Chronic kidney disease clinical pharmacy

1. Chronic Kidney
Disease (CKD)

2. Staging of CKD

3. CKD is defined as abnormalities of kidney structure or function, present
for > 3 months
Diagnostic criteria of CKD
Either of the following should be
present for >3 months
Markers of kidney damage
• Albuminuria (ACR≥30mg/g)
• Urine sediment abnormalities
• Histological abnormalities
• Structural abnormalities
• Electrolyte abnormalities
• History of kidney transplantation
Decreased GFR
GFR <60
ml/min/1.73 m2

4. Management of CKD
HTN
CKD Nutritional
management
Hyperlipidemia
Diabetes
Management of CKD patients involve:
1. Nutritional management
2. Management of significant comorbidities.

5. Nutritional management
Protein intake should not exceed 1.3 g/kg/day in any adult with CKD.
Protein intake should be lowered to 0.8 g/kg/day in adults with diabetes or people
with GFR < 30 ml/min/1.73 m2 who are not on dialysis.
Pts receiving dialysis should maintain protein intake of 1.2 g/kg/day and maintain a
caloric intake of 30 to 35 kcal/kg (125–147 kJ/kg) of ideal body weight.
Limiting salt intake to <2 g (90 mmol) of sodium per day (equivalent to 5 g
NaCl) will help to control blood pressure and reduce water retention in CKD.
Physical activity with a goal of at least 30 minutes five times per week, to
achieve a healthy weight, with a goal BMI of 20 to 25.
Smoking cessation

6. Hypertension & CKD
ACEI or ARB are recommended for management of
HTN in non dialysis CKD pts.
For most adultpatientswithCKD not receivingdialysis,the target is SBP
<120/80 mm Hg .

7. • The KDIGO guidelines 2012 recommend that patients with CKD
who have an AER less than 30 mg/day should achieve a blood
pressure target of less than or equal to 140/90 mm Hg.
• If AER is 30 mg/day or greater, the blood pressure goal is less
than or equal to 130/80 mm Hg.

9. Diabetes & CKD
HbA1c target of ~7.0% is recommended
HbA1c target can be extended above 7.0% in individuals with
comorbidities or limited life expectancy and risk of hypoglycemia.
Treatment generally involves intensive insulin therapy for type 1 DM or
insulin-dependent type 2 DM or optimizing doses of oral hypoglycemic
agents in patients with non-insulin-dependent type 2 DM.

12. Dyslipidemia & CKD
All newly diagnosed
CKD pts
•Assess for dyslipidemia by
lipid profile
•Lifestyle modifications
Any CKD pts with
hypertriglyceridemia

15. Complications: Anemia & CKD
Definition:
Hgb<13 g/dl in males
or <12 g/dl in
females
Frequency of testing
Pts without anemia:
Stage 3: at least annually
Stages 4 or 5 (no dialysis):
at least twice a year
Stage 5 on dialysis: at least
every 3 months
Frequency of testing
Pts with anemia:
Stages 3-5 (no HD or
peritoneal dialysis): at least
every 3 months
Stage 5 on hemodialysis: at
least monthly
Non dialysis pts: oral or IV
iron acc. T
o presence of
venous access, prior
response to iron therapy, pt.
compliance, cost
Address all correctable
causes of anemia before
initiating ESA
Start ESA in stage 5 on
dialysis when pts Hgb is
between 9-10 g/dl

17. Studies have
demonstrated a
significant
association between
hyperphosphatemia
and increased
cardiovascular
mortality and
hospitalization of HD
patients.
In HD patients, serum
phosphate levels of
and
(>6.5 mg/dl)
calcium × phosphorus
(Ca × P) product (>45.9
mg2/dl2 ) are associated
with a significantly
increased mortality risk.
An increased Ca × P
product is associated
with calcium–
phosphate precipitation
in blood vessels,
myocardium and heart
valves

18. Ca, Po4 Balance
FGF 23
PTH
Vit D
Calcium and Phosphorus homeostasis
Intestine
Kidney
Bone

20. absorption
via (NPT2b)
reabsorption
via (NaPi-2a
and 2c)
Po4 absorption

22. Inc
FGF 23
Inc
FGF 23

23. •PTH, FGF23
decrease P tubular
reabsorption,
increase Ca level.
1
• So, P and Ca levels
return to normal
at expense of high
PTH, FGF23 levels.
2 • When GFR < 30
ml/min, tubular
reabsorption cannot
further be lowered so
causing more increase
in level of PTH, FGF23.
3

24. •Vicious cycle in which
high phosphorus causes
PTH secretion and PTH
causes more
hyperphosphatemia.

25. Secondary
Hyperparathyrodism
Renal
osteodystrophy
Cardivasscular
complication

27. CKD–Mineral Bone Disorder (CKD-MBD)
• Signs and symptoms
a. Insidious onset: Patients may experience fatigue and
musculoskeletal and GI pain; calcification may be visible
on radiography; bone pain and fractures can occur if
progression is left untreated.
b. Laboratory abnormalities
i. Phosphorus
ii. Corrected calcium (measured Ca + 0.8[4 – serum
albumin])
iii. Intact PTH
iv. Alkaline phosphatase
v. 25-hydroxyvitamin D

30. CKD–Mineral Bone Disorder (CKD-MBD)
C- Diagnostic testing
i. Bone mineral density (BMD) testing: Suggested for
patients with CKD G3a–G5D with evidence of CKD-MBD
and/or risk factors for osteoporosis if results will affect
treatment decisions (KDIGO 2017, grade 2B)
ii. Bone biopsy: Reasonable to perform if knowledge
of type of renal osteodystrophy will affect treatment
decisions (KDIGO 2017, not graded)

31. CKD–Mineral Bone Disorder (CKD-MBD)
4. Treatment
b. Nondrug therapy
i. Dietary phosphorus restriction 800–1000 mg/day in stage 3
CKD or higher
ii. Dialysis removes various amounts of phosphorus, depending
on treatment modalities; however, by itself it is insufficient to
maintain phosphorus balances in most patients.
iii. Parathyroidectomy: Reserved for patients with unresponsive
hyperparathyroidism
c. Drug therapy
i. Phosphate binders : Take with meals to bind phosphorus in
the gut; products from different groups may be used together for
additive effect.

32. Phosphate
binders
Aluminium
containing
binders
Lanthanum
carbonate
Sevelamer
Calcium
containing
binders

33. CKD–Mineral Bone Disorder (CKD-MBD)
(a) Aluminum-containing phosphate
binders (aluminum hydroxide, aluminum
carbonate, and sucralfate) effectively lower
phosphorus concentrations.
• In general, avoid. Not used as often because
of aluminum toxicity (adynamic bone disease,
encephalopathy, and erythropoietin
resistance).
• Use should be limited to a single short-term
(4-week) course.

34. CKD–Mineral Bone Disorder (CKD-MBD)
(b) Calcium-containing phosphate binders
(calcium carbonate and calcium acetate)
(1) Widely used phosphate binder. Calcium binders are often the initial binder of
choice for stage 3 and 4 CKD. Calcium or nonionic binders are considered initial
binder of choice in stage 5 CKD. Carbonate salt is inexpensive.
(2) Carbonate is also used to treat hypocalcemia, which sometimes occurs in
patients with CKD, and can decrease metabolic acidosis.
(3) Calcium acetate is a better binder than carbonate and contains
less elemental calcium. Less calcium absorption
(4) Use may be limited by development of hypercalcemia; reduce dose or
discontinue.
(5) Total elemental calcium is 2000 mg/day (1500-mg binder; 500-
mg diet).

36. CKD–Mineral Bone Disorder (CKD-MBD)
(c) Sevelamer: A non absorbable phosphate binder
(1) Effectively binds dietary phosphorus
(2) As with calcium, considered primary therapy in stage 5 CKD. In particular,
consider whether the patient has hypercalcemia or whether calcium intake
exceeds the recommended dose with calcium-containing binders.
(3) Decreases low-density lipoprotein cholesterol and increases high-density
lipoprotein cholesterol
(4) Metabolic acidosis may worsen with sevelamer hydrogen
chloride (HCl).
(d) Lanthanum carbonate
(1) As effective as aluminum in phosphate-binding capability. Not widely used,
but indications similar to sevelamer
(2) Flavorless, chewable tablet
(3) Consider using if patient has hypercalcemia

38. Vitamin D
and
vitamin D
analogues
Ergocalciferol
Cholecalciferol
Calcitriol
Paricalcitol
Doxercalciferol

39. CKD–Mineral Bone Disorder (CKD-MBD)
ii. Vitamin D and vitamin D analogs: Suppress PTH
synthesis and reduce PTH concentrations; therapy is
limited by resultant hypercalcemia.
(a) Ergocalciferol (vitamin D2): Inactive form of
vitamin D. May be used in stage 3–5 CKD for
concentrations; repeat vitamin D levels after
months of therapy. Usually doses weekly
patients with low serum 25-hydroxyvitamin D
6
or
monthly (Table 10).
(b) Cholecalciferol (vitamin D3): Inactive vitamin D.
May be used as alternative to ergocalciferol. Usually
dosed daily.

41. CKD–Mineral Bone Disorder (CKD-MBD)
(c) Calcitriol (Calcijex, Rocaltrol): The pharmacologically
active form of 1,25-dihydroxyvitamin D3 is FDA label
approved for the management of hypocalcemia and the
prevention and treatment of secondary
hyperparathyroidism.
(1) Oral and parenteral formulations
(2) Does not require hepatic or renal activation
(3) Low-dose daily oral therapy reduces hypocalcemia but
does not reduce PTH concentrations significantly.
(4) High incidence of hypercalcemia, limiting PTH
suppression
(5) Dose adjustment at 4-week intervals

43. CKD–Mineral Bone Disorder (CKD-MBD)
(d) Paricalcitol (Zemplar): Vitamin D analog; FDA label approved for
the treatment and prevention of secondary hyperparathyroidism
(1) Parenteral and oral formulations
(2) Does not require hepatic or renal activation
(3) Lower incidence of hypercalcemia compared with calcitriol
(decreased mobilization of calcium from the bone and decreased
absorption of calcium from the gut)
(e) Doxercalciferol (Hecterol): Vitamin D analog; FDA label
secondary
approved for the treatment and prevention of
hyperparathyroidism
(1) Parenteral and oral formulations
(2) Prodrug; requires hepatic activation; may have more physiologic
levels
(3) Lower incidence of hypercalcemia compared with calcitriol
(decreased mobilization of calcium from the bone and decreased
absorption of calcium from the gut)

45. CKD–Mineral Bone Disorder (CKD-MBD)
iii. Cinacalcet HCl (Sensipar): A calcimimetic that attaches to the
calcium receptor on the parathyroid gland and increases the
sensitivity of receptors to serum calcium concentrations, thus
reducing PTH. Especially useful in patients with high calcium and
phosphate concentrations and high PTH concentrations when
vitamin D analogs cannot be used or cannot be increased.
(a) The initial dose is 30 mg, irrespective of PTH concentration.
(b) Monitor serum calcium every 1–2 weeks (risk of hypocalcemia
is about 5%); do not initiate therapy if corrected serum calcium is
less than 8.4 mg/dL.
(c) Can be used in patients irrespective of phosphate binder or
vitamin D analog use

46. CKD–Mineral Bone Disorder (CKD-MBD)
(d) Caution in patients with seizure disorder
(hypocalcemia may exacerbate)
(e) Adverse effects are nausea (30%) and diarrhea
(20%).
(f) Cinacalcet inhibits cytochrome P450 (CYP) 2D6
metabolism, thereby inhibiting the metabolism of
CYP2D6 substrates such that dose reductions in drugs
with narrow therapeutic indices may be required (e.g.,
tricyclic antidepressants).
(g) Cinacalcet is metabolized primarily by CYP3A, so
drugs that are potent
(ketoconazole) may
inhibitors of CYP3A
increase cinacalcet
concentrations up to twofold.