CKD PART II

Clinical Pharmacy II & Pharmacotherapeutics (PHP006)

Department of Pharmacy Practice
CASE
A 66-year-old man has an eGFR of 55 mL/minute/1.73 m2. His ACR is
100 mg/g. His Hgb is currently 13.2 g/dL, with normal red blood cell
indices without treatment. Which best reflects the recommended
minimum frequency of Hgb monitoring in this patient?
A. Monthly.
B. Every 3 months.
C. Every 6 months.
D. Every 12 months.
ANSWER
Answer: D
This patient whose eGFR is 55 mL/minute/1.73 m2 would be classified as having
stage 3 CKD because his eGFR is less than 60 mL/minute/1.73 m2. He does not
currently have anemia because his Hgb concentration is greater than 13 g/dL.
Therefore, Hgb should be monitored according to his CKD stage. For stage 3 CKD,
monitoring is recommended at least every 12 months (Answer D is correct). For
patients with stage 4 and stage 5 CKD who are not yet receiving dialysis, monitoring
should occur at least every 6 months (Answer C is incorrect). Monitoring should occur
at least every 3 months once patients in stage 5 CKD are receiving dialysis (Answer B
is incorrect). Monthly monitoring is never recommended for a patient who is not
currently anemic (Answer A is incorrect).
INDICATIONS FOR DIALYSIS:

A: Acidosis (not responsive to bicarbonate)

E: Electrolyte abnormality (hyperkalemia, hyperphosphatemia)
I: Intoxication (boric acid, ethylene glycol, lithium, methanol,
phenobarbital, salicylate, theophylline)
O: Fluid overload (symptomatic [pulmonary edema])
U: Uremia (pericarditis and weight loss)
Goals of Dialysis:
Remove toxic metabolites to decrease uremic symptoms

Correct electrolyte abnormalities

Restore acid–base status

Maintain normal volume status

Decrease the morbidity and mortality associated with ESKD

Improve quality of life

HEMODIALYSIS
PRINCIPLES OF HEMODIALYSIS:
• Hemodialysis consists of the perfusion of blood and a physiologic salt solution
(dialysate) on opposite sides of a semipermeable membrane.
• The counter-current flow maintains the concentration gradient across the membrane at
a maximum and increases the efficiency of the dialysis.
• Ultrafiltration is the movement of water across the membrane due to hydrostatic
or osmotic pressure, and is the primary means for removal of excess body water.
HEMODIALYSIS ACCESS:
Permanent access to the bloodstream for hemodialysis may be accomplished by
several techniques, including creation of an arteriovenous (AV) fistula, the AV graft,
and venous catheters.

Preferred route
Dialysis membranes
a. Conventional: Not often used anymore. Small pores, smaller surface area
b. High flux (large pores) and high efficiency (large surface area). Can remove
drugs that were impermeable to standard membranes (vancomycin). Large
amounts of fluid removed (ultrafiltrate)
COMPLICATIONS OF HEMODIALYSIS:
• It is of great importance to prevent the complications before they occur.
• Some complications may not threaten the patients’ life but deteriorate the quality of
life of the patients.
• The treatment of these complications provides a longer life and a better quality of life
for the patients.
(1) VASCULAR ACCESS COMPLICATIONS:
(a) Vascular Access stenosis and Thrombosis
(b) Vascular Access Infection
• Access infections, usually involving grafts to a greater extent than a native fistula, are predominantly caused by
Staphylococcus aureus or Staphylococcus epidermidis. Infections with gram-negative organisms as well as
Enterococcus species occur with a lower frequency. Access infections can lead to bacteremia and sepsis with or
without local signs of infection.
• Antibiotics that permit dosing during or after each dialysis session or antibiotics whose pharmacokinetics are
unaffected by dialysis should be chosen. Treatment usually is initiated with vancomycin 20 mg/kg loading
dose infused during the last 60 to 90 minutes of dialysis, and then 500 mg
• Cefazolin 20 mg/kg after each dialysis session can be used instead of vancomycin in dialysis
units with a low prevalence of methicillin-resistant staphylococci.
• Empiric antibiotic therapy should also include coverage for gram-negative bacilli. For
example, gentamicin (or tobramycin) 1 mg/kg, not to exceed 100 mg infused after each
dialysis session can be used for empiric gram-negative coverage with appropriate serum
concentration monitoring.

(2) HYPOTENSION

(3) MUSCLE CRAMPS

(4) DIALYSIS DISEQUILIBRIUM

(5) DIALYZER REACTIONS

PERITONEAL DIALYSIS
PRINCIPLES OF PERITONEAL DIALYSIS
The three basic components of dialysis—namely, a blood- filled compartment separated from a
dialysate-filled compartment by a semi permeable membrane—is also used for PD.
CONTINUOUS AUTOMATED PERITONEAL Peritoneal Dialysis (PD)
AMBULATORY DIALYSIS (APD) Modalities:
PERITONEAL DIALYSIS • APD is a new treatment method that • Peritoneal dialysis can be performed
is performed at home, at night while manually or via automated systems.
(CAPD) Manual PD is termed continuous
• Done regularly 3 or 4 or 6 times you sleep, using a cycler machine. ambulatory peritoneal dialysis
daily. (CAPD). Automated peritoneal dialysis
• Allows freedom of movement. (APD) can be performed as continuous
cyclic peritoneal dialysis (CCPD),
intermittent peritoneal dialysis (IPD),
tidal peritoneal dialysis (TPD), or
continuous flow PD (CFPD). The PD Plus
modality uses both manual and
automated exchanges.
COMPLICATIONS OF PERITONEAL DIALYSIS

a. Peritonitis – Infection of the peritoneal cavity

i. Older adults or those with diabetes have a higher infection rate.
ii. Diagnosis: At least two of the following:
(a) Clinical features consistent with peritonitis (i.e., abdominal pain and/or cloudy dialysis
effluent)
(b) Dialysis effluent WBC greater than 100/mm3 or greater than 0.1 × 103 cells/m3 (after a
dwell time of at least 2 hours) with greater than 50% polymorphonuclear leukocytes
(c) Positive dialysis effluent culture (International Society for Peritoneal Dialysis [ISPD]
guideline)
N.B. Patients on peritoneal dialysis presenting with cloudy effluent can be presumed to have
peritonitis and can be treated as such until diagnosis can be confirmed or excluded (ISPD
guideline).
•Treatment based on ISPD guidelines
(a) Empiric treatment should cover gram-positive and gram-negative bacteria.
(b) Vancomycin or a first-generation cephalosporin is administered to cover gram-positive organisms, and
a third-generation cephalosporin, an aminoglycoside, or aztreonam is added to cover gram-negative
organisms. Intraperitoneal administration is preferred unless the patient has another systemic site of
infection.
b. Catheter exit-site infections
i. Recommended that daily topical application of antibiotic (mupirocin or gentamicin) cream or ointment be
applied to catheter exit site for prophylaxis. (ISPD guideline)
ii. Prompt treatment of exit-site or catheter tunnel infection is recommended to reduce subse-quent
peritonitis risk (ISPD guideline).
c. Hyperglycemia
d. Fluid overload
e. Electrolyte abnormalities: Hypercalcemia, hypocalcemia
f. Malnutrition: Hypoalbuminemia
g. Hernia
PRACTICAL CASES
CASE 1
Which of the following pharmacokinetic parameters describes a drug
that will be most effectively removed by hemodialysis?
A. Serum protein binding 90% and volume of distribution of 2.5 L/kg
B. Serum protein binding 30% and volume of distribution of 2.5 L/kg
C. Serum protein binding 90% and volume of distribution of 0.3 L/kg
D. Serum protein binding 30% and volume of distribution of 0.3 L/kg
ANSWER
Answer: D
While the method of dialysis can affect the extent of drug removal, the
pharmacokinetic properties of medications is also important in determining drug
removal. Drugs that are highly protein bound (>90%) are not well dialyzed
because of the large molecular weight of the binding proteins (Answers A and C
are incorrect).
Those drugs that are widely distributed (i.e., volume of distribution > 2 L/kg) are
also poorly removed by dialysis because such a small amount of drug is in the
central compartment (Answers A and B are incorrect).
A drug that has a relatively small volume of distribution (0.3 L/kg) and low protein
binding (30%) will be most
effectively removed by dialysis (Answer D is correct).
CASE 2
A patient with CKD on peritoneal dialysis presents with fever and abdominal pain.
She also notes that her peritoneal dialysate has become cloudy. Laboratory
evaluation of dialysate reveals many white blood cells, primar-
ily neutrophils. Gram stain and culture of the fluid are ordered. According to the
2016 International Society for Peritoneal Dialysis Peritonitis Recommendations, which
is the best empiric therapy for this patient?

A. Intravenous metronidazole plus gentamicin.

B. Intravenous clindamycin plus vancomycin.
C. Cefazolin plus ceftazidime instilled intraperitoneally.
D. Vancomycin instilled intraperitoneally.
ANSWER
Answer: C
Empiric coverage for the treatment of peritoneal dialysis–related peritonitis should
include activity against both gram-positive and gram-negative organisms (Answers
B and D are incorrect). Intraperitoneal administration is preferred to intravenous
administration. Cefazolin will provide activity against Staphylococcus unless an
area has a high rate of methicillin-resistant organisms (Answer C). The choice of
antibiotic for gram-negative coverage can include a third-generation
cephalosporin with activity against Pseudomonas (e.g.,ceftazidime, cefepime)
(Answer C) or an aminoglycoside. Short-term use of an aminoglycoside should not
adversely affect residual renal function. For patients with dialysis-related
peritonitis, empiric anaerobic coverage is unnecessary (Answers A and B are
incorrect).
CASE 3
A patient undergoing long-term HD has intradialytic hypotension.
After nonpharmacologic approaches have been optimized, which
medication is best to manage his low blood pressure?
A. Levocarnitine.
B. Sodium chloride tablets.
C. Fludrocortisone.
D. Midodrine.
ANSWER
Answer: D
The best-studied agent is midodrine, an α1-agonist (Answer D). Levocarnitine
(Answer A) has been tried, but data are limited on its benefit. Fludrocortisone
(Answer C) is a synthetic mineralocorticoid that is used for hypotension in other
situations; however, its primary mechanism is caused by sodium and water
retention in the kidney; therefore, this drug is less likely to work. Sodium
chloride tablets (Answer B) would not work acutely, and they should generally
be avoided.
THANK YOU