Treatment of CKD-MBD
Treatment of CKD-MBD
Samuel Makar Professor of Pediatric Nephrology Cairo University Scope
• Introduction and definitions • Aim of treatment • Target Values • Tools available ( conventional and new) • Using The Tools
Introduction
Definition of CKD-MBD : – The Kidney Disease: Improving Global Outcomes (KDIGO) defines CKD-MBD as a broad clinical systemic bone syndrome due to : 1. Mineral abnormalities 2. Skeletal abnormalities 3. Vascular abnormalities that occur in association with CKD
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. Kidney Int Suppl 2017 Triad of CKD-MBD
Laboratory abnormalities Bone abnormalities
Renal Osteodystrophy Ca Ph CVD PTH Fractures Mortality
Vascular calcification Coronary artery calcification in a dialysis patient Bone abnormalities or Renal osteodystrophy
• Renal osteodystrophy is only one aspect of CKD-MBD that refers to the bone pathology alone.
It is similar in children as adults regarding fractures, bone pain, and avascular necrosis),
but also unique to children (eg, growth failure and skeletal deformities) Bone abnormalities (Renal osteodystrophy) Consists of several different forms based on bone biopsy that include
1. Osteitis fibrosa cystica 2. Adynamic bone disease 3. Mixed osteodystrophy 4. Osteomalacia.
Osteitis fibrosa cystica Bone abnormalities or Renal osteodystrophy
1. Osteitis fibrosa cystica – Elevated PTH and low serum calcium 2. Adynamic bone disease – low PTH and elevated serum calcium 3. Mixed osteodystrophy, and 4. Osteomalacia. The severity of bone disease rises with increasing progression of CKD Bone abnormalities or Renal osteodystrophy
• Accurate diagnosis of renal osteodystrophy • — Bone biopsy is the gold standard for establishing the type of renal osteodystrophy.
• However, in most clinical settings, it is not necessary to identify the specific form of renal osteodystrophy by bone biopsy, but rather determine if bone turnover activity is abnormally high or low.
• In most clinical settings serum parathyroid hormone (PTH) is used as a surrogate marker to determine whether CKD-MBD is present. Bone abnormalities or Renal osteodystrophy
• In children with CKD stage 3 to 4, the most likely form of CKD- MBD is osteitis fibrosa cystica, and a bone biopsy is not routinely needed and elevated or rising serum PTH concentration is indicative of increased bone turnover
• In children with CKD stage 5, a combination of serum PTH and calcium test results can usually distinguish between high (eg, osteitis fibrosa cystica) and low (eg, adynamic bone disease) turnover
Bone abnormalities or Renal osteodystrophy KDOQI guidelines for bone biopsy in children with stage 5 disease in whom:
– Non-traumatic bone fractures – Suspected aluminum exposure, or – Persistent hypercalcemia with a serum intact PTH (iPTH) between 400 and 600 pg/ml
• KDIGO guidelines recommend bone biopsy in the setting of: – persistent bone pain, – unexplained hypophosphatemia, and
• Only if knowledge of the type of renal osteodystrophy will impact treatment decisions
Triad of CKD-MBD
Laboratory abnormalities Bone abnormalities
Renal Osteodystrophy Ca Ph CVD PTH Fractures Mortality
Vascular calcification The players (target for treatment)
• Phosphorus: • Calcium: • PTH: • 1,25 (OH)2 Vit D: • FGF23: The players (target for treatment)
• Phosphorus: The unlucky one with bad choices • Calcium: less bad choices • PTH: The Lost • 1,25 (OH)2 Vit D: The good-hearted, naïve • FGF23: The Selfish, evil Increased 1,25(OH)2 Increased Calcium Vit D Phosphorus
PTH FGF23 Renal Phosphate reabsorption Stimulates Inhibits The players (target for treatment)
• Phosphorus: The unlucky one with bad choices • Calcium: less bad choices • PTH: The Lost • 1,25 (OH)2 Vit D: The good-hearted, naïve • FGF23: The Selfish, evil Aims of Treatment
• The specific aims of management of CKD-MBD are:
1. Maintain serum calcium and phosphorus near normal limits
2. Prevent hyperplasia of the parathyroid glands and to maintain serum PTH at levels appropriate for stage of CKD
3. Avoid the development of extraskeletal calcifications
4. Prevent or reverse the accumulation of toxic substances such as aluminum, b2-microglobulin, and likely also FGF23.
Phosphorus
In pediatrics serum phosphate vary substantially by age. • 0-6 months : 5.2–8.4 mg/dL • 6-12 months : 5.0–7.8 mg/dL • 1–5 years: 4.5–6.5 mg/dL • 6–12 years 3.6–5.8 mg/dL • Adolescents (ages 13–20 years): 2.3–4.5 mg/dL PTH Target Level
The KDOQI guidelines for i-PTH at different stages of CKD :
• Stage 2 and 3 disease • – 35 to 70 pg/mL • Stage 4 disease – 70 to 110 pg/mL • Stage 5 disease – 200 to 300 pg/mL K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis 2005
• The ESPN CKD-MBD and Dialysis WG guidelines recommend PTH levels should be kept at two to three times the upper limit of the normal range in end-stage renal disease (ESRD) .
Klaus G, et al. European guidelines. Pediatr Nephrol 2006; 21:151. PTH Target Level
• The KDIGO suggests for patients on dialysis, PTH levels are maintained in the range of approximately 2-9 times the upper normal limit.
K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis 2005
• Data from the IPPN supports a PTH target range of 100 to 300 pg/mL in children on peritoneal dialysis
Borzych D, et al. Kidney Int 2010
Ca x Pi product Target Level the KDOQI guidelines recommend that the calcium phosphate product be maintained below the following values :
• Less than 65 mg2/dL2 in children younger than 12 years of age
• Less than 55 mg2 /dL2 in children older than 12 years of age
• This is best achieved by maintaining : – Phosphate within the age specific target range and – Calcium between 8.8 and 9.7 mg/dL (2.2 to 2.37 mmol/L).
K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis 2005 Wesseling-Perry and Salusky, Pediatr Nephrol 2015 Treatment Tools
Phosphorus Restriction Early
Old Binders Late Binders conventional
Newer Binders
conventional Vit D Newer Analogues
Calcimimetics Conventional and newer Others
Treatment of adynamic bone disease Adynamic Bone disease Caused by oversuppression of PTH
Bone pains Fractures
Low bone turnover (low PTH , high Calcium)
Hypercalcemia Vascular Calcification Treatment of Adynamic Bone disease Remove factors suppressing PTH
Stop Calcium spplm. Calcium suppresses PTH Non Ca-Binders
Low Ca dialysate
Vit D sterols suppresses PTH Stop vit D Phosphorus
Restriction Binders
Old Binders
conventional
Newer Binders Phosphorus Restriction
• Intake is approximately 1,500–2,000 mg/day, and 60–70 % of the dietary intake is absorbed.
• However, strict adherence to dietary phosphate restriction is often difficult because: – low-phosphate diets are unpalatable – phosphorous intake is directly linked to protein intake, (10 mg of phosphorus accompanying each gram of protein) – Phosphates present in food additives
Phosphorus Restriction
• Industrially processed and “fast” foods have much higher phosphorus content than the natual counterparts because food additives, including:
– Sodium phosphate – Calcium phosphate – Potassium phosphate – Orthophosphoric acid diphosphate, triphosphate and polyphosphate, that are used for food preservation.
• These additives are not regulated by the USA Food and Drug Administration.
Phosphorus Restriction
• Adequate protein intake is important in CKD patients In adults with CKD should ingest between 0.8- 1 g/kg/day of protein In children, depending on age, from 1 to 2.5 g/kg/day
• This translates to a minimum phosphate ingestion of 800 mg/day in an 80 kg person.
• In early CKD, dietary phosphate restriction is sufficient in preventing hyperphosphatemia.
Phosphorus Restriction in Dialysis ?
• Patients treated with dialysis require dietary phosphorous restriction, in addition to phosphate-binder therapy, because standard prescription peritoneal dialysis and hemodialysis remove insufficient amounts of phosphate (300–400 mg/day for peritoneal dialysis and 800 mg/treatment for hemodialysis) Phosphorus Restriction Early
Old Binders Late Binders conventional
Newer Binders
conventional Vit D Newer Analogues
Calcimimetics Conventional and newer
Others Phosphate Binders
• Definition:
– Reduce intestinal phosphate absorption by forming poorly soluble complexes with phosphorus in the intestinal tract.
• Administration
– Phosphate binders should be taken 10 to 15 minutes before or during the meal. – The effect is less when taken between meals, since most dietary phosphorus has already been absorbed
Phosphate Binders
Timing Types
AL-based (history) With Phosph
Ca - Based
Early(before Phosph) Non Ca - Based
New Binders Early Phosphate Binders
• Early in CKD , the levels of PTH and FGF23 are elevated despite normal serum Phosphorus
• Their levels are increased early to cause reduction in tubular phosphate reabsorption to keep normal phosphorus level.
Portale AA, et al. Clin J Am Soc Nephrol 2014 Slatopolsky E,et al. J Clin Invest 1971 Early Phosphate Binders
• Trials testing the potential benefits of phosphate binders in early stages of CKD when serum phosphate levels are within the normal range but when FGF23 and PTH levels are elevated.
• The results and the outcome are still controversial. Phosphate Binders
Timing Types
AL-based (history) With Phosph
Ca - Based
Early(before Phosph) Non Ca - Based
New Binders Aluminum- based Phosphate Binders
• Aluminum-containing phosphate binders were used frequently in the past, but long-term treatment led to bone disease, encephalopathy, and anemia
• Now restricted only to the treatment of patients with severe hyperphosphatemia associated with hypercalcemia or an elevated calcium phosphorous ion product, because both conditions will be aggravated by calcium-containing compounds.(newer binders replaced this indication as well)
Aluminum free, Calcium - based Binders
• To avoid aluminum-related bone disease and encephalopathy, the use of aluminum-free phosphate calcium-containing salts are used for control of hyperphosphatemia
• Serve as a source of supplemental calcium as well
• Several calcium salts, including
– Calcium carbonate – Calcium acetate – Calcium citrate Calcium - based Binders
• Types:
– Calcium carbonate most commonly used compound
– Calcium acetate binds twice as much as phosphorus, but may increase incidence of hypercalcemia.
– Calcium ketoglutarate is less calcemic than calcium carbonate and has anabolic benefits, but gastrointestinal side effects and high cost of therapy often limit its use
Birck R, et al . Nephrol Dial Transplant. 1999
Calcium - based Binders
Dose: • Proportional to the phosphorous content of the meal and is adjusted to achieve acceptable serum levels of calcium and phosphorus.
• Intake should not exceed 2 g/day, with less than 1,500 mg of calcium given as calcium-containing phosphorous binders
K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis. 2005
• Large doses of calcium carbonate may cause hypercalcemia, particularly in patients treated with vitamin D or those with adynamic bone
Calcium - based Binders
• In Hypercalcemia ( to avoid the development and progression of cardiovascular calcifications) :
– reduce in the dose of oral calcium salts – reduce dose of vitamin D sterol – and if on dialysis, reduce dialysate calcium concentrations
Calcium and Aluminum- Free Phosphate Binders
• Sevelamer hydrochloride (RenaGel), a calcium- and aluminum-free phosphate binder was developed to limit:
– Vascular calcification risks associated with the use of calcium salts – Bone and neurologic toxicity associated with aluminum hydroxide
Shown to lower serum phosphorus, the calcium- phosphorous ion product, and PTH without inducing hypercalcemia in adult patients treated with hemodialysis
Block GA, et al. Kidney Int. 2005 Sevelamer : Aluminum free, Calcium - based Binders • Other Functions: – halts the progression of vascular calcification.
– Decreases total serum cholesterol and low-density lipoprotein cholesterol
– Increases high-density lipoprotein levels .
– Reduction in cardiovascular complications in patients with end-stage renal disease.
Sevelamer : Aluminum free, Calcium - based Binders
Dose: • Starting Dose for Adult Patients Not Taking a Phosphate Binder is 0.8 to 1.6 g taken orally with meals based on serum phosphorus level
Sevelamer : Aluminum free, Calcium - based Binders
Pediatric dose : • <6 years: Safety and efficacy not established • In children aged ≥6 yr :Initial dose (not taking phosphate binder) – BSA ≥0.75 to <1.2 m²: 800 mg per meal/snack; titrate up or down by 400 mg-increments – BSA ≥1.2 m²: 1600 mg per meal/snack; titrate up or down by 800 mg-increments
Switching from Calcium binder to Sevelamer Acidosis may occur in patients treated with sevelamer Hydrochloride thus, a newer form , Sevelamer Carbonate, has been introduced recently with less potential to induce acidosis Has a powder form for oral suspension for children (400 and 800mg) Other (Newer) Phosphate binders
• Other alternative phosphate-binding agents include:
– Lanthanum carbonate • Lowers phosphate and PTH levels without causing hypercalcemia, adynamic bone disease, or osteomalacia
• However, lanthanum is a heavy metal that accumulates in animal livers and bones and long-term studies therefore needed to confirm its safety profile
Other Newer Phosphate binders
– Iron compounds
• ferric polymaltose complex • ferric citrate • Sucroferric oxyhydroxyde
• Proved to be effective phosphate binders in short- and long-term studies
• FDA approved in adults but not in children yet
Other (Newer) Phosphate binders
• Nicotinamide : • Intestinal phosphate absorption is regulated by NPT2b
• Therefore treatment with niacin (vitamin B3) or its metabolite nicotinamide/niacinamide, both of which modulate NPT2b expression
• Treatment with Nicotinamide resulted in a sustained reduction in serum phosphate levels in CKD patients
Ix JH , et al. Am J Kidney Dis. 2011
Other Phosphate binders
• A hyperphosphoric salivary content correlates linearly with serum phosphate in CKD and dialysis patients
• Targeting salivary phosphate using phosphate-binding chewing gum has also been proposed for decreasing phosphate absorption .
• Chewing 20 mg of chitosan-loaded chewing gum twice daily showed phosphorus lowering benefit in HD patients
Vincenzo Savica , et al. JASN 2009
Phosphorus Restriction Early
Old Binders Late Binders conventional
Newer Binders
conventional Vit D Newer Analogues
Calcimimetics Conventional and newer
Others Vitamin D sterols
• Treatment with Active Vitamin D Sterols affects the CKD- MBD through:
– increasing calcium absorption in the gut and kidney – binding to the CaSR – increasing skeletal sensitivity to PTH – altering prepro-PTH transcription Vitamin D sterols
• Assessment of 25(OH)D Deficiency and levels are important in the management of SHPT in patients with CKD.
(1) Severe deficiency, defined as a serum level less than 5 ng/mL (2) Mild deficiency, equivalent to serum concentrations of 5– 15 ng/mL (3) Insufficiency, with levels between 16 and 30 ng/mL.
• Thus, ergocalciferol treatment should be initiated in patients with CKD when 25(OH)D levels fall below 30 ng/mL.
There are several similar protocols:
• Severe deficiency (<5 ng/mL) :
– should be treated with 50,000 IU orally, once a week for 12 weeks then 50,000 IU orally once a month for a total of 6 months – Alternatively, 500,000 IU may be given as a single intramuscular dose.
There are several similar protocols:
• Mild deficiency (5-15 ng/mL) :
– should be treated with 50,000 IU orally, once a week for 4 weeks then 50,000 IU orally once a month for a total of 6 months
• Insufficiency (16-30 ng/mL) :
– should be treated with 50,000 IU orally once a month for a total of 6 months
• In D-deficient patients, serum 25(OH)D levels should be rechecked after completion of the 6 month course of therapy.
• The ESPN CKD-MBD and Dialysis WG guidelines recommend an intensive replacement phase followed by a maintenance phase in children with CKD stage 2 to 5D
Replacement phase :
• Age <1 year – 600 IU/ day
• Age >1 year: – 20 to 30 ng/mL (50 to 75 nmol/L) – 2000 IU/ day – 5 to 20 ng/mL (12 to 50 nmol/L) – 4000 IU/ day – <5 ng/mL (<12 nmol/L) – 8000 IU/ day
Maintenance phase :
• Age <1 year – 400 IU/ day
• Age >1 year: 1000-2000 IU /day
• Lab levels done one month following initiation of therapy, every three months during therapy, and with any dose change. Calcitriol
• In children with CKD stages 2 to 4, active vitamin D analogue (eg, calcitriol) should be considered if all of the following criteria are met:
• Serum 25-hydroxyvitamin D is >30 ng/mL (>75 nmol/L) • Serum PTH is above the target range • Serum calcium level is <10 mg/dL (<2.37 mmol/L) • Serum phosphorus level is less than the age-appropriate upper limits for the stage of CKD
• In children with CKD stage 5 disease and serum PTH >300 pg/mL, calcitriol should be administered to reduce the serum PTH to 200 to 300 pg/mL Oral 1a-(OH)D3 (alfacalcidol)
• 1a-(OH)D3 (alfacalcidol) undergoes 25-hydroxylation in the liver to form calcitriol
• This agent is used widely in Europe, Japan, and Canada and Egypt .
• Calcitriol and 1a-(OH)D3 are similarly effective for the treatment of secondary hyperparathyroidism in patients with CKD. • Although calcitriol and alfacalcidol are effective in decreasing PTH levels , treatment with these sterols in combination wit calcium-based binders often results in
– hypercalcemia – hyperphosphatemia – which contributes to the development of soft tissue calcification
• Thus the development of newer vit D analogues was proposed New Viamin D analogues
• Developed to prevent or minimize intestinal calcium and phosphorous absorption
• Meanwhile suppress PTH levels as effectively as calcitriol.
• Three of these new vitamin D analogs are already on the market for use in patients with CKD:
– Maxacalcitol ( 22-oxacalcitriol ) in Japan – Paricalcitol (19-nor-1,25-(OH)2D2) and – Doxercalciferol (1 a-(OH)D2 ) in the United States.
Phosphorus Restriction Early
Old Binders Late Binders conventional
Newer Binders
conventional Vit D Newer Analogues
Calcimimetics Conventional and newer
Others Calcimimetics
• A calcimimetic : drug that mimics the action of calcium on tissues, by allosteric activation of the calcium-sensing receptor (CaSR) that is expressed in various human organ tissues.
• Cinacalcet was the first calcimimetic to be approved.
• Cinacalcet mimics calcium at the parathyroid hormone receptor. This binding will increase the sensitivity of CaSR on the parathyroid gland.
• As a result of the receptor "thinking" there is sufficient calcium, parathyroid hormone (PTH) secretion will be reduced. Lower calcium levels will be seen as well.
Calcimimetics
• Cinacalcet has been shown to decrease the calcium- phosphorous ion product in adult patients treated with maintenance dialysis, regardless of the specific phosphate- binding agent Wada M and Nagano N , Nephrol Dial Transplant. 2003
• Calcimimetics have antiproliferative effect halting the progression of parathyroid cell hyperplasia .This shows promise to use them as “medical parathyroidectomy.”
Calcimimetics
• Calcimimetic therapy could also reduce vascular calcification burden in dialysis patients
• However, the EVOLVE Trial done on 3,883 adults with advanced secondary hyperparathyroidism ) failed to demonstrate a beneficial effect of calcimimetics on either CV events or on mortality Chertow GM, N Engl J Med. 2012
• Interesting, therapy with calcimimetics has been found to be associated with reductions in FGF23 in hemodialysis patients Wetmore ,et al. Clin J Am Soc Nephrol. 2010
Luciano Pereira , et al. Clin Kidney J 2018 • Calcimimetics can be used concomitantly with vitamin D therapy.
• Calcimimetic use can have side effects. Common including: – Nausea and vomiting – Hypocalcemia – Adynamic bone disease if intact parathyroid hormone (iPTH) levels drop below 100pg/mL.
• Because of the potential for hypocalcemia and owing to the presence of the calcium-sensing receptor on the growth plate, these agents are not approved and should be used with caution in growing children.
Newer Calcimimetics
• In 2015 Amgen Inc. announced a new calcimimetic, Etelcalcetide (formerly velcalcetide) for the treatment of SHPT in chronic kidney disease (CKD) patients on hemodialysis
• Etelcalcetide is administered intravenously thrice weekly at the end of each dialysis session.
• Etelcalcetide binds to the CaSR on the parathyroid gland, which results in receptor activation and ultimately reduction in PTH.
Luciano Pereira , et al. Clin Kidney J 2018 Etelcalcetide
• Etelcalcetide is superior to cinacalcet in achieving the reduction of PTH and FGF-23 concentrations in ESRD patients
• Leads to more frequent episodes of hypocalcaemia that could be more pronounced at beginning of treatment.
• Etelcalcetide given at the end of HD sessions, improves medication adherence and reduces pill burden and represents a significant advance in treatment of SHPT
Luciano Pereira , et al. Clin Kidney J 2018 Phosphorus Restriction Early
Old Binders Late Binders conventional
Newer Binders
conventional Vit D Newer Analogues
Calcimimetics Conventional and newer
Others Parathyroidectomy
• Indications for Parathyroidectomy:
– Presence of hyperplasia and/or hypertrophy of the parathyroid glands (documented by biochemical and radiographic features and, if necessary, the findings of osteitis fibrosa cystica on bone biopsy) with autonomous growth – Elevated serum PTH levels unresponsive to vitamin D sterol therapy – Persistent hypercalcemia – Pruritus unresponsive to dialysis or other medical treatment – Progressive extra-skeletal calcification – Severe skeletal pain or fractures
Parathyroidectomy
• Rule out first : • Aluminum-related bone disease • Other causes of hypercalcemia: – Sarcoidosis – Malignancy-related hypercalcemia – Unchecked intake of calcium supplements – Presence of adynamic/aplastic bone lesions not related to aluminum.
Parathyroidectomy- Hungry Bone Syndrome
• Within 24–36 h after surgery, marked hypocalcemia (below 7–8 mg/dL) may develop. This condition may be associated with serious symptoms, including seizures
• Special attention post-operatively for marked hypocalcemia caused by the “hungry bone” syndrome.
• Because of the severity of the bone disease in CKD, hypocalcemia can be much more marked and prolonged than after parathyroidectomy for primary hyperparathyroidism.
• Renal patients should receive daily oral calcitriol (1.0–3.0 mg) or some sort of intravenous active vitamin D sterol for 2–6 days before parathyroid surgery and during the pos-operative period to stimulate intestinal calcium absorption and to maximize the effectiveness of oral calcium salts. Parathyroidectomy
• IV calcium gluconate should be started in the operating room, upon removal of the parathyroid glands.
• Calcium gluconate should be initiated at a rate of 100 mg of calcium ion per hour (rate may exceed 200 mg/hour if needed)
• Monitoring serum Calcium every 4–6 h .
• Once patient is able to tolerate oral intake enteral calcium carbonate ,4-6 times per day is initiated , along with an active vitamin D sterol in excess .
Parathyroidectomy
• The intravenous calcium drip is weaned as soon as the oral intake of calcium salts is able to maintain normal serum calcium levels.
• The duration of intravenous calcium requirements varies greatly between patients – most patients require IV therapy for 2–3 days, but severe hypocalcemia may persist for several weeks or months, necessitating permanent central catheter access for daily home infusions of 800–1,000 mg of calcium ion.
• Serum phosphorous levels may fall to subnormal levels postoperatively
patients should not be treated with phosphate unless serum phosphorus falls to
below 2.0 mg/dL as phosphate treatment will markedly aggravate
the hypocalcemia
Parathyroidectomy
• Hyperplasic parathyroid glands may be infiltrated with ethanol or calcitriol to cause sclerosis of the parathyroid tissue.
• Only few centers used currently this technique worldwide
Treatment with Growth Hormone
• Recombinant human growth hormone (rhGH) should be considered in children with growth failure that does not respond to – Optimization of nutrition – Correction of acidosis – Control of renal osteodystrophy.
Treatment with Growth Hormone
Before treatmanet with rhGH
• Serum phosphorous < 1.5 times the upper limit for age
• PTH < than 1.5 times the upper target values for the CKD .
• GH therapy should be discontinued temporarily if PTH levels exceed three times the upper target value for the CKD stage • KDOQI clinical practice guideline for nutrition in children with CKD: 2008 update. Executive summary. Am J Kidney Dis. 2009
Treatment with Growth Hormone
• It is expected in the first months of GH treatment that PTH may increase (monthly PTH monitoring)
• NB: GH as it directly directly increases bone formation rate, (independently of PTH values), a distortion in the relationship between PTH and bone formation rate occurs
Ca x Pi product
low High
PTH low PTH = PTH high PTH low PTH normal PTH Or low 1.3 x normal above target Or low Or elevated extremely normal level normal elevated
Stop Vit D Continue current Increase Consider Consider subtotal Use low Ca Vit D dose and Active vit D ADBD parathyroidectomy dialysate Ca-Binder Reduce Ca- binder Stop Vit D Use low Ca dialysate Reduce Ca- binder
Phosphorus Calcium High High
Increase Pi binder Stop Vit D European guidelines. Pediatr Nephrol 2006 Dietary counseling Use Ca free binder stop vit D Use low Ca dialysate
Question 1 : Calcitriol should be used if :
A) Serum PTH is above the target range B) Serum 25-hydroxyvitamin D is >30 ng/mL (>75 nmol/L) C) Serum calcium level is <10 mg/dL (<2.37 mmol/L) D) All of the above E) If there is severe 25 hydoxyvitamin D deficiency < 5 ng/ ml prior to th use of ergocalciferol
Question 2 : One answer is correct:
• A) Nicotinamide should be restricted in CKD diet with hyperphopshatemia as it increases intravascular calcification • B) New Iron-based phosphate binders suppresses FGF23 • C) Etalcalcetide is a new oral calcimimetic that can cause medical parathyroidectomy • D) Paricalcitol suppress PTH without causing hypercalcemia Question 3 : One answer is correct:
A) Sevelamer is still not FDA approved yet in children
B) Sevelamer hydrochloride is better used in children as it replenishes chloride deficiency and corrects acidosis
C) Calcium acetate binds twice as much as phosphorus, but may increase incidence of hypercalcemia
D) Lanthanum carbonate lowers phosphate and PTH levels but is known for causing hypercalcemia, adynamic bone disease