Transcript Clinical presentation of anemia of CKD

CKD COMPLICATIONS
DONE BY:
DIMA SALAH
NAHID ARAR
CKD COMPLICATIONS
#Among these complications are :
*fluid and electrolyte abnormalities,
*anemia,
*hyperphosphatemia,
*hyperparathyroidism,
*metabolic acidosis,
*cardiovascular complications,
*poor nutritional status.
CKDbCKD
CKD
 Often , these complications go
unrecognized or are inadequately managed
during the earlier stages of CKD,leading to
poor outcomes by the time a patient is in
need of dialysis therapy.
CKD
#Fluid And Electrolyte
Abnormalities:
Sodium and water 
#patient with CKD maintain sodium balance but are
volume expanded.
#the most common manifestation of increasd
intravascular volume is systemic hypertension.
#the goal in managing sodium and water balance is to
maintain a normal serum sodium concentration while
preventing fluid overload or volume depletion
(i.e.,maintaining hemodynamic stability).
#Fluid And Electrolyte
Abnormalities:
#By achieving these goals , the risk of developing
hypertension secondary to volume overload is also
reduced , although hypertension is already present in
many patients with stage 3 to 4 CKD.
Clinical presentation of impaired
sodium and water homeostasis
General
Alterations in sodium and water balance in CKD
manifests as increased edema.
SYMPTOMS
Nocturia can present in stage 3 CKD.
Edema generally presents in stage 4 CKD or later.
SIGNS
Cardiovascular :worsening hypertension,edema.
Genitourinary:change in urine volume and consistency.
Laboratory tests
Increased blood pressure
Sodium levels remain within the normal range.
Urine osmolality is generally fixed at 300 mOsm/l.
management
# the ability of the kidney to adjust to abrupt changes in
sodium intake is greatly diminished in patients with
CKD.
1) Sodium restriction beyond a no-added-salt diet
should not be recommended except in the face of
hypertension or edema.(2-4 g/day).
• Saline –containing IV solutions should be used
cautiously in patients with CKD because the ability
of kidney to excrete a salt load is impaired and such
patients are prone to volume overload.
management
2) Fluid restriction is generally unnecessary provided
sodium intake is controlled ,although fluid intake
between dialysis sessions is generally limited for
hemodialysis patients (avoid <2 L/dl)
3) Diuretic therapy is often necessary to control edema
or blood pressure.
Loop diuretics,particularly when administered by 
continuous infusion,increase urine volume and renal
sodium excretion.
management
 Thiazide diuretics are ineffective in patients with a
GFR <30 ml/min.the possible exception is used of the
thiazide-like diuretic,metolazone,which may retain its
effect at reduced eGFRs.
#as kidney failure progresses,manifestations of excess
fluid accumulation develop that are resistant to more
conventional interventions, and dialysis will be
required to control volume status.
Potassium
homeostasis(hyperkalemia)
Hyperkalemia is defined as a serum potassium
concentration greater than 5.5mEq/L.
Hyperkalemia can result from a combination of
factors, including:
$ diminished renal potassium excretion,
$ redistribution of potassium into the extracellular fluid
owing to metabolic acidosis,
$ excessive potassium intake.
Rare if GFR >15 without an endogenous or exogenous
load of potassium.
Potassium
homeostasis(hyperkalemia)
 It can be further classified according to its severity:
 Mild hyperkalemia(serum potassium 5.5-6mEq/L)
 Moderate hyperkalemia (6.1-6.9mEq/L)
 Severe hyperkalemia(>7mEq/L)
#the chronic goal is to maintain potassium
concentrations of approximately 4.5 to 5.5 mEq/L.
Hyperkalemia- clinical presentation
• Frequently, asymptomatic ,however,the patient may
complain of heart palpitations or skipped heartbeats.
• the earliest ECG change (serum potassium 5.56mEq/L) is peaked T waves.
 The sequence of change with further increases
is:*prolongation of the PR interval,
*widening of the QRS complex,
*loss of the P wave,
*merging of the QRS complex with the T wave
resulting in a sine-wave pattern.
Hyperkalemia- clinical presentation
Hyperkalemia- clinical presentation
• Hyperkalemia ECG changes are uncommon at
potassium concentrations of <7 mEq/L,but occur
regularly at concentrations>8mEq/L.
• Ventricular arrhythmias or cardiac arrest may
ensure if no effort to lower serum potassium.
• Laboratory tests
• Increased serum potassium levels.
clinical presentation of
hyperkalemia
General
Hyperkalemia is generally asymptomatic in patients with
CKD until serum potassium levels are greater than 5.5
mEQ/L,when cardiac abnormalities present.
Symptoms
mild hyperkalemia is generally not associated with overt
symptoms.
Signs
Cardiovascular:ECG changes.
Hyperkalemia-Management
• Generally,treatment is unnecessary if the potassium
concentration is<6.5 mEq/L and there are ECG
changes.
• If potassium concentrations rise above 6.5 mEq/L and
especially if they are accompanied by neuromuscular
symptoms or changes in the ECG, treatment should be
instituted .
• Chronic management involves prevention of
hyperkalemia by :
Hyperkalemia-Management
Limiting potassium intake to 50 to 80 mEq/day
II. Avoiding the use of agents that could elevate
potassium levels
III. Constipation in patients with CKD can interfere
with colonic potassium excretion ,therefore a good
bowel regimen is important
I.
Hyperkalemia-Management
 Acute management involves :
• reversal of cardiac effects with calcium administration
• Reduction of serum potassium which can be achieved by
shifting potassium intracellularly with administration of :
#glucose and insulin
# B-adrenergic agonists
# alkali therapy ( if metabolic acidosis is a contributing factor)
• Removing excess potassium from the body
# loop or thiazide diuretics
# exchange resins to remove potassium
# dialysis using a low-potassium dialysate bath
Metabolic acidosis :
 A clinically significant metabolic acidosis is commonly seen when the
GFR drops below
20-30 ml/min.
 the major factors responsible for the development of metabolic
acidosis in advanced kidney disease:#reduced bicarbonate reabsorption
#impaired production of ammonia by the kidney
 Consequences of metabolic acidosis include:
1. renal bone disease (bone buffering of some of the excess hydrogen
ions is associated with the release of calcium and phosphate from
bone,ex. Promoting bone resorption),
Metabolic acidosis
2.Fatigue and decreased exercise tolerance.
3.Reduced cardiac contractility
4.Increasd vascular irritability
5.Protein catabolism(uremic acidosis can increase
skeletal muscle breakdown and diminish albumin
synthesis)
The goals of therapy for patients with CKD are:


to normalize the PH of the blood (PH of approximately 7.35-7.45)
maintain the serum bicarbonate within the normal range(2228mEq/L).
Metabolic acidosis-management
 Asymptomatic patient with mild acidosis(bicarbonate of
12-20 mEq/L,PH of 7.2 to 7.4)generally don’t require
emergent therapy and gradual correction over days to
weeks is appropriate.
 When plasma bicarbonate less than 20mEq/L, give
NAHCO3 orally
• each 650 mg tablet of sodium bicarbonate provides 8 mEq of sodium
and 8 mEq of bicarbonate.
• Dose mEq= 0.5*WT*(24-serum bicarbonate)
#the calculated amount of bicarbonate replacement therapy should
be administered over several days to prevent volume overload from
excessive sodium intake.
Metabolic acidosis-management
 Should be administered over several days to avoid
volume overload from Na.
 Daily dose should not exceed 0.5 mEq/Kg/day and
should be given in divided dose.
 GI distress from CO2 production.
 Patients with severe acidosis (serum bicarbonate <8
mEq/L, PH<7.2) may require IV therapy.
Other Electrolyte and Metabolic
Disturbances Of CKD
 Hypermagnesemia
• is due to decreased elimination of magnesium by the
kidney.
• Magnesium is eliminated by the kidney to the extent
required to achieve normal serum magnesium
concentratinos(1.7-2.2 mg/dl) until eGFR is <30
ml/minute/1.73 m2).
• Serum magnesium concentrations <5 mEq/L rarely cause
symptoms.
• Higher cons can lead to
nausea,vomiting,lethargy,confusion,and diminished
tendon reflexes,
Other Electrolyte and Metabolic
Disturbances Of CKD
• Severe hypermagnesemia may depress cardiac
conduction.
• The risk of hypermagnesemia can reduced by
#avoiding magnesium –containing antacids and
laxatives.
#use of magnesium-free dialysate in patients with
stage 5 CKD requiring dialysis.
Other Electrolyte and Metabolic
Disturbances Of CKD
 Hyperphosphatemia
• Is a result of decreased phosphorus elimination by the
kidneys.
• Patients should reduce dietary phosphorus to 8001000 mg/day while maintaining adequate nutritional
needs.
• Phosphorus-containing laxatives and enemas should
also be avoided.
• Hyperphosphatemia is associated with low serum
calcium concentrations.
Other Electrolyte and Metabolic
Disturbances Of CKD
 Asymptomatic hyperurecemia.
• Happen due to diminished urinary excretion of uric
acid.
• In the absence of a history of gout or urate
nephropathy , asymptomatic hyperuricemia doesn’t
require treatment .
Anemia
 Anemia appears as early as stage 3 CKD.
 Usually is normochromic and normocytic.
 The primary cause of anemia in patient with CKD is
erythropoietin(EPO) defeciency.
 Other factors include:
 Decreased lifespan of red blood cells secondary to uremia,
 Blood loss from frequent phlebotomy and HD,GI bleeding,
 Severe hyperparathyroidism ,protein malnutrition,severe
infections,and inflammatory conditions
 Uremic toxins may inhibit the production of EPO, the bone marrow
response to EPO,and the synthesis of heme.
Anemia
 Iron deficiency
 Vitamin B12 and folate deficiency ,occurs more frequently in dialyzed
patients since folic acid is removed by dialysis.
 Aluminium intoxication(RBCs are typically microcytic).the major
source is aluminium-containing antacids.
Anemia
 the recommended thresholds for diagnosis and evaluation of anemia should
not be interpreted as being thresholds for treatment of anemia but simply for
the identification of this complication. Practice preferences with respect to
treatment strategies should be directed according to local resources.
 Evaluation of anemia in people with CKD
#to identify anemia in people with CKD measure Hb concentration:
• When clinically indicated in people with GFR<60 ml/min/1.73m2.
• At least annually in people with GFR 30-59 ml/min/1.73m2.
• At least twice per year in people with GFR<30 ml/min/1.73m2.
Anemia-clinical presentation and
diagnosis
Pallor and fatigue are the earliest clinical signs,with other 
manifestations(exertional
dyspnea,dizziness,headache)developing as anemia worsens
progressively with declining kidney function.
A significant consequence of anemia is development of left 
ventricular hypertrophy (LVH), further contributing to
cardiovascular complications and mortality in patients
with CKD >>>CHF,angina.
>>>Early and aggressive treatment of anemia of CKD before
the development of stage 5CKD is important.
Anemia-clinical presentation and
diagnosis
A more complete and regular workup for nemia of 
CKD is recommended for patients with eGFR <60
ml/min/1.73m2.this workup includes:
Monitoring of hemoglobin and hematocrit,
Assessment of iron indices with correction if iron 
deficiency is present,
Evaluation for sources of blood loss,such as bleeding 
from the GI tract.
Clinical presentation of anemia of
CKD
 General
Anemia of CKD generally presents with fatigue and
decreased quality of life.
 Symptoms
Anemia of CKD is associated with symptoms of cold
intolerence, shortness of breath,and decreased exercise
capacity.
 Signs
Cardiovascular:left ventricular hypertrophy,ECG
changes,congestive heart failure.
Neurologic:impaired mental cognition
Genitourinary:sexual dysfunction.
Clinical presentation of anemia of
CKD
 Laboratory tests
Decreased RBC count,Hgb,and Hct
Decreased serum iron level,TIBC,serrum ferritin ,and
TSAT.
Decreased erythropoietin levels relative to the degree of
hypoxia that is present.
TIBC:total iron binding capacity
TSAT:transferrin saturation
Goals of Anemia therapy:
1-increase oxygen-carrying capacity
2-decrease signs and symptoms of anemia like Easy
fatigue, rapid heat beat, particularly with exercise,
headache Difficulty concentrating ,Dizziness , Pale skin
,Leg cramps Insomnia
3-improve the patient’s quality of life
4-decrease the need for blood transfusions
oTo achieve this goals we must combine ESA with iron
supplement
oHb is the preferred parametet to moniter blood cell
production because it is not affected by storage
condition
Initiation of ESA therapy should be considered in all
CKD patients when Hb is between 9 and 10 g/dL
ESA dose should be decreased or interrupted when Hb
is above 10 g/dL in CKD patients not receiving dialysis or
above 11 g/dL in patients receiving dialysis.
As CKD worsens, a progressive decline in Hb despite
ESA therapy may be observed so we must add iron
supplement
Parameters used to monitor iron level:
TSat, an indicator of iron immediately available for
delivery to the bone marrow
(Transferrin is the carrier protein for iron and, as a
protein, may be affected by nutritional status)
serum ferritin, an indirect measure of storage iron.
*Serum ferritin is an acute-phase reactant, meaning it may be
elevated under certain inflammatory conditions and give a
false indication of storage iron.
The content of hemoglobin in reticulocytes (CHr) is
also recommended as a parameter to assess iron status in
hemodialysis patients
Anemia management :
Nonpharmacologic therapy
maintain adequate dietary intake of iron as well as
folate and B12 like chicken , tuna ,salmon Peanut Butter
Spinach Cereal ,Nuts ,Dried frutit
Patients on hemodialysis or peritoneal dialysis should
be routinely supplemented with water-soluble vitamins
(vitamins B, C, and folic acid) as these vitamins are often
depleted with dialysis therapy.
small amount of dietary iron , approximately 1 to 2 mg
is absorbed so oral intake from dietary sources alone is
insufficient to meet the increased iron requirements
Pharmacologic Therapy
Pharmacologic therapy for anemia of CKD is based on a
foundation of ESA therapy to correct erythropoietin
deficiency and iron supplementation to correct and prevent
iron deficiency caused by ongoing blood loss and increased
iron demands associated with the initiation of
erythropoietic therapy.
Erythropoietin: a glycoprotein hormone secreted by the
kidney in the adult and by the liver in the fetus, which acts
on stem cells of the bone marrow to stimulate red blood cell
production and hemoglobin in the bone marrow, in
response to low levels of oxygen in the tissues.
 Iron supplementation is first-line therapy for anemia of
CKD if iron deficiency is diagnosed
1) Iron (Parenteral and Oral Form)
Anemia in CKD patient must be treated by iron agents
depending on iron test
iron therapy appears not to be limited to patient iron
deficiency.

Goals of iron therapy are:
1)avoid storage iron depletion
2) prevent iron-deficient erythropoietin
3) achieve and maintain target Hgb levels
 Monitoring iron level
Every month during initial ESA treatment
At least every 3 months during stable ESA treatment
Oral Iron Preparation
Oral ferrous sulphate (glutamate, fumarate)
200mg/day of elemental iron is taken on empty stomach
in 2-3 doses to maximize absorption, unless no side
effects in GI
In case of GI side effect:
I. oral iron can be taken with small snack
II. ferrous sulphate solution, iron polysaccharide
complex or sustained-release preparation may be
used but with the latter two bioavailability is the
problem
GI side effects ( nausea, abdominal pain, diarrhea,
constipation, dark stools).
drug interactions with oral iron (e.g., antacids,
quinolones)
Food and CaCO3 delay iron absorption
iron should be taken 1 hr
before or 2 hr after CaCO3
•The ferrous form of iron is absorbed three times more
readily than the ferric form
•Drugs that decrease iron absorption:
1)Mg , Al, and Ca containing antacid
2)Tetracycline and doxycycline
3)Histamine2 antagonist
4)Proton pump inhibitor
5)Cholestyramine
Iron drug interaction:
1-levodopa (chelate with iron)
2-methyldopa ( decrease efficacy)
3-levothyroxine (decrease efficacy)
4-penicillamine (chelate with iron)
5-fluoroquinolones (form complex)
6-mycophenolate (decrease absorption)
Parental iron preparation:
1- iron dextran
•100mg during each HD session by IV push over 2 min
for 10 session
50 mg each week during dialysis for 10
weeks
•ADR:(Arthralgias, myalgias, serum sickness-like
syndrome, hypotension.
•25mg in adults should be administered IV before
initiating therapy to detect small risk of anaphylaxis
2- ferric gluconate
3- iron sucrose
4- Ferumoxytol
( these agents have less ADR compared to dextran)
2) Folic Acid 1 mg/day
3) Blood Transfusion: may result in iron overload,
infections, suppression of erythropoietin . Only use it in
persistent anemia .
4) Erythropoiesis- Stimulating Agent (ESA): The
erythropoietin deficiency evident in patients with CKD can
be corrected by the exogenous administration of ESA . Two
such agents are currently available:
A- Epoetinalfa (recombinant human erythropoietin)
B- Darbepoetin Alfa
The benefits of ESA:
1- improvements in quality of life
2- increased energy levels
3- greater capacity for work and exercise
4- improved appetite and participation in social
activities
5- reduced depression and fatigue
oEpoetin Alfa:
SC administration is preferred because cost is lower
than with IV administration and less frequency
•the half-life of epoetin alfa (8.5 hours IV, 24.4 hours
SC), so administered one to three times per week with
SC and three times per week for IV
oDarbepoetin alfa:
• has a longer half life and prolonged biological activity
•Starting dose in patients not previously receiving
epoietin-alpha therapy is 0.45 mcg/kg IV or SC once
weekly.
•In dialysis and nondialysis patients with CKD receiving
ESA therapy, the selected Hgb target should generally be
in the range of 11.0 to 12.0 g/dL and not be greater than
13g/dL.
• We prefer SC in non-hemodialysis-CKD patients and IV
in HD (hemodialysis)-CKD patients
ESA resistance causes:
1-Fe,folate and B12 deficiency
2-inflammtion (less Fe delivered)
3-Hyperparathydism
KDIGO guideline:
oESAs not be started in adult non-dialysis CKD
patients with Hgb concentrations ≥10 g/dL.
 For non-dialysis CKD patient with Hgb <10 g/dL,
the treatment individualized depend on:
the rate of fall in Hgb concentration, response to
iron therapy,
In dialysis patients, KDIGO suggests initiating ESAs
when the Hgb concentration is below 10 g/dL.
The KDIGO 2012 guidelines suggest that ESAs should
generally not be used to maintain Hgb concentrations
above 11.5 g/dL, but that individualization of therapy
will be necessary as some patients may have
improvements in quality of life at Hgb ≥11.5 g/dL and
will be prepared to accept the risks
The KDIGO guidelines recommended that ESAs not
be used to maintain Hgb ≥13 g/dL.
The 2012 KDIGO guidelines recommended that ESAs
be used in caution with malignancy, or with a history
of stroke
• Calcium–phosphorus balance play an important role
parathyroid gland by on bone, GI tract, kidney, and
many hormones like
*PTH (↑ serum calcium, ↓ serum phosphate(
*Vitamin D: ↑ Ca and P
*fibroblast growth factor 23:inhibits the
production of 1,25(OH)2D )↓serum phosphate)
by the kidney
The major sequelae of CKD is its impact on bone
mineral homeostasis:
deficient 1,25(OH)2D production
retention of phosphate
reduction in ionized calcium levels
secondary hyperparathyroidism that results from the
parathyroid gland response to lowered serum ionized
calcium and low 1,25(OH)2D.
FGF23 levels are also increased in part due to the
increased phosphate, which further reduce 1,25(OH)2D
production by the kidney
*Kidney produce vitamin D and when
kidney disease progresses, renal
activation of vitamin
D is impaired , which reduces gut
absorption of calcium ,which lead to low
blood calcium concentration resulting in
increase secretion of Parathyroid hormone
(PTH)
When renal function declines, serum calcium
balance can be maintained only at
the expense of increased bone resorption
Which leads to change in bone morphology
bone pain and fractures.
1)altered lipid metabolism and insulin secretion
2)impaired neurologic and immune functions
3)Resistance to erythropoietic therapy
4)Increase mortality
1-Osteitis Fibrosa cystica : bone become deformed and
soft because of high bone turnover
2-osteomalacia:softening of bone
3-adynamic bone disease: inactive bone
*When symptoms appears the disease will not be
easily treated
The desired ranges of calcium , phosphorus,
calcium-phosphorus product and PTH based on K/DOQI
parameter
Stage 3
Stage 4
stage 5
Corrected calcium
(mg/dl)
Normal”
Normal”
8.4-9.5
Phosphorus(mg/dl
)
2.7-4.6
2.7-4.6
3.5-5.5
Ca*p(mg^2/dl^2)
<55
<55
<55
Intact PTH
(pg/ml)
35-70
70-110
150-300
MONITERING:
Lab tests should be repeated every 12
months for stage 3 patient and every 3 month for stage
4 patient and monthly for stage 5
Patient
The KDIGO guideline recommend measuring
of bone-specific alkaline phosphate which is
useful for diagnosis and assessment of severity of
metabolic bone disease including Paget disease,
osteomalacia, and other states of high bone turnover
Bone biopsy: gold standard and invasive test that is
not easily performed for diagnosis of bone architecture,
this test recommended when symptoms is not clear or in
patient with more biochemical abnormalities
*including patient with fractures, persistent
hypercalcemia and aluminum toxicity. However when
aluminum concentration (60-200mcg/L)a Deferoxamine
test should be done (test used for diagnosis of
aluminum-related osteodystrophy)
Bone biopsy test described turnover rate ,volume
and miniralization
Bone mineral density test is not recommended in
advanced CKD stages because has not been shown
to predict the fracture risk
*Electron Beam computed
tomography(EBCT): noninvasive and
sensitive method for detecting cardiovascular
calcification and used in CKD
studies
Calcification: build up of calcium in body tissue
where there normally is not any calcium leading to
organ dysfunction or vessel defect, calcification
occur by aging,surgery,radiation and infection
Management of
renalosteodystrophy:
Dietary phosphate restriction
Phosphate binder (calcium and non-calcium)
Vitamin D analogues
Calcium supplement
Calimimetic(not approved for CKD patients)
1)Oral calcium supplement: are first line for
controlling both calcium and phosphate level, but
elemental calcium should not more than 1500mg/day
*IF Ca x P >55mg^2/dl^2 according to K/DOQI
high risk for soft tissue formation and calcification
leading to calcific uremic artereopathy (CUF)
However KDIGO guideline suggest no clinical
information of Ca * P than individual value in treatment
2)Dietary phosphate restriction:
The normal level of phosphate from 2.4-4.1mg/dl
in all CKD stages according to KDIGO. However
K/DOQI allow phosphate eve from 3.5-5.5 mg/dl
in stage 5 patient
Dietary phosphorus restriction (800 to 1,000
mg/day) should be first-line intervention for
stage 3 or higher CKD
Sources of phosphate:
Protein rich food
Organic phosphate (plant seeds,nuts,legumes,meat)
50% absorbed
Inorganic phosphate(preservative and additive salts
found in processed food) should be minimized because
90% absorbed
Dark carbonated beverage should be discouraged
Some phosphate are removed by dialysis
3) Phosphate-Binding Agents:
•Dietary phosphate restriction is difficult to achieve specially
when GFR <30ml/minute/1.73m so phosphate-binding agents
are necessary
•These agents reduce phosphate absorption from the gut and
should be administered with meals to maximize the effect
•These agents are first-line agents for controlling both serum
phosphorus and calcium
Concentrations
•K/DOQI guidelines recommend that elemental calcium from
calcium containing binders should not exceed 1,500 mg/day
and the total daily intake from all sources should not exceed
2,000 mg. This may necessitate combination of calcium- and
noncalcium-containing products
Adverse effects of calcium-containing phosphate
binders:
1) constipation,
2) nausea, vomiting,
3)abdominal pain.
oTo avoid potential drug interactions, phosphate
binders should be administered 1 hour before or 3 hours
after other oral medications.
4) Vitamin D Therapy:
Calcium (less than 9.5 mg/dl) and phosphorus (less than
4.6 mg/dl) must be controlled before vitamin D therapy is
initiated.
Calcitriol (1,25-dihydroxyvitamin D3)
directly suppresses PTH synthesis and secretion and up
regulates vitamin D receptors, which ultimately may
reduce parathyroid hyperplasia. The dose depends on the
stage of CKD and type of dialysis.
 If hypercalcemia withhold treatment .
Ergocalciferol:in stage 3 and 4 if 25-hydroxyvitamin D is
less than 30 ng/dl Ergocalciferol is recommended
•The recommended dose between 600-800 units per
day
5)Calcimimetics
Cinacalcet
•reduces PTH secretion by increasing the sensitivity of
the calcium-sensing receptor. The most common
adverse events are nausea
and vomiting.
• The starting dose is 30 mg daily, which can be titrated
to the desired PTH and calcium concentrations every 3
to 4 weeks and to a
maximum of 180 mg daily
*Sensipar (cinacalcet) is the first calcimimetic FDA
approved
Cinacalet lowers serum calcium and may cause
hypocalcemia so this agent should not be used if serum
level is less than 8.4mg/dl
Step 1
The initial focus in managing sHPT should be the management of
hyperphosphatemia. Among patients with hyperphosphatemia
restricting dietary phosphate intake.
Step 2
 Among patients with hyperphosphatemia despite dietary
phosphorus restriction after two to four months phosphate
binders should be administred
 For patients with an initial serum calcium levels less than 9.5
mg/dl (<2.37 mmol/L), a calcium containing phosphate binder
should be administered as long as hypercalcemia does not
develop. For patients with an initial serum calcium level greater
than 9.5 mg/dl (<2.37 mmol/L), a non-calcium based phosphate
binder rather than a calcium-containing phosphate binder. Either
sevelamer or lanthanum carbonate can be given in this setting
Treatment with ergocalciferol should be initiated if
vitamin D deficiency exists, as demonstrated by a
25(OH)-vitamin D (calcidiol) level of less than 30 ng/ml
if elevated PTH levels remain despite ergocalciferol and
phosphate binder therapy over a six-month period , low
dose of active vitamin D analog should be adminidtered
If the serum level of corrected total calcium exceeds 10.2
mg/dL (2.54 mmol/L)
ergocalciferol therapy and all forms of vitamin
D therapy should be discontinued
Step 3
Decide whether phosphate binder therapy is sufficient or
whether a vitamin D analogue should be added. This is
based upon calcium, phosphate, and PTH levels that are
measured when administering optimal phosphate binder
therapy.
Step 4
Among predialysis patients with sHPT, the use of
cinacalcet is controversial. Some experts and the KDIGO
working group recommend NOT giving cinacalcet given
the paucity of data concerning efficacy and safety in
predialysis patient with CKD
Bisphosphonate:
We do not describe it if GFR<30ml/min/1.73m^2
Note:
•Indication of bisphoohonate are osteoporosis,
corticosteroid therapy and Paget disease.
•In CKD patient if GFR >60ml/min/1.73m^2 with
osteoporosis and at high risk for fracture also if GFR
between 30-60ml/min/1.73m^2 with normal
PTH,osteoporosis or high risk for fracture treatment
should be as normal population
Hyperlipidemia:
The prevalence of hyperlipidemia increases as renal
function declines
Target LDL-C in people with diabetes and CKD stages 1-4
should be < 100 mg/dl; <70 mg/dl is a therapeutic option
People with diabetes, CKD stages 1-4, and LDL-C ≥ 100
mg/dl should be treated with a statin.
Treatment with a statin should not be initiated in patients
with type 2 diabetes on maintenance hemodialysis who do
not have a specific cardiovascular indication for treatment
Lipid profile should be reassessed at least annually and 2 to
3 months after changing treatment
HMG-CoA reductase inhibitors may have some other
advantages that may help to reduce kidney disease
progression in addition to lipid reduction, such as: reduction
of monocyte infiltration, mesangial cell proliferation,
mesangial matrix expansion, and tubulointerstitial
inflammation and fibrosis
ATP III suggests that chronic kidney failure is a
contraindication to fibrates.
New phosphate-binding agent sevelamer hydrochloride
appears to lower lipid levels by mechanisms similar to
those of bile acid sequestrants.
 KDIGO guidelines for lipid management in CKD
recommend treatment with a statin in adults aged 50 and
older with stage 1 to 5 CKD (not on dialysis)
The statin/ezetimibe combination may be used in
patients in stage 3 to 5 CKD (not on dialysis)
KDIGO only recommends statins in adults aged 18 to
49 years with stage 1 to 5 CKD (not on dialysis) who have
one or more of the following: known coronary disease,
diabetes mellitus, prior ischemic stroke, and an
estimated 10- year incidence of coronary death or
nonfatal myocardial infarction >10%
It is not recommended that statins or statin/ezetimibe
be initiated in patients with stage 5 CKD on dialysis;
however, therapy with theseagents may be continued if
patients were receiving these medications at the time of
dialysis initiation.
Due to the risk of adverse events with statins with stage 3
to 5 CKD, KDIGO recommends using statins at doses
shown to be beneficial (atorvastatin 20 mg, fluvastatin 80
mg, rosuvastatin 10 mg, simvastatin 20 mg)
Patients who are on hemodialysis with type 2 diabetes
will not be improved by atorvastatin according to study
results
Some medication increase the level of statin so should be
avoided or reduce statin dose
Hypertension
 The pathogenesis of hypertension in patient with CKD
is multifactorial.
Hypertension
Anorexia and malnutrition
 Limited data defining CKD stage where malnutrition
develops
 Malnutrition is common in patients with advanced
chronic renal disease because of:a lower food
intake(principally due to anorexia),decreased
intestinal absorption and digestion, and metabolic
acidosis.
 Studies have shown a strong correlation between
malnutrition and death in maintenance dialysis
patients.
Anorexia and malnutrition
 It is desirable to monitor the nutritional status of patients
with chronic kidney disease.
NKF K/DOQI guidelines:evaluate for signs of malnutrition
when GFR<60 ml/min/1.73 m2.
 A low plasma concentration of albumin and/or
creatinine(which varies with muscle mass as well as GFR)
may be indicative of malnutrition.
 Nutrition assessment
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dietry protein
Calorie intake
Serum albumin
Urine protein
Malnutrition -Management
 Protein-energy malnutrition is common in patient
with stage 4 or 5 CKD.
 Daily protein intake should be 1.2g/Kg for patient
undergoing hemodialysis and 1.2 to 1.3g/kg for those
undergoing peritoneal dialysis.
 Daily energy intake should be 35 Kcal/kg for patients
undergoing any type of dialysis, the intake should be
lowered to 30-35 kcal/kg for patients older than 60
years.
Malnutrition -Management
 Water-soluble vitamins should be supplemented to
replace dialysis-induced loss.
 L-carnitine is not recommended for patients with
ESKD unless the disordes for which it has shown
benefit(eg:hypertriglyceridemia,hypercholesterimia,a
nd anemia) don’t respond to standard therapies.
Questions??