BMS207, BMS305

Chronic Kidney Diseases

Faculty of Medicine, Spring 2024

Galala University

gu.edu.eg
 G A L A L A U N I V E R S I T Y T H E F U T U R E S T A R T S H E R E

Lec 4.
BMS207, BMS305
UroGenital tract diseases

Drugs used in chronic kidney disease

and its complications
Dr.Amany Nasr Ahmed
Galala University

T H E F U T U R E S T A R T S H E R E
4/17/2024
Intended Learning Outcomes
By the end of this LECTURE session, you should be
able to:

1) Choose the best drugs in treatment of hypertension in CKD

2) Choose the best preparation of vitamin D in treatment of renal
osteodystrophy.
3) Identify the role of erythropoietin in treatment of anemia of
CKD
4) Explain why iron should be given by intravenous route in CKD
Chronic kidney disease
• It is progressive, irreversible kidney damage characterized by
decreased estimated glomerular filtration rate (eGFR) or evidence of kidney
damage for at least 3 months.
• Three primary functions kidney:
• Excretory (excrete fluid, electrolytes, and solutes)
• Metabolic (metabolize vitamin D and some drugs, such as insulin
and some beta-lactams)
• Endocrine (produce erythropoietin [EPO])
• The above primary functions of the kidney are affected in
CKD
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Optimal Blood Pressure Control in CKD
• Optimum control of blood pressure is one of the most
important therapeutic measures

• Reductions in blood pressure are associated with:

❑ A decrease in proteinuria
❑ leading to a decrease in the rate of progression of
kidney disease.

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• Hypertension causes damage to the intrarenal vasculature
resulting in thickening and hyalinisation of the walls of
arterioles and small vessels.

• This damage effectively reduces renal perfusion,

contributing to stimulation of the Renin-Angiotensin-
Aldosterone System.

• Arteriolar vasoconstriction, sodium and water retention

result, which in turn exacerbates the hypertension.
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 Optimal Blood Pressure Control in CKD
1-Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II
receptor blockers (ARB)

1. Diabetic patients with micro/macroalbuminuria and CKD should be treated

with ACE inhibitors or ARBs regardless of blood pressure.
2. Drugs can reduce proteinuria and thus reduce progression of CKD
3. Resulting vasodilatation and reduced sodium retention
4. Produce a reduction in GFR by preventing the angiotensin II mediated
vasoconstriction of the efferent glomerular arteriole – that reduce intra-
glomerular hypertension and hyper-filtration - protect the glomerulus

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Optimal Blood Pressure Control in CKD
• Calcium channel blockers
• For patients without proteinuria(calcium channel blockers are the
agents of choice).
• They produce vasodilatation principally by reducing Ca2+ influx
into vascular muscle cells
• Also, promotes sodium excretion in hypertension associated
with fluid overload
• Nondihydropyridine calcium channel blockers, verapamil and
diltiazem- decrease protein excretion in patients with and without
diabetes-reduction in proteinuria
• Headache, facial flushing and oedema are common adverse effects
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Optimal Blood Pressure Control in CKD
• β-Blockers
• β-Blockers are commonly used in the treatment of hypertension in
CKD
• β-blockers can reduce cardiac output, also cause peripheral
vasoconstriction and exacerbate peripheral vascular disease
• More cardioselective β-blockers, atenolol or metoprolol are advisable
to use
• Atenolol is excreted renally and consequently should require dosage
adjustment in renal failure.
• Metoprolol is a better choice, since it is cleared by the liver and needs
no dosage adjustment
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• Anaemia is a common consequence affects most of the people with
CKD stages 4 and 5.
• The fall in haemoglobin level is a slow, insidious process
accompanying with decline in renal function.
• The progenitor cells of the kidney produce 90% of the hormone
erythropoietin, which stimulates red blood cell production.
• Reduction in the number of functioning nephrons decreases renal
production of erythropoietin, which is the primary cause of
anemia in patients with CKD

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Anemia of CKD
• The first-line replacement of iron stores with iron
supplements.
• Alone iron supplementation is not sufficient to increase Hgb
levels, erythropoiesis-stimulating agent (ESAs) are necessary
to replace erythropoietin.
• ESAs are synthetic formulations of erythropoietin produced by
recombinant human DNA technology.
• Use of ESAs increases the iron demand for RBC production

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Anemia of CKD - Oral iron therapy
• Iron Supplementation: Oral and parenteral iron therapy
• Oral iron therapy
• Ferrous sulfate
• Ferrous gluconate
• Ferrous fumarate
• Oral iron therapy: the first-line treatment for patients with CKD not
receiving hemodialysis.
• Ferrous salts are most efficiently absorbed.
• Common adverse effects of oral iron therapy :
• Nausea, epigastric discomfort, abdominal cramps, constipation, and
diarrhea.
• Oral iron therapy develops black stools
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 Anemia of CKD - Parenteral iron therapy
• Parenteral iron therapy
• To increase iron stores or for patients receiving hemodialysis, IV iron should be
administered
• Iron dextran
• Is a stable complex of ferric oxyhydroxide and dextran polymers
• Indication: Patients with iron deficiency in whom oral iron is unsatisfactory
• Warnings- risk of anaphylactic reactions -a small test dose of iron dextran
should always be given before full intramuscular or intravenous doses
• Adverse effects: headache, light-headedness, fever, arthralgias, nausea and
vomiting, back pain, flushing, urticaria, bronchospasm, and, rarely,
anaphylaxis and death
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Anemia of CKD - Parenteral iron therapy
• Sodium ferric gluconate, iron sucrose, and ferric carboxymaltose are
associated with fewer severe reactions and a much lower risk of
anaphylaxis and do not require a test dose, making them the preferred
agents in CKD

• Ferumoxytol
• Is a superparamagnetic iron oxide nanoparticle coated with
carbohydrate.
• The carbohydrate shell is removed in the reticuloendothelial system,
allowing the iron to be stored as ferritin, or released to transferrin
• Indication: Adults with iron deficiency anemia associated with CKD
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• ESAs may be considered if Hgb levels remain persistently low to
improve symptoms of anemia
• ESAs are recommend when Hgb is less than 10 g/dL ‫مهم جدا‬
• ESAs - Epoetin alfa, Epoetin beta, Darbepoetin alfa and
Methoxy PEG-epoetin beta

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Anemia of CKD - Erythropoiesis-Stimulating Agents
• Epoetin α and epoetin β have the same biological activities as
endogenous erythropoiesis
• Darbepoetin alfa has two additional carbohydrate side chains
that increase the half-life compared with epoetin α and
endogenous erythropoiesis
• Methoxy PEG-epoetin beta has the addition of an amide bond
that produces a longer half-life than the other
• Most common adverse effects:
• increase blood pressure, seizures and pure red cell aplasia
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• ++++ parathyroid hormone (PTH) occur early as
kidney function begins to decline.
• The actions of PTH on bone turnover lead to CKD-
mineral and bone disorders (CKD-MBD).
• The parathyroid glands release PTH in response to
decreased serum calcium and increased serum
phosphorus levels.

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Phosphate-Binding Agents Used to Treat
Hyperphosphatemia in CKD
• Phosphate- binding agents are used to bind dietary phosphate in the
GI tract to form an insoluble complex that is excreted in the feces.
• Phosphorus absorption is decreased decreasing serum phosphorus
levels
• Resin-based binders - Sevelamer carbonate
• Elemental-based binders- Lanthanum
• Iron-based binders- Sucroferric oxyhydroxide and Ferric citrate
• Calcium-containing binders- Calcium carbonate and Calcium acetate
• Aluminum-based binders- Aluminum hydroxide
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Phosphate-Binding Agents Used to Treat
Hyperphosphatemia in CKD
• Sevelamer has an added benefit of reducing LDL-C by
up to 30% and increasing HDL-C levels.
• Sevelamer carbonate may have benefit to aid in the
correction of metabolic acidosis, another complication
of kidney failure.

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Phosphate binders
• Sucroferric oxyhydroxide is a non-calcium, iron-based phosphate binder
• It controls serum phosphorus levels in adults with chronic kidney disease on
haemodialysis or peritoneal dialysis.
• It is used in form of chewable tablets.
• MOA-
• It preserves the phosphate adsorption capacity.
• Dietary phosphate binds strongly to sucroferric oxyhydroxide in the
gastrointestinal tract.
• The bound phosphate is eliminated in the feces and thereby prevented from
absorption into the blood.
• As a consequence of the decreased dietary phosphate absorption, serum
phosphorus concentrations are reduced.
• Diarrhea and discolored feces are common GIT-related adverse effects
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Phosphate-Binding Agents Used to Treat
Hyperphosphatemia in CKD
• Calcium carbonate can also aid in the correction of
metabolic acidosis
• The use of calcium-containing binders in CKD affects
calcium balance, so restricting the dose in all stages of
CKD
• Aluminum-containing phosphate-binding agents
are not recommended for chronic use in patients with
CKD to avoid aluminum accumulation, leading to
encephalopathy, bone disease, and anemia.
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Treatments for Secondary
Hyperparathyroidism -Vitamin D Therapy
• Vitamin D regulates : Calcium and phosphorus absorption from
the GI tract and kidney, PTH secretion, maintaining muscle,
cardiovascular, immune and brain function, and glucose control.
• In CKD, a decrease in renal metabolism of vitamin D - decreases
circulating concentrations of the activated form of vitamin D,
calcitriol (1,25-dihydroxyvitamin D) and its precursor 25-
hydroxyvitamin D
• Vitamin D deficiency begins early in CKD and increases as
kidney function declines
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Vitamin D (prohormone):
• Vitamin D2 –Ergocalciferol
• Cholecalciferol, vitamin D3
• Active vitamin D: Calcitriol, active Vit D
• Vitamin D analogs: Paricalcitol and Doxercalciferol

• MOA-
➢facilitate intestinal absorption of calcium,
➢stimulates the absorption of phosphate and magnesium ions.
➢In the absence of vitamin D, dietary calcium is not absorbed at all
efficiently.
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Vitamin D
• Ergocalciferol
• Is natural highly lipid soluble
• several weeks are required to saturate body stores and achieve a
maximal effect.
• a long half-life.
• Prolonged periods of hypercalcemia occur after overdose with
ergocalciferol.

• Dihydrotachysterol (DHT)
• Is a synthetic vitamin D analogue
• with an onset of maximal effect and biological half-life between those of
ergocalciferol and calcitriol.
• Toxicity resulting from hypercalcemia still can be prolonged (up to 30
days).
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Vitamin D
• Calcitriol
▪ Is the vitamin D metabolite of choice to provide calcemic
actions because it has the most rapid onset of maximal
action and the shortest biologic half-life.
▪ Calcitriol is approximately 1000 times as effective as
parent vitamin D.

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 Treatments for Secondary
Hyperparathyroidism -Vitamin D Therapy

In patients with chronic renal failure:

1- deficiency in producing 1,25(OH)2D
2-impaired phosphate excretion and intestinal calcium absorption leads to secondary
hyperparathyroidism.
calcitriol analogs Such drugs are proving useful in the management of secondary
hyperparathyroidism accompanying chronic kidney disease and may be useful in selected
cases of primary hyperparathyroidism.
Vitamin D supplements can be used to lower serum PTH levels in
patients with CKD.

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 Treatments for Secondary
Hyperparathyroidism -Vitamin D Therapy
• Ergocalciferol, cholecalciferol, and calcifediol
• Effective in lowering PTH secretion in patients with
CKD G3
• Useful in later stages of CKD to maintain adequate 25-
hydroxyvitamin D levels for extrarenal functions

• Calcitriol - In CKD G4 and G5, used to decrease PTH

secretion in severe hyperparathyroidism
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 Treatments for Secondary
Hyperparathyroidism
CALCIMIMETICS
Cinacalcet: activates the calcium-sensing receptor (CaSR). CaSR
is widely distributed but has its greatest concentration in the PG. inhibits PTH
secretion.
Cinacalcet is approved for the treatment of secondary hyperparathyroidism in
chronic kidney disease and for the treatment of parathyroid carcinoma.

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• Old female patient with anemia secondary to chronic kidney disease and a hemoglobin level of 8.6 g/dl can treated with which of
the following drug?
a) Oral folic acid
b) Oral iron
c) Parantral iron
d) Epoetin alfa

• In CKD G4 and G5, which Vitamin D preparation we used to decrease PTH secretion in severe hyperparathyroidism?
a) Calcitriol
b) Ergocalciferol
c) Cholicalciferol
d) calcitonine

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