Estimating CrCl/GFR

Elderly: CG IBW

Obese: CG IBW (ABW if BMI > 40) or CKD-EPI individualized for BSA

PK Changes

A: ↓ = ↓ peristalsis, gut edema, chelation interactions; ↑ = uremic CYP inhibition and ↓ 1st pass

D: ↓ protein binding due to hypoalbuminemia and displacement by uremic toxins; ↑ Vd due to tissue
protein binding

M/E: ↓ renal clearance of renally-eliminated drugs…duh. ↓ CYP transcription/direct inhibition due to

uremia

CKD stages (the ones where we care)

- 3a: 45-59
- 3b: 30-44
- 4: 16-29
- 5: <15

If drug renally eliminated, can either ↓ dose or ↑ interval

Albuminuria stages: A1 (ACR <3), A2 (ACR 3-30), A3 (ACR >30)

CV risk factor targets

- Blood pressure < 140/90 (130/80 if diabetic CKD with ACR > 3)
- AIC < 7% (if type 2 DM), FBG between 4-7 mmol/L (if type 1 DM)
- ACR ≤ 3
- LDL < 2 or >50% reduction

ACEI/ARB monitoring

- SCr and serum K+ : At baseline and in 1-2 weeks (after initiation and dose change); up to 30%
increase in SCr expected (reduce dose if 30-50% increase, if>50% increase, d/c)
- Avoid K+-sparing diuretics and restrict dietary K+; may stop ACEI if K+ > 5.5
- ADRs: hyperkalemia, orthostatic hypotension (dizziness, fainting, falls), dry cough (ACEI > ARB),
angioedema (ACEI > ARB)
- Benefits: ACEIs/ARBs ↓ BP and albuminuria, ↓ CV mortality and slowing progression of CKD
- Albuminuria and CKD ↑ CV events
- Indications: CVD, >55yo with CV risk factors, diabetic microvascular complications
- Agents/protective doses: perindopril 8 mg daily, ramipril 10 mg daily, telmisartan 80 mg daily
(8,10,80)

Diagnostic criteria for CKD

- ≤ 60 ml/min or 2/3 ACRs ≥ 3 for 3+ months

Sick day management (diabetes))

 - If unable to maintain adequate hydration when sick, avoid:
- Sulfonylureas (hypoglycemia)  Glyuride, Glimeperie, Gliclazide
- ACEIs, aliskiren  “pril”
- Diureticsfurosemide, HCTZ, spironolactone, etc
- Metformin (lactic acidosis)
- ARBs
- NSAIDs
- SGLT2 inhibitors  “flozins”

Bolded can cause drug-induced pre-renal acute renal failure in hypovolemic patients.

DM2 Treatments in CKD

- CV/CKD benefit: (all decrease by increments of 15)

- Canagliflozin (avoid < 45 ml/min/1.73m2; do not initiate if < 60)
- Empagliflozin (avoid < 45 ml/min/1.73m2)
- Metformin (avoid < 30 ml/min/1.73m2)
- Liraglutide (avoid < 15 ml/min/1.73m2)

Dializability of CV meds

- ALL ACEIs ( except fosinopril)

- ALL Beta blockers (except bisoprolol).
- No : ARBs, CCBs, and α blockers are dialyzed.

Diuretics :

- Furosemide (Loop diuretics): require no dosage adjustment with declining renal function.
- HCTZ (Thiazide diuretic): Does not work well <30 ml/min.
- Spironolactone, Eplerenone( K+-sparing diuretic): Avoid due to hyperkalemia risk.

LDL-lowering in CKD

- No statins in dialysis.
- Use low doses of statins pre-dialysis if primary prevention; use high dose if secondary
prevention
- Atorvastatin: 1° (20 mg daily), 2° (80 mg daily)
- Rosuvastatin: 1° (10 mg daily), 2° (40 mg daily)
- Simvastatin: 1° = 40 mg daily (20 mg with 10 mg ezetimibe)

Lifestyle modification

- Smoking cessation
- Diet (low fat, low sodium, be mindful of carbs if diabetic)
- Exercise
- Weight loss

Metabolic acidosis

- Sodium bicarbonate slows progression of CKD in patients with metabolic acidosis.

 - Bicarb target: >22 mol/L
- Oral tabs/injection; not in dialysis since part of dialysate
- Avoid baking soda!

Hyperkalemia (Serum targets)

- Target: 4-5 mmol/L (>5.5 concerning, >6.5 or ECG changes = emergency)

Hyperkalemia (Non-pharmacological treatment)

- Restrict dietary K+/supplements

- Attend dialysis if on dialysis
- Correct underlying metabolic acidosis

Hyperkalemia (Pharmacological treatment)

- Kayexalate (sodium polystyrene sulfonate): non-urgent K+ lowering; mix 30g with 125 ml of
water (not juice!); Avoid oral suspension due to colonic necrosis; Space 3h from all PO meds
- Insulin+dextrose( emergency): shifts K+ into ICF
- IV calcium (emergency) reverses cardiotoxicity
- Dialysis

Bowel prep in CKD

- Recommended: PEG 2L + bisacodyl 10-15 mg

- Avoid: PO42-/PO43-, Mg2+, Na+ picosulfate, and citric acid-based regimens

Autosomal dominant polycystic kidney disease (ADPKD)

- Tolvaptan (vasopressin receptor antagonist) prevents cyst growth and slows decline of renal
function in ADPKD patients.
- Requires liver enzyme monitoring as potential for liver damage.
- Given as 2 doses per day (1 large dose in am and 1 small dose in pm since want to avoid
urination at night; reverse order if shift work at night); titrate dose q3 months prn
- Interactions: substrate of 3A4/pgp so avoid 3A4 and pgp inhibitors/inducers

Bones and CKD

In CKD:

- ↑ PO4 due to ↓ excretion (PO4 can complex with Ca2+ and ↓ free Ca2+); complex causes
vascular calcification; also ↑ PTH
- ↓ Ca2+ due to above and because kidney cannot activate vitamin D = ↓ GI Ca2+absorption and
Ca2+ mobilization
- ↑ PTH due to hypocalcaemia = ↑ PO4 and ↑ Ca2+ reabsorption except kidneys suck so must
increase Ca2+ by promoting bone resorption = bone problems (osteomalacia, fractures, osteitis
fibrosa cystica)
- ↑ acid due to ↓ renal excretion = metabolic acidosis; associated with Ca2+ loss and ↑K+
Hyperphosphatemia and 2° Hyperparathyroidism

- Targets (stage 5 CKD): PO4 < 1.8 mmol/L, PTH < 55 pmol/L, corrected Ca 2.2-2.5 mmol/L

Hyperphosphatemia treatment

Phosphate binders (up to TID since taken with meals; space 2h from oral iron, levothyroxine,
fluoroquinolones, and tetracyclines)

- Calcium carbonate/acetate: max out calcium first (max 2g elemental/day); can make case for
coverage of other binders if insufficient response or hypercalcaemia; constipation
- Sevelamer: do not chew/crush, covered in NS; N/V, diarrhea/constipation
- Lanthanum: chew, covered in NS with conditions; N/V, diarrhea/constipation
- Magnesium hydroxide: avoid since diarrhea

Hyperparathyroidism treatment (DON’T use below if : if ↑ Ca2+ or ↑ PO4– use above)

Vitamin D analogues : Calcitriol and Alfacalcidiol

- Calcitriol (po/inj): fully activated

- Alfacalcidol (po): requires liver activation so avoid if hepatic impairment
- ADRs: N/V, itching, headache, constipation, loss of appetite
- Initial dose: 0.25 mcg/day (titrate q4-12 wks); covered in NS

Cinacalcet  Only if: PTH > 88 on 2 occasions that are 6 weeks apart (hyperparathyroidism) – the
normal pth levels are between 0.6-55 pmol/L

- ADRs: N/V, diarrhea, hypocalcaemia

- PK: 2D6 inhibitor, 3A4 substrate; not dialyzable (not covered if not on dialysis)
- Take whole with food.
- Monitoring: Assess PTH in 4-6 weeks, Ca2++PO4 once/week for 3 weeks

Anemia in CKD

Targets: TSAT > 20%, Hgb 95-115 g/L, ferritin > 200,

- If :TSAT <20% and Hgb < 100 g/L: Give PO or IV iron (PO first; if not successful -> IV)
- If TSAT < 20%, switch to IV Iron

PO Iron (200 mg elemental/day needed): (This is to raise TSAT, not Hgb)

- Gluconate:30mg,Sulphate:60mg,Fumarate:100mg

IV: iron sucrose (Venofer): Watch pt for 30 minutes post-IV for allergic reaction

- *Check TSAT and ferritin 7 days after ANY IV formulation ***

When TSAT > 20% + Hgb <95:

- Initiate ESA (TSAT target has been reached; now want to↑ Hgb to 95-115g/L; but the
patient should continue their maintenance dose of iron to maintain TSAT>20%)
 - SC epoetin- Dose: 50-100 U/kg . Frequency: once/week. (T1/2=30 hours)
- IV epoetin: Dose: 50-100 U/kg. Frequency: 3 times/week (T1/2=5-11 hours)
- IV/SC darbepoetin: Dose: 0.45-0.9 mcg/kg Frequency: once/wk(dialysis), once/2weeks if
pre-dialysis
- *Titrate : ↑ Any or ↓ must be 25% of the dose; do not exceed >10 g/L increase in Hgb
during any 2-week period

Anemia For HD and PD:

- Start ESA when HgB=90-100 g/L, but never when HgB<90 g/L. Target: 95-115 g/L
- Assuming iron stores (TSAT>20%): Continue iron maintenance dose if on iron
- If Hgb level < target (90-95g/L): ↑ ESA dose
- If Hgb level > target (>115g/L ) ↓ ESA dose or hold to prevent ↑ BP (stroke/MI risk)

Pruritus

- Uremic causes: dry skin, anemia, inadequate dialysis, hyperparathyroidism

- Non-pharm: moisturizers
- Local (Pharm): topical corticosteroids
- Generalized (Pharm): antihistamines, gabapentin, pregabalin (renal dose adjustment required!)

Restless leg syndrome (RLS)

- Likely causes in CKD: drug-induced (antipsychotics, metoclopramide, antidepressants,

stimulants, carbamazepine, lithium), iron deficiency anemia
- Non-pharm: discontinue offending substance if possible, move legs during dialysis
- Pharm: pramipexole/ropinirole or gabapentin/pregabalin (renal dose adjustment!)

Dosing of common drugs in CKD

Anticoagulants

- NOACs: avoid if CrCl < 30 EXCEPT apixaban < 15); dabigatran dialyzable (80%)
- Warfarin: adjust dose based on INR (no adjustment baed on CrCl)
- LMWH (Dalteparin, Tinzaparin, Enoxaparin): adjust dose if CrCl < 30

Antibiotics

- Most require renal dose adjustment;

- Exceptions: cloxacillin, azithromycin, clindamycin, metronidazole, doxycycline, moxifloxacin) –
– DM CAM :CC TO ALL
- Mnemonic: Likes: Moxi’s boobs + Clits, Dislikes: Chlamydia 1st line tx and getting clox’d in the
face while getting on the Parisian metro
- Monitor levels of : Aminoglycosides and Vancomycin.
- For dialyzable antibiotics: dose after dialysis.

Analgesics

Avoid: [Morphine,Mepiridine, Codeine] (active/neurotoxic renally cleared metabolites)

Caution: oxycodone, tramadol, TCAs

 Preferred: [Hydromorphone, Fentanyl, Methadone], Gabapentin, Acetaminophen

Gout drugs (A and C come first; higher adjustment, F comes later, lower adjustment)

- Allopurinol: adjust dose < 50 ml/min

- Febuxostat: Avoid if < 30 ml/min.
- Do not use NSAIDs tx; use Colchicine : adjust dose < 50 ml/min
- Mnemonic: Allo, did you Col me 50 times/min? iSAID, STOP it, I’ll be on the bux in < 30
mins, STAT!

Other

Adjust doses of gabapentin, ranitidine, metoclopramide, and digoxin.

OTC meds

- Cough/cold: Avoid PO decongestants (↑BP)

- Allergies: 2nd gen antihistamines > 1st gen (drowsiness)
- Diarrhea: Loperamide preferred
- Constipation: Avoid:Enemas+Mg2+laxatives; Preffered: PEG or Senna/Bisacodyl
- Pruritis: Preferred: Moisturizers, Low potency topical steroids, capsaicin, menthol/camphor
topicals; Avoid: Topical NSAIDs
- Pain: Avoid NSAIDs/codeine/ASA > 325 mg; Preferred: Acetaminophen
- GI: Avoid Al3+/Mg2+ antacids, Peptobismol (bismuth subsalicylate); Preferred: CaCO32- ,H2RAs
(after dialysis), simethicone, dimenhydrinate
- Vitamin supplementation: Replavite post-dialysis (B vitamins, folic acid, vitamin C); avoid
multivitamins if advanced CKD and not on dialysis due to accumulation

NHPs to avoid in CKD

*In general, don’t use them!

- Hypertension (Ma-Huang, white willow bark, ginseng): The asian sound shit=DOJO=tension
- Diuretic effects (Parsley, juniper, uva ursi): “I would DIE(uretic) if I went to Junipers ,Marsley,
or Uranus (Uva Ursi)
- Hyperkalemia (alfalfa, dandelion, noni juice, nettle): “K+, Alfalfa got Hyper after drinking his
noni’s juice, so he relieved his steam (nettle) running in dandelion fields.
- Hypokalemia (licorice): “Eating black LiK+Orice is nasty, it makes me hypoactive”

Acute kidney failure

- Labs: Acute ↑in SCr and Acute↓in GFR+urine output; fractional excretion of sodium < 1% in
pre-renal and BUN ↑
- Anuric AKF: <50 ml urine/day
- Oliguric: 50-400 ml urine/day
- Goal: >400 ml/day

Types
Pre-renal

- Cause: ↓ renal perfusion

- Conditions/drugs: HF, sepsis (hypotension, vomiting), dehydration, vascular obstruction (VTE,
MI, stroke), and drug-related (ACEIs/ARBs, diuretics, NSAIDs)
- Tx: Discontinue offending agent and replace fluids (unless volume overload as in CHF).

Intrinsic

- Acute tubular necrosis: drugs kill tubular epithelium directly (aminoglycosides, cyclosporine,
contrast dyes, lithium, acyclovir, amphotericin B, cisplatin); discontinue offending agent

- Mnemonic: “Amin, NO! .. Cycling is a good sport, in fact, it’s LIT. In contrast, Acyclists, are
inactive and only eat plats of pho”. Amin,NO=Aminoglycosides, Cycling is a good
sport=Cyclosporine, LIT=Lithium, Contrast=Contrast dyes, Acycysys=Acyclovir, Plats=Cisplatin,
Pho=Amphotericin B

- Acute interstitial nephritis: allergic hypersensitivity (beta-lactams, sulfonamides, rifampin,

allopurinol, ranitidine); discontinue offending agent :

- Mnemonic: “Allo, 911? My fam got pinpoint pupils from the beta-carrots that he ate when he
went tidine after his sulphone died. We forgot that he’s allergic to carrots and hypersensitive”.
- “Allo=Allopurinol”, “Fam has pin” =Rifampin that he, beta-carrots=beta-lactams,
tidine=rantidine, sulphone=sulfonamides
-
- Glomerulonephritis: infections (e.g. Staph infections of kidney), immune-related (e.g. lupus)

Post-renal

- Caused by downstream obstruction (kidney stones, prostate/bladder/cervical tumors, BPH,

acyclovir crystals)

Hemodialysis vs peritoneal dialysis

Hemodialysis

Pros:

- Better clearance
- Low technique failure rate
- Allows for close monitoring of patient

Cons:

- Loss of autonomy
- Complications (hypotension, fatigue, blood loss/anemia, leg cramps, etc.)
- Vascular access (via cardiac catheter or arm fistula) increases risk of infection and thrombosis
- Residual renal function disappears

Peritoneal dialysis
Pros:

- Hemodynamic stability, no blood loss/anemia

- Preserves residual renal function
- More convenient

Cons:

- Protein/amino acid loss in dialysate

- Infection (peritonitis, exit site infections)
- Dialysate leaks
- Inadequate clearance
- Patient burnout/technique failure
- Dialysate contains glucose so high exposure (bad for obese or diabetic patients)
- Abdominal hernia

Dialyzability of drugs

Drug factors

- MW (low MW drugs are dialyzed)

- Protein binding (drugs with high protein binding are not dialyzed since only free drug can be
removed)
- Volume of distribution (high Vd = high tissue binding so less available in plasma for removal; low
Vd drugs dialyzable)
- Water solubility (water-soluble drugs can be dialyzed; lipophilic drugs are not)

Dialysis factors

- Dialysis membrane pore size (bigger pore size allows higher MW drugs to be removed)
- Blood/dialysate flow rates (flow in opposite directions to generate concentration gradient,
increasing blood flow rate during HD permits greater clearance)

Other

- Non-renal clearance (if drug is mostly cleared through the biliary route, not likely to be dialyzed;
if eliminated by the kidney, then will be dialyzed)