Download mg/dl

New NKF-K/DOQI
guidelines
Kidney Disease Outcome Quality Initiative
Shahrzad Ossareh-M.D.
Definition of Chronic Kidney Disease
Criteria
1.
Kidney damage ≥ 3 months as defined by
structural or functional abnormalities of the
kidney, with or without decreased GFR,
manifested by either:

Pathologic abnormalities; or

Markers of damage including abnormalities in
blood or urine tests or imaging studies.
2.
GFR< 60 ml/min/1.73 m2 for ≥ 3 months, with
or without kidney damage

Estimated GFR (mL/min/1.73 m2)
1.
Cockraft-Gault Formula
2.
MDRD study formula:
186 x [SCr(-1.154)] x [Age(-0.203)] x (0.742 if female)
x (1.21 if African American)
Stages of Chronic Kidney Disease
Stage
Description
GFR (ml/min/1.73 m2)
(Prevalence)
1
Kidney damage with
normal or ↑GFR
90
2
3
(3.3%)
Kidney damage with
mild ↓GFR
60-89
Moderate ↓GFR
30-59
(3%)
(4.3%)
4
Severe ↓GFR
15-29
(0.2%)
5
Kidney failure
<15 or on dialysis (0.1%)
Guidelines for
Bone Metabolism in
Chronic Kidney Disease
GUIDELINE 1.
Evaluation of Ca and P metabolism

1.1- Serum levels of calcium, phosphorus,
and intact PTH should be measured in all
patients with CKD and GFR <60 ml/min/1.73
m2. (EVIDENCE)
Frequency of measurement of PTH and
Ca/P by stage of CKD
CKD
stage
GFR
Range
PTH
measurement
Ca/P
measurement
3
30-59
Q 12 mo
Q 12 mo
4
15-29
Q 3 mo
Q 3 mo
5
<15 or
dialysis
Q 3 mo
Every month
*More frequently in patients receiving therapy for the abnormalities in Ca, P
or PTH and in transplant recipients.
Target Range of plasma iPTH by CKD
stage
CKD stage
GFR range
Target iPTH
3
30-59
4
15-29
5
<15 or
dialysis
35-70
(opinion)
70-110
(opinion)
150-300
(evidence)
Relationship between serum I-PTH levels and CCR based on data extracted from Martinez et al
(1997). Values on the y-axis are serum I-PTH levels (pg/ml). Values on the x-axis are CCR in
ml/min. The lines fitted to the data set are based on 4 different mathematical functions (power,
linear, exponential, and logarithmic), rather than on any assumptions about an underlying
physiological mechanism. The horizontal line represents the upper limit of the normal range of
serum I-PTH levels.

Newer assays specific for 1-84 PTH.

The normal range for the new assay for 1-84 PTH is 7 to
36 pg/ml compared to 16 to 65 pg/ml for iPTH.

Thus the relationship between the 2 assays is about 1:2
(1-84 PTH to intact PTH).

The differences in the levels between the 2 types of
assays are a reflection of the levels of circulating PTH
fragments that are detected by the intact PTH assay but
not by the new 1-84 PTH assay.
GUIDELINE 2. ASSESSMENT OF
BONE DISEASE
ASSOCIATED WITH CKD
2.1- The most accurate diagnostic test for
determining the type of bone disease in CKD is
iliac crest bone biopsy with double tetracycline labeling
and bone histomorphometric analysis.
(EVIDENCE)
2.2- It is not necessary to perform bone biopsy for most
situations in clinical practice. It should be considered in
patients with kidney failure (Stage 5) who have:
2.2- It is not necessary to perform bone biopsy for most
situations in clinical practice. It should be considered in
patients with kidney failure (Stage 5) who have:
2.2a- Fractures with minimal or no trauma (pathological
fractures); (OPINION)
2.2- It is not necessary to perform bone biopsy for most
situations in clinical practice. It should be considered in
patients with kidney failure (Stage 5) who have:
2.2a- Fractures with minimal or no trauma (pathological
fractures); (OPINION)
2.2b- Intact PTH levels between 100 and 500 pg/ml (in CKD
Stage 5) with coexisting conditions such as unexplained
hypercalcemia, severe bone pain, or unexplained increases in
bone alkaline phosphatase activity;(OPINION)
2.2- It is not necessary to perform bone biopsy for most
situations in clinical practice. It should be considered in
patients with kidney failure (Stage 5) who have:
2.2a- Fractures with minimal or no trauma (pathological
fractures); (OPINION)
2.2b- Intact PTH levels between 100 and 500 pg/ml (in CKD
Stage 5) with coexisting conditions such as unexplained
hypercalcemia, severe bone pain, or unexplained increases in
bone alkaline phosphatase activity;(OPINION)
2.2c- Suspected aluminum bone disease, based upon
clinical symptoms or history of aluminum exposure
(OPINION)
2.3- Bone radiographs are not indicated for the assessment
of bone disease of CKD, (EVIDENCE) but they are useful
in detecting severe peripheral vascular calcification
(OPINION) and bone disease due to ß2-microglobulin
amyloidosis. (EVIDENCE)
2.4- Bone mineral density (BMD) should be measured by
dual energy X-ray absorptiometry (DEXA) in patients with
fractures and in those with known risk factors for
osteoporosis. (OPINION)
2.3- Bone radiographs are not indicated for the assessment
of bone disease of CKD, (EVIDENCE) but they are useful
in detecting severe peripheral vascular calcification
(OPINION) and bone disease due to ß2-microglobulin
amyloidosis. (EVIDENCE)
2.4- Bone mineral density (BMD) should be measured by
dual energy X-ray absorptiometry (DEXA) in patients with
fractures and in those with known risk factors for
osteoporosis. (OPINION)

Beginning at Stage 3, patients with CKD almost always
have secondary hyperparathyroidism and elevated PTH.

In these patients, the classical lesion seen in bone biopsy is
osteitis fibrosa cystica althoug increasing prevalence of
other bone lesions such as low-turnover bone disease has
recently been shown.
Factors Prevalent in CKD patients Which May
Influence the Type of Osteodystrophy Lesion







Prolonged Al exposure
G.C. therapy in patients with parenchymatous kidney
disease & renal Tx recipients
Previous PTX
Vitamin D Rx
Diabetes Mellitus*
2 microglobulin amyloidosis
Hypophosphatemia secondary to aggressive dietary
phosphate restriction or excessive use of P binders
*Responsible for 30-40% of ESRD cases
GUIDELINE 3.
EVALUATION OF SERUM P

3.1- In CKD patients (Stages 3 and 4),
the serum P should be maintained between
2.7 mg/dl (EVIDENCE) and 4.6 mg/dl. (OPINION)

3.2- In CKD patients with kidney failure (Stage 5)
and those treated with HD or PD, the serum P should
be maintained between 3.5 and 5.5 mg/dl.
(EVIDENCE)

Prolonged hyperphosphatemia causes soft-tissue and
vascular calcification due at least in part to an increase in
Ca-P product and is associated with increased morbidity and
mortality.

Prolonged hyperphosphatemia causes soft-tissue and
vascular calcification due at least in part to an increase in
Ca-P product and is associated with increased morbidity and
mortality.

Hyperphosphatemia exerts a direct calcifying effect on
vascular smooth muscle cells.

Prolonged hyperphosphatemia causes soft-tissue and
vascular calcification due at least in part to an increase in
Ca-P product and is associated with increased morbidity and
mortality.

Hyperphosphatemia exerts a direct calcifying effect on
vascular smooth muscle cells.

Calcification of coronary arteries, cardiac valves, and
pulmonary tissues produces cardiac disease, the leading
cause of death in patients with CKD.

Prolonged hyperphosphatemia causes soft-tissue and
vascular calcification due at least in part to an increase in
Ca-P product and is associated with increased morbidity and
mortality.

Hyperphosphatemia exerts a direct calcifying effect on
vascular smooth muscle cells.

Calcification of coronary arteries, cardiac valves, and
pulmonary tissues produces cardiac disease, the leading
cause of death in patients with CKD.

It is therefore imperative to prevent hyperphosphatemia and
maintain serum P levels within the normal range.

Most data indicate that < 30% of dialysis patients are
able to maintain P in the suggested target range.

The goal should be to increase the percentage of
patients in this target range.

1.
2.
3.
4.
This needs:
An increased dietitian-to-patient ratio,
Educational tools to increase patient compliance,
Studies for dialytic techniques that are better able to
control serum P (such as nocturnal or daily HD),
The widespread availability and affordability of
different phosphate binders, regardless of patient
insurance.
GUIDELINE 4. RESTRICTION OF
DIETARY PHOSPHORUS IN
PATIENTS WITH CKD

4.1- Dietary phosphorus should be restricted to 800 to
1,000 mg/day (adjusted for dietary protein needs):
1.
When the serum P >4.6 mg/dl at Stages 3 and 4 of CKD,
(OPINION) and >5.5 mg/dl at stage 5 kidney failure
(EVIDENCE).
2.
When the plasma iPTH are elevated. (EVIDENCE)

The serum P should be monitored every month following
the initiation of dietary phosphorus restriction. (OPINION)
GUIDELINE 5. USE OF
PHOSPHATE BINDERS

5.1- If P or intact PTH levels cannot be controlled despite
dietary P restriction, phosphate binders should be
prescribed. (OPINION)

Either calcium-based phosphate binders and other
noncalcium-, nonaluminum-, nonmagnesium- phosphate
binders (such as sevelamer HCl) may be used as the primary
therapy.

5.4- In dialysis patients who remain hyperphosphatemic
(P >5.5 mg/dl) despite the use of either of phosphate
binders, a combination of both should be used.
(OPINION)

5.5- The total dose of elemental calcium provided by the
calcium-based phosphate binders should not exceed 1,500
mg/day (OPINION), and the total intake of elemental
calcium (including dietary calcium) should not exceed
2,000 mg/day. (OPINION)

5.5- The total dose of elemental calcium provided by the
calcium-based phosphate binders should not exceed 1,500
mg/day (OPINION), and the total intake of elemental
calcium (including dietary calcium) should not exceed
2,000 mg/day. (OPINION)

5.6- Calcium-based phosphate binders should not be used in
dialysis patients who are hypercalcemic (corrected serum
Ca >10.2 mg/dl, or have plasma PTH <150 pg/ml on 2
consecutive measurements. (EVIDENCE)

5.7- Noncalcium-containing phosphate binders are preferred
in dialysis patients with severe vascular and/or other soft
tissue calcifications. (OPINION)

5.7- Noncalcium-containing phosphate binders are preferred
in dialysis patients with severe vascular and/or other soft
tissue calcifications. (OPINION)

5.8-In patients with serum P>7.0 mg/dl, aluminum-based
phosphate binders may be used as a short-term therapy (4
weeks), and for one course only, to be replaced thereafter by
other phosphate binders. (OPINION) In such patients, more
frequent dialysis should also be considered. (EVIDENCE)
GUIDELINE 6. SERUM Ca &
Ca-P PRODUCT

In CKD Patients (Stages 3 and 4):
6.1- The serum levels of corrected total calcium should be
maintained within the "normal" range for the laboratory
used. (EVIDENCE)

In CKD Patients With Kidney Failure (Stage 5):
6.2- Serum levels of corrected total calcium should be
maintained within the normal range for the laboratory
used, preferably toward the lower end (8.4 to 9.5 mg/dl).
(OPINION)

6.3- In the event corrected total serum Ca >10.2 mg/dl,
therapies that cause serum Ca to rise should be adjusted as
follows:

6.3- In the event corrected total serum Ca >10.2 mg/dl,
therapies that cause serum Ca to rise should be adjusted as
follows:
6.3a- In patients taking calcium-based phosphate binders,
the dose should be reduced or therapy switched to a
noncalcium-, nonaluminum-, nonmagnesium-containing
phosphate binder. (OPINION)
6.3b- In patients taking active vitamin D sterols, the dose
should be reduced or therapy discontinued until the serum
levels of corrected total calcium return to the target range
(8.4 to 9.5 mg/d). (OPINION)
6.3b- In patients taking active vitamin D sterols, the dose
should be reduced or therapy discontinued until the serum
levels of corrected total calcium return to the target range
(8.4 to 9.5 mg/d). (OPINION)
6.3c- If hypercalcemia persists despite modification of
therapy, dialysis using low dialysate calcium (1.5 to 2.0
mEq/L) may be used for 3 to 4 weeks. (OPINION)

In CKD Patients (Stages 3 to 5):
6.4-Total elemental calcium intake (dietary calcium+
calcium-based phosphate binders) should not exceed
2,000 mg/day. (OPINION)
6.5-The serum Ca-P product should be maintained at <55
mg2/dl2. (EVIDENCE) This is best achieved by
controlling serum levels of P within the target range.
(OPINION)

6.6- Patients whose serum Ca level are below the lower
limit (<8.4 mg/dl) should receive therapy to increase serum
Ca if:

6.6- Patients whose serum Ca level are below the lower
limit (<8.4 mg/dl) should receive therapy to increase serum
Ca if:
6.6a-There are clinical symptoms of hypocalcemia such as
paresthesia, Chvostek’s and Trousseau’s signs,
bronchospasm, laryngospasm, tetany, and/or seizures
(OPINION); or

6.6- Patients whose serum Ca level are below the lower
limit (<8.4 mg/dl) should receive therapy to increase serum
Ca if:
6.6a-There are clinical symptoms of hypocalcemia such as
paresthesia, Chvostek’s and Trousseau’s signs,
bronchospasm, laryngospasm, tetany, and/or seizures
(OPINION); or
6.6b-The plasma iPTH level is above the target. (OPINION)
6.7-Therapy for hypocalcemia should
include calcium salts such as calcium
carbonate (EVIDENCE) and/or oral
vitamin D sterols. (EVIDENCE)
GUIDELINE 7.
PREVENTION AND TREATMENT
OF VITAMIN D INSUFFICIENCY
AND DEFICIENCY IN CKD
PATIENTS
In CKD Patients (Stages 3 and 4):

7.1- If plasma intact PTH is above the target range
serum 25-(OH)D should be measured at first
encounter. If it is normal, repeat annually.
(EVIDENCE)

7.2- If the serum level of 25-(OH)D is <30 ng/ml,
supplementation with vitamin D2 should be
initiated.(OPINION)

7.3- Following initiation of vitamin D therapy:
7.3a- The use of ergocalciferol therapy should
be integrated with the serum Ca & P.
7.3b- The serum Ca and P level should be
measured at least every 3 months. (OPINION)

7.3c- If the serum Ca >10.2 mg/dl discontinue
ergocalciferol and all forms of vitamin D therapy.
(OPINION)

7.3d- If the serum P >4.6 mg/dl, add or increase the dose
of phosphate binder. If hyperphosphatemia persists,
discontinue vitamin D therapy. (OPINION)
7.3e- Once patients are replete with vitamin D,
continued supplementation with a vitamin-Dcontaining multi-vitamin preparation should be used
with annual reassessment of serum levels of 25(OH)D, and the continued assessment of corrected
total Ca and P every 3 months. (OPINION)

In CKD Patients With Kidney Failure (Stage 5):
7.4- Active vitamin D sterol (calcitriol, alfacalcidol,
paricalcitol, or doxercalciferol) should be given
if iPTH is >300 pg/ml (OPINION)
In CKD patients with serum P<4.6 mg/dl, serum Ca<9.5 mg/dl,
& serum PTH in the higher target range for CKD stage
Measure serum 25(OH)D
Is serum 25(OH)D
<30 ng/ml?
No
See guideline 8A
Yes
Oral vitamin D2 or D3
Initiate or increase
P binder or restrict
Dietary P
Measure serum Ca & P
Hold vitamin D dose
No
Is serum Ca<10.2 mg/dl?
Yes
Is serum P<4.6 mg/dl?
Yes
Continue or resume
vitamin D2 or D3
No
Recommended Supplementation for vitamin D
deficiency/insufficiency in CKD stages 3 & 4
Serum
25(OH)D
(ng/ml)
Definition
Ergocalcifero
l Dose
Duration
(months)
Comment
<5-15
Severe
vitamin D
deficiency
50,000 IU/wk
PO12 wk,
then monthly
500,000 IU as
single IM
dose
6 months
Measure 25 (OH)D
after 6 months
Assure patient
adherence; measure
25(OH) at 6 months
5-15
Mild vitamin 50,000 IU/wk
D deficiency
 4 weeks
then 50,000
IU/month PO
16-30
Vitamin D
insufficiency
50,000
IU/month PO
Assure patient
adherence; measure
25(OH) at 6 months
GUIDELINE 8.A-VITAMIN D THERAPY
IN CKD STAGE 3 & 4

8A.1- In patients with CKD Stages 3 and 4, therapy with
an active oral vitamin D sterol (calcitriol, alfacalcidol, or
doxercalciferol) is indicated when serum levels of
25(OH)D are >30 ng/ml, and plasma iPTH above the
target. (EVIDENCE)

8A.1a- Treatment with an active vitamin D should be
undertaken only in patients with serum Ca < 9.5 mg/dl
and serum P < 4.6 mg/dl. (OPINION)

8A.1b- Vitamin D should not be prescribed for patients
with rapidly worsening kidney function or those who are
noncompliant with medications or follow-up.
(OPINION)

8A.2- During therapy with vitamin D sterols, serum
levels of Ca and P should be monitored at least every
month for the first 3 months, then every 3 months
thereafter. Plasma PTH levels should be measured at
least every 3 months for 6 months, and every 3 months
thereafter. (OPINION)

8A.3- Dosage adjustments:
8A.3a- If plasma levels of intact PTH fall below the target,
hold active vitamin D until plasma PTH rise to above the
target, then resume treatment with half dose active
vitamin D.
-If the lowest daily dose of the active vitamin D is being
used, reduce to alternate-day dosing. (OPINION)

8A.3b If serum Ca >9.5 mg/dl, hold active
vitamin D until serum calcium <9.5 mg/dl,
then resume treatment at half dose.

If the lowest daily dose of the active vitamin D
sterol is being used, reduce to alternate-day
dosing. (OPINION)

8A.3c- If serum P level rise to >4.6 mg/dl,
hold active vitamin D, initiate or increase dose
of phosphate binder until P < 4.6 mg/dl;
then resume the prior dose of active vitamin D.
(OPINION)
In CKD patients stages 3 & 4 with stable renal function, compliant with
medications, with serum P < 4.6 mg/dl, serum Ca < 9.5 mg/dl,
& 25(OH)D  30 ng/ml:
Measure serum PTH
Is serum PTH >70 pg/ml (stage 3)
or > 110 pg/ml (stage 4)?
No
Monitor according
to guidline 1
Yes
Begin vitamin D sterol
Hold or reduce
vitamin D dose
Initiate or increase
P binder or restrict
Dietary P
Measure serum Ca & P
No
Stop or reduce
dose of Ca-based
P-binder or reduce
Ca supplement
<35 pg/ml (stage 3)
or <70 pg/ml (stage 4)
Is serum Ca <9.5 mg/dl?
Yes
Is serum P< 4.6 mg/dl?
Yes
Measure serum
PTH
No
Continue oral dose of
vitamin D
>70 pg/ml (stage 3)
or >110 pg/ml (stage 4)
Serum levels of PTH, Ca & P required for initiation of
oral vitamin D sterol & recommended initial dose in
stages 3 & 4 CKD
Plasma PTH
(pg/ml)
Ca
(mg/dl)
P
(mg/dl)
>70 (stage 3) or
> 110 (stage 4)
< 9.5
<4.6
Dose Oral
Calcitriol
Dose Oral
Dose Oral
Alfacacidiol Doxercalciferol
0.25 g/day 0.25 g/day
0.25 g 3  wk
GUIDELINE 8B.
VITAMIN D THERAPY IN PATIENTS
ON DIALYSIS
(CKD STAGE 5)

8B.1-Patients treated with HD or PD with serum
iPTH >300 pg/ml should receive an active vitamin D
sterol (such as calcitriol, alfacalcidol, paricalcitol, or
doxercalciferol; to reduce the serum levels of PTH to
a target range of 150 to 300 pg/ml. (EVIDENCE)

8B.1a-The intermittent, IV calcitriol is more effective
than daily oral calcitriol in lowering serum PTH.
(EVIDENCE)

8B.1b-In patients with high serum Ca &/or P, a trial
of alternative vitamin D analogs, such as paricalcitol
or doxercalciferol may be warranted. (OPINION)

8B.2-When therapy with vitamin D sterols is initiated
or the dose is increased, serum Ca & P should be
monitored at least every 2 weeks for 1 month and
then monthly thereafter.

The plasma PTH should be measured monthly for at
least 3 months and then every 3 months once target
levels of PTH are achieved. (OPINION)

8B.3-For PD patients, oral doses of calcitriol (0.5 to
1.0 µg) or doxercalciferol (2.5 to 5.0 µg) can be given
2 or 3 times weekly. Alternatively, a lower dose of
calcitriol (0.25 µg) can be administered daily.
(OPINION)

8B.4- When either HD or PD patients are treated with
active vitamin D sterols, management should
integrate the changes in serum Ca & P and plasma
PTH.
Algorithm 3. Managing Vitamin D sterols based on serum Ca levels
Measure serum Ca
Ca>10.2 mg/dl
Ca=9.5-10.2 mg/dl
Ca<9.5 mg/dl
Reduce dose of Ca containing
P-binders & change to or ↑ dose
of non-Ca containing
P-binders
Stop vitamin D Rx
Ca>10.2 mg/dl
Measure serum Ca
Continue or modify
vitamin D using
Algorithm 4 & 5
Ca<9.5 mg/dl
Ca=9.5-10.2 mg/dl
Measure serum
PTH
Optional
Dialysate Ca
2 meq/L for 2-3 HD Rx
Is serum
PTH>300 pg/ml?
No
Continue or modify
vitamin D using
Algorithm 4 & 5
Yes
Optional
Change to less calcemic
vitamin D sterol
Algorithm 4. Managing Vitamin D sterols based on serum Pi levels
Measure serum P
P> 6.0 mg/dl
P <5.5 mg/dl
P=5.5- 6.0 mg/dl
Hold vitamin D Rx
Increase
P-binders dose
Continue or modify
vitamin D using
Algorithm 1 & 5
Measure serum P
Is serum
P<5.5 mg/dl?
No
Yes
If patient has been on vitamin D
reduce dose by 25-50%
If vitamin D has been held
Resume at dose lowered by 25-50%
PTH>300 pg/ml
P< 5.5 mg/dl
Ca< 9.5 mg/dl
Raise vitamin D
dose by 25-50%
Measure serum PTH
PTH=150-200 pg/ml
PTH=200-300 pg/ml
PTH< 150 pg/ml
Hold vitamin D
Rx for 1 month
Maintain same
vitamin D dose
for 3 months
Reduce vitamin D dose by
half for 2 months
PTH<150 pg/ml
Measure
Serum PTH
PTH>300 pg/ml
If on Vitamin D, raise vitamin D
dose by 25-50%
If vitamin D has been held,
resume 75% of initial dose for 3 mo
Hold vitamin D
Rx for 3 month
PTH=150-200 pg/ml
If on Vitamin D, raise vitamin D
dose by 25-50%
If vitamin D has been held,
resume therapy with earlier dose
PTH=200-300 pg/ml
Maintain same
vitamin D dose
for 3 months

When intact PTH is between 300-500 pg/ml and
changes in 2 successive determinations are small
(<25%), there is no need to change vitamin D dose, as
far as Ca and P are within the desired limits.

When intact PTH is persistently >500-800 pg/ml and
P is 5-6.5 mg/dl &/or Ca is 10.2-10.5 mg/dl, a trial
with a less calcemic analog may be warranted for 3-5
months. If such a patient fails to respond,
parathyroidectomy may be required.
MDRD study equation
Estimated GFR (mL/min/1.73 m2) =
 186 x [SCr(-1.154)] x [Age(-0.203)] x
(0.742 if female) x (1.21 if African
American)
 This equation is also equivalent to:
 Estimated GFR (mL/min/1.73 m2) =
exp(5.228 - 1.154 X ln (SCr) - 0.203 x ln
(Age) - (0.299 if female) + (0.192 if
African American)
