension
DKA
What are the benefits of GLP-1 agonists?
evidence for CV benefits and favorable kidney benefits
-FLOW trial in 2024 to provide more info on renal benefits
What are the KDIGO recommendations for GLP-1 agonists in CKD?
use if A1C targets not achieved with metformin/SGLT2 inhibitors
How does smoking increase the progression of CKD?
increased BP and HR
decreased renal blood flow (constriction)
vascular injury
also a risk factor for CV events
What are some examples of nephrotoxic drugs?
NSAIDs, COX-2 inhibitors
lithium
aminoglycosides
amphotericin B
calcineurin inhibitors
cisplatin
avoid combinations, especially like ACEI/ARB, NSAID, diuretic
Describe sick day management in CKD.
when patients with CKD become acutely ill and are unable to maintain adequate fluid intake, recommend to hold potentially nephrotoxic or renally excreted drugs
-SAD MANS
=sulfonylureas, ACEI, diuretics, metformin, ARB, NSAID, SGLT2i
What is the leading cause of death in patients with CKD?
cardiovascular disease
-most patients with CKD will die from CVD before RRT
What are the common CV risk factors that patients with CKD should be screened for?
DM
HTN
dyslipidemia
smoking
obesity
LVH
What are the statin indicated conditions?
ASCVD
most diabetics
CHRONIC KIDNEY DISEASE
-most guidelines recommend a statin regardless of LDL
What are the KDIGO guidelines for the treatment of dyslipidemia in CKD?
> 50 yrs old with eGFR < 60 and not on dialysis
-low dose statin or statin/ezetimibe
50 yrs old with CKD and eGFR > 60
-tx with statin
18-49 yrs old with CKD
-tx with statin if estimated CV risk is > 10%
if on dialysis: do not initiate therapy
-continue therapy if already on it
kidney transplant
-tx with statin (in some cases)
What is the difference in recommendations for statins in CKD between KDIGO and the dyslipidemia guidelines?
KDIGO:
-stick with low dose statin (fire and forget)
-limitation: studies were only done in dialysis patients
dyslipidemia guidelines:
-high intensity statin therapy (atorv 80, rosuv 40)
What is the benefit of the “fire and forget” strategy for statins in CKD?
CV risk reduction and mortality
-no benefits to slowing CKD progression
What is the role of antiplatelet therapy in CKD?
no role in primary CV prevention in CKD
used in secondary prevention
What are the forms of renal replacement therapy?
dialysis
-hemodialysis
-peritoneal dialysis
-continuous renal replacement therapy
kidney transplant
-preferred option for eligible patients (better mortality)
-subject to organ availability
When is renal replacement therapy initiated in CKD?
no set GFR at which RRT is required
-based on clinical status of the patient
-most require at GFR ~ 10ml/min
signs and symptoms indicated need for RRT:
-serositis, acid-base or elyte abnormalities, pruritis
-inability to control volume status or BP
-malnutrition refractory to dietary intervention
-cognitive impairment
Describe hemodialysis.
most common RRT modality
patients blood is passed through an external filter to remove wastes and fluid
-solutes move from the blood across the filter into the dialysis solution down their concentration gradient
-filtered blood is returned to the body
-requires chronic vascular access that can withstand high blood-flow rates
can be done at home or in a dialysis clinic
3-5x/week at the clinic (3-5hrs per visit)
What are the types of hemodialysis?
AV fistula
-preferred method, requires months to heal before start
synthetic AV graft
-susceptible to infection
catheter in neck
-highest complication risk
Which systemic therapy is given during hemodialysis and why?
anticoagulation
-prevents blood clot in the machine
What are the common adverse effects of hemodialysis?
fatigue
hypotension (massive fluid shifts)
hypertension
cramps
N/V
What are the vascular access problems associated with hemodialysis?
infection
clotting
bleeding
Which micronutrients are removed from the body during dialysis?
water soluble vitamins (B and C)
-all dialysis patients require Replative (1 tab po OD)
-avoid multivitamins containing minerals, vit A or D
Which micronutrients require monitoring in dialysis patients?
serum folate and B12 q6-12mo
Describe peritoneal dialysis.
relies on patients own peritoneal membrane to act as a filter for fluid and waste
-2-3L of dialysate is instilled in the peritoneal cavity through an indwelling catheter in the abdominal wall
-wastes and fluid diffuse across the peritoneal membranes down their concentration gradient
-dialysate is drained and replaced with fresh solution
preferred in pts continuing to work, travel, etc BUT requires patients to be diligent
What are the two types of peritoneal dialysis?
continuous ambulatory peritoneal dialysis (CAPD)
-manual exchange, 4-5x/day
-each exchange takes 30-45min
automated peritoneal dialysis
-automated using a machine while sleeping
-takes 8-10hrs
What is the most frequent complication of peritoneal dialysis?
peritonitis
-treated with local or systemic antibiotics
Describe continuous renal replacement therapy.
used in acute settings
-not suitable for chronic RRT
for patients who cannot tolerate abrupt fluid shifts with HD
-hemodynamically unstable patients requiring RRT for AKI
