Nephrology Flashcards
Acid/Bases Review
pH >7.4
HCO3 is UP
PCO2 normal or UP
= METABOLIC alkalosis
PCO2 is DOWN
HCO3 normal or down
= RESPIRATORY alkalosis
pH<7.4
PCO2 is up
=Respiratory
acidosis
HCO3 is down
= metabolic
acidosis
- Compensation?
-Metabolic Acidosis 1:~1 (↓ HCO3 :↓ CO2) *winter’s formula/last 2 digits of pH ± 2
-Metabolic Alkalosis 1:0.7 (↑ HCO3 : ↑ CO2)
-Respiratory Alkalosis (↓ CO2 : ↓ HCO3). Chronic (10:4-5) / Acute (10:2)
-Respiratory Acidosis (↑ CO2 : ↑ HCO3). Chronic (10: 3-4)/ Acute (10:1)
Metabolic Acidosis- calculations
- Calculate the anion gap: Na – Cl – HCO3
– Adjust for albumin (every decrease in albumin by 10, add 2.5mEq/L to
the AG) - Calculate the “delta-delta”: ΔAG (12-AG):Δbicarb(24-bicarb)
– The delta AG (from normal = 12) should be equal to the change in
bicarb (from normal = 24) when pure AGMA
– See next slide - Calculate the osmol gap: [calculated osm: 2xNa + Gluc + BUN] –
[serum measured osm]
– Normal osmolar gap = 10; higher means additional unmeasured
osmoles− think EtOH or toxic alcohol (dangerous to miss!)
– Could have high osmolar gap with normal anion gap early in toxic alcohol
Delta:Delta
∆AG»_space;∆HCO3 >2, bicarb doesn’t change enough, meaning a secondary alkalosis is opposing the acidosis.
Concurrent Metabolic alkalosis (HCO3 higher than expected) with anion gap metabolic acidosis.
∆HCO3 ≈ ∆AG 0.8-2, Pure AG acidosis
∆AG «_space;∆HCO3 <0.8, Bicarb changes more than expected, meaning a secondary acidosis is present
Concurrent non AG metabolic acidosis (with HCO3 lower than expected) with high AG acidosis
Causes of AGMA (GOLDMARK)
G- Glycols
O- Oxoproline*
L- Lactate
D- D-lactate
M- Methanol
A- ASA
R- Renal failure
K- Ketones
Causes of Increased Osmolar Gap
Anion Gap Metabolic Acidosis-
Organic alcohol poisoning:
* Methanol
* Ethylene glycol (antifreeze)
Paraldehyde
Ketoacidosis (Etoh + Diabetic)
Lactic acidosis
Severe CKD
No Metabolic Acidosis
Ethanol
Isopropyl alcohol (rubbing ETOH)
Mannitol
Sorbitol
*pseudohyponatremia
*Early toxic alcohol!
Acid/Base Disorder Pearls
In organic alcohol intoxications, the osmolar gap and anion gap
may exist at different times
– Early on: osmolar gap without anion gap
– Later: anion gap without osmolar gap
If you see an ABG with pH 7.4, be alert for mixed disorders
– E.g. if the bicarb is low, go through all of the steps for metabolic acidosis
NAGMA Approach
Is NH4 excretion high, as
expected if kidney
working appropriately
Yes
(UAG «0)
-GI HCO3 loss (diarrhea)
Pancreatic fistula
NJ tube
No
(UAG >0) = RTA
Check urinary anion gap:
Urine(Na+) + Urine(K+) – Urine(Cl)
Urine anion gap: If its Negative its
Not the kidney!
NEGUTIVE = the gut
Causes of metabolic alkalosis
Urine Cl < 25: (will be Chloride/NS responsive)
– GI loss (NG tube, vomiting, villous adenoma, chloride diarrhea)
– Renal loss (diuretics)
– Sweating (Cystic fibrosis)
Urine Cl >25: (will not be chloride/NS responsive)
– High BP:
* Hyperaldosterone (htn, hypoK, alkalosis, high aldo)
* Liddle’s (htn, hypoK, alkalosis, low aldo)
* Cushings
– Low BP:
* Barter’s (mimics Loops – low K, low Mg)
* Gittleman’s (mimics thiazides – low K, low Na, high Ca)
– Excess bicarb ingestion
Hyponatremia- correction calculation
The most important questions to answer on initial assessment:
– Is this a medical emergency?
– Is this symptomatic or asymptomatic?
– Is this acute, chronic, or acute-on-chronic?
* Acute <48hrs
Hyponatremia correction formula:
– Volume infusate to give = TBW x (desired Na – Serum Na)/ [Na] infusate
– Infusate = solution you choose to give
* Hypertonic saline 3%- 513mmol/L Na
* Normal Saline 0.9% - 154mmol/L Na
* Ringers Lactate- 130mmol/L Na
TBW= Total Body Water
Female- 50% of Wt (Kg) or Wt (Kg) x 0.5
Hyponatremia: Severe Symptoms
Severe and symptomatic (usually also acute).
* (ie) 60 kg woman presenting with seizures, Na of 110.
– Goal: increase serum Na by 4-5 mmol/L immediately
– Volume infusate to give = TBW x (desired Na – Serum Na)
[Na] infusate
* = (60kg x0.5) x (115 – 110)
513
* = 0.292L ~ 300mL
– Therefore, give ~300cc of 3% saline to raise this patient’s serum Na by
5mmol/L
Non-acute hyponatremia
- If not symptomatic/acuteà there is time
- Hypertonic saline usually not needed (some exceptions likely not for the
scope of this exam)
Obtain Uosm, S osm, Una
* Stop thiazides
* Thorough history (medications, diet, fluid intake, volume status)
While waiting for tests:
* If they are hypotensive -> bolus and repeat levels
* If they are hypovolemic -> 1ml/kg/hr
Hyponatremia Etiology
- Hyponatremia is a problem of too much water in the body
Too much water comes from
1. Too much water intake compared to salt
– Psychogenic polydipsia, beer potomania, D5W
– ADH off – pee out excess water –dilutes urine –low urine osm (<200)
High Water:Solute intake
* ADH is appropriately off (U osm <200)
- Causes
– psychogenic polydipsia- urine osm typically <100
– Beer potomania/tea and toaster: low solute diet –Urine osm ~100-300 - If you only eat 200 mOsmol/day and can only dilute urine to 100
mOsmol/L, max UO = 2L/d. Drink more than 2L/day, and you will retain
free water and drop Na
– Iatrogenic: eg IV D5 ++
– Treatment: Fluid restrict, salt/urea tabs (increases solute load AND will
increase water diuresis)
- Reabsorption from urine (ADH mediated) – ADH on –reabsorb water from urine –concentrate urine + dilutes the serum – high urine osm (>300) + hyponatremia
– ADH is on because of appropriate and inappropriate reasons
Inappropriate ADH secretion (U osm >300, Una>40)
1. SIADH
* Nausea/vomiting, Pain, Drugs- TCAs, SSRIs, carbamazepine, ecstasy/MDMA, Thiazides, CNS disorders, tumors (SCC
lung), Pneumonia/ lung infections, adrenal insufficiency, hypoT4
– Treatment: fluid restriction (next step is to add salt tablets 1 g BID/TID and/or urea 15 mmol BID)
Appropriate ADH secretion (U osm >300, Una<25):
1. True hypovolemia
– Causes: burns, bleeds, GI losses, pancreatitis
– Treatment = fluid resuscitation (NS/LR) (1ml/kg/hr)
2. Decreased effective circulating volume
– Causes: CHF, cirrhosis, hypoalbuminemia
– Treatment: Optimize underlying condition, Furosemide, Water restriction
Over-Correction of Hyopnatremia
Tip: “If urine output exceeds 150 ml/hr page MD”
– Indicates that ADH has turned off and patient will suddenly start
peeing free water thus raising serum sodium faster than
expected
– IF overcorrected:
– DDAVP
– D5W
– Call nephro
targret 6-8mmol/L per 24 hours
(4-6 if risk factors)
Hyponatremia pearls
Isotonic hyponatremia (sOsm 280-295): Pseudohyponatremia -hypertriglyeridemia
-paraproteinemia (multiple myeloma)
-obstructive jaundice
Hypertonic (sOsm >295) hyponatremia -hyperglycemia
-mannitol
-Immunoglobulins (IVIG)
Hyponatremia in the dialysis population: they’re drinking too much water
inbetween sessions! Treatment : fluid restriction (not salt restriction)
Management of Hypernatremia
Dehydration or Free Water Deficit
1. Calculate Water Deficit= % change in [Na] x TBW
– Where % change in [Na] = Serum Na- 140
140
- Determine rate of correction of water deficit:
– Acute (e.g. postop central DI, nephrogenic DI): Correct quickly (rare)
– Chronic (e.g. dementia LTC patients): Correct water deficit slowly: maximum 0.5 mmol/L
per hour/ 12 points over 24 hours (Avoid cerebral edema!)
* IF POSSIBLE USE ENTERAL ROUTE (If NG, give free water flushes)
* Large volumes of D5 –>hyperglycemia –> glucosuria & a solute diuresis, worsening polyuria and
hypernatremia
Diabetes Insipidus (DI)
Clinical clues: polyuria + hypernatremia
– (and polydipsia if patient is able to drink)
* Types of DI:
– Central DI (brain can’t make/secrete ADH)
– Nephrogenic DI (kidney can’t respond to ADH)
– causes: Lithium, hypercalcemia, hereditary, resolution of obstructive nephropathy
Diagnosis:
– Step 1: One of:
* Labs: high serum Na with inappropriately low urine osmolality confirms diagnosis
* Water deprivation test: Urine osmolality does not rise appropriately despite
rising serum osmolality/ serum Na
– Step 2: DDAVP (2-4 mg IV/SC) test to differentiate between central and nephrogenic DI
Hyperkalemia- Causes
Increased intake – unlikely to be sole cause
Decreased excretion
– Decreased tubular flow: CKD, Volume depletion – Drugs- ACEi/ARB, NSAIDs, MRAs
-Hypoaldosteronism: adrenal insufficiency, RTA type 4
* Shifting
– Cell lysis- TLS, Rhabdo, burns
– Metabolic- Acidosis, low insulin
– Hyperosmolarity: glucose, mannitol
– Familial hyperkalemic periodic paralysis
*
Factitious
– Fist clenching/ tourniquet – Hypercellular blood ( ie- heme malignancies)
* High WBCs, thrombocytosis * Do a VBG/ABG! – no tourniquet and no centrifuge
= no hemolysis in tube
– Hemolyzed sample
Treatment of Hyperkalemia
Treat hyperkalemia with C-BIG K:
C- calcium gluconate 1g IV – stabilize the heart
B- beta agonist (Ventolin)/ Bicarbonate
I-insulin (10 units insulin R IV)
G- glucose (1 amp D50 BEFORE insulin)
K- K removal: Furosemide/K binders/ dialysis
Potassium Binders
1) Lokelma/ sodium zirconium cyclosilicate (ZS-9) * Exchanges Na and H+ for K in the GI tract
– See drop in K within 2-4 hours of administration
* Safety shown in patients with CKD, can be used long term to facilitate continued RAAS
blockade (HARMONIZE trial)
* Safety shown in IHD patients with chronic pre-HD hyperkalemia (DIALYZE study)
* Side effects- edema, GI symptoms,
* $$$ a barrier, off formulary typically
2) Patiromer: binds K in the colon, in exchange for Calcium
3) Kayexalate (Polystyrene sulfonates)
- exchange Na+ in stomach for H+, which is then exchanged in colon for K+ and resin
is excreted
- Caution if GI obstruction, risk of hypoCa and hypoMg also
- Associated with cases of colonic necrosis, bleeding, ischemic colitis, perforation
Hypokalemia- causes
- Decreased intake
- Check Serum Mg!
- Shifting (usually causes acute hypokalemia)
– Endocrine causes
* ++Insulin, thyrotoxic periodic paralysis
– Stress: ++ catecholamines
– Acid/base- Metabolic alkalosis
– Alcohol withdrawal
– Hypothermia
– Drugs
* Amphetamines, antipsychotics (rare)
Chronic hypokalemia: K loss
Step 1: Check urine lytes
Extra renal: Low urine K < 20*
I.E. Diarrhea, laxatives, villous adenoma
*In real life look at Urine K: creat ratio
(<2 with extra renal loss, > 2 renal)
Renal Loss (Urine K> 20)
Step 2: acidosis vs. alkalosis
-Met Acidosis- Type 1 or 2 RTA
Met Alkalosis- Step 3
Hypertensive vs.
Normo/ hypotensive
Hypertension- Low Renin/ Low Aldo:
e.g. Cushings, Liddles,
Licorice, Florinef,
steroids
High Renin/ high Aldo:
e.g. RAS/Reninoma
Low Renin/ high Aldo:
Adrenal problem
e.g. Conns
Normo/ Hypotensive:
Urine Chloride-
Urine Cl <20:
Vomiting or intermittent
diuretic use ( already
“worn off”)
Urine Cl > 20: Barrter.
Gitelman
or recent diuretic use
HTN- first line therapy
Long-acting thiazide (chlorthalidone)/thiazide-like diuretics preferred over
hydrochlorothiazide (HCTZ)
– Watch for hypoK + hypoNa if using thiazide monotherapy
* ACEi monotherapy
– Do not use in Black patients without other indications
– Not first line in isolated systolic hypertension
* ARB
* Long-acting CCB
* β-blockers can be considered first line only if <60 years old
– Do not use alpha-blocker first line
BP Targets – CKD
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 Less Certaintin for tHE Patients EXCLUDED FROM SPRINT
– Post transplant: long term <130/80, use DHP-CCB or ARB first line
Hyperaldosteronism: – Who to Screen: Patients with hypertension AND 1 or more:
- Unexplained spontaneous hypokalemia <3.5 or marked diuretic related hypokalemia <3.0
- Htn & resistant to treatment with ≥ 3 drugs
- Incidental adrenal adenoma AND Htn
How to Screen
* Plasma aldosterone and plasma renin activity or plasma renin concentration
* Do not use plasma renin conc. In women on OCP (false +)
* Drugs that interfere (MRAs > ACEi/ARB»_space; BB, CCB)
* Hold MRA, K sparing and K wasting diuretics at least 4 weeks prior to testing
* If result non diagnostic, hold ACE/ARB, BB, DHP-CCB 2 weeks and repeat testing
* BP meds that do not interfere: alpha blockers, non DHP CCBs, hydralazine
– If screening test positive do confirmatory test with:
* Saline loading test (2L NS over 4h, measure plasma aldo afterward, abN if >280 pmol/L
* Captopril suppression test
* Plasma aldosterone to renin ratio > 1400 pmol/L/ng/mL/h (or > 270 pmol/L/ng/L), with plasma
aldosterone > 440 pmol/L ((HTN 2020)
Renovascular HTN- who to screen and How
Who to screen
– Patients presenting with 2 or more of the following
* 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 emergency
- How to Screen
– Any of: Renal Doppler US, captopril renogram, MRA, CTA - Avoid captopril and CTA if renal GFR <60 ml/min/1.73m2
ACEi or ARB not contraindicated with bilateral renal artery stenosis
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
Pheochromocytoma – Who to Screen and How to screen
Paroxysmal, unexplained, labile, and/or severe (≥ 180/110) sustained HTN refractory to usual
therapy
– HTN + symptoms of catecholamine excess (headaches, palpitations, sweating, flushing)
– HTN triggered by beta-blockers, MAO-Is, surgery, anesthesia, micturition
– Incidental adrenal adenoma
– Hereditary causes– such as Von-Hippel-Lindau, MEN 2A or 2B, neurofibomatosis type 1
How to Screen
– Biochemical screening test first
– YES ✓ – 24hr urine total metanephrines and catecholamines (and Creatinine to ensure
adequate collection)
– MAYBE – Plasma free metanephrines and free normetanephrines may also be considered
– NOT ❌ urinary VMA
FMD related Renal Artery Stenosis- Work-up
Work up for FMD if Htn and one of 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
* Once FMD is confirmed:
– Screen vasculature from head to pelvis with either CTA or MRA
(cervicocephalic lesions, intracranial aneurysms, lesions in other vascular
beds)
Hypertensive Emergency
Elevated BP + evidence of end organ damage
– Pulmonary edema, cardiac ischemia, neurologic deficits, acute renal
failure, aortic dissection, and eclampsia
Treatment:
1) Admit to Step down/ICU level of care for continuous BP
monitoring
2) Lower BP by 20-25% only within first 1-2 hours
* Lower the blood pressure by 25% in 1-2 hours and then to
160/100 over the next 2-6 hours, and then gradually to normal
over few days
* Certain conditions (ie. Aortic dissection, eclampsia) may require
rapid control of BP whereas other conditions (ie stroke) require
even slower lowering of BP (<15% lowering)
3) Use of IV medications to lower BP (rapid acting and easily
titratable)
* Oral meds may have delayed GI absorption and can suddenly tank
BP if they’re all absorbed at a later time
4) IV med options: IV labetalol, esmolol, nicardipine, hydralazine,
nitroglycerin
5) Transition to PO medications and transfer to wards
6) Consider work up of secondary hypertension
Interpreting urine microscopy
AIN or pyelonephritis= WBC casts
ATN=Muddy brown casts
Glomerular disease:
-Nephritic- RBC casts &
dysmorphic RBC
-Nephrotic-Oval fat bodies
or fatty casts
Glomerulonephritis- Anti-GBM disease
Fulminant disease, limited to lung and kidney
– Called Goodpasture’s if RPGN is accompanied by pulmonary hemorrhage
* Treatment:
– Pulse corticosteroids
– Cyclophosphamide
– Plasma exchange (until 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 6 months/ Cyclophosphamide 2-3 months
* No maintenance therapy!
Pauci-immune / ANCA Vasculitis
Microscopic Polyangiitis (MPA)
Granulomatosis with polyangiitis (GPA)
Eosinophilic granulomatosis with polyangiitis (EGPA)
Clinical features:
– Constitutional symptoms
– Arthralgias, rash
– Sinusitis, asthma,
pulmonary hemorrhage
– Nephritis
– Mononeuritis multiplex
Pauci-immune / ANCA Vasculitis - treatment
INDUCTION: Methylprednisolone up to 1g x 3 days + Cyclophosphamide or Rituximab
RPGN, Creat > 354 à 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)
Also consider PLEX:
KDIGO: If ANCA+ GN vital organ / life threatening, Creat > 500
ACR: Patients at ↑ risk of progression to ESRD (accept a potential ↑ risk of infection)
Immune complex: Low C3 nephritis
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 if considering other glomerular disorders, or course varies from typical trajectory
i.e. severe AKI requiring dialysis: this is uncommon with PSGN
Immune complex: Low C4 nephritis
Low C4: MPGN
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
Hepatitis C and CKD- recommendations
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…”
Immune complex: Low C3/C4- SLE- dx and tx
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
Immune Complex: Normal C3/C4- IGA nephropathy dx and tx
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 - 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)
What is nephortic syndrome?
Nephrotic Syndrome:
* Nephrotic range proteinuria (>3.5g)
* Edema
* hypoalbuminemia
* Dyslipidemia & lipiduria
Management of Nephrotic Syndrome
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, add other diuretics as needed)
– Hypercholesterolemia: Statins, heart healthy diet
– Proteinuria: ACEi, BP control
– Thrombosis: CONSIDER “Prophylactic” full-dose anticoagulation w 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
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
Buzzword Infections and GN
- HCV renal disease: MPGN +/- cryoglobulinemia
– Classically low C4 (but not always); high RF
– Clinically: nephritic/proliferative picture, palpable purpura, arthralgias,
weakness, peripheral neuropathies - HBV renal disease: membranous, MPGN, polyarteritis nodosa (PAN)
– 1-5% of patients with HBV develop PAN (think of this if stem points to PAN)
– Clinically: pre-renal AKI, renal infarcts with PAN - HIV-associated nephropathy (HIVAN): collapsing FSGS
– Clinically: Black males, advanced HIV (CD4 <200), nephrotic, high Cr
– Treatment: HAART and RAS blockade
Common causes of AKI
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
Acute interstitial nephritis [AIN]- causes and tx
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
– Immunotherapy - Treatment
– Remove offending agent.
– If severe renal failure, often biopsy – especially if requiring dialysis!
– In select cases, consider empiric glucocorticoids if severe renal failure, but also arrange for bx.
Contrast Induced Nephropathy
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
Rhabdomyolysis
- 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
Causes of AKI in transplant
ACUTE REJECTION! (always suspect this)
– Often varying degree of proteinuria, hematuria – Requires biopsy to diagnose
– Immunosuppressive med levels can be low
* Medication induced (Cyclosporine, Tacrolimus)
* Reversible, bland sediment, no blood or protein, immunosuppressive med levels will be high
* 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 with dopplers
* Hydronephrosis
* Recurrence of primary disease
* PTLD (later complication)
* (Causes of AKI in native kidneys)
Causes of AKI in Cancer Patients
- Secondary to chemotherapy
– Volume depletion from nausea, vomiting, diarrhea
– Sepsis from immunosuppression
– Chemotherapy related nephrotoxicity (cisplatin, carboplatin, mtx, gemcitabine, paclitaxel, doxorubicin, vincristine) -> can
be directly nephrotoxic or cause TMA, AIN, hypertension - Secondary to malignancy spread
– Tumor infiltration of the kidney (seen on renal imaging)
– Obstructive nephropathy from retroperitoneal lymphadenopathy (seen on renal imaging) - Hematologic emergencies
– DIC (hemolysis)
– TLS (high K, high uric acid, high phos!) - Hypercalcemia
- GN (membranous nephropathy à will see nephrotic range proteinuria)
- Malignancy specific
– Multiple myeloma à Cast chain nephropathy (will cause non albumin proteinuria)
– Waldenstrom à hyperviscosity
– Amyloid à fibril deposition (congo red positive + nephrotic range proteinuria)
Common Nephrotoxic Drugs
- Contrast (see AKI with Angiography slide)
- ACEi / ARB: pre-renal azotemia/ischemic ATN
– Failure of efferent arteriole to constrict if volume contracted
– Usually concomitant history of poor PO intake and/or GI losses - NSAIDs: pre-renal azotemia/ischemic ATN, AIN, membranous nephropathy, minimal change
disease
– Prostaglandin inhibition- constriction of afferent arteriole (mechanism of pre renal) - Lithium: tubular disease
– Nephrogenic DI
– Chronic tubular-interstitial disease (use amiloride) - Aminoglycosides/cisplatinum chemo: toxic ATN/ tubular injury
– Non-oliguric; - Vancomycin: rare; mechanism unclear, associated with supratherapeutic levels – Recent systematic review/ meta analysis in Critical Care Med: continuous infusion of vanco associated
with 53% reduction in odds of AKI (Flannery et al. June 2020) - PPI’s: Acute interstitial nephritis
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
Prevent progression: CKD Targets
- 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: (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 à 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
àIn 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
Summary of targets in CKD
– Hb 100-110, Tsat >30%
– 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
Management of Complications in CKD - hemoglobin
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
Management of Complications- K & H
Hyperkalemia: target K <5
– Potassium-restricted diet
– Diuretics may help
– K binders (sodium zirconium)
– Avoid NSAIDs, look at other medications
- Metabolic acidosis: target normal HCO3
– Sodium bicarb tabs to keep HCO3 >22
– RCT evidence to slow decline in GFR!
Management of Complications – Ca & Phos
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
Hypocalcemia: target normal Ca
–Decreased 1-α-hydroxylase activity
–Rx: calcium carbonate and calcitriol (1,25 Vit. D)
**Can’t use vitamin D if hyperphosphatemic
Management of Complications - PTH
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 (calcimimetic): activates Ca-sensing receptor to shut off PTH secretion
– Surgical parathyroidectomy in selected patients
Management of Complications CKD - Osteoporosis
Management of Complications - Osteoporosis
- 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)”… - In real life:
- 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-OP meds are not the answer for dialysis patients
Indications for Dialysis
- Urgent/In hospital indications: 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
Note: Anuria/oliguria is technically NOT in itself an indication to start
**AKIKI and STARRT AKI (see bonus slides for trial summaries) - Non-urgent/Outpatient
- Uremic symptoms/ Quality of life
Uremic Symptoms on History
- 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
CKD and Diabetes- management
First line for diabetes with CKD
1. metformin (gfr >30)
* eGFR 30-44 – initiate at 1⁄2 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 (empa, cana), Hospitalization for HF, Progression of nephropathy
Add On:
1. GLP 1 agonist
↓ MACE (liraglutide, semaglutide)
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 – now in Canada)
– For DM2, gfr >25 ml/min, normal K, albuminuria 30mg/g despite max RASi
Clinical evaluation of the kidney (UA)
Urinalysis dipstick
– Protein: hypertension, diabetes, MM, GN, orthostatic proteinuria, nonpathological (illness, fever, exercise, pregnancy)
– Glucose: DM, pregnancy, SGLT 2 inhibitor, tubular dysfunction (MM)
– Ketones: starvation, DKA, alcohol, poisoning
– Leukocyte esterase and nitrites
- Urinalysis microscopy
– Erythrocytes > 3 - Isomorphic vs dysmorphic
- blood on dipstick with negative erythrocytes = rhabdomyolysis, hemolysis, mechanical valve
– Leukocytes > 5 : infection
– epithelial cells
- Squamous: contamination. Renal tubular epithelial: ATN, transitional : ureters
- Casts:
– Hyaline cast: CKD
– WBC cast: AIN or infection
– RBC cast: GN
– Granular cast: ATN
– Tamm Horsfall : normal - Crystals
– Calcium phosphate, calcium oxalate, uric acid, struvite
Imaging of the kidneys
Ultrasound
– Echogenicity: acute or chronic parenchymal disease
* Kidney stone: non contrast CT
* Hematuria: CT urography or cystoscopy
* Renal mass: MRI
* Doppler/CTA/MRA: renal artery stenosis
Kidney biopsy
- Indications: nephrotic/nephritic, especially when it will change management
- Risks:
– Most common complication: bleeding (hematuria is expected), pain at biopsy site
– Need for transfusion 1%, requirement for intervention to control bleeding < 1%, death 0.06% - Medication management
– Ideally would be best to stop antiplatelets 5 days before and resume 5 days post biopsy. But research shows that
patients continuing asa at time of biopsy did not report increased risk of bleeding
– Anticoagulation: involve a specialist! Individualize management - Warfarin: allow INR < 1.5, * bridge with heparin depends on patient
- IV heparin: stop 6 hours prior and allow apTT to normalize, resume 12-24 hours later
- LMWH: stop the day prior and resume 48-72 hours later
- DOAC: there is no data
– DDAVP is commonly given to prevent bleeding
– Blood pressure should be controlled < 160 pre biopsy - Contraindications:
– UTI, uncooperative patient, bleeding diathesis, uncontrolled hypertension, poor visualization, infection
– Relative: solitary kidney, hydronephrosis, small kidneys
LUMPS IN THE KIDNEY- renal cysts management
Renal Cysts - Bosniak classification (based on CT)
(CT preferred, however it is with Contrast! If CKD or contraindication to contrast: radiologists will also classify based
on US)
* Bosniak 1 and 2: <5% are cancer
– Simple cysts with thin walls, no (stage 1) or fine (stage 2) calcifications, and no (1) or thin (2) septae, no enhancement
– No need to follow up
- Bosinak 2F (F for ‘follow-up’) – approx 10% are cancer
– Smooth, minimally thickened wall. May have multiple septa, but smooth without contrast enhancement
– Needs active surveillance: repeat imaging at 6 mo, 12 mo, then yearly - Bosniak 3: 50% are cancer
– One or more enhancing thick or irregular walls or septa - Bosniak 4: 90% are cancer
– Like Bosniak 3 but also have a solid enhancing nodule
Bosniak 3 and 4 should be referred for partial nephrectomy
– If not fit for surgery, go for perc biopsy or active surveillance. Possible thermal ablation if candidate
Solid Renal Mass-dx
Solid Renal Mass
* Image CT or MRI
* <1cm: too small to really workup
– Needs active surveillance
* >1cm: vast majority are actually cancer
– If scan shows lesion is clearly an angiomyolipoma, then no further w/u is needed
– Otherwise, first check for metastases, then:
– If life expectancy >5 years, partial nephrectomy
– If life expectancy <5 years, or not fit for surgery,
consider perc biopsy, active surveillance or thermal
ablation (Beyond the scope of this exam!)
Autosomal Dominant Polycystic KD (ADPKD)- dx
- Polycystic Kidney Disease is an autosomal dominant disorder resulting in growth of renal cysts that
destroy normal renal parenchyma - Affects 1/1000 live births
- Diagnosis done by family history and imaging: Unified Criteria
in absence of family history, NO validated criteria to diagnose ADPKD based on US imaging
PKD1 progresses faster than PKD 2
Unified Criteria (for US diagnosis of
ADPKD in patients with + family
history):
-If age 15-39 ≥ 3 cysts total
-If age 40-59 ≥ 2 cysts per kidney
Common symptoms:
– HTN
– pain- most common symptom; abdo pain common in cyst rupture
– hematuria- often from cyst rupture, proteinuria
– Stones- uric acid stones , Ca Oxalate
– UTI- 4 weeks antibiotics if infected cyst!
– concentrating deficit- thirst, polyuria, polydipsia, nocturia
– Erythrocytosis- ↑ epo levels
– Extra-renal manifestations- liver cysts, diverticuli, cerebral aneurysms, pancreatic cysts
Mitral Valve Prolapse/ AI most common cardiac anomalies
ADPKD- Treatment
Recommend all ADPKD patients be referred to nephrology for initial assessment,
which should include imaging and consideration of genetic testing
* Diagnose on imaging:
– If known family history of PCKD– Ultrasound is serially preferred imaging
– If no prior family history, US, MRI, or CT can be used
– ALL patients should have baseline imaging to assess total kidney volume (TKV)- preferred
method is MRI or CT
– Follow up imaging should not exceed a frequency of once yearly
- Treatment
– Sodium restriction to <2g/day, high fluid intake
– 18-50 years with eGFR >60 and without significant CV morbidities target BP of ⩽110/75 mm
Hg
– Tolvaptan therapy for specific patients– For reference only, outside the scope of this exam - TEMPO candidates: 18 to 50 years with TKV >750 mL and eGFR >60
- REPRISE candidates: 18 to 55 years with eGFR of 25 to 65 OR 56 to 65 years with eGFR of 25 to 44
with evidence of a decline in eGFR >2/year
Nephrolithiasis-patho
- Pathogenesis:
– Increased excretion of solutes: calcium, oxalate, uric acid
– Decreased urine volume
– Abnormal urine pH - Alkaline: calcium phosphate, struvite
- Acidic: calcium oxalate – most common, uric acid, cysteine (AR, genetic)
– Absence of inhibitors: citrate, magnesium
– Structural kidney disease - General work-up (outside of acute setting):
– Urinalysis, urine culture
– Electrolytes, Cr, Ca, PO4, PTH, uric acid
– 24 hour collection for volume, Na, Ca, PO4, uric acid, oxalate, citrate, Mg,
– Urine Creat (to assess for adequate sample)
Heme Malignancies and the Kidney
Myeloma Kidney (Seen with myeloma and
other monoclonal gammopathies)
– Cast nephropathy
– Light chains both toxic to and clog tubules à AKI
– Other mechanisms of AKI: hypercalcemia, hyperviscocity syndrome (Waldenstroms)
– Tubular proteinuria, but dipstick negative
(dipstick for albumin only!)
– Fanconi’s like syndrome
– Risk factors: NSAIDs, Lasix, IV contrast
– Treat the myeloma
– Extracorporeal methods to remove SFLC
(plasmapheresis and high cutoff dialysis) can be
used as adjunctive therapy – not great evidence
and not for the scope of this exam
Amyloid Kidney
– Deposition of fibrils in tissues
– Congo red positive, apple-green birefringence
– Deposit in glomerulus- leak albumin à
nephrotic syndrome
AL amyloid: clonal light chains deposit in
glomerulus
– Treat with chemotherapy
Other: MGRS (monoclonal gammopathy of
renal significance – multiple etiologies)
Note AA amyloid: chronic inflammatory
disease leads to amyloid creation, deposits in
kidney – Treat underlying disease: e.g. RA, TB, chronic osteomyelitis
