By : Shereef MamdouhBy : Shereef MamdouhAssistant lecturer of internal Assistant lecturer of internal

medicinemedicineNephrology departmentNephrology department

Elshahat saad abd dayem, 44ys old male patient, from Rashid, smoker, not married

A CRF patient on HD since 15ys15ys Complaining of :

Generalized Bony aches since 5ys5ys

Bilateral shoulder, hip pain since 3ys3ys

Low back pain since 3ys3ys

20 years ago patient presented by generalized oedema, HTN

Investigations revealed nephrotic range proteinuria and renal impairment, Renal biopsy was done and revealed MPGN , lab investigations revealed no secondary cause and patient diagnosed as primary MPGNprimary MPGN

Treatment started in the form of corticosteroidscorticosteroids and cyclophosphamidecyclophosphamide pulse for 3m, then patient lost follow up

5 years later, patient developed ESRD and started HD HD 3 times per week, 4hrs a session, QB 300-350 ml/min

Patient was compliant and did not miss HD sessions with Kt/V > 1.2Kt/V > 1.2

5ys ago patient started to complain of gradual onset of generalized bony aches moderatemoderate in intensity with fairfair response to analgesia

No history of pruritus, muscle weakness

Patient was conscious, alert, average Wt and Ht

Patient was vitally stable

No signs of volume overload

No signs of CTS

Investigations revealed Investigations revealed

CaCa 10.510.5 9.2 9.5

PhPh 44 4 4.3

PTHPTH 11051105 785 554

US neck US neck revealed parathyroid parathyroid adenoma adenoma within the Rt

inferior parathyroid gland measuring 9X9 mm

Parathyroid sestamibi scanParathyroid sestamibi scan revealed failure to demonstrate any

hyperactive parathyroid gland

““patient diagnosed as patient diagnosed as 2ndry 2ndry

hyperparathyroidism, hyperparathyroidism, high turn over bone high turn over bone

disease”disease”

Treatment guidelines Treatment guidelines of 2ndry of 2ndry

hyperparathyroidismhyperparathyroidism

For dialysis patients, we suggest the following For dialysis patients, we suggest the following target goals: target goals:

Serum levels of phosphatephosphate should be maintained between 3.5 and 5.5 mg/dL

Serum levels of corrected total calcium corrected total calcium should be maintained between 8.4 and 9.5 mg/dL

Intact PTH Intact PTH (second generation PTH assay) should be maintained between 150 to 300 pg/mL

A) A) Correction of Correction of serum phosphorusserum phosphorus

“Moderate Ph restriction is recommended Moderate Ph restriction is recommended provided that this can be done without provided that this can be done without

compromising nutritional state”compromising nutritional state”

Avoid unnecessary dietary Ph unnecessary dietary Ph (Ph containing food additives, dairy

products, certain vegetables, processed food and cola)

Increase high-biologic-value protein high-biologic-value protein (meat and eggs)

““Ph > 5.5Ph > 5.5””

Hypocalcemic patientsHypocalcemic patientsCalcium containing Ph binder (calcium acetate)

Normocalcemic patients Normocalcemic patients calcium containing or non-calcium containing P

binder (?? calciphylaxis, ? adynamic bone diseasecalciphylaxis, ? adynamic bone disease))

Hypercalcemic patientsHypercalcemic patientsNon calcium containing P binder (sevelamair 800-

1600mg tds, lanthanum 1500-3000mg/d)

K “We suggest that, in patients with hyperphosphatemia, calcitriol or another vitamin D sterol should be reduced or stopped (2D).”

Hemodialysis regimenHemodialysis regimen

Increased frequency

Extended HD

Nocturnal

B) B) Correction of Correction of serum calciumserum calcium

If Ca < 8.4 mg/dlIf Ca < 8.4 mg/dlgive 1-2 gm elemenlal Ca (Ca carbonate

contain 40% elemental Ca)

If Ca is in the target range If Ca is in the target range give 1 tablet of calcium carbonate 500

mg daily or eod

If calcium level > 9.5 mg/dl If calcium level > 9.5 mg/dl

1.Stop Ca carbonate and acetate

2.Reduce or Stop Vit D

K “We recommend that, in patients with hypercalcemia, calcitriol or

another vitamin D sterol be reduced or stopped (1B).”

C) C) Correction of Correction of PTHPTH

Calcitriol, Alpha-1 calcidol :Calcitriol, Alpha-1 calcidol : hyper Ca, P > suppression of PTH

Newer synthetic vit D analogs : Newer synthetic vit D analogs : (doxercalciferol, paricalcitol)(doxercalciferol, paricalcitol)

suppression of PTH > hyper Ca, P

Patient should fulfill the following criteriaPatient should fulfill the following criteria

Ca < 9.5 mg/dl P <5.5 mg /dl Ca X P product < 55 PTH > 150 pg/ml

DoseDose“Limit the dose of vit D because of risk of hyper Ca,P”

CalcitriolCalcitriol : 0.50.5 (physiological dose )- 22 mic after HD Alpha calcidol Alpha calcidol : 0.50.5 (physiological dose ) - 22 mic after HD Doxercalciferol Doxercalciferol : 11 (physiological dose )- 33 mic after HD Paricalcitol Paricalcitol : 22 (physiological dose )- 66 mic after HD

CINACALCIT 30mg (up to 180 mg ) given if CINACALCIT 30mg (up to 180 mg ) given if patient fulfill the following criteriapatient fulfill the following criteria

PTH > 300 + PTH > 300 + Ca > 8.4 mg/dl +/- P > 5.5 mg/dl +/- Ca x P product > 55

““Cinacalcet should be stopped if Ca <7.5 Cinacalcet should be stopped if Ca <7.5 mg/dl”mg/dl”

Indications for parathyroidectomy : Indications for parathyroidectomy :

Persistent PTH> 800 pg/ml + Persistent PTH> 800 pg/ml +

Severe spontaneous hypercalcemia

Progressive, debilitating hyperparathyroid bone disease

Intractable pruritus

Progressive extra skeletal calcification or calciphylaxis

Otherwise unexplained symptomatic myopathy.

Ca 10.5

Ph 4

PTH 1105

ThusThusWe started treatment in We started treatment in the form of cinacalcitthe form of cinacalcit ((mimparamimpara)) 30 mg once 30 mg once

dailydaily

After 1m investigations wasAfter 1m investigations was

CaCa 10.510.5 9.29.2 9.5

PhPh 44 44 4.3

PTHPTH 11051105 785785 554

Patient was maintained on : Patient was maintained on :

Alpha-1 calcidol (Alpha-1 calcidol (one alphaone alpha) ) 2 mic after each HD

Cinacalcit (Cinacalcit (mimparamimpara)) 30mg/d (we could not increase the dose because of financial problem )

After 1m fu investigations wasAfter 1m fu investigations was

CaCa 10.510.5 9.29.2 9.59.5

PhPh 44 44 4.34.3

PTHPTH 11051105 785785 554554

During the following period, During the following period, patient was maintained on :patient was maintained on :

Calcium carbonate Calcium carbonate 1 tab/d if Ca 8.4-9.5 mg/dl

Alpha-1 calcidol Alpha-1 calcidol 2 mic after each HD session iif Ca < 9.5 mg/dl, P < 5.5 mg/dl and Ca X P product <55

Cinacalcet Cinacalcet 30mg/d (some times is not available, and we can not increase the dose when needed)

But PTH did not But PTH did not reach the targetreach the target

))150-300mg/dl150-300mg/dl((

3ys ago patient start to complain of bilateral severesevere shoulder pain, not relieved not relieved by analgesia, this was associated with back pain

No symptoms of CTS

Beta 2 microglobulin done and was 70 mg/dl 70 mg/dl

“NormalNormal” except for

Decreased bone mineral density

Fracture of both styloid process of ulna

““we suspect we suspect DRA”DRA”

After 20 sessions After 20 sessions

Patient symptoms improved markedly

FU beta2 microglobulin was 8.7 8.7 mg/dl mg/dl

Years

0 5 10 15 20

1ry MPGN ESRD2ry Hyperparathyroidism

DRA

Steroids, Steroids,

CPACPA Regular HDRegular HD

Cincalcet, Cincalcet,

Vit D,Vit D,

CaCa HDF

CaCa 10.510.5 9.29.2 9.59.5

PhPh 44 44 4.34.3

PTHPTH 11051105 785785 554554

APAP 601601520520

Consider possibility of DRA in HD patients with intractable musculoskeletal pain, particularly if improvement is not matching with control of hyperparathyroid BMD

Online HDF is a promising approach to reduce Beta 2 microglobulin and improve features of DRA [[Role of dialysis technology Role of dialysis technology in removal of uraemic toxins. Hemodial Int in removal of uraemic toxins. Hemodial Int 2011;15: S49- 532011;15: S49- 53]]