Chronic Kidney Disease (CKD)

Renal Disorders PharmacotherapyRenal Disorders Pharmacotherapy
Chapter 3
Chronic Kidney Disease [CKD]
Renal Disorders Pharmacotherapy
By: Tsegaye Melaku
[B.Pharm, MSc, Clinical Pharmacist]
March, 2017March, 2017
tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.et
+251913765609+251913765609
Chapter 3
Chronic Kidney Disease [CKD]

Lesson Objectives
 Upon completion of the chapter, you will be able to:
 List the risk factors for development and progression of chronic
kidney disease (CKD).
 Explain the mechanisms associated with progression of CKD.
 Develop a therapeutic approach to slow progression of CKD,
including lifestyle modifications and pharmacologic therapies.
 Identify complications associated to CKD
 Design an appropriate therapeutic approach for specific
consequences associated with CKD.
 Monitor and evaluate therapeutic outcomes
 List the risk factors for development and progression of chronic
kidney disease (CKD).
 Explain the mechanisms associated with progression of CKD.
 Develop a therapeutic approach to slow progression of CKD,
including lifestyle modifications and pharmacologic therapies.
 Identify complications associated to CKD
 Design an appropriate therapeutic approach for specific
consequences associated with CKD.
 Monitor and evaluate therapeutic outcomes

Case Scenario
 A.A, a 41 year-old male, from who has a longstanding history of hypertension
and diabetes and presents JUMC , medical ward with a complaint of pruritis,
lethargy, lower extremity edema, nausea and emesis. He denies any other
medical illnesses.
 On physical exam the patient is a well-developed, well-nourished male in
moderate distress. Blood pressure 180/110, pulse 80, respirations 24 and he
was afebrile. Body weight 76.5 kg. Cardiac exam had an S1, S2 and S4. The
remainder of the exam was remarkable for 2+ lower extremity edema and
superficial excoriations of his skin from scratching.
 A.A, a 41 year-old male, from who has a longstanding history of hypertension
and diabetes and presents JUMC , medical ward with a complaint of pruritis,
lethargy, lower extremity edema, nausea and emesis. He denies any other
medical illnesses.
 On physical exam the patient is a well-developed, well-nourished male in
moderate distress. Blood pressure 180/110, pulse 80, respirations 24 and he
was afebrile. Body weight 76.5 kg. Cardiac exam had an S1, S2 and S4. The
remainder of the exam was remarkable for 2+ lower extremity edema and
superficial excoriations of his skin from scratching.

A.A’s Laboratory Data result
Chemistry Result Normal Values Urinalysis
Sodium 133 136-146 mmol/L
PH 6.0
Specific gravity
1.010
Protein 1+
Glucose –Ve
Acetone –ve
Occult blood –ve
Bile -ve
Waxy casts
Potassium 6.2 3.5-5.3 mmol/L
Chloride 100 98-108 mmol/L
Total CO2 15 23-27 mmol/L
BUN 170 7-22 mg/dl
Creatinine 16.0 0.7-1.5 mg/dl
U/S: both shrinked Kidney
PH 6.0
Specific gravity
1.010
Protein 1+
Glucose –Ve
Acetone –ve
Occult blood –ve
Bile -ve
Waxy casts
Creatinine 16.0 0.7-1.5 mg/dl
Glucose 108 70-110 mg/dl
Calcium 7.2 8.9-10.3 mg/dl
Phosphorus 10.5 2.6-6.4 mg/dl
Alkaline
Phosphatase
306 30-110 IU/L
Parathyroid
Hormone
895 10-65 pg/ml
Hemoglobin 8.6 14-17 gm/dl
Hematocrit 27.4 40-54 %
Mean cell
volume
88 85-95 FL

1. “Presents with a complaint of pruritis, lethargy, lower extremity edema, nausea
and emesis." what does the symptoms suggest to you?
2. What does S4 signify? What cardiac findings will you expect to find in a
hypertensive?
3. Is the cause of this patient’s renal failure acute or chronic? How did you arrive at
that conclusion?
4. What are risk factors for his current diagnosis?
5. What is the calculated GFR?
6. Why is the parathyroid hormone elevated?
7. What is the most likely cause of this patient’s anemia?
8. General approach of management??
Viva questions
1. “Presents with a complaint of pruritis, lethargy, lower extremity edema, nausea
and emesis." what does the symptoms suggest to you?
2. What does S4 signify? What cardiac findings will you expect to find in a
hypertensive?
3. Is the cause of this patient’s renal failure acute or chronic? How did you arrive at
that conclusion?
4. What are risk factors for his current diagnosis?
5. What is the calculated GFR?
6. Why is the parathyroid hormone elevated?
7. What is the most likely cause of this patient’s anemia?
8. General approach of management??

Introduction: CKD
 CKD Defined
Abnormalities in kidney structure or function, present for≥ 3 months
Progressive loss of function over several months to years,
» Characterized by gradual replacement of normal kidney
architecture with parenchymal fibrosis.
 The KDIGO classification system based on CGA staging
(Cause, GFR, Albuminuria).
 CKD Defined
Abnormalities in kidney structure or function, present for≥ 3 months
Progressive loss of function over several months to years,
» Characterized by gradual replacement of normal kidney
architecture with parenchymal fibrosis.
 The KDIGO classification system based on CGA staging
(Cause, GFR, Albuminuria).
KDIGO: Kidney Disease: Improving Global Outcomes

Epidemiology
 Globally, 8% to 16% of the general population has CKD
 1.9 million patients are undergoing renal replacement therapy[RRT].
 Prevalence of CKD increases with age: ~30% in >70 years old.
 Diabetes and hypertension are also important risk factors for CKD.
 In patients with type 2 diabetes, prevalence of 27%.
 Among T1DM; 17% to 25% of patients developed diabetic chronic
kidney disease (DCKD) after 30 years.
 Globally, 8% to 16% of the general population has CKD
 1.9 million patients are undergoing renal replacement therapy[RRT].
 Prevalence of CKD increases with age: ~30% in >70 years old.
 Diabetes and hypertension are also important risk factors for CKD.
 In patients with type 2 diabetes, prevalence of 27%.
 Among T1DM; 17% to 25% of patients developed diabetic chronic
kidney disease (DCKD) after 30 years.

Epidemiology…
Incident rates of end-stage renal disease (ESRD) by primary diagnosis (1980-2012)

Etiology/Risk Factors
 The Kidney Disease Outcomes Quality Initiative (KDOQI):
 CKD risk factor categories
Susceptibility factors
Initiation factors
Progression factors
 The Kidney Disease Outcomes Quality Initiative (KDOQI):
 CKD risk factor categories
Susceptibility factors
Initiation factors
Progression factors

 Susceptibility factors:
Advanced age, reduced kidney mass and low birth weight, family
history, low income, systemic inflammation, dyslipidemia.
Most of them are not amenable to pharmacologic or lifestyle
interventions.
Useful for identifying populations at high risk for CKD.
Etiology/Risk Factors…
 Susceptibility factors:
Advanced age, reduced kidney mass and low birth weight, family
history, low income, systemic inflammation, dyslipidemia.
Most of them are not amenable to pharmacologic or lifestyle
interventions.
Useful for identifying populations at high risk for CKD.

 Initiation Factors:
Conditions that result in direct kidney damage
Modifiable by pharmacologic therapy
DM, Hypertension, Glomerulonephritis: the most common
leading causes of CKD.
 DM: a cause for 45% of new ESRD cases in 2010, followed
by HTN (29%), US
 Initiation Factors:
Conditions that result in direct kidney damage
Modifiable by pharmacologic therapy
DM, Hypertension, Glomerulonephritis: the most common
leading causes of CKD.
 DM: a cause for 45% of new ESRD cases in 2010, followed
by HTN (29%), US

 Progression risk factors
Factors associated with further decline in kidney function in patients
who already have kidney damage
Persistence of the underlying initiation factors of CKD (e.g., DM, HTN,
glomerulonephritis)
– Serve as predictors of progressive CKD
Other factors associated with progression
– Factors consequent to the underlying kidney disease, e.g, HTN, proteinuria
– Factors independent of underlying kidney disease, e.g., smoking, obesity
 Progression risk factors
Factors associated with further decline in kidney function in patients
who already have kidney damage
Persistence of the underlying initiation factors of CKD (e.g., DM, HTN,
glomerulonephritis)
– Serve as predictors of progressive CKD
Other factors associated with progression
– Factors consequent to the underlying kidney disease, e.g, HTN, proteinuria
– Factors independent of underlying kidney disease, e.g., smoking, obesity

Diabetes
 Hyperglycemia: an initiation and progression risk factor for CKD
 Without treatment,
~80% of patients with DM-2 and microalbuminuria will develop overt
nephropathy
~50% of those with DM-1, nephropathy, and HTN will develop stage 5 CKD within
10 years.
 Lifetime risk of developing CKD
Type 1 DM patients: 40%
 Greater prevalence of type 2 DM compared to type 1
13
 Hyperglycemia: an initiation and progression risk factor for CKD
 Without treatment,
~80% of patients with DM-2 and microalbuminuria will develop overt
nephropathy
~50% of those with DM-1, nephropathy, and HTN will develop stage 5 CKD within
10 years.
 Lifetime risk of developing CKD
 Greater prevalence of type 2 DM compared to type 1

Hypertension
 Hypertension: both a cause of CKD and a result of CKD
 Early treatment of HTN and achievement of target BP
Slow the rate of progression of CKD
 BP goal in CKD is to control at all stages of CKD regardless of the
underlying cause.
 Lifetime risk of stage 5 CKD for patients with HTN: 5.6%
Elevated BP increases risk for developing CKD
14
 Hypertension: both a cause of CKD and a result of CKD
 Early treatment of HTN and achievement of target BP
Slow the rate of progression of CKD
 BP goal in CKD is to control at all stages of CKD regardless of the
underlying cause.
 Lifetime risk of stage 5 CKD for patients with HTN: 5.6%
Elevated BP increases risk for developing CKD

Glomerulonephritis
 Glomerulonephritis …..includes a wide variety of lesions caused by
immunologic, vascular, and other idiopathic diseases.
It is the third leading cause of ESRD
 Chronic glomerular diseases progress at variable rates
Loss of GFR 1.4 to 9.5 mL/min/year
15
 Glomerulonephritis …..includes a wide variety of lesions caused by
immunologic, vascular, and other idiopathic diseases.
It is the third leading cause of ESRD
 Chronic glomerular diseases progress at variable rates
Loss of GFR 1.4 to 9.5 mL/min/year

Proteinuria
 In diabetes with CKD, an albumin excretion rate >30 mg/24 hrs
strongly predicted the development of progression of CKD.
 Proteinuria alone may promote progressive loss of nephrons through
direct cellular damage
 Filtered proteins are toxic to kidney tubule cells
Albumin, transferrin, complement factors, immunoglobulins,
cytokines, angiotensin II
 Presence of proteins in renal tubules activates tubular cells
leads to ed production of inflammatory and vasoactive
cytokines such as endothelin (potent VC)
16
 In diabetes with CKD, an albumin excretion rate >30 mg/24 hrs
strongly predicted the development of progression of CKD.
 Proteinuria alone may promote progressive loss of nephrons through
direct cellular damage
 Filtered proteins are toxic to kidney tubule cells
Albumin, transferrin, complement factors, immunoglobulins,
cytokines, angiotensin II
 Presence of proteins in renal tubules activates tubular cells
leads to ed production of inflammatory and vasoactive
cytokines such as endothelin (potent VC)

 Proteinuria is also associated with the activation of complement
components on the apical membrane of proximal tubules
 Intratubular complement activation may be the key mechanism of
damage in the progressive proteinuric nephropathies  
Interstitial scarring
Progressive loss of structural nephron units
Reduction in GFR
Proteinuria…
17
 Proteinuria is also associated with the activation of complement
components on the apical membrane of proximal tubules
 Intratubular complement activation may be the key mechanism of
damage in the progressive proteinuric nephropathies  
Interstitial scarring
Progressive loss of structural nephron units
Reduction in GFR

Smoking
 Smoking is associated with ….
Acute reduction in GFR
Increase in urinary albumin excretion, HR, and BP, likely
secondary to nicotine exposure
 May promote initiation & progression of CKD in DM patients
 Smoking has been associated with ….
Diagnosis of CKD in those with HTN
Development of stage 5 CKD
18
 Smoking is associated with ….
Acute reduction in GFR
Increase in urinary albumin excretion, HR, and BP, likely
secondary to nicotine exposure
 May promote initiation & progression of CKD in DM patients
 Smoking has been associated with ….
Diagnosis of CKD in those with HTN
Development of stage 5 CKD

Dyslipidemia
 CKD with/without nephrotic syndrome is frequently accompanied by
abnormalities in lipoprotein metabolism.
 In patients with CKD and proteinuria >3 g/day, the major lipid
abnormalities are:
Elevation of plasma total and LDL cholesterol
Low HDL cholesterol (<35 mg/dL)
Elevated triglycerides (>200 mg/dL)
 Lipid abnormality treatment may slow CKD progression
 Treatment of proteinuria resolves the hyperlipidemia in most patients
with nephrotic syndrome.
19
 CKD with/without nephrotic syndrome is frequently accompanied by
abnormalities in lipoprotein metabolism.
 In patients with CKD and proteinuria >3 g/day, the major lipid
abnormalities are:
Elevation of plasma total and LDL cholesterol
Low HDL cholesterol (<35 mg/dL)
Elevated triglycerides (>200 mg/dL)
 Lipid abnormality treatment may slow CKD progression
 Treatment of proteinuria resolves the hyperlipidemia in most patients
with nephrotic syndrome.

Obesity***
 Studies demonstrate increased risk of stage 5 CKD in overweight
and obese subjects
BMI ≥25 kg/m2 associated with 3-fold increase in CKD risk.
Obesity (BMI ≥30 kg/m2)associated with 3- to 4 fold increased
in CKD risk
 Weight reduction as part of the treatment of progressive kidney
disease is suggested.
20
 Studies demonstrate increased risk of stage 5 CKD in overweight
and obese subjects
BMI ≥25 kg/m2 associated with 3-fold increase in CKD risk.
Obesity (BMI ≥30 kg/m2)associated with 3- to 4 fold increased
in CKD risk
 Weight reduction as part of the treatment of progressive kidney
disease is suggested.
***a major risk factor for essential hypertension, diabetes, and other
comorbid conditions
Puts more strain on the kidneys

Bottom line
 Clinical Factors
Diabetes
Hypertension
Obesity
Autoimmune
diseases
Systemic
infections
Urinary tract
infections
Urinary stones
Lower urinary
tract obstruction
Neoplasia
Family history of
CKD
Recovery from
acute kidney
injury
Reduction in
kidney mass
Exposure to
certain drugs
Low birth weight
 Sociodemographic Factors
Older age
Exposure to certain chemical and
environmental conditions
Low income/education
Diabetes
Hypertension
Obesity
Autoimmune
diseases
Systemic
infections
Urinary tract
infections
Urinary stones
Lower urinary
tract obstruction
Neoplasia
Family history of
CKD
Recovery from
acute kidney
injury
Reduction in
kidney mass
Exposure to
certain drugs
Low birth weight
Older age
Exposure to certain chemical and
environmental conditions
Low income/education

Pathophysiology
 Precise mechanism of kidney damage dependent on the etiology
of the disease.
 Heterogeneous causes
Diabetic nephropathy: glomerular mesangial expansion
Hypertensive nephrosclerosis: kidney's arterioles have arteriolar
hyalinosis
Polycystic kidney disease: renal cysts develop
 Precise mechanism of kidney damage dependent on the etiology
of the disease.
 Heterogeneous causes
Diabetic nephropathy: glomerular mesangial expansion
Hypertensive nephrosclerosis: kidney's arterioles have arteriolar
hyalinosis
Polycystic kidney disease: renal cysts develop

 Key elements of the pathway to ESRD:
Loss of nephrons mass,
Glomerular capillary hypertension,
Proteinuria.
Pathophysiology…
 Key elements of the pathway to ESRD:
Loss of nephrons mass,
Glomerular capillary hypertension,
Proteinuria.

 Exposure to initiation risk factors can result in loss of nephrons mass
 The remaining nephrons hypertrophy to compensate for the loss of nephrons mass
and kidney function
 Compensatory hypertrophy may be adaptive
Over time, hypertrophy may lead to intraglomerular hypertension
Possibly mediated by angiotensin II
 High intraglomerular capillary pressure impairs the size-selective function of
the glomerular permeability barrier
Resulting in increased urinary excretion of albumin and proteinuria
Pathophysiology…
 Exposure to initiation risk factors can result in loss of nephrons mass
 The remaining nephrons hypertrophy to compensate for the loss of nephrons mass
and kidney function
 Compensatory hypertrophy may be adaptive
Over time, hypertrophy may lead to intraglomerular hypertension
Possibly mediated by angiotensin II
 High intraglomerular capillary pressure impairs the size-selective function of
the glomerular permeability barrier
Resulting in increased urinary excretion of albumin and proteinuria

Proposed mechanisms of progression of kidney disease.

GFR Categorya GFR (mL/min2 [mL/s/]) Terms
1 >90 (>0.87) Normal or high
2 60–89 (0.58–0.86) Mildly decreased
3a 45–59 (0.43–0.57) Mildly to moderately
decreased
CKD Stages Based on KDIGO Classification
Mildly to moderately
decreased
3b 30–44 (0.29–0.42) Moderately to severely
decreased
4 15–29 (0.14–0.28) Severely decreased
5 <15 (<0.14) Kidney failure
aTo meet criteria for CKD there must be a significant reduction in GFR (categories 3a-5) or there must
also be evidence of kidney damage (categories 1 and 2) for 3 months or greater.
 CKD can be present with normal/near normal GFR if other markers of kidney disease are
present

Prognosis of CKD
 Dependent on the following factors:
Cause of kidney disease;
GFR at time of diagnosis;
Degree of albuminuria;
Presence of other comorbid conditions.
 End-stage renal disease (ESRD) GFR <15 mL/min/: need chronic
dialysis or kidney transplantation
 Dependent on the following factors:
Cause of kidney disease;
GFR at time of diagnosis;
Degree of albuminuria;
Presence of other comorbid conditions.
 End-stage renal disease (ESRD) GFR <15 mL/min/: need chronic
dialysis or kidney transplantation

Clinical Pictures and Assessment
 Often asymptomatic
 Symptoms
Fatigue, weakness, shortness of breath, mental confusion, nausea and
vomiting, bleeding, and loss of appetite, itching, cold intolerance, and
peripheral neuropathies.
 Signs
Edema, weight gain (from accumulation of fluid), changes in urine
output (volume and consistency), “foaming” of urine (indicative of
proteinuria), and abdominal distension.
 Often asymptomatic
 Symptoms
Fatigue, weakness, shortness of breath, mental confusion, nausea and
vomiting, bleeding, and loss of appetite, itching, cold intolerance, and
peripheral neuropathies.
 Signs
Edema, weight gain (from accumulation of fluid), changes in urine
output (volume and consistency), “foaming” of urine (indicative of
proteinuria), and abdominal distension.

…Assessment
 Laboratory Tests
 Decreased: eGFR, bicarbonate (metabolic acidosis), Hb/hematocrit (Hct) (anemia),
transferrin saturation (TSat) and/or ferritin (iron deficiency; note: ferritin may be
increased due to inflammatory conditions), vitamin D levels, albumin (malnutrition),
glucose (may result from decreased degradation of insulin with impaired kidney function
or poor oral intake), and calcium (in early stages of CKD).
 Increased: Serum creatinine, blood urea nitrogen, potassium, phosphorus, PTH, FGF-23,
ACR, PCR blood pressure (hypertension is a common cause and result of CKD), glucose
(uncontrolled diabetes is a cause of CKD), low-density lipoprotein (LDL) and
triglycerides, and calcium (more likely in CKD 5).
 Other: May be hemoccult-positive if GI bleeding occurs secondary to uremia.
 Decreased: eGFR, bicarbonate (metabolic acidosis), Hb/hematocrit (Hct) (anemia),
transferrin saturation (TSat) and/or ferritin (iron deficiency; note: ferritin may be
increased due to inflammatory conditions), vitamin D levels, albumin (malnutrition),
glucose (may result from decreased degradation of insulin with impaired kidney function
or poor oral intake), and calcium (in early stages of CKD).
 Increased: Serum creatinine, blood urea nitrogen, potassium, phosphorus, PTH, FGF-23,
ACR, PCR blood pressure (hypertension is a common cause and result of CKD), glucose
(uncontrolled diabetes is a cause of CKD), low-density lipoprotein (LDL) and
triglycerides, and calcium (more likely in CKD 5).
 Other: May be hemoccult-positive if GI bleeding occurs secondary to uremia.
Fibroblast growth factor 23

 Urine sediment abnormalities (hematuria, red blood cell and white blood cell casts, renal
tubular epithelial cells)
 Pathologic abnormalities indicating glomerular, vascular, tubulointerstitial disease, or
cystic and congenital diseases
 Structural abnormalities such as polycystic kidneys, renal masses, renal artery stenosis,
cortical scarring due to infarcts and pyelonephritis, or small kidneys (common in more
severe CKD) detected by imaging studies (eg, ultrasound, computed tomography,
magnetic resonance imaging, angiography)
 Other Diagnostic Tests
…Assessment
 Urine sediment abnormalities (hematuria, red blood cell and white blood cell casts, renal
tubular epithelial cells)
 Pathologic abnormalities indicating glomerular, vascular, tubulointerstitial disease, or
cystic and congenital diseases
 Structural abnormalities such as polycystic kidneys, renal masses, renal artery stenosis,
cortical scarring due to infarcts and pyelonephritis, or small kidneys (common in more
severe CKD) detected by imaging studies (eg, ultrasound, computed tomography,
magnetic resonance imaging, angiography)
 CKD stages 3, 4, 5 require additional workup
 Anemia, CV disease, metabolic bone disease, malnutrition, fluid & electrolyte, disorders

Treatment of CKD
 General
Identify the presence and causes of secondary complications
and comorbid conditions.
Interprofessional approach
Dietary education, and social/financial concerns.
Comprehensive medication management (CMM) /Drug-dosing
 General
Identify the presence and causes of secondary complications
and comorbid conditions.
Interprofessional approach
Dietary education, and social/financial concerns.
Comprehensive medication management (CMM) /Drug-dosing

Desired Outcome
 Delay or prevent progression of the disease
 Minimizing the development or severity of associated complications.
 Plan for RRT(HD or PD) starting from CKD
 Sustain and improve, if possible, the patient’s quality of life [CKD 5]
 Prevent adverse outcomes by aggressively managing complications of
CKD.
 Delay or prevent progression of the disease
 Minimizing the development or severity of associated complications.
 Plan for RRT(HD or PD) starting from CKD
 Sustain and improve, if possible, the patient’s quality of life [CKD 5]
 Prevent adverse outcomes by aggressively managing complications of
CKD.

Non-pharmacologic management
 Diet
Protein restriction to 0.8 g/kg/day in eGFR <30 mL/min(i.e,
CKD 4).
Decreasing sodium intake <2 g or 90 mEq (mmol)/day
(corresponding to 5 g NaCl)
 Smoking Cessation, Exercise, and Weight Loss
 Diet
Protein restriction to 0.8 g/kg/day in eGFR <30 mL/min(i.e,
CKD 4).
Decreasing sodium intake <2 g or 90 mEq (mmol)/day
(corresponding to 5 g NaCl)
 Smoking Cessation, Exercise, and Weight Loss

Pharmacologic management
 Proteinuria
Initiate ACEIs/ARBs
DCKD: ACEI/ARB 1st line therapy [urine albumin excretion is in
category A2 or greater (ACR between 30-300 mg/g)]
Increase dose until albuminuria is reduced by 30% to 50% or side
effects [e.g. >30% decrease in eGFR or elevation in serum potassium
occur]
ACEI + ARB ??
ACEI/ARB+ Aldosterone antagonist??
 Proteinuria
Initiate ACEIs/ARBs
DCKD: ACEI/ARB 1st line therapy [urine albumin excretion is in
category A2 or greater (ACR between 30-300 mg/g)]
Increase dose until albuminuria is reduced by 30% to 50% or side
effects [e.g. >30% decrease in eGFR or elevation in serum potassium
occur]
ACEI + ARB ??
ACEI/ARB+ Aldosterone antagonist??
DCKD: Diabetic CKD

 Dihydropyridine CCBs do not appear to have any beneficial effects
beyond those attributable to reducing BP.
 Nondihydropyridine agents (diltiazem and verapamil]:yielded beneficial
effects on proteinuria, although not as profoundly as ACEIs.
2nd antiproteinuric drugs [ACEI/ARB is contraindicated/not tolerated]
Suppress of glomerular hypertrophy,
Inhibit of platelet aggregation, and
Decrease in salt accumulation.
Pharmacologic management…
 Dihydropyridine CCBs do not appear to have any beneficial effects
beyond those attributable to reducing BP.
 Nondihydropyridine agents (diltiazem and verapamil]:yielded beneficial
effects on proteinuria, although not as profoundly as ACEIs.
2nd antiproteinuric drugs [ACEI/ARB is contraindicated/not tolerated]
Suppress of glomerular hypertrophy,
Inhibit of platelet aggregation, and
Decrease in salt accumulation.

Hypertension
 Recommended BP goals based on the degree of albuminuria and
the choice of antihypertensive agent.
 KDIGO: ≤140/90 mm Hg for those with category A1 albuminuria.
 Category ≥A2 albuminuria :≤ 130/80 mm Hg
 Subjects with proteinuria greater than 300 mg/day did benefit
from the lower blood pressure target.
 1st line: ACEI/ARB,, if not at goal, add diuretic(s)
 Recommended BP goals based on the degree of albuminuria and
the choice of antihypertensive agent.
 KDIGO: ≤140/90 mm Hg for those with category A1 albuminuria.
 Category ≥A2 albuminuria :≤ 130/80 mm Hg
 Subjects with proteinuria greater than 300 mg/day did benefit
from the lower blood pressure target.
 1st line: ACEI/ARB,, if not at goal, add diuretic(s)

Hypertension
management algorithm for patients
with CKD

Therapeutic strategies to
prevent progression of
renal disease in non-
diabetic individuals.

Diabetes
 Patients with DM should be screened annually for CKD
Start at the time of diagnosis of T2DM
5 years after the diagnosis of T1DM
 Reduction of proteinuria and achievement of desired BP & HbA1c [7%]
 CKD 3 and 4 are at higher risk of developing hypoglycemia
Reduction in metabolism of insulin by the kidney as GFR declines.
Require reduced doses of oral or injectable hypoglycemic agents
 Metformin:
 Continued: eGFR ≥45 mL/min; Reviewed: eGFR 30 to 44 mL/min,
 Discontinued: eGFR <30 mL/min
 Patients with DM should be screened annually for CKD
Start at the time of diagnosis of T2DM
5 years after the diagnosis of T1DM
 Reduction of proteinuria and achievement of desired BP & HbA1c [7%]
 CKD 3 and 4 are at higher risk of developing hypoglycemia
Reduction in metabolism of insulin by the kidney as GFR declines.
Require reduced doses of oral or injectable hypoglycemic agents
 Metformin:
 Continued: eGFR ≥45 mL/min; Reviewed: eGFR 30 to 44 mL/min,
 Discontinued: eGFR <30 mL/min

Therapeuticstrategiestopreventprogressionofrenaldiseaseindiabetic
individuals
Therapeuticstrategiestopreventprogressionofrenaldiseaseindiabetic
individuals

Recommendations
Nonpharmacologic
Exercise 30 minutes five times per week [1D]
Weight loss if BMI >25 kg/m2 [1D]
Smoking cessation [1D]
Alcohol: Two standard drinks per day for men and one standard drink per day for women[2D]
If hypertension: Low-sodium diet (<2 g/day, <90 mmol/day) [1C]
Pharmacologic
Adjust medication doses for kidney function [1A]
Seek pharmacist or medical advice before using over-the-counter medicines or nutritional protein
supplements [1B]
Herbal medicines are not recommended [1B]
Temporarily discontinue potentially nephrotoxic/renally excreted drugs if eGFR <60 mL/min/1.73
m2 in patients who are acutely unwell or hypovolemic (eg, metformin, RAAS blockers, diuretics,
NSAIDs/COX II inhibitors, lithium, digoxin) [1C]
Vaccines:
 Influenza yearly [1B]
 Pneumococcal vaccine if eGFR <30 mL/min/1.73 m2, nephrotic syndrome, diabetes, or receiving
immunosuppression. Single booster dose at year 5 [1B]
 Hepatitis B vaccine if eGFR <30 mL/min/1.73 m2 and risk of progression of CKD [1B]
ASA suggested for patients at risk for atherosclerotic events unless there is an increased bleeding
risk [2B]
Avoid oral phosphate-containing bowel preparations in people with a GFR <60 mL/min/1.73
m2 (<0.58 mL/s/m2) or in those known to be at risk of phosphate nephropathy [1A]
Pharmacologic
Adjust medication doses for kidney function [1A]
Seek pharmacist or medical advice before using over-the-counter medicines or nutritional protein
supplements [1B]
Herbal medicines are not recommended [1B]
Temporarily discontinue potentially nephrotoxic/renally excreted drugs if eGFR <60 mL/min/1.73
m2 in patients who are acutely unwell or hypovolemic (eg, metformin, RAAS blockers, diuretics,
NSAIDs/COX II inhibitors, lithium, digoxin) [1C]
Vaccines:
 Influenza yearly [1B]
 Pneumococcal vaccine if eGFR <30 mL/min/1.73 m2, nephrotic syndrome, diabetes, or receiving
immunosuppression. Single booster dose at year 5 [1B]
 Hepatitis B vaccine if eGFR <30 mL/min/1.73 m2 and risk of progression of CKD [1B]
ASA suggested for patients at risk for atherosclerotic events unless there is an increased bleeding
risk [2B]
Avoid oral phosphate-containing bowel preparations in people with a GFR <60 mL/min/1.73
m2 (<0.58 mL/s/m2) or in those known to be at risk of phosphate nephropathy [1A]
1=recommended; 2= suggested;; A=high quality, B=Moderate, C= Low; D= Very low

Monitor and evaluate
 Effectiveness and safety
 Monitor for HTN, DM, others related conditions
 Clinical signs and symptoms

Recommended Monitoring Intervals for Outcome
Albuminuria Stage (based on ACR in mg/g)
KDIGO GFR
Category eGFR (mL/min) A1: <30 mg/g
(<3 mg/mmol)
A2: 30-300 mg/g
(3-30 mg/mmol)
A3: >300 mg/g (>30
mg/mmol)
1 ≥90 12 months 12 months 6 months1 ≥90 12 months 12 months 6 months
2 60-89 12 months 12 months 6 months
3a 45-59 12 months 6 months 4 months
3b 30-44 6 months 4 months 4 months
4 15-29 4 months 4 months 2-3 months
5 <15 1-3 months 1-3 months 1-3 months
ACR, albumin-to-creatinine ratio

Complications of CKD
 Frequent complications of advanced CKD:
Altered sodium and water balance,
Hyperkalemia, metabolic acidosis, anemia,
CKD-related mineral and bone disorder (CKD-MBD),
Cardiovascular disease (CVD).
 Frequent complications of advanced CKD:
Altered sodium and water balance,
Hyperkalemia, metabolic acidosis, anemia,
CKD-related mineral and bone disorder (CKD-MBD),
Cardiovascular disease (CVD).

Other Complications of CKD
Organ System or
Complication Clinical Manifestations
Amyloidosis Accumulation of β2-microglobulin
Carpal tunnel syndrome
Blood and immune
disorders
Bleeding diathesis
Impaired cell-mediated immunity
Lymphopenia
Platelet dysfunction
Endocrine Hypoglycemic episodes (result of decreased
degradation of insulin by the kidney)
GI Nausea, vomiting, anorexia (from uremia)
Delayed gastric emptying
Gastroesophageal reflux
GI bleeding
Protein–energy wasting Malnutrition
Neurologic Peripheral neuropathies
Restless leg syndrome
Uremic encephalopathy
Uremic pruritus Generalized itching predominantlyof back, face, and
extremity used for vascular access, but may affect any
area
May be more severe during or immediately after
hemodialysis
Organ System or
Complication Clinical Manifestations
Amyloidosis Accumulation of β2-microglobulin
Carpal tunnel syndrome
Blood and immune
disorders
Bleeding diathesis
Impaired cell-mediated immunity
Lymphopenia
Platelet dysfunction
Endocrine Hypoglycemic episodes (result of decreased
degradation of insulin by the kidney)
GI Nausea, vomiting, anorexia (from uremia)
Delayed gastric emptying
Gastroesophageal reflux
GI bleeding
Protein–energy wasting Malnutrition
Neurologic Peripheral neuropathies
Restless leg syndrome
Uremic encephalopathy
Uremic pruritus Generalized itching predominantlyof back, face, and
extremity used for vascular access, but may affect any
area
May be more severe during or immediately after
hemodialysis

Anemia of CKD
 Primary cause: decrease in production of erythropoietin.
 Normochromic -normocytic anemia.
 Iron deficiency is also common in advanced kidney disease (i.e, CKD
4 and 5):
Decreased GI absorption of iron
Inflammation, Frequent blood testing,
Blood loss from hemodialysis (HD),
Increased iron demands from erythropoiesis stimulating agent
(ESA) therapy.
leading cause of resistance to ESAs and the reason frequent iron supplementation is necessary.
 Primary cause: decrease in production of erythropoietin.
 Normochromic -normocytic anemia.
 Iron deficiency is also common in advanced kidney disease (i.e, CKD
4 and 5):
Decreased GI absorption of iron
Inflammation, Frequent blood testing,
Blood loss from hemodialysis (HD),
Increased iron demands from erythropoiesis stimulating agent
(ESA) therapy.
leading cause of resistance to ESAs and the reason frequent iron supplementation is necessary.

 Additional factors contributing to the development of anemia of
CKD:
Decreased red cell life span (from the normal of 120 days to
approximately 60 days in individuals with CKD 5D),
Effects of accumulation of uremic toxins and inflammatory
cytokines,
vitamin B12 and folate deficiencies.
Anemia of CKD…
 Additional factors contributing to the development of anemia of
CKD:
Decreased red cell life span (from the normal of 120 days to
approximately 60 days in individuals with CKD 5D),
Effects of accumulation of uremic toxins and inflammatory
cytokines,
vitamin B12 and folate deficiencies.

 Sign & sxs of anemia:
Fatigue, shortness of breath, cold intolerance, chest pain, tingling in
the extremities, tachycardia, headaches, and general malaise.
 CBC: Hb concentrations [<13 g/dL for male & <12 g/dL for females]
Annually in CKD 3,
biannually in CKD 4-5, and
At least every 3 months in CKD 5 patients.
 Iron status; Tsat, serum ferritin
 Vitamin B12 or folate, Guaiac test
Anemia of CKD…Dx
 Sign & sxs of anemia:
Fatigue, shortness of breath, cold intolerance, chest pain, tingling in
the extremities, tachycardia, headaches, and general malaise.
 CBC: Hb concentrations [<13 g/dL for male & <12 g/dL for females]
Annually in CKD 3,
biannually in CKD 4-5, and
At least every 3 months in CKD 5 patients.
 Iron status; Tsat, serum ferritin
 Vitamin B12 or folate, Guaiac test

 Note: The risk of mortality and CV events is higher in CKD patients treated
to higher Hb target values with an ESA.
 KDOQI suggest:
Hb range of 11 to 12 g/dL for all CKD patients.
TSat of greater than 20% (>0.20
Serum ferritin
 > 100 ng/mL for CKD patients not requiring HD
 > 200 ng/mL for CKD 5HD patients.
Anemia of CKD…Rx
 Note: The risk of mortality and CV events is higher in CKD patients treated
to higher Hb target values with an ESA.
 KDOQI suggest:
Hb range of 11 to 12 g/dL for all CKD patients.
TSat of greater than 20% (>0.20
Serum ferritin
 > 100 ng/mL for CKD patients not requiring HD
 > 200 ng/mL for CKD 5HD patients.

 Higher risk of dialysis access thrombosis and uncontrolled blood pressure
in the higher Hb.
Almost twofold increase in the risk of stroke (5%)
High-dose ESA use was associated with greater risk of death.
 Non-pharmacologic Therapy
Dietary intake of iron, folate and B12
Anemia of CKD…Rx…
 Higher risk of dialysis access thrombosis and uncontrolled blood pressure
in the higher Hb.
Almost twofold increase in the risk of stroke (5%)
High-dose ESA use was associated with greater risk of death.
 Non-pharmacologic Therapy
Dietary intake of iron, folate and B12

Anemia of CKD: Pharmacologic Rx
 Iron Supplementation
Provide the elemental iron required for production of Hb.
Warranted in individuals with a TSat < 30% (<0.30) and a ferritin < 500
ng/mL in whom an increase in Hb or a decrease in ESA dose is desired.
Oral preparations: ferrous salts (ferrous sulfate, ferrous fumarate,
and ferrous gluconate), polysaccharide iron complex, and carbonyl
iron.
Differ in terms of the amount of elemental iron: ferrous sulfate
(20%), ferrous gluconate (12%), ferrous fumarate (33%), iron
polysaccharide (100%), and carbonyl iron (100%).
 Iron Supplementation
Provide the elemental iron required for production of Hb.
Warranted in individuals with a TSat < 30% (<0.30) and a ferritin < 500
ng/mL in whom an increase in Hb or a decrease in ESA dose is desired.
Oral preparations: ferrous salts (ferrous sulfate, ferrous fumarate,
and ferrous gluconate), polysaccharide iron complex, and carbonyl
iron.
Differ in terms of the amount of elemental iron: ferrous sulfate
(20%), ferrous gluconate (12%), ferrous fumarate (33%), iron
polysaccharide (100%), and carbonyl iron (100%).
 Oral absorption??

 IV iron preparations are colloids
To correct absolute iron deficiency, especially if they are receiving
an ESA.
Improves the responsiveness to ESA therapy & lower doses can be
used to maintain the target Hb in HD patients
In patients with CKD 5HD GI absorption of iron is often inadequate
Thus the IV route is preferred for almost all HD patients.
 If oral therapy is initiated a 1- to 3-month trial is recommended to assess
response.
Anemia of CKD: Pharmacologic Rx…
 IV iron preparations are colloids
To correct absolute iron deficiency, especially if they are receiving
an ESA.
Improves the responsiveness to ESA therapy & lower doses can be
used to maintain the target Hb in HD patients
In patients with CKD 5HD GI absorption of iron is often inadequate
Thus the IV route is preferred for almost all HD patients.
 If oral therapy is initiated a 1- to 3-month trial is recommended to assess
response.

Iron dosing
 Oral therapy:
200 mg of elemental iron per day
1- to 3-month trial in the non-HD CKD prior to initiating IV therapy.
 For the HD population: IV preferred
1-g course of IV iron (in divided doses) recommended.
 Typical repletion dosing regimens for IV iron:
100 mg as iron sucrose over 10 dialysis sessions or
125 mg of sodium ferric gluconate over 8 dialysis sessions.
 Oral therapy:
200 mg of elemental iron per day
1- to 3-month trial in the non-HD CKD prior to initiating IV therapy.
 For the HD population: IV preferred
1-g course of IV iron (in divided doses) recommended.
 Typical repletion dosing regimens for IV iron:
100 mg as iron sucrose over 10 dialysis sessions or
125 mg of sodium ferric gluconate over 8 dialysis sessions.
Test dose needed for IV iron (iron dextran)

Algorithm for iron therapy in
management of anemia
of CKD
ESA, erythropoiesis-stimulating
agent; Hb, hemoglobin; TSat,
transferrin saturation; ND-CKD, non-
dialysis CKD patients; PD-
CKD, peritoneal dialysis patients;
HD-CKD, hemodialysis patients.)

Iron Adverse Effects
 Primarily GI in nature and include constipation, nausea, and
abdominal cramping; more likely as the dose is escalated.
 IV iron: hypotension, dizziness, dyspnea, headaches, lower back
pain, arthralgia, syncope, and arthritis, anaphylaxisanaphylaxis 0.60.6% to 0.7%% to 0.7%
So, decrease the dose or rate of infusion
 Primarily GI in nature and include constipation, nausea, and
abdominal cramping; more likely as the dose is escalated.
 IV iron: hypotension, dizziness, dyspnea, headaches, lower back
pain, arthralgia, syncope, and arthritis, anaphylaxisanaphylaxis 0.60.6% to 0.7%% to 0.7%

Iron Drug Interactions
 Iron absorption is decreased by
Other elements (eg, calcium in calcium-containing phosphate
binders),
Medications that increase the pH of the GI tract such as PPIs and
H2As , and antibiotics [doxycycline and tetracycline].
 Iron also decreases absorption of other drugs such as antibiotics
(fluoroquinolones, doxycycline)
 Iron absorption is decreased by
Other elements (eg, calcium in calcium-containing phosphate
binders),
Medications that increase the pH of the GI tract such as PPIs and
H2As , and antibiotics [doxycycline and tetracycline].
 Iron also decreases absorption of other drugs such as antibiotics
(fluoroquinolones, doxycycline)

Erythropoiesis-Stimulating Agent Therapy
 Are recombinant erythropoietin with similar amino acid sequence.
Darbepoetin alfa = long t1/2
Epoetin alfa
 Administered by either IV or SubQ route.
 Don’t make dosing changes too soon
 Are recombinant erythropoietin with similar amino acid sequence.
Darbepoetin alfa = long t1/2
Epoetin alfa
 Administered by either IV or SubQ route.
 Don’t make dosing changes too soon
Hb continues to increase until the life span of the cells stimulated by ESA therapy is reached
(mean 2 months; range 1-4 months in patients with ESRD)

 ESA’s Efficacy:
Respond to ESA therapy in a dose-related fashion.
Most common causes of therapeutic resistance:
Erythropoiesis-Stimulating Agent Therapy
 ESA’s Efficacy:
Respond to ESA therapy in a dose-related fashion.
Most common causes of therapeutic resistance:

ESA Adverse Effects
 Hypertension, Hypertensive encephalopathy.
Don’t be used in those with uncontrolled blood pressure.
 Seizures: within 3months of initiation
 Thrombosis of the HD vascular access site and other thromboembolic
events esp. in higher hemoglobin [>13 g/dL]
 ESAs are not indicated in patients receiving myelosuppressive
chemotherapy when the anticipated outcome is cure.
 Hypertension, Hypertensive encephalopathy.
Don’t be used in those with uncontrolled blood pressure.
 Seizures: within 3months of initiation
 Thrombosis of the HD vascular access site and other thromboembolic
events esp. in higher hemoglobin [>13 g/dL]
 ESAs are not indicated in patients receiving myelosuppressive
chemotherapy when the anticipated outcome is cure.

ESA dosing and administration
 Hb levels should be monitored at least monthly (weekly may be
preferred) until stable and then monthly thereafter.
 Dose adjustments should be made based on Hb response
 An acceptable rate of increase in Hb is 1 to 2 g/dL/month.
 25% increase in dose if Hb not increased by 1 g/dL after 4 weeks.
 25% decrease in dose if Hb increased >1 g/dL in a 2-week
 Hb levels should be monitored at least monthly (weekly may be
preferred) until stable and then monthly thereafter.
 Dose adjustments should be made based on Hb response
 An acceptable rate of increase in Hb is 1 to 2 g/dL/month.
 25% increase in dose if Hb not increased by 1 g/dL after 4 weeks.
 25% decrease in dose if Hb increased >1 g/dL in a 2-week

(ESA) therapy in management of
anemia of CKD

KDIGO ESA use recommendation
ND-CKD CKD 5HD and CKD 5PD Pediatric CKD
ESA initiation If Hb <10 g/dL (<100 g/L; <6.21
mmol/L). Consider rate of fall of Hb,
prior response to iron, risk of needing a
transfusion, risk of ESA therapy, and
presence of anemia symptoms before
initiating an ESA. [2C]
Do not initiate if Hb ≥10 g/dL (≥100
g/L; ≥6.21 mmol/L). [2D]
Use ESAs to avoid drop in Hb to <9
g/dL (<90 g/L; <5.59 mmol/L) by
starting an ESA when Hb is between
9 and 10 g/dL (90 and 100 g/L; 5.59
and 6.21 mmol/L). [2B]
Selection of Hb concentration at which to
initiate ESA therapy should include
consideration of potential benefits (eg,
improvement in QOL, school attendance,
avoidance of blood transfusions) and
potential harms. [2D]
If Hb <10 g/dL (<100 g/L; <6.21
mmol/L). Consider rate of fall of Hb,
prior response to iron, risk of needing a
transfusion, risk of ESA therapy, and
presence of anemia symptoms before
initiating an ESA. [2C]
Do not initiate if Hb ≥10 g/dL (≥100
g/L; ≥6.21 mmol/L). [2D]
Hb level Do not use ESAs
to intentionally increase Hb above 13
g/dL (130 g/L, 8.07 mmol/L). [1A]
Do not use ESAs to maintain Hb above
11.5 g/dL (115 g/L; 7.14 mmol/L). [2C]
Do not use ESAs
to intentionally increase Hb above 13
g/dL (130 g/L, 8.07 mmol/L). [1A]
Do not use ESAs to maintain Hb
above 11.5 g/dL (115 g/L; 7.14
mmol/L). [2C]
Suggest Hb range of 11-12 g/dL (110-120
g/L, 6.83-7.45 mmol/L). [2D]
Iron initiationb If TSat is ≤30% (≤0.30) and ferritin is
≤500 ng/mL (μg/L; ≤1,120 pmol/L).
[2C]
If TSat is ≤30% (≤0.30) and ferritin is
≤500 ng/mL (μg/L; ≤1,120 pmol/L).
[2C]
If TSat is ≤20% (≤0.20) and ferritin is
≤100 ng/mL (μg/L; ≤225 pmol/L). [1D]
CKD, chronic kidney disease; ESA, erythropoiesis
stimulating agent; Hb, hemoglobin; ND-CKD, non-
dialysis CKD patients; QOL, quality of life; TSat,
transferrin saturation.
 Serum ferritin is an acute-phase reactant-use
clinical judgment when above 500 ng/mL

Transfusions
 Red blood cell transfusions carry many risks
 Should only be used in select situations, such as
Acute management of symptomatic anemia,
Following significant acute blood loss
 Red blood cell transfusions carry many risks
 Should only be used in select situations, such as
Acute management of symptomatic anemia,
Following significant acute blood loss

Evaluation of Therapeutic Outcomes
 Iron status at least every 3 months if on stable ESA regimen.
 Iron status every month:
 Hb levels :
 Iron status at least every 3 months if on stable ESA regimen.
 Iron status every month:
 Hb levels :

CKD-Related Mineral and Bone Disorder
 Include abnormalities in PTH, Ca, P, Vit. D, fibroblast growth factor-
23 (FGF-23), bone turnover, as well as soft-tissue calcifications.
 The pathophysiology of CKD-MBD is complex.
 Include abnormalities in PTH, Ca, P, Vit. D, fibroblast growth factor-
23 (FGF-23), bone turnover, as well as soft-tissue calcifications.
 The pathophysiology of CKD-MBD is complex.

Pathophysiology of CKD-MBD
(Ca, calcium; FGF-23, fibroblast growth factor-23; PTH,
parathyroid hormone.) aFGF-23 also increases in
response to 1,25-dihydroxyvitamin D3.

 The abnormalities of CKD-MBD lead to alterations in structural integrity
of bone and other associated consequences.
 Continuous high rate of production of PTH by the parathyroid glands
promotes parathyroid hyperplasia.
 Bone abnormalities are almost universal in dialysis patients and
observed in the majority of those with CKD 3-5.
Osteitis fibrosa cystica (high bone turnover disease): Most common
Osteomalacia (low bone turnover disease), disease.
CKD-MBD
 The abnormalities of CKD-MBD lead to alterations in structural integrity
of bone and other associated consequences.
 Continuous high rate of production of PTH by the parathyroid glands
promotes parathyroid hyperplasia.
 Bone abnormalities are almost universal in dialysis patients and
observed in the majority of those with CKD 3-5.
Osteitis fibrosa cystica (high bone turnover disease): Most common
Osteomalacia (low bone turnover disease), disease.
Characterized by areas of peritrabecular fibrosis.
Its result in bone marrow fibrosis and decreased erythropoiesis

Vitamin D metabolism
DBP, vitamin D binding protein; NVD, nutritional
vitamin D; VDRs, vitamin D receptors.)

Dx of CKD-MBD
 Alterations in serum phosphorus, calcium, PTH, and 25(OH)D.
 Evaluation of bone architecture
 Gold standard: bone biopsy for histologic analysis[very invasive]
 Other: based on patient presentation
 Alterations in serum phosphorus, calcium, PTH, and 25(OH)D.
 Evaluation of bone architecture
 Gold standard: bone biopsy for histologic analysis[very invasive]
 Other: based on patient presentation

 Goal of therapy:
Normalize” the biochemical parameters
Prevent bone manifestations, CV and extravascular calcifications,
and the associated morbidity and mortality
 Management of PTH, phosphorus, and calcium is important.
 Combination of dietary intervention, phosphate-binding
medications, vitamin D, and calcimimetic therapy (for ESRD patients).
Rx of CKD-MBD
 Goal of therapy:
Normalize” the biochemical parameters
Prevent bone manifestations, CV and extravascular calcifications,
and the associated morbidity and mortality
 Management of PTH, phosphorus, and calcium is important.
 Combination of dietary intervention, phosphate-binding
medications, vitamin D, and calcimimetic therapy (for ESRD patients).

CKD-MBD… Non-pharmacologic RX
 Dietary phosphorus restriction:
To manage hyperphosphatemia
Should be initiated for most patients with CKD 3-5.
Phosphorus restriction to 800 to 1,000 mg/day
 Parathyroidectomy: therapeutic option
Persistently elevated PTH associated with hypercalcemia and/or
hyperphosphatemia [refractory to medical therapy]
 Dietary phosphorus restriction:
To manage hyperphosphatemia
Should be initiated for most patients with CKD 3-5.
Phosphorus restriction to 800 to 1,000 mg/day
 Parathyroidectomy: therapeutic option
Persistently elevated PTH associated with hypercalcemia and/or
hyperphosphatemia [refractory to medical therapy]
When PTH >800 pg/mL

 Phosphate-Binding Agents
Especially for those with ESRD; to limit GI absorption and
thereby control serum phosphorus.
Includes: elemental calcium, iron, and lanthanum-containing
compounds, and the non-elemental agent [sevelamer]
 Vitamin D Therapy
 Calcimimetics: Cinacalcet acts by increasing the sensitivity of the
calcium-sensing receptor.
CKD-MBD… Pharmacologic RX
 Phosphate-Binding Agents
Especially for those with ESRD; to limit GI absorption and
thereby control serum phosphorus.
Includes: elemental calcium, iron, and lanthanum-containing
compounds, and the non-elemental agent [sevelamer]
 Vitamin D Therapy
 Calcimimetics: Cinacalcet acts by increasing the sensitivity of the
calcium-sensing receptor.

Cardiovascular Complications of CKD
(AFIB, atrial fibrillation; AMI, acute myocardial infarction; ASHD, atherosclerotic heart disease;
CHF, congestive heart failure; CKD, chronic kidney disease; CVA/TIA, cerebrovascular
accident/transient ischemic attack; CVD, cardiovascular disease; PAD, peripheral arterial
disease; SCA/VA, sudden cardiac arrest and ventricular arrhythmias.)
Read on management of
specific CV disorders among
CKD patients
Read on management of
specific CV disorders among
CKD patients
ACEI/ARBs
Aspirin
Statin

Management of Dyslipidemia in CKD
Dyslipidemia Goal Initial Therapy Modification in
Therapya Alternativea
TG ≥500
mg/dL
TG<500
mg/dL
TLC TLC + fibrate
or niacin
Fibrate or niacin
LDL 100–129
mg/dL
LDL <100
mg/dL
TLC TLC + low-
dose statin
Bile acid
sequestrant
or niacin
LDL 100–129
mg/dL
LDL <100
mg/dL
TLC + low-
dose statin
Bile acid
sequestrant
or niacin
LDL ≥130
mg/dL
LDL <100
mg/dL
TLC + low-
dose statin
TLC +
maximum-
dose statin
Bile acid
sequestrant
or niacin
TG ≥200
mg/dL and non-
HDL
≥130mg/dL
Non-HDL <130
mg/dL
TLC + low-
dose statin
TLC +
maximum-
dose statin
Fibrate or niacin
aDosing of selected agents by class: fibrate (gemfibrozil 600 mg twice daily); niacin (1.5–3 g/day of immediate-release
product); statin (simvastatin 10–40 mg/day if GFR<30 mL/min [<0.50 mL/s], 20–80 mg/day if GFR >30 mL/min [>0.50
mL/s]); bile acid sequestrant (cholestyramine 4–16 g/day).

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