Management of complication of CKD

Question 1

Renal Filtration

Answer 1

• 1000-1200mL of blood passes through glomeruli/min
  
  • 650mLs = plasma
    
    • 120-125 mL = force into renal tubules
    • three processes:
      
      • glomerular filtration
      • tubular reabsorption
      • secretion

Question 2

Assessment of CKD should include

Answer 2

• Scr
• UA
• BP
• Serum electrolytes
• and/or imaging studies

Question 3

Primary marker for kidney damage

Answer 3

Proteinuria

• urinary protein excretion > 300mg/day, or 20mcg/min
• spot protein dipstick > 30mg/dL = 300mg/L
• urine protein/creatinine >200mg/g
• Microalbuminuria
  
  • 30-300mg/day of albumin in urine
  • urine albumine/creatinine = 30-300mg/g

Question 4

Non-pharmacologic tx of CKD

Answer 4

• nutritional management:
  
  • reduced protein intake
    
    • GFR <25mL/min/1.73m2 (not on dialysis) → 0.6g/kg/day
      
      • watch for malnutrition
    • ESK with dialysis → 1.2-1.3 g/kg/day

Question 5

Pharmacological Reduction of Proteinuria

Answer 5

• ACE-I & ARBs can reduced proteinuria up to 35-40% → ****Drugs of choice for HTN with CKD****
• nondihydropyridine Calcium Channel Blockers (i.e. verapamil and diltiazem) → reduce protein excretion – for DM patients only, not for non-DM
  
  • Dihydropyridine Calcium channel blockers (amlodipine, nifedipine, felodipine) worsen protein excretion d/t afferent vasodilation
• Others:
  
  • tx the hyperlipidemia
  • smoking cessation
  • treating anemia → reduces CV effects and progression of CKD

Question 6

nondihydropyridine CCB

Answer 6

CCB = calcium channel blockers

i.e. verapamil, diltiazem

used for reducing proteinuria in diabetic patients

Question 7

dihydropyridine CCB

Answer 7

CCB = calcium channel blocker

amlodipine, nifedipine, felodipine

Question 8

Consequences of CKD

Answer 8

• impaired water and sodium homeostasis
• hyperkalemia
• hyperphosphatemia
  
  • bone disorder and secondary hyperparathyroidism
• anemia → low EPO production
• metabolic acidosis due to impaired generation of ammonia and H excretion
• Uremic bleeding due to platelet dysfunction in uremic environment
• pruritus

Question 9

Impaired Sodium and water balance in CKD

Answer 9

• normal Kidneys excrete 1-3% Na into urine
  
  • but as number of nephrons decrease (like in CKD) → increased FeNa by 10-20%
    
    • causes osmotic diuresis → kidneys cannot concentrate urine → dilute urine → urine osmo = plasma osmo (300mOsm/kg) → nocturia
    • Eventually → Na excretion overwhelms nephrons and “reach saturation” point which causes decrease in Na excretion → Na accumulation → increased thirst, fluid retention → volume overload → HTN and pulmonary edema

Question 10

Tx of impaired sodium/water balance in CKD

Answer 10

• limit Na intake to 2g/day
• maintain fluid intake ~2L/day
• diuretics to prevent fluid overload
  
  • Loop = increase water and Na secretion
  • Thiazides = ineffective for GFR < 30mL/min/1.73m2

Question 11

Impaired K+ homeostasis in CKD

Answer 11

• reduced # of nephrons = reduced overall K+ excretion → hyperK+
• body initially tries to compensate by producing aldosteration → promotes K+ elimination → allows body to maintain K+ wnl through CKD stage 1-4
  
  • GFR <20% of normal → kidneys can no longer eliminate K+
  • drugs may worsen hyperK+
    
    • ACEI/ARB → reduce aldosterone levels → retain K+
    • K+-sparing diuretics

Question 12

Anemia and CKD

Answer 12

• kidney cells make erythropoietin (EPO) → stimulates RBC production
• reduced # of nephrons → decreased EPO → anemia → decreased oxygen delivery → increased CO2 → ventricular hypertrophy → CV and mortality risk increases
  
  • Hgb <13 g/dL males
  • hgb <12g/dL females
• risk of anemia increases as GFR declines
• Contributing factorsL
  
  • B12 & folate deficiencies
  • hemolysis
  • bleeding
  • bone marrow suppression
  • uremia → shortens the life span of a RBC to 60 days (vs 120 day normal)

Question 13

Tx of Anemia in CKD

Answer 13

• screen for anemia when GFR <60mL/min or SCr >2mg/dL
• Start Erythropoiesis stimulating agents (ESA)
  
  • Hgb < 10g/dL (no other causes, & no dialysis)
  • hgb < 9g/dL (on dialysis)
  • Goal: hgb 10-12g/dL → no higher or else increased mortality
• Iron Storage assessment:
  
  • S_erum ferritin goals_:
    
    • non dialysis: >100 ng/mL (but <500 ng/mL)
    • dialysis: > 200 ng/mL ( but <500 ng/mL
  • TSAT (transferrin saturation) goals:
    
    • ND and Dialysis: >20% (but <30%)

Question 14

Erythropoiesis Stimulating Agents (ESA)

Answer 14

• Synthetic Recombinant human DNA
  
  • epoetin alfa (Epogen or Procrit)
  • darbepoetin alfa (Aranesp)
    
    • addition of sugar side chains = increased half life (every week dosing)
• SE: increased BP → may need anti-HTN
  
  • HA, tachycardia, fever, N/V/D
  • DARBEpoetin: increased risk of stroke, subcutaneous is more predictable than IV

Question 15

PO Iron Supplements

Answer 15

• Carbonyl iron: 100% elemental iron
  
  • microparticles of highly purified elemental iron
  • dissolves in gastric secretion and converted to hydrochloride salt
  • absorption rate is slow (1-2 days)
  • less toxic than iron salts → but need higher dosage
• Ferrous fumarate: 33%
  
  • similar efficacy and tolerability as ferrous sulfate
• Ferrous gluconate: 12%
  
  • similar efficacy and tolerability
• Ferrous sulfate: 20% → formulation of choice for tx of iron-deficiency anemia
  
  • low cost, high efficacy, high tolerability
  • Ferrous Sulfate, dried: 30% same as above.

Question 16

IV Iron Supplements

Answer 16

• Iron dextran → BLACKBOX WARNING (anaphylaxis, trial with small amount 1st)
  
  • → pts with iron deficiency that cannot be resolved with PO iron
• Ferric gluconate
  
  • → adult and peds Hemodialysis(HD) pts > 6years receiving ESA therapy
• Iron Sucrose (preferred)
  
  • → HD pts with CKD receiving ESA therapy
    
    • non-HD- CKD pts receiving or not receiving ESA therapy
    • PD pts receiving ESA therapy

Question 17

Calcitriol

Answer 17

activated by PTH

promotes Calcium absorption from GI

increases Calcium mobilization from bone

Question 18

secondary HyperPTH and bone disorders

Answer 18

• when GFR <30mL/min → phosphate excretion is decreased → calcitriol production reduced → hyperPTH
  
  • hyperplasia of Parathyroid glands
  • renal osteodystrophy (ROD) → promotes caclium resorption → bone thinning and weakening bone structure

Question 19

Treatment of Secondary HyperPTH and bone disorders

Answer 19

• Goals
  
  • Maintain corrected Ca, Phos, and PTH levels as close to normal as possible
    
    • Ca2+ corrected = Ca2 obs + 0.8 (4-obs albumin)
      
      • normal range: 8.5-10.3mg/dL
      • phos normal range: 2.5-4.5mg/dL
      • PTH normal range: 11-54 pg/mL
• Dietary Phosphorus restriction: 800-1000mg/d
• avoid aluminum exposure: i.e. antacids
• Last resort = parathyroidectomy:
  
  • consider for pts with PTH > 800pg/mL
    
    • need to monitor Ca2+ closely after procedure
    • IV Ca2+ may be needed then PO vitamin D + Calcium

Question 20

Phosphate Binders

Answer 20

• ***consume all with meals***
• CaCO₃ aka TUMS: 40% elemental
• Calcium acetate: 25% elemental
• Sevelamer HCL (Renagel)
  
  • lowers LDL, for pts with high Ca2+, more expensive
• Sevelamer Carbonate
  
  • same as above

Question 21

Vitamin D

Answer 21

• acts direction on parathyroid gland → reduces PTH level
  
  • when to use: reduction of phos levels does not reduce PTH level enough
• 3 forms of Vitamin D:
  
  • ergocalciferol (vitamin D2, lowers PTH for stage 3 CKD)
  • cholecalciferol (vitamin D3, lowers PTH in stage 3 CKD)
  • Calcitriol: (1,25-dihydroxyvitamin D) = MOST ACTIVE
    
    • good for CKD stage 4-5
      
      • because kidneys cant produce 1-alpha-hydroxylase (which normally converts D2 and D3 to active form)

Question 22

Types of Vitamin D

Answer 22

• Vitamin D precursor
  
  • ergocalciferol (Vitamin D2)
  • Cholecalciferol (vitamin D3)
• Active Vitamin D
  
  • Calcitriol
• Vitamin D analogs
  
  • Paricalcitol
  • Doxercalciferol
• Calcimimetics
  
  • Cinacalcet

Question 23

Calcimimetics and monitoring

Answer 23

• Cinacalcet
  
  • increased sensitivity of receptor on Parathyroid gland to calcium levels in blood → reduces PTH
• Reduces serum calcium (5%) and phos (3-8%)
  
  • good for pts with high PTH, Ca2+, and Phos
    
    • not for pts with Ca2+ <8.4mg/dL
      
      • low Ca2+ → low seizure threshold
• once started:
  
  • monitor Ca2+, phos within 1 week
    
    • then Q1-3 months once at goals
  • PTH within 4 weeks
    
    • then every 3 months if at goals
• SEs:
  
  • N/V/D, rashes, dizziness
  • hypotension/HTN, HA, hypoCa2+, hyperK+
  • QT prolongation, seizures

Question 24

Chronic Metabolic Acidosis and CKD

Answer 24

• GFR <20-30mL/min
  
  • H+ excretion reduced (i.e. can’t produce NH4+)
  • metabolic acidosis (pH <7.35) → increased protein breakdown and reduced albumin synthesis
    
    • → muscle wasting, altered bone metabolism
    • worsens cardiac disease, glucose, tolerance, and thyroid function
• Goals: maintain serum HCO3- = 23-29mEq/L
• Tx:
  
  • correct 1st ½ over 8-12 hours, then 2nd ½ over 24 hours
    
    • i.e. if pt has a 140mEq deficit, 70mEq over 8-12hours, then 70mEq over 24 hours
      *

Question 25

Tx of Chronic Acidosis

Answer 25

• NaHCO3 tab
• Na citrate/citric acid
  
  • citrate → HCO3- ; citric → CO2 + H2O
• Polycitra (Na+/K+ -citrate)
  
  • 1mEq (Na+) + 1mEq(K+) +2mEq (citrate = HCO3-)
  • can promote hyperK+
  • citrate → increased aluminum absorption → toxicity

Question 26

Uremic Bleeding Pathophys and Bleeding

Answer 26

• pathophys: protein metab (produces urea and creatinine) → can’t eliminate → uremia (decreased activity of von Willebrand’s factor) → bleeding (i.e. ecchymosis, prolonged clotting time)
• Tx: Dialysis if severe (mostly in ESKD)
  
  • DDAVP (desmopressin)
    
    • synthetic analog of vasopressin (ADH)
    • → promote release of von Willebrand’s factor from endothelial cells
    • SEs: flushing, dizziness, HA
    • Repeated dose can cause tachyphylaxis due to depletion of stored von Willibrand’s factor
• Conjugated Estrogens → to decrease bleeding time
  
  • SEs: hot flashes, fluid retention, and HTN
• Cryoprecipitate = precipitate from the centrifuged thawed FFP
  
  • rich in clotting factors
  • decrease bleeding time within 1 hour
    
    • Expensive and risk of infection –limited use
    • reserved for pts not responsive or unable to use DDAVP

Question 27

Pruritus and CKD

Answer 27

• unknown pathophys
  
  • adequate dialysis = first line
    
    • limite phos and protein intake
    • UVB phototherapy
  • antihistamines
    
    • hydroxyzine
    • diphenhydramine
  • cholestyramine
  • activated Charcoal
  • gabapentin → Caution! Risk of neurotoxicity
  • SSRI, ondansetron, naloxone, and topical capsaicin → reported efficacy

Question 28

ACE-I

Answer 28

captopril, lisinopril, benzapril, etc. “-pril”

not for GFR <30

good for reducing proteinuria in CKD pts with HTN

Question 29

ARBs

Answer 29

losartan, candesartan, valsartan, etc “-sartan”

good for reducing proteinuria in CKD pts with HTN

Question 30

Parathyroidectomy

Answer 30

last resort

• consider for pt with PTH > 800pg/mL
• need to monitor Ca²⁺ after procedure
• IV Ca²⁺ may be needed then PO vit D + calcium