New NKF-K/DOQI New NKF-K/DOQI

guidelinesguidelines

Shahrzad Ossareh-Shahrzad Ossareh-M.D.M.D.

Kidney Disease Outcome Quality Initiative

Definition of Chronic Kidney Definition of Chronic Kidney DiseaseDiseaseCriteriaCriteria

1.1. Kidney damage ≥ 3 months as defined by Kidney damage ≥ 3 months as defined by

structuralstructural or or functionalfunctional abnormalities of the abnormalities of the

kidney, with or without decreased GFR, kidney, with or without decreased GFR,

manifested by manifested by either:either:

Pathologic abnormalities; orPathologic abnormalities; or

Markers of damage including abnormalities in Markers of damage including abnormalities in

blood or urine tests or imaging studies.blood or urine tests or imaging studies.

2.2. GFR< 60 ml/min/1.73 mGFR< 60 ml/min/1.73 m22 for ≥ 3 months, with for ≥ 3 months, with

or without kidney damageor without kidney damage

Estimated GFR (mL/min/1.73 m2)Estimated GFR (mL/min/1.73 m2)

1.1. Cockraft-Gault FormulaCockraft-Gault Formula

2.2. MDRD study formula:MDRD study formula:

186 x [SCr(-1.154)] x [Age(-0.203)] x (0.742 if 186 x [SCr(-1.154)] x [Age(-0.203)] x (0.742 if

female) x (1.21 if African American)female) x (1.21 if African American)

Stages of Chronic Kidney Stages of Chronic Kidney DiseaseDisease

StageStage DescriptionDescription GFR (ml/min/1.73 mGFR (ml/min/1.73 m22))

(Prevalence)(Prevalence)

11 Kidney damage Kidney damage with normal or with normal or

↑↑GFRGFR

9090

(3.3%)(3.3%)

22 Kidney damage Kidney damage with mild ↓GFRwith mild ↓GFR

60-8960-89 (3%)(3%)

33 Moderate ↓GFRModerate ↓GFR 30-5930-59 (4.3%)(4.3%)

44 Severe ↓GFRSevere ↓GFR 15-2915-29

(0.2%)(0.2%)

55 Kidney failureKidney failure <15<15 or on dialysis or on dialysis (0.1%)(0.1%)

Guidelines for

Bone Metabolism in

Chronic Kidney Disease

GUIDELINE 1. GUIDELINE 1.

Evaluation of Ca and P metabolism Evaluation of Ca and P metabolism

1.1- 1.1- Serum levels of calcium, phosphorus, Serum levels of calcium, phosphorus,

and intact PTH should be measured in all and intact PTH should be measured in all

patients with CKD and patients with CKD and GFR <60GFR <60

ml/min/1.73 mml/min/1.73 m22. (EVIDENCE). (EVIDENCE)

CKD CKD

stagestage

GFR GFR RangeRange

PTH PTH measurementmeasurement

Ca/PCa/P

measurementmeasurement

33 30-5930-59 Q 12 moQ 12 mo Q 12 moQ 12 mo

44 15-2915-29 Q 3 moQ 3 mo Q 3 moQ 3 mo

55 <15 or <15 or dialysisdialysis

Q 3 moQ 3 mo Every monthEvery month

Frequency of measurement of PTH and Frequency of measurement of PTH and Ca/P by stage of CKDCa/P by stage of CKD

*More frequently in patients receiving therapy for the *More frequently in patients receiving therapy for the abnormalities in Ca, P or PTH and in transplant recipients.abnormalities in Ca, P or PTH and in transplant recipients.

Target Range of plasma iPTH by CKD Target Range of plasma iPTH by CKD stagestage

CKD stageCKD stage GFR rangeGFR range Target iPTHTarget iPTH

33 30-5930-59 35-7035-70

(opinion)(opinion)

44 15-2915-29 70-11070-110

(opinion)(opinion)

55 <15 or <15 or dialysisdialysis

150-300150-300

(evidence)(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.Newer assays specific for 1-84 PTH.

The normal range for the new assay for 1-84 PTH is The normal range for the new assay for 1-84 PTH is 7 to 7 to 36 pg/ml36 pg/ml compared to compared to 16 to 65 pg/ml16 to 65 pg/ml for iPTH. for iPTH.

Thus the relationship between the 2 assays is about Thus the relationship between the 2 assays is about 1:21:2 (1-84 PTH to intact PTH). (1-84 PTH to intact PTH).

The differences in the levels between the 2 types of The differences in the levels between the 2 types of assays are a reflection of the levels of circulating PTH assays are a reflection of the levels of circulating PTH fragments that are detected by the intact PTH assay but fragments that are detected by the intact PTH assay but not by the new 1-84 PTH assay. not by the new 1-84 PTH assay.

GUIDELINE 2. ASSESSMENT OF GUIDELINE 2. ASSESSMENT OF

BONE DISEASE BONE DISEASE

ASSOCIATED WITH CKDASSOCIATED 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)

2.2-2.2- It is not necessary to perform bone biopsy for most It is not necessary to perform bone biopsy for most situations in clinical practice. It should be considered insituations in clinical practice. It should be considered in patients with kidney failure (patients with kidney failure (Stage 5Stage 5) who have:) who have:

2.2-2.2- It is not necessary to perform bone biopsy for most It is not necessary to perform bone biopsy for most situations in clinical practice. It should be considered in situations in clinical practice. It should be considered in patients with kidney failure (patients with kidney failure (Stage 5Stage 5) who have:) who have: 2.2a-2.2a- FracturesFractures with minimal or no trauma (pathological with minimal or no trauma (pathological fractures); (OPINION)fractures); (OPINION)

2.2-2.2- It is not necessary to perform bone biopsy for most It is not necessary to perform bone biopsy for most situations in clinical practice. It should be considered in situations in clinical practice. It should be considered in patients with kidney failure (patients with kidney failure (Stage 5Stage 5) who have:) who have: 2.2a-2.2a- Fractures with minimal or no trauma (pathological Fractures with minimal or no trauma (pathological fractures); (OPINION)fractures); (OPINION) 2.2b-2.2b- Intact PTHIntact PTH levels between levels between 100 and 500100 and 500 pg/ml (in CKD pg/ml (in CKD Stage 5Stage 5) with coexisting conditions such as ) with coexisting conditions such as unexplained unexplained hypercalcemiahypercalcemia, , severe bone painsevere bone pain, or , or unexplained increases inunexplained increases in bone alkaline phosphatase activitybone alkaline phosphatase activity;(OPINION);(OPINION)

2.2-2.2- It is not necessary to perform bone biopsy for most It is not necessary to perform bone biopsy for most situations in clinical practice. It should be considered in situations in clinical practice. It should be considered in patients with kidney failure patients with kidney failure (Stage 5)(Stage 5) who have: who have: 2.2a-2.2a- Fractures with minimal or no trauma (pathological Fractures with minimal or no trauma (pathological fractures); (OPINION)fractures); (OPINION) 2.2b-2.2b- Intact PTH levels between 100 and 500 pg/ml (in CKD Intact PTH levels between 100 and 500 pg/ml (in CKD Stage 5) with coexisting conditions such as unexplained Stage 5) with coexisting conditions such as unexplained hypercalcemia, severe bone pain, or unexplained increases in hypercalcemia, severe bone pain, or unexplained increases in bone alkaline phosphatase activity;(OPINION)bone alkaline phosphatase activity;(OPINION)

2.2c-2.2c- Suspected Suspected aluminum bone diseasealuminum bone disease, based upon , based upon clinical symptoms or history of aluminum exposure clinical symptoms or history of aluminum exposure (OPINION) (OPINION)

2.3-2.3- Bone radiographsBone radiographs are not indicated for the assessment are not indicated for the assessment

of bone disease of CKD, (EVIDENCE) but they are useful of bone disease of CKD, (EVIDENCE) but they are useful

in detecting in detecting severe peripheral vascular calcificationsevere peripheral vascular calcification

(OPINION) and bone disease due to (OPINION) and bone disease due to ß2-microglobulin ß2-microglobulin

amyloidosisamyloidosis. (EVIDENCE). (EVIDENCE)

2.4- 2.4- Bone mineral density (BMD) should be measured by Bone mineral density (BMD) should be measured by

dual energy X-ray absorptiometry (DEXA) in patients with dual energy X-ray absorptiometry (DEXA) in patients with

fracturesfractures and in those with and in those with known risk factors for known risk factors for

osteoporosisosteoporosis. (OPINION). (OPINION)

2.3-2.3- Bone radiographs are not indicated for the assessment Bone radiographs are not indicated for the assessment

of bone disease of CKD, (EVIDENCE) but they are useful of bone disease of CKD, (EVIDENCE) but they are useful

in detecting in detecting severe peripheral vascular calcificationsevere peripheral vascular calcification

(OPINION) and bone disease due to (OPINION) and bone disease due to ß2-microglobulin ß2-microglobulin

amyloidosisamyloidosis. (EVIDENCE). (EVIDENCE)

2.4- 2.4- Bone mineral density (BMDBone mineral density (BMD)) should be measured by should be measured by

dual energy X-ray absorptiometry (DEXA) in patients with dual energy X-ray absorptiometry (DEXA) in patients with

fracturesfractures and in those with and in those with known risk factors for known risk factors for

osteoporosisosteoporosis. (OPINION). (OPINION)

Beginning Beginning at Stage 3at Stage 3, patients with CKD almost always , patients with CKD almost always

have secondary hyperparathyroidism and elevated PTH.have secondary hyperparathyroidism and elevated PTH.

In these patients, the classical lesion seen in bone biopsy is In these patients, the classical lesion seen in bone biopsy is

osteitis fibrosa cysticaosteitis fibrosa cystica althoug increasing prevalence of althoug increasing prevalence of

other bone lesions such as low-turnover bone disease has other bone lesions such as low-turnover bone disease has

recently been shown.recently been shown.

Factors Prevalent in CKD patients Which May Factors Prevalent in CKD patients Which May Influence the Type of Osteodystrophy LesionInfluence the Type of Osteodystrophy Lesion

Prolonged Al exposureProlonged Al exposure G.C. therapy in patients with parenchymatous kidney G.C. therapy in patients with parenchymatous kidney

disease & renal Tx recipientsdisease & renal Tx recipients Previous PTXPrevious PTX Vitamin D RxVitamin D Rx Diabetes Mellitus*Diabetes Mellitus* 22 microglobulin amyloidosis microglobulin amyloidosis Hypophosphatemia secondary to aggressive dietary Hypophosphatemia secondary to aggressive dietary

phosphate restriction or excessive use of P bindersphosphate restriction or excessive use of P binders

*Responsible for 30-40% of ESRD cases

GUIDELINE 3. GUIDELINE 3.

EVALUATION OF SERUM P EVALUATION OF SERUM P

3.1-3.1- In CKD patients ( In CKD patients (Stages 3 and 4Stages 3 and 4), ),

the the serum Pserum P should be maintained between should be maintained between

2.72.7 mg/dl (EVIDENCE) and mg/dl (EVIDENCE) and 4.64.6 mg/dl. (OPINION) mg/dl. (OPINION)

3.2-3.2- In CKD patients with kidney failure ( In CKD patients with kidney failure (Stage 5Stage 5) )

and those treated with and those treated with HDHD or or PDPD, the , the serum Pserum P should should

be maintained between be maintained between 3.5 3.5 andand 5.5 5.5 mg/dl. mg/dl.

(EVIDENCE)(EVIDENCE)

Prolonged hyperphosphatemia causes Prolonged hyperphosphatemia causes soft-tissue and soft-tissue and vascular calcificationvascular calcification due at least in part to an due at least in part to an increase in increase in Ca-P productCa-P product and is associated with increased morbidity and and is associated with increased morbidity and mortality.mortality.

Prolonged hyperphosphatemia causes soft-tissue and Prolonged hyperphosphatemia causes soft-tissue and vascular calcification due at least in part to an increase in vascular calcification due at least in part to an increase in Ca-P product and is associated with increased morbidity and Ca-P product and is associated with increased morbidity and mortality.mortality.

Hyperphosphatemia exerts a Hyperphosphatemia exerts a direct calcifying effect on direct calcifying effect on vascular smooth muscle cells.vascular smooth muscle cells.

Prolonged hyperphosphatemia causes soft-tissue and Prolonged hyperphosphatemia causes soft-tissue and vascular calcification due at least in part to an increase in vascular calcification due at least in part to an increase in Ca-P product and is associated with increased morbidity and Ca-P product and is associated with increased morbidity and mortality.mortality.

Hyperphosphatemia exerts a direct calcifying effect on Hyperphosphatemia exerts a direct calcifying effect on vascular smooth muscle cells.vascular smooth muscle cells.

Calcification of coronary arteriesCalcification of coronary arteries, , cardiac valvescardiac valves, and , and pulmonary tissuespulmonary tissues produces produces cardiac diseasecardiac disease, the leading , the leading cause of death in patients with CKD.cause of death in patients with CKD.

Prolonged hyperphosphatemia causes soft-tissue and Prolonged hyperphosphatemia causes soft-tissue and vascular calcification due at least in part to an increase in vascular calcification due at least in part to an increase in Ca-P product and is associated with increased morbidity and Ca-P product and is associated with increased morbidity and mortality.mortality.

Hyperphosphatemia exerts a direct calcifying effect on Hyperphosphatemia exerts a direct calcifying effect on vascular smooth muscle cells.vascular smooth muscle cells.

Calcification of coronary arteries, cardiac valves, and Calcification of coronary arteries, cardiac valves, and pulmonary tissues produces cardiac disease, the leading pulmonary tissues produces cardiac disease, the leading cause of death in patients with CKD.cause of death in patients with CKD.

It is therefore imperative to prevent hyperphosphatemia and It is therefore imperative to prevent hyperphosphatemia and maintain serum P levels within the normal range.maintain serum P levels within the normal range.

Most data indicate that Most data indicate that < 30%< 30% of dialysis patients are of dialysis patients are able to maintain P in the suggested target range.able to maintain P in the suggested target range.

The goal should be to increase the percentage of The goal should be to increase the percentage of patients in this target range. patients in this target range.

This needs:This needs:

1.1. An increased dietitian-to-patient ratio,An increased dietitian-to-patient ratio,

2.2. Educational tools to increase patient compliance, Educational tools to increase patient compliance,

3.3. Studies for dialytic techniques that are better able to control serum P (such as Studies for dialytic techniques that are better able to control serum P (such as nocturnal or daily HD), nocturnal or daily HD),

4.4. The widespread availability and affordability of different phosphate binders, The widespread availability and affordability of different phosphate binders, regardless of patient insurance.regardless of patient insurance.

GUIDELINE 4. RESTRICTION OF GUIDELINE 4. RESTRICTION OF

DIETARY PHOSPHORUS IN DIETARY PHOSPHORUS IN

PATIENTS WITH CKD PATIENTS WITH CKD

4.1-4.1- Dietary phosphorus should be restricted to Dietary phosphorus should be restricted to 800 to 800 to

1,0001,000 mg/day (adjusted for dietary protein needs):mg/day (adjusted for dietary protein needs):

1.1. When the serum When the serum PP >4.6 mg/dl>4.6 mg/dl at Stages 3 and 4 of CKD, at Stages 3 and 4 of CKD,

(OPINION) and (OPINION) and >5.5 mg/dl>5.5 mg/dl at stage 5 kidney failure at stage 5 kidney failure

(EVIDENCE).(EVIDENCE).

2.2. When the plasma When the plasma iPTH are elevated.iPTH are elevated. (EVIDENCE) (EVIDENCE)

The serum P should be monitored The serum P should be monitored every monthevery month following following

the initiation of dietary phosphorus restriction. (OPINION)the initiation of dietary phosphorus restriction. (OPINION)

GUIDELINE 5. USE OF GUIDELINE 5. USE OF

PHOSPHATE BINDERS PHOSPHATE BINDERS

5.1-5.1- If P or intact PTH levels cannot be controlled despite If P or intact PTH levels cannot be controlled despite

dietary P restriction, dietary P restriction, phosphate bindersphosphate binders should be should be

prescribed. (OPINION)prescribed. (OPINION)

Either calcium-based phosphate binders and other Either calcium-based phosphate binders and other

noncalcium-, nonaluminum-, nonmagnesium- phosphate noncalcium-, nonaluminum-, nonmagnesium- phosphate

binders (such as sevelamer HCl) may be used as the primary binders (such as sevelamer HCl) may be used as the primary

therapy. therapy.

5.4-5.4- In dialysis patients who remain hyperphosphatemic In dialysis patients who remain hyperphosphatemic

(P(P >5.5 mg/dl)>5.5 mg/dl) despite the use of either of phosphate despite the use of either of phosphate

binders, a binders, a combinationcombination of both should be used. of both should be used.

(OPINION)(OPINION)

5.5-5.5- The The total dose of elemental calciumtotal dose of elemental calcium provided by the provided by the

calcium-based phosphate binders should not exceed calcium-based phosphate binders should not exceed 1,5001,500

mg/day (OPINION), and the mg/day (OPINION), and the total intake of elemental total intake of elemental

calciumcalcium (including dietary calcium) should not exceed (including dietary calcium) should not exceed

2,0002,000 mg/day. (OPINION) mg/day. (OPINION)

5.5-5.5- The total dose of elemental calcium provided by the The total dose of elemental calcium provided by the

calcium-based phosphate binders should not exceed 1,500 calcium-based phosphate binders should not exceed 1,500

mg/day (OPINION), and the total intake of elemental mg/day (OPINION), and the total intake of elemental

calcium (including dietary calcium) should not exceedcalcium (including dietary calcium) should not exceed

2,0002,000 mg/day. (OPINION)mg/day. (OPINION)

5.6- 5.6- Calcium-based phosphate binders should not be used in Calcium-based phosphate binders should not be used in

dialysis patients who are dialysis patients who are hypercalcemichypercalcemic (corrected serum (corrected serum

Ca >10.2 mg/dlCa >10.2 mg/dl, or have , or have plasma PTH <150 pg/mlplasma PTH <150 pg/ml on 2 on 2

consecutive measurements. (EVIDENCE)consecutive measurements. (EVIDENCE)

5.7-5.7- Noncalcium-containing phosphate bindersNoncalcium-containing phosphate binders are preferred are preferred

in dialysis patients with severe vascular and/or other soft in dialysis patients with severe vascular and/or other soft

tissue tissue calcificationscalcifications. (OPINION). (OPINION)

5.7-5.7- Noncalcium-containing phosphate binders are preferred Noncalcium-containing phosphate binders are preferred

in dialysis patients with severe vascular and/or other soft in dialysis patients with severe vascular and/or other soft

tissue calcifications. (OPINION)tissue calcifications. (OPINION)

5.8-5.8-In patients with serum In patients with serum P>7.0P>7.0 mg/dl, mg/dl, aluminum-based aluminum-based

phosphate bindersphosphate binders may be used as a short-term therapy ( may be used as a short-term therapy (4 4

weeksweeks), and for one course only, to be replaced thereafter by ), and for one course only, to be replaced thereafter by

other phosphate binders. (OPINION) In such patients, other phosphate binders. (OPINION) In such patients, more more

frequent dialysisfrequent dialysis should also be considered. (EVIDENCE) should also be considered. (EVIDENCE)

GUIDELINE 6. SERUM Ca & GUIDELINE 6. SERUM Ca &

Ca-P PRODUCTCa-P PRODUCT

In CKD Patients (Stages 3 and 4):In CKD Patients (Stages 3 and 4):

6.1-6.1- The serum levels of corrected total calcium should be The serum levels of corrected total calcium should be maintained within the "normal" range for the laboratory maintained within the "normal" range for the laboratory used. (EVIDENCE)used. (EVIDENCE)

In CKD Patients With Kidney Failure (Stage 5):In CKD Patients With Kidney Failure (Stage 5):

6.2-6.2- Serum levels of corrected total calcium should be Serum levels of corrected total calcium should be maintained within the normal range for the laboratory maintained within the normal range for the laboratory used, preferably toward the lower end (used, preferably toward the lower end (8.4 to 9.5 mg/dl8.4 to 9.5 mg/dl). ). (OPINION)(OPINION)

6.3-6.3- In the event corrected total serum In the event corrected total serum Ca >10.2Ca >10.2 mg/dl, mg/dl,

therapies that cause serum Ca to rise should be adjusted as therapies that cause serum Ca to rise should be adjusted as

follows:follows:

6.3-6.3- In the event corrected total serum In the event corrected total serum Ca >10.2Ca >10.2 mg/dl, mg/dl,

therapies that cause serum Ca to rise should be adjusted as therapies that cause serum Ca to rise should be adjusted as

follows:follows:

6.3a-6.3a- In patients taking In patients taking calcium-based phosphate binderscalcium-based phosphate binders, ,

the dose should be reduced or therapy switched to a the dose should be reduced or therapy switched to a

noncalcium-, nonaluminum-, nonmagnesium-containing noncalcium-, nonaluminum-, nonmagnesium-containing

phosphate binder. (OPINION) phosphate binder. (OPINION)

6.3b- 6.3b- In patients taking In patients taking active vitamin D sterolsactive vitamin D sterols, the dose , the dose

should be reduced or therapy discontinued until the serum should be reduced or therapy discontinued until the serum

levels of corrected total calcium return to the target range levels of corrected total calcium return to the target range

(8.4 to 9.5 mg/d).(8.4 to 9.5 mg/d). (OPINION) (OPINION)

6.3b- 6.3b- In patients taking active vitamin D sterols, the dose In patients taking active vitamin D sterols, the dose

should be reduced or therapy discontinued until the serum should be reduced or therapy discontinued until the serum

levels of corrected total calcium return to the target range levels of corrected total calcium return to the target range

(8.4 to 9.5 mg/d). (OPINION)(8.4 to 9.5 mg/d). (OPINION)

6.3c-6.3c- If hypercalcemia persists despite modification of If hypercalcemia persists despite modification of

therapy, dialysis using low dialysate calcium (therapy, dialysis using low dialysate calcium (1.5 to 2.0 1.5 to 2.0

mEq/LmEq/L) may be ) may be used for 3 to 4 weeks. used for 3 to 4 weeks. (OPINION) (OPINION)

In CKD Patients (Stages 3 to 5):In CKD Patients (Stages 3 to 5):

6.4-6.4-Total elemental calcium intakeTotal elemental calcium intake (dietary calcium+ (dietary calcium+

calcium-based phosphate binders) should not exceed calcium-based phosphate binders) should not exceed

2,000 2,000 mg/day. (OPINION) mg/day. (OPINION)

6.5-6.5-The serum The serum Ca-P productCa-P product should be maintained at should be maintained at <55 <55

mgmg22/dl/dl22. (EVIDENCE) This is best achieved by . (EVIDENCE) This is best achieved by

controlling serum levels of P within the target range. controlling serum levels of P within the target range.

(OPINION) (OPINION)

6.6-6.6- Patients whose serum Ca level are below the lower Patients whose serum Ca level are below the lower

limit (limit (<8.4<8.4 mg/dl) should receive therapy to increase serum mg/dl) should receive therapy to increase serum

Ca if:Ca if:

6.6-6.6- Patients whose serum Ca level are below the lower Patients whose serum Ca level are below the lower

limit (limit (<8.4<8.4 mg/dl) should receive therapy to increase serum mg/dl) should receive therapy to increase serum

Ca if:Ca if:

6.6a-6.6a-There are clinical symptoms of hypocalcemia such as There are clinical symptoms of hypocalcemia such as

paresthesia, Chvostek’s and Trousseau’s signs, paresthesia, Chvostek’s and Trousseau’s signs,

bronchospasm, laryngospasm, tetany, and/or seizures bronchospasm, laryngospasm, tetany, and/or seizures

(OPINION); or(OPINION); or

6.6-6.6- Patients whose serum Ca level are below the lower limit Patients whose serum Ca level are below the lower limit

((<8.4<8.4 mg/dl) should receive therapy to increase serum Ca if: mg/dl) should receive therapy to increase serum Ca if:

6.6a-6.6a-There are clinical symptoms of hypocalcemia such as There are clinical symptoms of hypocalcemia such as

paresthesia, Chvostek’s and Trousseau’s signs, bronchospasm, paresthesia, Chvostek’s and Trousseau’s signs, bronchospasm,

laryngospasm, tetany, and/or seizures (OPINION); orlaryngospasm, tetany, and/or seizures (OPINION); or

6.6b-6.6b-The plasma iPTH level is above the target. (OPINION)The plasma iPTH level is above the target. (OPINION)

6.7-6.7-Therapy for hypocalcemia should Therapy for hypocalcemia should

include calcium salts such as calcium include calcium salts such as calcium

carbonate (EVIDENCE) and/or oral carbonate (EVIDENCE) and/or oral

vitamin D sterols. (EVIDENCE) vitamin D sterols. (EVIDENCE)

GUIDELINE 7.GUIDELINE 7.

PREVENTION AND TREATMENT PREVENTION AND TREATMENT

OF VITAMIN D INSUFFICIENCY OF VITAMIN D INSUFFICIENCY

AND DEFICIENCY IN CKD AND DEFICIENCY IN CKD

PATIENTS PATIENTS

In CKD Patients (Stages 3 and 4):In CKD Patients (Stages 3 and 4):

7.1-7.1- If plasma intact PTH is above the target range serum If plasma intact PTH is above the target range serum 25-25-

(OH)D(OH)D should be measured at first encounter. If it is normal, should be measured at first encounter. If it is normal,

repeat annuallyrepeat annually. (EVIDENCE). (EVIDENCE)

7.2-7.2- If the serum level of 25-(OH)D is If the serum level of 25-(OH)D is <30 ng/ml<30 ng/ml, ,

supplementation with vitamin Dsupplementation with vitamin D22 should be initiated. should be initiated.

(OPINION)(OPINION)

7.3-7.3- Following initiation of vitamin D therapy: Following initiation of vitamin D therapy:

7.3a-7.3a- The use of ergocalciferol therapy should The use of ergocalciferol therapy should

be integrated with the serum Ca & P.be integrated with the serum Ca & P.

7.3b-7.3b- The serum Ca and P level should be The serum Ca and P level should be

measured at least every 3 months. (OPINION)measured at least every 3 months. (OPINION)

7.3c-7.3c- If the serum If the serum Ca >10.2Ca >10.2 mg/dl discontinue mg/dl discontinue

ergocalciferol and all forms of vitamin D therapy. ergocalciferol and all forms of vitamin D therapy.

(OPINION)(OPINION)

7.3d-7.3d- If the serum If the serum P >4.6P >4.6 mg/dl, add or increase the dose mg/dl, add or increase the dose

of phosphate binder. If hyperphosphatemia persists, of phosphate binder. If hyperphosphatemia persists,

discontinue vitamin D therapy. (OPINION)discontinue vitamin D therapy. (OPINION)

7.3e-7.3e- Once patients are replete with vitamin D, Once patients are replete with vitamin D,

continued supplementation with a vitamin-D-continued supplementation with a vitamin-D-

containing multi-vitamin preparation should be used containing multi-vitamin preparation should be used

with annual reassessment of serum levels of 25-with annual reassessment of serum levels of 25-

(OH)D, and the continued assessment of corrected (OH)D, and the continued assessment of corrected

total Ca and P every 3 months. (OPINION)total Ca and P every 3 months. (OPINION)

In CKD Patients With Kidney Failure (Stage 5):In CKD Patients With Kidney Failure (Stage 5):

7.4-7.4- Active vitamin D sterol (calcitriol, alfacalcidol, Active vitamin D sterol (calcitriol, alfacalcidol,

paricalcitol, or doxercalciferol) should be given paricalcitol, or doxercalciferol) should be given

ifif iPTH is >300 pg/mliPTH is >300 pg/ml (OPINION) (OPINION)

In CKD patients with serum In CKD patients with serum P<4.6P<4.6 mg/dl, serum mg/dl, serum Ca<9.5 Ca<9.5 mg/dl, & serum mg/dl, & serum PTH in the higher target rangePTH in the higher target range for CKD for CKD

stagestageMeasure serum 25(OH)D

Is serum 25(OH)D<30 ng/ml?

Oral vitamin D2 or D3

See guideline 8A

Measure serum Ca & P

Is serum Ca<10.2 mg/dl?

Is serum P<4.6 mg/dl?

Continue or resume vitamin D2 or D3

Initiate or increaseP binder or restrict

Dietary PHold vitamin D dose

No

Yes

Yes

Yes

No

No

Recommended Supplementation for vitamin D Recommended Supplementation for vitamin D deficiency/insufficiency in CKD stages 3 & 4deficiency/insufficiency in CKD stages 3 & 4

Serum Serum 25(OH)D 25(OH)D (ng/ml)(ng/ml)

DefinitionDefinition ErgocalciferoErgocalciferol Dosel Dose

Duration Duration (months)(months)

CommentComment

<5-15<5-15 Severe Severe vitamin D vitamin D deficiencydeficiency

50,000 IU/wk 50,000 IU/wk POPO12 wk,12 wk, then monthly then monthly

500,000 IU as 500,000 IU as single IM single IM

dosedose

6 months6 months Measure 25 (OH)D Measure 25 (OH)D after 6 monthsafter 6 months

Assure patient Assure patient adherence; measure adherence; measure 25(OH) at 6 months25(OH) at 6 months

5-155-15 Mild vitamin Mild vitamin D deficiencyD deficiency

50,000 IU/wk 50,000 IU/wk 4 weeks 4 weeks then 50,000 then 50,000

IU/month POIU/month PO

Assure patient Assure patient adherence; measure adherence; measure 25(OH) at 6 months25(OH) at 6 months

16-3016-30 Vitamin D Vitamin D insufficiencyinsufficiency

50,000 50,000 IU/month POIU/month PO

GUIDELINE 8.A-VITAMIN D GUIDELINE 8.A-VITAMIN D

THERAPY IN CKD STAGE 3 & 4THERAPY IN CKD STAGE 3 & 4

8A.1- 8A.1- In patients with CKD In patients with CKD Stages 3 and 4Stages 3 and 4, therapy with , therapy with

an active oral vitamin D sterol (calcitriol, alfacalcidol, or an active oral vitamin D sterol (calcitriol, alfacalcidol, or

doxercalciferol) is indicated when serum levels of doxercalciferol) is indicated when serum levels of

25(OH)D are >30 ng/ml25(OH)D are >30 ng/ml, and plasma iPTH above the , and plasma iPTH above the

target. (EVIDENCE)target. (EVIDENCE)

8A.1a-8A.1a- Treatment with an active vitamin D should be Treatment with an active vitamin D should be

undertaken only in patients with serum undertaken only in patients with serum Ca < 9.5Ca < 9.5 mg/dl mg/dl

and serum and serum P < 4.6P < 4.6 mg/dl. (OPINION) mg/dl. (OPINION)

8A.1b-8A.1b- Vitamin D should not be prescribed for patients Vitamin D should not be prescribed for patients

with rapidly worsening kidney function or those who are with rapidly worsening kidney function or those who are

noncompliant with medications or follow-up. (OPINION)noncompliant with medications or follow-up. (OPINION)

8A.2-8A.2- During therapy with vitamin D sterols, serum levels During therapy with vitamin D sterols, serum levels

of of Ca and PCa and P should be monitored should be monitored at least every monthat least every month for for

the first 3 months, the first 3 months, then every 3 monthsthen every 3 months thereafter. thereafter. Plasma Plasma

PTHPTH levels should be measured at least levels should be measured at least every 3 months for every 3 months for

6 months6 months, and , and every 3 months thereafterevery 3 months thereafter. (OPINION). (OPINION)

8A.3-8A.3- Dosage adjustments:Dosage adjustments:

8A.3a-8A.3a- If plasma levels of intact PTH fall below the target, If plasma levels of intact PTH fall below the target,

hold active vitamin D until plasma PTH rise to above the hold active vitamin D until plasma PTH rise to above the

target, then resume treatment with half dose active target, then resume treatment with half dose active

vitamin D.vitamin D.

-If the lowest daily dose of the active vitamin D is being -If the lowest daily dose of the active vitamin D is being

used, reduce to alternate-day dosing. (OPINION)used, reduce to alternate-day dosing. (OPINION)

8A.3b8A.3b If serum If serum Ca >9.5 mg/dlCa >9.5 mg/dl, hold active , hold active

vitamin D until serum calcium <9.5 mg/dl, vitamin D until serum calcium <9.5 mg/dl,

then resume treatment at half dose. then resume treatment at half dose.

If the lowest daily dose of the active vitamin D If the lowest daily dose of the active vitamin D

sterol is being used, reduce to alternate-day sterol is being used, reduce to alternate-day

dosing. (OPINION)dosing. (OPINION)

8A.3c-8A.3c- If serum P level rise to If serum P level rise to >4.6>4.6 mg/dl, mg/dl,

hold active vitamin D, initiate or increase dose hold active vitamin D, initiate or increase dose

of phosphate binder until P < 4.6 mg/dl;of phosphate binder until P < 4.6 mg/dl;

then resume the prior dose of active vitamin D. then resume the prior dose of active vitamin D.

(OPINION) (OPINION)

In CKD patients stages 3 & 4 with stable renal function, compliant In CKD patients stages 3 & 4 with stable renal function, compliant with medications, with serum with medications, with serum P < 4.6P < 4.6 mg/dl, serum mg/dl, serum Ca < 9.5Ca < 9.5

mg/dl, mg/dl, & 25(OH)D & 25(OH)D 30 30 ng/ml: ng/ml:

Measure serum PTH

Is serum PTH >70 pg/ml (stage 3) or > 110 pg/ml (stage 4)?

Begin vitamin D sterol

Monitor according to guidline 1

Measure serum Ca & P

Is serum Ca <9.5 mg/dl?

Is serum P< 4.6 mg/dl?

Measure serum PTH

Initiate or increaseP binder or restrict

Dietary P

Hold or reduce vitamin D dose

No

Yes

Yes

Yes

No

No

>70 pg/ml (stage 3) or >110 pg/ml (stage 4)

Continue oral dose of vitamin D

<35 pg/ml (stage 3) or <70 pg/ml (stage 4)

Stop or reducedose of Ca-basedP-binder or reduce

Ca supplement

Serum levels of PTH, Ca & P required for initiation of Serum levels of PTH, Ca & P required for initiation of

oral vitamin D sterol & recommended initial dose in oral vitamin D sterol & recommended initial dose in

stages 3 & 4 CKDstages 3 & 4 CKD

Plasma PTH Plasma PTH (pg/ml)(pg/ml)

Ca Ca (mg/dl)(mg/dl)

P P (mg/dl)(mg/dl)

Dose Oral Dose Oral CalcitriolCalcitriol

Dose Oral Dose Oral AlfacacidiolAlfacacidiol

Dose Oral Dose Oral DoxercalciferolDoxercalciferol

>70 (stage 3) or >70 (stage 3) or > 110 (stage 4)> 110 (stage 4)

< 9.5< 9.5 <4.6<4.6 0.25 0.25 g/dayg/day 0.25 0.25 g/dayg/day 0.25 0.25 g 3 g 3 wk wk

GUIDELINE 8B.GUIDELINE 8B.

VITAMIN D THERAPY IN VITAMIN D THERAPY IN

PATIENTS ON DIALYSIS PATIENTS ON DIALYSIS

(CKD STAGE 5)(CKD STAGE 5)

8B.1-8B.1-Patients treated with HD or PD with serum Patients treated with HD or PD with serum

iPTH >300 pg/mliPTH >300 pg/ml should receive an active vitamin D should receive an active vitamin D

sterol (such as calcitriol, alfacalcidol, paricalcitol, or sterol (such as calcitriol, alfacalcidol, paricalcitol, or

doxercalciferol; to reduce the serum levels of PTH to doxercalciferol; to reduce the serum levels of PTH to

a target range of a target range of 150 to 300 pg/ml150 to 300 pg/ml. (EVIDENCE). (EVIDENCE)

8B.1a-8B.1a-The The intermittent, IV calcitriolintermittent, IV calcitriol is more effective is more effective

than daily oral calcitriol in lowering serum PTH. than daily oral calcitriol in lowering serum PTH.

(EVIDENCE)(EVIDENCE)

8B.1b-8B.1b-In patients with high serum Ca &/or P, a trial In patients with high serum Ca &/or P, a trial

of of alternative vitamin D analogsalternative vitamin D analogs, such as paricalcitol , such as paricalcitol

or doxercalciferol may be warranted. (OPINION)or doxercalciferol may be warranted. (OPINION)

8B.2-8B.2-When therapy with vitamin D sterols is initiated When therapy with vitamin D sterols is initiated

or the dose is increased, serum Ca & P should be or the dose is increased, serum Ca & P should be

monitored at least monitored at least every 2 weeks for 1 month and every 2 weeks for 1 month and

then monthlythen monthly thereafter. thereafter.

The plasma PTH should be measured The plasma PTH should be measured monthly for at monthly for at

least 3 monthsleast 3 months and then and then every 3 monthsevery 3 months once target once target

levels of PTH are achieved. (OPINION)levels of PTH are achieved. (OPINION)

8B.3-8B.3-For PD patients, oral doses of calcitriol (0.5 to 1.0 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 µg) or doxercalciferol (2.5 to 5.0 µg) can be given 2 or 3

times weekly. Alternatively, a lower dose of calcitriol times weekly. Alternatively, a lower dose of calcitriol

(0.25 µg) can be administered daily. (OPINION)(0.25 µg) can be administered daily. (OPINION)

8B.4-8B.4- When either HD or PD patients are treated with When either HD or PD patients are treated with

active vitamin D sterols, management should integrate the active vitamin D sterols, management should integrate the

changes in serum Ca & P and plasma PTH.changes in serum Ca & P and plasma PTH.

Algorithm 3. Managing Vitamin D sterols based on serum Ca levelsAlgorithm 3. Managing Vitamin D sterols based on serum Ca levels

Measure serum Ca

Reduce dose of Ca containing P-binders & change to or ↑ dose

of non-Ca containingP-binders

Continue or modify vitamin D using Algorithm 4 & 5

Measure serum Ca

Measure serum PTH

Stop vitamin D Rx

No

OptionalDialysate Ca

2 meq/L for 2-3 HD Rx

Ca=9.5-10.2 mg/dl

Ca<9.5 mg/dlCa>10.2 mg/dl

Ca=9.5-10.2 mg/dl

Is serum PTH>300 pg/ml?

Continue or modify vitamin D using Algorithm 4 & 5

Yes

Ca<9.5 mg/dlCa>10.2 mg/dl

OptionalChange to less calcemic

vitamin D sterol

Algorithm 4. Managing Vitamin D sterols based on serum Pi levelsAlgorithm 4. Managing Vitamin D sterols based on serum Pi levels

Measure serum P

Increase P-binders dose

Continue or modify vitamin D using Algorithm 1 & 5

Measure serum P

Hold vitamin D Rx

No

P=5.5- 6.0 mg/dl

Is serum P<5.5 mg/dl?

If patient has been on vitamin Dreduce dose by 25-50%

If vitamin D has been heldResume at dose lowered by 25-50%

Yes

P <5.5 mg/dlP> 6.0 mg/dl

Measure serum PTH

Reduce vitamin D dose by half for 2 months

Maintain same vitamin D dose

for 3 months

Measure Serum PTH

Hold vitamin D Rx for 1 month

PTH=150-200 pg/ml

PTH=200-300 pg/mlPTH< 150 pg/ml

Raise vitamin D dose by 25-50%

PTH>300 pg/mlP< 5.5 mg/dlCa< 9.5 mg/dl

PTH>300 pg/mlPTH<150 pg/ml

Hold vitamin D Rx for 3 month

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

Maintain same vitamin D dose

for 3 months

If on Vitamin D, raise vitamin D dose by 25-50%

If vitamin D has been held,resume therapy with earlier dose

PTH=150-200 pg/mlPTH=200-300 pg/ml

When intact PTH is between When intact PTH is between 300-500300-500 pg/ml and pg/ml and

changes in 2 successive determinations are small changes in 2 successive determinations are small

(<25%), there is no need to change vitamin D dose, as (<25%), there is no need to change vitamin D dose, as

far as Ca and P are within the desired limits.far as Ca and P are within the desired limits.

When intact PTH is persistently When intact PTH is persistently >500-800>500-800 pg/ml and pg/ml and

P is 5-6.5P is 5-6.5 mg/dl &/or mg/dl &/or Ca is 10.2-10.5Ca is 10.2-10.5 mg/dl, a trial mg/dl, a trial

with a less calcemic analog may be warranted for 3-5 with a less calcemic analog may be warranted for 3-5

months. If such a patient fails to respond, months. If such a patient fails to respond,

parathyroidectomy may be required.parathyroidectomy may be required.

MDRD study equationMDRD study equation

Estimated GFR (mL/min/1.73 m2) =Estimated GFR (mL/min/1.73 m2) =186 x [SCr(-1.154)] x [Age(-0.203)] x 186 x [SCr(-1.154)] x [Age(-0.203)] x

(0.742 if female) x (1.21 if African (0.742 if female) x (1.21 if African American)American)

This equation is also equivalent to:This equation is also equivalent to:Estimated GFR (mL/min/1.73 m2) = Estimated GFR (mL/min/1.73 m2) =

exp(5.228 - 1.154 X ln (SCr) - 0.203 x exp(5.228 - 1.154 X ln (SCr) - 0.203 x ln (Age) - (0.299 if female) + (0.192 if ln (Age) - (0.299 if female) + (0.192 if African American)African American)