Volume 17 Number 1 Supplement 1; March 2006
Guidelines for the Management of the Mineral
Metabolism and Bone Disease
Chronic Kidney Disease Patients
In the era of the evidence based medicine and the presence of guidelines for practice
around the world, we started to formulate Saudi Guidelines for management of the
important problems such as anemia and bone disease in the chronic kidney disease (CKD)
patients. The feedback from the renal community on the publication of the guidelines for
the management of anemia in the CKD has encouraged the Saudi Center for Organ
transplantation to prepare the guidelines for the management of the bone disease and
mineral metabolism for the kidney disease centers in the Kingdom of Saudi Arabia (KSA).
In addition, the recent survey of attitudes of the physicians towards the management of
bone diseases and mineral metabolism in the KSA has demonstrated deficiencies such as
the unavailability of protocols that address the management of this important problem in the
dialysis centers in the KSA. Currently, there are more than 7500 dialysis patients in the
KSA who require attention in terms of the monitoring and management of mineral
metabolism and bone disease.
Our guidelines aim at having a baseline for the development of sound practices in the
context of the local experiences. We intend to develop and maintain these guidelines in
order to support the local protocols in each dialysis unit in the KSA. Such support may be
fruitful in more quality care management by the providers of the CKD care such as the
health planners, physicians and nursing staff.
Faissal A.M. Shaheen MD.,
& Muhammad Ziad Souqiyyeh MD.,
On behalf of the advisory committee
for the management of mineral metabolism
and bone disease in the CKD patients
Advisory Committee for the Management of Mineral
Metabolism and Bone Disease in Chronic Kidney Disease
Dr. Othman Alfureyh Dr. Mohammad Alsulaiman
Department of Medicine, Department of Nephrology,
King Faissal Specialist hospital Armed Forces Hospital
& Research Center, Riyadh
Prof. Jamal Al-Wakeel
Dr. Saeed Alghamdi Division of Nephrology,
Division of Nephrology, Department of Medicine,
Department of Medicine, King Khaled University Hospital,
King Faisal Specialist Hospital, Riyadh.
Dr. Ayman Karkar
Dr. Ali Alharbi Division of Nephrology,
Division of Nephrology, Department of Medicine,
Department Of Medicine, Dammam Central Hospital,
Security Forces Hospital, Dammam
Dr. Ali Lehbi
Dr. Khaled Almeshari Division of Nephrology,
Department of Medicine, Department of Medicine,
King Faissal Specialist hospital King Faissal Specialist hospital
& Research Center, & Research Center,
Dr. Abdulla Alkhader Alsayyari Dr. Saadi Taher
Division of Nephrology, Department of Medicine,
Department of Medicine, King Fahd National Guard hospital
King Fahd National Guard Hospital, Riyadh.
Introduction …………………………………………………………………………………… S2
Mineral disturbances and bone disease
in the CKD patients in Saudi Arabia ……………………………………………………..... S4
Guidelines statements ………………………………………………………………………… S11
1. Evaluation of calcium and phosphorus metabolism …………………………………….. S12
2. Assessment of bone disease associated with CKD ………………………………………. S12
3. Evaluation of serum phosphorus levels…………………………………………………... S12
4. Restriction of dietary phosphorus in patients with CKD ……………………………… . S13
5. Use of phosphate binders in CKD ………………………………………………………… S13
6. Serum calcium and calcium-phosphorus product ……………………………………….. S13
7. Prevention and treatment of vitamin D insufficiency
and vitamin D deficiency in CKD patients ……………………………………………….. S14
8. Vitamin D therapy in CKD patient ……………………………………………………….. S15
9. Dialysate concentrations …………………………………………………………………… S16
10. β2 microglobulin amyloidosis …………………………………………………………...... S16
11. Aluminum overload and toxicity in CKD ……………………………………………….. S17
12. Treatment of aluminum toxicity ………………………………………………………….. S17
13. Treatment of bone disease in CKD ……………………………………………………… S17
14. Parathyroidectomy in patients with CKD ………………………………………………. S18
15. Metabolic acidosis ………………………………………………………………………… S19
16. Bone disease in the kidney transplant recipient ……………………………………….. S19
References …………………………………………………………………………………….. S20
Disclaimer ……………………………………………………………………………………... S25
S2 Guidelines for management of bone and mineral metabolism in CKD
Introduction affect the function of the parathyroid
glands. With progressive loss of kidney
There are disturbances of the mineral function, a decrease in the number of
vitamin D receptors (VDR) and calcium-
metabolism and the bone environment in sensing receptors (CaR) in the parathyroid
CKD patients. There is increased mortality glands occurs, rendering them more resistant
and morbidity from these abnormalities to the action of vitamin D and calcium. 29
such as bone pain, increased incidence of In addition, the development of hyperphos-
bone fractures and deformity, myopathy, phatemia directly affects the function and
muscle pain, and ruptures of tendons and the growth of the parathyroid glands.30-32
soft tissue calcifications. Hyperphospha- These events will allow secondary hyper-
parathyroidism to worsen. The integration
temia also appears to be associated with of the following factors has been proposed
increased mortality, as well as the elevated to explain the pathogenesis of the hypo-
blood levels of parathyroid hormone calcemia; phosphate retention, skeletal
(PTH).1-12 The processes causing disordered resistance to the calcemic action of PTH,
mineral metabolism and bone disease have and altered vitamin D metabolism.
their onset in the early stages of CKD.13 The There is a skeletal resistance to the
stages of the CKD are shown in Table 1. calcium-mobilizing action of PTH, an
Chronic kidney disease is defined as either abnormality that occurs early in the course
kidney damage or GFR <60 mL/min/1.73 m2 of both acute and chronic kidney disease
for ≥ 3 months. Kidney damage is defined as and is not reversed by hemodialysis. 33-35
pathological abnormalities or markers of The PTH-PTHrP receptors are down regulated
damage, including abnormalities in blood or in many organs in uremia, including the
urine tests or imaging studies.14 kidney, liver, and heart, which is not due to
the high blood levels of PTH but rather to the
Table 1. Stages of chronic kidney disease. PTH-induced elevation in the basal levels of
intra-cellular concentrations of calcium (cyto-
Stag Description GFR solic calcium) in those organs. 36
e (mL/min/1.73 m2 ) Phosphate retention, which may develop
1 Kidney damage >90 with declining kidney function, plays a role
with normal or in the disturbances in 1,25(OH)2D3 production.
The effect of dietary phosphate on kidney
2 Kidney damage 60-89
with mild ↓ GFR production of 1,25(OH)2D3 could be media-
3 Moderate↓ GFR 30-59 ted through changes in transcellular flux of
4 Severe↓ GFR 15-29 phosphate and/or in the concentration of
5 Kidney↓ failure <15 (or dialysis) inorganic phosphorus in kidney cortical
cells.41 1,25 (OH)2D3 may have a direct
Patients with CKD almost always effect on the parathyroid glands. 42,43 The use
develop secondary hyperplasia of the of calcium compounds in patients with
parathyroid glands, resulting in elevated Stage 4 and 5 CKD results in the reduction
blood levels of parathyroid hormone in the serum levels of phosphorus due to the
(PTH).15-19 This abnormality is due to the ability of these compounds to bind phosphate
hypocalcemia 20,21 that develops during the
course of kidney disease and/or to a in the intestine. In addition, these calcium
deficiency of 1, 25-dihydroxycholecalci- compounds cause a rise in serum calcium
ferol (1, 25(OH)2D3) 22-28 that may directly levels, which would inhibit the parathyroid
Guidelines for management of bone and mineral metabolism in CKD S3
gland and results in a fall in blood PTH levels. consists of hydroxyapatite, with a molar Ca:
This would be followed by a reduction in Mg: P ratio similar to that of bone. In
serum levels of serum phosphorus. 44-46 contrast, the calcification found in visceral
organs (skeletal and myocardial muscle) is
Deficiency of 1,25 (OH)2D3 may initiate made of amorphous (CaMg)3(PO4)2, which
secondary hyperparathyroidism even in the has a much higher magnesium content.73-75
absence of overt hypocalcemia. 1,25 (OH)2 Recent studies suggest that increased
D3 acts directly on the PTH gene, causing a calcium intake including diet and calcium
decrease in its transcription and hence in salts could increase the risk of the soft-
the synthesis of PTH. The effect of calcium tissue calcifications even without causing
and phosphate on PTH synthesis is post- hypercalcemia.76-80
transcriptional.47 Administration of 1,25
(OH)2D3 to dialysis patients is associated The incidence of vascular calcification
with suppression of PTH secretion and with increased from 27% in those treated for less
a shift of the set-point to the left in response than 1 year to 83% in patients treated for
to hypocalcemia. 48-51 Moreover, very high more than 8 years.59-61 The vascular calci-
concentrations of 1,25 (OH)2D3 induce apo- fications may involve almost every artery
ptosis of parathyroid gland cells. 52 These and may be very extensive, rendering the
observations support the hypothesis that artery so rigid that the pulse is not palpable
deficiency of this vitamin D metabolite plays and the Korotkoff sounds may be difficult
an important role in the genesis of secondary to hear during the measurement of the
hyperparathyroidism in CKD. blood pressure. Arterial calcification shows
little tendency to regress; in some patients,
The two major types of bone disease that improvement or disappearance of arterial
are commonly encountered in patients with calcification occurs within months to years
CKD are enhanced bone resorption (osteitis after subtotal parathyroidectomy or renal
fibrosa) and adynamic bone disease transplantation.81-85
(ABD).53-55 This later entity is marked by
increased rates of overt fractures and Calcification of the myocardium, coro-
microfractures.56 Calcium uptake by the nary arteries, and cardiac valves result in
adynamic bone is reduced, and therefore congestive heart failure, cardiac arrhyth-
patients with ABD may develop mias, ischemic heart disease, and death.
hypercalcemia if calcium intake is Vascular calcification leads to ischemic
increased or if dialysate calcium is high. 55 lesions, soft-tissue necrosis, and difficulties
Osteosclerosis and osteoporosis may also be for kidney transplantation. 86,87
contributing factors, while chronic acidosis Prevention of the disturbances in mineral
of CKD may not play a major role in the and bone metabolism and their management
pathogenesis of bone disease in adult early in the course of chronic kidney disease
patients with CKD.57,58 are extremely important in improving patients'
Soft-tissue calcification constitutes a quality of life and longevity.
serious problem in CKD patients. These These guidelines are intended to aid
extra skeletal calcification may be localized in clinicians in developing an integrated appro-
the arteries (vascular calcification), 59-61 in the ach to their diagnosis and management of this
eyes (ocular calcification), 62,63 in the visceral complicated area, based on the best available
organs (visceral calcification), 64-69 around evidence. Ongoing research may result in
the joints (periarticular calcification),70 and improvements in care. Updating of guide-
in the skin (cutaneous calcification). 71,72
lines would be a dynamic process that depends
The chemical nature of soft-tissue calci- on the availability of new information about
fication may vary in different tissues. The
calcification found in nonvisceral tissue the subject.
(periarticular and vascular calcification)
S4 Guidelines for management of bone and mineral metabolism in CKD
Mineral disturbances and checked periodically and Vit D3 supplements
bone disease in the CKD may have to dis-continued.
patients in Saudi Arabia 2. In 1993, Huraib et al 89 studied the pattern of
renal osteodystrophy in hemodialysis
Over the past 20 years there were a patients in Saudi Arabia. They conducted a
reasonable body of research and reports multicenter study involving 209 patients. The
related to this issue from the dialysis centers in mean age of the patients was 39.4 ± 14
Saudi Arabia. We summarize these reports in (18-70) years, 128 were males and 81
chronological sequence in order to stimulate females. All patients were on acetate dial-
more research in the future: ysate and their mean duration on dialysis was
3.5 ± 1.5 years. The major symptom was
1. In 1990, Souqiyyeh et al evaluated the bone and joint pain (25.8 %). The mean
effects of high doses calcium carbonate serum calcium was 2.1 ± 0.26 mmol/l,
(CaC03) on serum phosphorus (P04--) and phosphorus 2.0 ± 0.36 mmol/l, alkaline
serum calcium (Ca ++) in chronic phosphatase 19.7 ± 14.6 u/l and parathyroid
hemodialysis patients, 45 patients (24M, 21F) hormone level was 8.9 ± 3.9 mg/ml. The
aged between 19-70 years on regular mean serum aluminium (AL) level was 25.4 ±
hemodialysis treatment (RDT) were 17.7 µg/l, while that of 1,25 vitamin D3 was
selected for a four weeks prospe-ctive 8.1 ± 4.2 ng/l and of fluoride was 92.2 ± 31.4
study. All the patients had been off micrograms/l. The major radiological
aluminum hydroxide therapy for four weeks finding was osteosclerosis (70%). Dual-
at least before receiving six grams of CaC03 photon absorp-tionnmetry (DPA) showed
as a standard dose in three divided doses low bone mineral density (LBM) in 65% of
after meals. All the patients had creatinine the patients. Forty-one patients had bone
clearance below 10 ml/min and all were on biopsies with AL staining of the biopsies. Of
dialysate calcium conce-ntration of 1.75 this group, 92% had changes of
mmol/l. The patients were divided into three hyperparathyroidism and 66% of them were
subgroups; group I renal dialysis treatment pure hyperparathyroidism. Sixty percent of
(RDT) three times per week and on Vitamin them had variable degrees of AL
D3 (Vit D3); group II, RDT three times per intoxication. The radiological skeletal survey
week without Vit D3; and group III: RDT of those patients could detect abnormalities
twice per week and on Vit D3. All the in only 46% while 70% of them had
study groups had significant increases of abnormal bone mineral density (BMD). They
the means of Ca ++ levels and significant concluded that osteosclerosis was the
decreases of the means of P04 - levels at commonest radiological finding in the
the end of fourth week of the study. dialysis patients, while secondary hyperpara-
Patients who were on frequent dialysis thyroidism was the main histopathological
three times a week and Vit. D3 supple- diagnosis in bone biopsy, even in patients
Guidelines for management of moreand mineral metabolismskeletal survey. AL intoxication
mentation developed hypercalcemia bone with normal in CKD S5
frequently than other groups. They conc- was a significant problem in their population.
luded that calcium carbonate could be used DPA was more sensitive in detecting bone
as a phosphate binder in hemodialysis abnormalities than X-radiography.
patients. Serum Ca ++ levels need to be 3. In 1994, Hussein et al 90 studied 325
patients in one dialysis centre over a 13-
year period. There were 19 patients (5.8%) and radiological investiga-tions including
who had pericarditis, 38% radiographic skeletal survey and dual photon
signs of renal bone disease and eight absorptionmetry. All the patients
patients required parathyroidectomy. Only underwent bone biopsy and the biopsy
two patients had carpal tunnel syndrome. material was subjected to morphometric
4.In 1994, George et al described a 40- studies, including staining for aluminum
year-old patient with end-stage renal disease deposits. The patients were divided into two
developed features of calci-phylaxis and groups: group 1, (16 patients, 39%) with
tumoral calcification after four and half negative aluminum staining. Bone pain and
years on regular hemo-dialysis. The patient its distribution as well as fractures were
had hyperphos-phatemia, with high calcium- similarly prevented in both groups. The levels
phosphate index and radiological evidence of of aluminum in the blood was significantly
hyper-parathyroidism before the onset of higher in group 2 (32.9 ± 20.2 vs 17.9 ± 11.2
symptoms. Conservative management was µg/l P<0.05), though it was lower than the
without success and the patient developed lowest accepted toxic level (40 µg/l). There
florid symptoms. Parathy-roidectomy was was no significant difference between the
delayed due to un-avoidable circumstances. two groups in the bio-chemical or hormonal
When it was eventually performed there was data, frequency of abnormal radiological
a prompt regression of the calcific masses, but signs and pattern of bone histology. This
not of the vascular calcifications. study indicated that increased aluminum
5.In 1995, Rassoul et al 92 studied the effect deposition in the bone was prevalent in
of intravenous calcitriol admini-stration on patients on main-tenance hemodialysis using
the PTH level in 14 patients on aluminum based phosphate binders, but
maintenance hemodialysis with serum PTH adynamic bone disease was not prevalent.
levels above 2,000 pmol/l over a 16-week Further studies were recommended on a
period. There was a significant reduction in Guidelines for management ofthe magnitude of the
S6 larger scale to assess bone and mineral metabolism in CKD
the PTH level (65%) and a rise of serum problem.
calcium to the normal range. There was a 7. In 1997, Huraib et al 94 conducted this study
significant reduction in serum PTH levels on 15 chronic hemodialysis patients to
before the serum calcium concentrations evaluate the efficacy of i.v. calcitriol over a
increased; suggesting that calcitriol directly 1-year period in the treatment of severe
inhibits PTH release with minimal side secondary hyper-parathyroidism (HPT), in
effects. particular its effect on bone mineral density
6. In 1995, Souqiyyeh et al 93 studied the (BMD) and parathyroid gland mass. Mean
extent of aluminum related bone disease in age was 39 ± 11.9 (20-65) years and
41 patients on regular maintenance dialysis duration was 58 ± 3 (19-130)
hemodialysis in two dialysis centers in months. i.v. calcitriol was given at a dose
Riyadh, Saudi Arabia. There were 22 of 1 µg post-dialysis 3 times/week for 3
males and 19 females aged 20 to 70 years weeks; the dose was then adjusted to
(mean 35.5 ± 11.2 years). Thirty eight of maintain the total serum calcium at less
the patients were on aluminum based oral than 2.88 mmol/l. The maximum dose was
phosphate binders. Investi-gations 3 μg 3 times/ week. Serum calcium (Ca)
performed included serum calcium, and phosphorus (P) were determined prior
magnesium, aluminum and para-thormone to treatment, then weekly for 6 weeks and
every 2 weeks thereafter. Skeletal survey, l) of F- content in drinking water. Control
dual photon densitometry and parathyroid subjects showed a mean serum F-
ultrasound (US) were done prior to concentration of 1.08 ± 0.350 μmol /l.
treatment and after 1 year. Bone biopsy was Males in control group showed slightly
done in 10 patients at the beginning of higher F- levels (1.15 ± 0.334, range
treatment. There was a significant 0.55-1.9 μmol/l) than females (0.92 ±
reduction (p < 0.01) in pre-treatment mid- 0.370, range 0.6-1.5 μmol/l). Mean serum
region serum parathyroid hormone (PTH) F- concentration did not correlate
from 1,476 ± 895 to 489 ± 485 pmol/l, as significantly with age and sex among
well as alkaline phosphatase (p < 0.04) from control subjects, whereas such corre-lation
236.5 ± 221 to 116.3 ± 49 U/l. This was was observed in patients with ESRD on
without a significant increase in serum Ca dialysis. Mean serum F- concentration was
(2.15 ± 0.25 to 2.44 ± 0.26 mmol/l, p = significantly higher in patients on dialysis
0.08). Three patients had recurrent hyper- (2.67 ± 1.09, range 0.8-5.2 μmol/l) than
calcemia which responded to reduction of Ca normal controls. When grouped according
in dialysate. There was a significant to sex, the mean serum F- concentration in
increase in BMD over the spine from 1.071 males (3.05 ±1.04, range 1.8-5.2 μmol/l)
± 0.25 to 1.159 ± 0.22 g/cm2 (p < 0.003) was significantly higher than females (2.38
with a percent increase of 9.3 - 8.9 % as ± 1.08, range 0.8-5.2 μmol/l). When
well as over the femoral neck from 0.834 ± patients were grouped according to age, it
0.002 to 0.89± 0.09 g/cm2 (p < 0.001) with was observed that F- concentration was
a percent increase of 7.45-6.81 %. Five significantly higher in patients with age
patients had enlarged parathyroid glands by groups 21-70 (2.86 ± 1.05) than those with
US and in 3 of them there was a significant age group 13-20 years (1.42 ± 0.531). Thus
reduction to normal with treatment. Bone F- concentration correlated with age and
biopsy was done in 10 patients. Six patients sex, being higher in males and above 20
had pre-dominant hyperparathyroid bone years. Despite appreciable clearance of F-
disease and 4 had mixed uremic (39-90%) across the peritoneum, patients on
osteodystrophy. They concluded that long- CAPD showed
term i.v. treatment with calcitriol was
effective in the treatment of severe
secondary HPT. PTH decreased without a
significant increase in serum Ca. BMD also
increased during therapy.
8.In 1997, Al-Wakeel et al 95 evaluated the
serum fluoride (F-) level in patients with
chronic renal failure (CRF) and end-stage
renal disease (ESRD), which is asso-ciated
with risk of renal osteodystrophy and other
bone changes. Seventeen healthy controls
(12 males, 5 females) and 39 ESRD
patients on dialysis (17 males, 22 females)
were recruited in the study in a community
with 47.4 ± 3.28 μmol/l (range 44-51 μmol/
Guidelines for management of bone and mineral metabolism in CKD S7
higher serum F- concentration than those (adynamic) bone in four, and aluminum
on HD (3.1 ± 1.97 vs 2.5± 1.137 μmol/l). deposition in one. All of the patients who
Of the total 39 patients on dialysis 39% showed evidence of bone involvement on
had their serum F-concentration above 3.0 BBX had abnormal BMD suggesting that
μmol/l, posing risk of renal BMD is a good non-invasive screening test
osteodystrophy. for ROD but indiscriminative for the type
9.In 1998, Mitwalli et al 96 evaluated renal of bone disease. They concluded that BBX
osteodystrophy (ROD) by performing bone was still the diagnostic tool to differentiate
biopsies in 57 patients with end-stage renal and classify different types of bone disease.
failure (ESRF) on dialysis, 46 on 10. In 1998, al-Homrany et al 97 reported the
hemodialysis (HD) and 11 on peritoneal rare occurrence of diffuse pulmonary calci-
dialysis (PD). There were 29 males (mean nosis in a patient who presented with a
age of 42 years) and 28 females (mean age pathological femoral fracture during end-stage
of 39 years). Relevant presenting clinical renal failure. Associated metastatic soft
features were pruritis in 46 cases, bone tissue calcification with parathyroid
pains in 32, acute pseudogout in three, hyperplasia requiring parathyroidectomy was
bone deformities in two, conjunctival calci- observed. Roentgenologic evidence of
fication in two, cutaneous calcification in two, hyperparathyroidism with osteitis fibrosa
and corneal calcification in one. The mean cystica and a high product of the cal-cium
value of predialysis blood investi-gations and phosphate values were indications for
were as follows: urea 33.9 mmol/L, the parathyroidectomy. Literature review of
creatinine 913 μmol/l, bicar-bonate 18 mmol/ pulmonary calcinosis and multiple soft tissue
L, calcium 2.36 mmol/L, albumin 40 g/L, calcifications was also presented.
phosphorus 1.69 mmol/L, alkaline 11. In 1998, Huraib et al 98 studied the effect
phosphatase 178 U/L, parathyroid hormone of alfacalcidol on lymphocyte phenol-type.
543 pmol/L, magnesium 1.06 mmol/L and There were 15 patients (10 males, 5
aluminum 1.81 mmol/L. Skeletal survey females) with a mean age of 54.3 ± 14.4
showed no changes in 24 patients (42%), years who had been on chronic main-
hyper-parathyroid cystic changes of bones tenance hemodialysis for a mean period of
in seven, osteoporosis as the predominant 3.2 ± 1.5 years. Intravenous alfacalcidol
features in seven, mixed picture of ROD in was given three times weekly during
12, subperiosteal resorption of the meta- dialysis for duration of 6 months. Our
carpals in two, osteosclerosis (Rugger results show a significant increase in
Jersey Spine) in two and osteomalacia in natural killer( NK) cells from 0.20 ± 0.12
two patients. Bone mineral density (BMD) to 0.27 ± 0.28 (P=0.001), without a
was measured by dual x-ray significant change in CD2, CD19, CD4,
absorptiometry in the lumbar spine (LS) CD8 population, and CD4/CD8 ratio.
and femoral neck (FN). All patients had 12. In 2000, Mitwalli et al 99studied the effect
low BMD (both LS and FN). Bone biopsy of oral vs intravenous alfacalcidol on
(BBX) revealed mixed picture in 30 cases, secondary hyperparathyroidism and renal
predominantly secondary hyper-parathyroid osteodystrophy (ROD in 19 ESRD
changes in 10, mild hyper-parathyroid patients, who were on dialysis (13 on
changes in five, predo-minant osteoporosis hemodialysis and six on peritoneal dia-
in three, osteo-malacia in four, aplastic lysis) for longer than six months and having
S8 Guidelines for management of bone and mineral metabolism in CKD
serum parathormone levels at least four and June 2003. There was a similar
times normal and serum calcium less than decrease in serum phosphate values over
2.1 mmol/L, were randomly allocated to the course of the study with both sevelamer
treatment with oral or intra-venous (i.v.) (-3.3± 2.2 mg/dl) and calcium carbonate
alfacalcidol for a period of 12 months. (-3.9± 2.8 mg/dl). Fifty-two percent of
There were six patients on hemodialysis patients developed serum calcium greater
(HD) and three on peri-toneal dialysis (PD) than 2.75 mmol/l (11.0 mg/dl) while
in the oral treatment group while in the i.v. receiving calcium carbonate versus 26% of
group there were seven patients on HD and patients receiving sevelamer (p<0.05). The
three on PD. Clinical and serial incidence of hypercalcemia for sevel-amer
biochemical assess-ments showed no was not different from the incidence of
statistically significant difference between hypercalcemia during the washout period.
the orally- and i.v.-treated patients in terms Patients treated with sevelamer also
of suppressing secondary sustained a 13% mean decrease in serum
hyperparathyroidism and osteodystrophy. cholesterol levels. They concluded that
However, patients with features of mild sevelamer was effective in contro-lling
ROD on bone histology had more hyperphosphatemia without an increase in
satisfactory changes in bioche-mistry when the incidence of hypercal-cemia seen with
compared to others. The results further calcium carbonate. This agent appeared
supported the use of intermittent oral quite effective in the treatment of
alfacalcidol in ESRD patients because of its hyperphosphatemia in hemo-dialysis patients
cost effectiveness, ease of administration mineral metabolism in CKD advantageous in the
Guidelines for management of bone and and its usage may be S9
and convenience, especially for peritoneal treatment of dialysis.
dialysis patients. 15.In 2006, Souqiyyeh et al 102 studied the
13.Gacha et al described a patient with attitude of the physicians in the Kingdom of
periarticular calcifications that resolved Saudi Arabia (KSA) towards the treatment
spontaneously post transplantation. of the bone disease in the dialysis centers.
14.In 2004, Shaheen et al evaluated the They sent a question-naire to 168
use of a calcium- and metal-free phos- physicians; the heads of the 146 active
phate-binding polymer, sevelamer, in dialysis centers in the KSA and 34 more
hemodialysis and compared it with the consultants working in them. This covered
standard calcium-based phosphate binder decision makers in 110 (75.3 %) centers in
in an open-label, randomized, cross-over ministry of health (MOH), 14 (9.5%) centers
study. After a 2-week phos-phate binder in govern-mental (non-MOH) and 22 (15.2
washout period, stable hemodialysis %) centers in private sector for a
patients were given either sevelamer or population of more than 7214 chronic
calcium carbonate, and the dosages were hemodialysis (HD) patients. The study was
titrated to achieve phos-phate control over conducted from April-June 2005. There
an 8-week period. After a 2-week washout were 134 out of 168 (78.6%) physicians
period, patients crossed over to the who answered the questionnaire from 134
alternate agent for 8 weeks. Twenty patients (91.7%) of the dialysis centers that cover
from the Dialysis Unit of King Fahd Hospital, 7030 (97.6%) of the dialysis patients in the
Jeddah, Kingdom of Saudi Arabia, were KSA. There were 133 (99.3%) of the
recruited for the study between March 2003 respondents who believed that the bone
disease and meta-static calcifications in the phosphate binder the maximum
HD patients is an important problem, 71 recommended dose for the dialysis patients
(53.4%) had a protocol for management of and 69(52.3%) believed that this dose was
bone disease at their centers, while adequate to control phosphorus in the
87(67.4%) believed that the current results dialysis patients. Almost all the
of management of bone disease were respondents use vitamin D mostly by daily
satisfactory at their centers. There were oral administration or a combi-nation with
112 (84.2%) respondents who would check intravenous route (59% vs. 41%
calcium once a month on the dialysis respectively). There were 59 (44.4%)
patients and 110 (82.7%) who would check respondents who believed that sevelamer
phosphorus once a month, while only 33 plus vitamin D were a better regimen to
(24.6%) would check PTH once every control PTH than Calcium based phosphate
three months and 44(32.8%) did not have binder plus vitamin D, While 51(38.3%)
this latter test available in their centers. had no idea about this issue. There were
There were 63(47.4%) respon-dents who 57(42.5%) respondents who believed that
would check the bone X-rays of the hands high intake of calcium would increase the
and clavicles once every year, while risk of vascular and metastatic calcifications
51(38.4%) would perform the X-rays as without hyper-calcemia in the dialysis
indicated by the clinical status. There were patients, while 43(32.1%) had no idea.
125(94.7%) respon-dents who would never There were 58(43.9%) respondents who
have a bone biopsy performed on HD believed that the role of calcimmetics was
patients, and 84(64.6%) would not do any well established in the management of
more tests besides those mentioned above bone disease in dialysis patients, while
to evaluate the bone disease in their 48(36.4%) had no idea. In comparison to
dialysis patients. There were 87 (64.9%) non-MOH and private dialysis centers,
respondents who would aim by therapy at there was a significantly lower percentage
mid normal serum calcium level and of the MOH centers to have protocol for
75(56.8 %) would target the mid normal management of bone disease in the dialysis
serum phosphorus level, while only patients, higher percentage of unavailability
36(29.3%) would target three times normal Guidelines for assay, lower tendencymineral metabolism in CKD
S10 of PTH management of bone and of the
level of the PTH. There were 81(60.4) physicians to target low normal level of
respondents who believed that continued phosphorus and higher percentage to target
abnormality of these parameters carry more normal levels of PTH in the dialysis
risk of morbidity and mortality in a larger patients. In addition, MOH physicians had
percentage of chronic dialysis patients than significantly less tendency to consider
anemia or inefficient dialysis. There were sevelamer the best phosphate binder for the
only 58(43.3%) respondents who believed dialysis patients and less believe that high
that sevelamer would be a safer phosphate intake of calcium can increase the risk of
binder than calcium or metal based one, vascular and metastatic calcifications
while the calcium based phosphate binder without hypercalcemia in the dialysis
was still considered by 66 (49.3%) patients. They concluded that the current
respondents as a safer binder. There were practices
68(51.5%) respondents who considered
1600 mg elemental calcium daily dose as a
concerning the bone disease management in
the dialysis centers in the KSA require
refinement in terms of the need to enforce
the use of a protocol to guide evaluation
and therapy in each dialysis unit. There was
also a need to increase the awareness of
physicians in those centers to the
importance of the details of such treatment
and the national guidelines in this regard.
Guidelines for management of bone and mineral metabolism in CKD S11
S12 Guidelines for management of bone and mineral metabolism in CKD
1. Evaluation of Calcium and 2. Assessment of Bone Disease
Phosphorus Metabolism associated with CKD
1.1Serum levels of calcium, phosphorus, 2.1 The most accurate diagnostic test for
and intact plasma parathyroid hormone determining the type of bone disease
(PTH) should be measured in all patients associated with CKD is iliac crest
with CKD and GFR <60 mL/min/1.73 m . 2 bone biopsy with double tetracycline
The frequency of these measure-ments labeling and bone histomorphometric
should be based on the stage of chronic analysis.
kidney disease, (Table 2). 2.2 It is not necessary to perform bone
biopsy for most situations in clinical
Table 2. Frequency of measurement of PTH and
practice. However, a bone biopsy should
calcium/phosphorus by stage of CKD
be considered in patients with kidney
CKD GFR Measuremen Measurement
failure (Stage 5) who have:
Stag Range t of PTH of Calcium/ 2.2a Pathological fractures, which are fractu-
e (mL/min Phosphorus res with minimal or no trauma.
/ 2.2b Intact plasma PTH levels 100 - 500
1.73 m2) pg/mL (11.0 - 55.0 mol/L) (in CKD
3 30-59 Every Every 12 Stage 5) with coexisting conditions such
12months months as unexplained hypercalcemia, severe
4 15-29 Every 3 Every 3 bone pain, or unexplained increases in
bone alkaline phosphatase activity.
5 <15 or Every 3 Every month
dialysis months 2.2c Suspected aluminum bone disease,
based upon clinical symptoms or history
of aluminum exposure.
1.2These measurements should be made 2.3 Bone radiographs are not indicated for
more frequently if the patient is receiving the assessment of bone disease of CKD,
concomitant therapy for the abnormalities in but they are useful in detecting severe
the serum levels of calcium, phosphor-rus or peripheral vascular calcification and bone
PTH. disease due to β2-microglobulin amyloi-
1.3Measurement of plasma PTH levels may be dosis.
done less frequently for those with levels within 2.4 Bone mineral density (BMD) should be
the low end of the target levels (Table 3). measured by dual energy X-ray absorptio-
1.4The target range of plasma levels of intact metry (DEXA) in patients with fractures
PTH in the various stages of CKD are and in those with known risk factors for
denoted in Table 3. osteoporosis.
Table 3. Target range of intact plasma PTH by
3. Evaluation of Serum Phosphorus
stage of CKD
CKD GFR Range Target intact" PTH 3.1 In CKD patients (Stages 3 and 4), the
Stag (mL/min/1.73 m2) pg/mL [pmol/L] serum level of phosphorus should be
e maintained at or above 0.87 mmol/L
3 30-59 35-70 [3.85-7.7] and no higher than 1.48 mmol/L.
3.2 In CKD patients with kidney failure
4 15-29 70-110 [7.7-12.1] (Stage 5) and those treated with hemo-
dialysis or peritoneal dialysis, the serum
5 <15 or dialysis 150-300 [16.5-33.0]
levels of phosphorus should be maintained
between 1.13 - 1.78 mmol/L.
Guidelines for management of bone and mineral metabolism in CKD S13
4. Restriction of Dietary Phosphorus in binders should not exceed 1,500 mg/day,
Patients with CKD and the total intake of eleme-ntal calcium
(including dietary calcium) should not
4.1 Dietary phosphorus should be restricted exceed 2,000 mg/day.
to 800 to 1,000 mg/day (adjusted for 5.6Calcium-based phosphate binders should
dietary protein needs) when the serum not be used in dialysis patients who are
phosphorus levels are elevated > 1.49 hypercalcemic (corrected serum calcium of
mmol/L (Stages 3 and 4 of CKD) and >2.54 mmol/L), or whose plasma PTH levels
>1.78 mmol/L in those with kidney are <150 pg/mL (16.5 pmol/L) on two
failure (Stage 5). consecutive measu-rements.
4.2 Dietary phosphorus should be restricted 5.7Noncalcium-containing phosphate bind-
to 800 to 1,000 mg/day (adjusted to die- ers are preferred in dialysis patients with
tary protein needs) when the plasma severe vascular and/or other soft tissue
levels of intact PTH are elevated above calcifications.
target range of the CKD stage. 5.8In patients with serum phosphorus levels
4.3 The serum phosphorus levels should be >2.26 mmol/L, aluminum-based phosphate
monitored every month following the binders may be used as a short-term therapy
initiation of dietary phosphorus restriction. (4 weeks), and for one course only, to be
replaced there-after by other phosphate
5. Use of Phosphate Binders in CKD binders. In such patients, more frequent
dialysis should also be considered.
In CKD Patients (Stages 3 and 4):
6. Serum Calcium and Calcium-
5.1 If phosphorus or intact PTH levels cannot Phosphorus Product
be controlled within the target range,
despite dietary phosphorus restriction, In CKD Patients (Stages 3 and 4):
phosphate binders should be prescribed.
5.2 Calcium-based phosphate binders are 6.1 The serum levels of corrected total
effective in lowering serum phosphorus calcium should be maintained within the
levels and may be used as the initial binder "normal" range for the laboratory used.
In CKD Patients with Kidney Failure
In CKD Patients with Kidney Failure (Stage 5):
6.2 Serum levels of corrected total calcium
5.3Both calcium-based phosphate binders and should be maintained within the normal
other noncalcium-, non-metal phosphate- range for the laboratory used, preferably
binding agents (such as sevelamer HCl) are toward the lower end 2.10 - 2.37 mmol/
effective in lowering serum phos-phorus L.
levels and either may be used as the 6.3 In the event corrected total serum
primary therapy. calcium level exceeds 2.54 m mol/L,
5.4In dialysis patients who remain hyper- therapies that cause serum calcium to
phosphatemic (serum phosphorus >1.78 rise should be adjusted as follows:
mmol/L) despite the use of either of calcium- 6.3a In patients taking calcium-based pho-
based phosphate binders or other non- sphate binders, the dose should be
calcium-, nonaluminum-, nonmag-nesium- reduced or therapy switched to a non-
phosphate-binding agents, a combination of Guidelines calcium-, non-aluminum-,mineral metabolism in CKD
S14 for management of bone and non-magne-
both should be used. sium-containing phosphate binder.
5.5The total dose of elemental calcium 6.3b In patients taking active vitamin D
provided by the calcium-based phosphate sterols, the dose should be reduced or
therapy discontinued until the serum 6.7 Therapy for hypocalcemia should
levels of corrected total calcium return to include calcium salts such as calcium
the target range (2.10 - 2.37 mmol/L). carbonate and/or oral vitamin D sterols.
6.3c If hypercalcemia (serum levels of
corrected total calcium > 2.54 mmol/L) 7. Prevention and Treatment of
persists despite modification of therapy Vitamin D insufficiency and Vitamin D
with vitamin D and/or discontinuation Deficiency in CKD Patients
of calcium-based phosphate binders,
dialysis using low dialysate calcium In CKD Patients (Stages 3 and 4):
(1.25 - 1.5 mmol/L) may be used for 3
- 4 weeks. 7.1 If plasma intact PTH is above the target
range for the stage of CKD, serum 25-
In CKD Patients (Stages 3 to 5): hydroxyvitamin D should be measured
at first encounter. If it is normal, repeat
6.4 Total elemental calcium intake annually.
(including both dietary calcium intake 7.2 If the serum level of 25-hydroxy
and calcium-based phosphate binders) vitamin D is <30 ng/mL, supplementa-
should not exceed 2,000 mg/day. tion with vitamin D2, (ergocalciferol)
6.5 The serum calcium-phosphorus product should be initiated, (Table 4).
should be maintained at < 4.5 mmol2L2. 7.3 Following initiation of vitamin D therapy:
This is best achieved by controlling ser-
um levels of phosphorus within the 7.3a The use of ergocalciferol therapy
target range. should be integrated with the serum
6.6 Patients whose serum levels of calcium and phosphorus.
corrected total calcium are below the 7.3b The serum levels of corrected total
lower limit for the laboratory used (< calcium and phosphorus should be mea-
2.10 mmol/L) should receive therapy to sured at least every 3 months.
increase serum calcium levels if: 7.3c If the serum levels of corrected total
6.6a There are clinical symptoms of hypocal- calcium exceeds 2.54 mmol/L, discontinue
cemia such as paresthesia, Chvostek's ergocalciferol therapy and all forms of
and Trousseau's signs, bronchospasm, vitamin D therapy.
laryngospasm, tetany, and/or seizures. 7.3d If the serum phosphorus exceeds 1.49
6.6b The plasma intact PTH level is above mmol/L, add or increase the dose of
the target range for the CKD Stage. phosphate binder. If hyperphosphatemia
persists, discontinue vitamin D therapy.
Table 4. Recommended supplementation for vitamin D deficiency/insufficiency in patients with CKD stages 3 and 4
Serum 25(OH) ng/mL Definition Ergo-calciferol Dose Comment
[nmol/L] (Vitamin D2)
Duration x 6 months.
Severe vitamin D 50,000 lU/wk orally x 12 Measure 25(OH)D levels
<5 deficiency wks; then monthly
 after 6 months
500,000 IU as single I.M. Assure patient adherence
5-15 Mild vitamin D deficiency orally Duration x 6 months.
50,000 lU/wk x 4 weeks, measure 25(OH)D levels
[12-37] then 50,000 IU/month after 6 months
16-30 Vitamin D insufficiency 50,000 lU/month orally
Guidelines for management of bone and mineral metabolism in CKD S15
7.3d If the serum phosphorus exceeds 1.49 first 3 months, then every 3 months
mmol/L, add or increase the dose of thereafter. Plasma PTH levels should be
phosphate binder. If hyperphospha- measured at least every 3 months for 6
temia persists, discontinue vitamin D months, and every 3 months thereafter.
therapy. 8A.3 Dosage adjustments for patients
7.3e Once patients are replete with vitamin receiving active vitamin D sterol
D, continued supplementation with a therapy should be made as follows:
vitamin-D-containing multi-vitamin pre- 8A.3a If plasma levels of intact PTH fall
paration should be used with annual below the target range for the CKD
reassessment of serum levels of 25- stage, hold active vitamin D sterol
hydroxyvitamin D, and the continued therapy until plasma levels of intact
assessment of corrected total calcium PTH rise to above the target range,
and phosphorus every 3 months. then resume treatment with the dose
of active vitamin D sterol reduced by
In CKD Patients with Kidney Failure half. If the lowest daily dose of the
(Stage 5): active vitamin D sterol is being used,
reduce to alternate-day dosing.
7.4 Therapy with an active vitamin D sterol 8A.3b If serum levels of corrected total
(calcitriol, alfacalcidol, paricalcitol, or calcium exceed 2.37 mmol/L, hold
doxercalciferol) should be provided if the active vitamin D sterol therapy until
plasma levels of intact PTH is >300 serum calcium returns to < 2.37
pg/mL (300 ng/L). mmol/L, then resume treatment at half
the previous dose. If the lowest daily
8. Vitamin D Therapy in CKD Patients dose of the active vitamin D sterol is
being used, reduce to alternate-day
8A Active Vitamin D Therapy in Patients dosing.
with Stages 3 and 4 CKD 8A.3c If serum levels of phosphorus rise
to >1.49 mmol/ L, hold active vitamin
8A.1 In patients with CKD Stages 3 and 4, D therapy, initiate or increase dose of
therapy with an active oral vitamin D phosphate binder until the levels of
sterol (calcitriol, alfacalcidol, or doxer- serum phosphorus fall to < 1.49 mmol/
calciferol) is indicated when serum levels L; then resume the prior dose of active
of 25(OH)-vitamin D are >30 ng/mL, vitamin D sterol.
and plasma levels of intact PTH are
above the target range for the CKD 8B. Vitamin D Therapy in Patients on
stage. Dialysis (CKD Stage 5)
8A.la Treatment with an active vitamin D
sterol should be under taken only in 8B.1 Patients treated with hemodialysis or
patients with serum levels of corrected peritoneal dialysis with serum levels of
total calcium< 2.37 mmol/L and serum intact PTH levels >300 pg/mL (33.0
phosphorus<1.47 mmol/L. pmol/L) should receive an active vitamin
8A.lb Vitamin D sterols should not be D sterol (such as calcitriol, alfacalcidol,
prescribed for patients with rapidly paricalcitol, or doxercalciferol; to reduce
worsening kidney function or those the serum levels of PTH to a target
who are noncompliant with medica- range of 150 - 300 pg/mL (16.5 - 33.0
tions or follow-up. pmol/L).
8A.2 During therapy with vitamin D sterols, 8B.la The intermittent, intravenous admini-
serum levels of calcium and phosphorus stration of calcitriol is more effective
should be monitored at least every than daily oral calcitriol in lowering
month after initiation of therapy for the serum PTH levels.
S16 Guidelines for management of bone and mineral metabolism in CKD
8B.lb In patients with corrected serum 9. Dialysate Concentrations
calcium and/or phosphorus levels
above the target range, a trial of 9.1 The dialysate calcium concentration in
alternative vitamin D analogs, such as hemodialysis or peritoneal dialysis
paricalcitol or doxercalciferol may be should be 1.25 mmol/L.
warranted, (Table 5). 9.2 Higher or lower dialysate calcium levels
8B.2 When therapy with vitamin D sterols is are indicated in selected patients.
initiated or the dose is increased, serum
levels of calcium and phosphorus should 10. β 2-Microglobulin Amyloidosis
be monitored at least every 2 weeks for
1 month and then monthly thereafter. 10.1 Screening for α2-microglobulin amyloi-
The plasma PTH should be measured dosis, including measurement of serum
monthly for at least 3 months and then levels of β2-microglobuIin, is not recom-
every 3 months once target levels of PTH mended.
are achieved. 10.1a No currently available therapy (except
8B.3 For patients treated with peritoneal kidney transplantation) can stop disease
dialysis, oral doses of calcitriol (0.5 - progression of β2-microglobulin amyloi-
1.0 µg) or doxercalciferol (2.5 - 5.0 µg) dosis or provide symptommatic relief.
can be given 2 or 3 times weekly. 10.1b Kidney transplant should be considered
Alternatively, a lower dose of calcitriol to stop disease progression or provide
(0.25 µg) can be administered daily. symptomatic relief in patients with β2-
8B.4 When either hemodialysis or peritoneal microgIobulin amyloidosis.
dialysis patients are treated with active 10.1c In patients with evidence of, or at risk for
vitamin D sterols, management should β2-microglobulin amyloidosis noncupro-
integrate the changes in serum calcium, phane, high-flux dialyzers should be used.
serum phosphorus, and plasma PTH.
Table 5. Recommended initial dosing for vitamin D sterols by serum PTH, serum calcium and serum
Plasma PTH pg/ Serum Serum Dose Dose Dose
ml calcium Phosphorus per HD per HD per HD
or mmol/L mmol/L Calcitriol Paricalcitol Doxercalciferol
300-600 <2.37 <1.78 IV:0.5-1.5 µg 2.5-5.0 µg Oral: 5 µg
[33-66] Oral:0.5-1.5 µg IV: 2 µg
600-1000 < 2.37 <1.78 IV:1.0-3.0 µg 6.0-10 µg Oral: 5-10 µg
[66-110] Oral:1-4 µg IV: 2-4 µg
>1000 <2.50 < 1.78 IV:3.0-5.0 µg 10-15 µg Oral: 10-20 µg
 Oral:3-7µg IV: 4-8 µg
Guidelines for management of bone and mineral metabolism in CKD S17
11. Aluminum overload and toxicity in 12. Treatment of Aluminum Toxicity
12.1 In all patients with baseline serum
11.1To prevent aluminum toxicity, the regular aluminum levels > 60 µg/L, a positive DFO
administration of aluminum should be avoided test, or clinical symptoms consi-stent with
and the dialysate concentration of aluminum aluminum toxicity, the source of aluminum
should be maintained at<10 µg/L. should be identified and eliminated.
11.1a CKD patients ingesting aluminum 12.2 In symptomatic patients with serum
should not receive citrate salts simulta- aluminum levels > 60 µg/L but < 200 µg/L or
neously. a rise of aluminum after DFO >50 µg/L, DFO
11.2To assess aluminum exposure and the should be given to treat the aluminum
risk of aluminum toxicity, serum alumi-num overload.
levels should be measured at least yearly and 12.3To avoid DFO-induced neurotoxicity in
every 3 months in those receiving aluminum- patients with serum aluminum >200 µg/L, DFO
containing medications. should not be given until intensive dialysis (6
11.2a Baseline levels of serum aluminum days per week) with high-flux dialysis
should be <20 µg/L. membrane and a dialysate alumi-num level of
11.3 A deferoxamine (DFO) test should be < 5 µg/L and until the pre-dialysis serum
performed if there are elevated serum aluminum level has been reduced to <200
aluminum levels (60 to 200 µg/L); clinical µg/L.
signs and symptoms of aluminum toxicity,
or prior to parathyroid surgery if the 13. Treatment of Bone Disease in CKD
patient has had aluminum exposure.
11.3a The test is done by infusing 5 mg/kg of
DFO during the last hour of the dialysis The therapeutic approach to bone disease
session with a serum aluminum measured in CKD is based on its specific type i.e.
before DFO infusion and 2 days later, high-turnover and mixed bone disease;
before the next dialysis session. osteomalacia; and adynamic bone disease.
11.3b The test is considered positive if the
increment of serum aluminum is > 50 13A. Hyperparathyroid (High-Turnover)
µg/L. and mixed (High-Turnover with
11.3c A DFO test should not be performed Mineralization Defect) Bone Disease
if the serum levels of aluminum are
>200 µg/L to avoid DFO-induced 13A.1 In CKD patients who have plasma
neurotoxicity. levels of intact PTH >70 pg/mL (7.7
11.4 The presence of aluminum bone disease pmol/L) in stage 3 or >110 pg/mL (12.1
can be predicted by a rise in serum pmol/L) in stage 4 on more than 2
aluminum of ≥ 50 µg/L following DFO consecutive measurements, dietary phos-
challenge combined with plasma levels phate intake should be restricted. If this
of intact PTH of < 150 pg/mL (16.5 is ineffective in lowering plasma PTH
pmol/L). However, the gold standard for levels, calcitriol, or its analogs alfacal-
the diagnosis of aluminum bone disease cidol or doxercalciferol, should be given
is a bone biopsy showing increased to prevent or ameliorate bone disease.
aluminum staining of the bone surface (> 13A.2 In CKD patients who have elevated
15% to 25%) using aluminum stain and plasma levels of intact PTH (>300
often adynamic bone or osteomalacia. pg/mL [33.0 pmol/L]) in stage 5, calci-
triol or its analogs doxercalciferol,
alfacalcidol or paricalcitol should be used
to reverse the bone features of PTH
overactivity (i.e. high-turnover bone
S18 Guidelines for management of bone and mineral metabolism in CKD
disease), and to treat defective mine- intact PTH >800 pg/mL [88.0 pmol/L]),
ralization. associated with hypercalcemia and/or
hyperphosphatemia that are refra-ctory to
13B. Osteomalacia medical therapy.
14.2Effective surgical therapy of severe
13B.1 Osteomalacia due to aluminum toxicity hyperparathyroidism can be accompli-shed
should be prevented in dialysis patients by subtotal parathyroidectomy, or total
by maintaining aluminum concentration parathyroidectomy with parathy-roid tissue
in dialysate fluid at <10 µg/L and avoiding autotransplantation.
the use of aluminum-containing compo- 14.3In patients who undergo parathyroid-
unds (including sucralfate). ectomy the following should be done:
14.3a The blood level of ionized calcium
13B.2 Aluminum overload leading to aluminum should be measured every 4 to 6
bone disease should be treated with hours for the first 48 to 72 hours
deferoxamine (DFO). after surgery, and then twice daily
13B.3 Osteomalacia due to vitamin D2 or D3 until stable.
deficiency or phosphate depletion, though 14.3b If the blood levels of ionized or
uncommon, should be treated with vita- corrected total calcium fall below
min D2 or D3 supplementation and/or normal (<0.9 mmol/L or corres-
phosphate administration, respectively. ponding to corrected total calcium
13B.3a If osteomalacia due to vitamin D of 1.8 mmol/L), a calcium gluconate
deficiency fails to respond to ergo- infusion should be initiated at a rate
calciferol or cholecalciferol, particu- of 1 to 2 mg elemental calcium per
larly in patients with kidney failure kilogram body weight per hour and
(Stage 5), treatment with an active adjusted to maintain an ionized
vitamin D sterol may be given. calcium in the normal range (1.15 to
13B.3b Doses of phosphate supplementation 14.3c The calcium infusion should be
should be adjusted upwards until gradually reduced when the level of
normal serum level of phosphorus is ionized calcium attains the normal
achieved. range and remains stable.
14.3d When oral intake is possible, the
13C. Adynamic Bone Disease patient should receive calcium
carbonate 1 to 2 g 3 times a day, as
well as calcitriol of up to 2 µg/day,
13C.1 Adynamic bone disease in stage 5 CKD and these therapies should be
(as determined either by bone biopsy or adjusted as necessary to maintain
intact PTH <100 pg/ml [11.0 pmol/L]) the level of ionized calcium in the
should be treated by allowing plasma normal range.
levels of intact PTH to rise in order to 14.3e If the patient was receiving phos-
increase bone turnover. phate binders prior to surgery, this
13C.la This can be accomplished by decreasing therapy may need to be disconti-
doses of calcium-based phosphate binders nued or reduced as dictated by the
and vitamin D or eliminating such therapy. levels of serum phosphorus, and some
patients may require phosphate
14. Parathyroidectomy in patients with supplements.
CKD 14.4 Imaging of parathyroid glands with"Tc-
Sestamibi scan, ultrasound, CTscan, or
14.1Parathyroidectomy should bone and mineral metabolismshould be done prior to re-
Guidelines for management of be recom- MRI in CKD S19
mended in patients with severe hyper- exploration parathyroid surgery.
parathyroidism (persistent serum levels of 15. Metabolic Acidosis
16.2 During the first week after kidney
15.1In CKD Stages 3, 4 and 5, the serum transplantation, serum levels of phos-
level of total CO2 should be measured. phorus should be measured daily. Kidney
transplant recipients who develop persi-
15.1a The frequency of these measurements stently low levels of serum phosphate
should be based on the stage of (<0.81 mmol/L) should be treated
CKD, (Table 6). with phosphate supplementation.
16.3 To minimize bone mass loss and
Table 6. Frequency for measurement of serum oste-onecrosis, the immunosuppressive
levels of total Co2 regimen should be adjusted to the lowest
CKD Stage GFR Range ml/ Frequency of effective dose of glucocorticoids.
min/1.73m2 Measurement 16.4 Kidney transplant recipients should
(At least) have bone mineral density (BMD)
3 30-59 every 12 measured by dual energy X-ray
months absorptiometry (DEXA) to assess the
4 15-29 every 3 months presence or development of
5 <15 every month 16.4a DEXA scans should be obtained
at time of transplant, 1 year, and 2
16.4b If BMD t-score is equal to or ≤ 2 at
15.2In these patients, serum levels of total the time of the transplant or at
CO2 should be maintained at > 22 mmol/L. If subsequent evaluations, therapy with
necessary, supplemental alkali salts (such as parenteral amino-bisphosphonates
NaHCo3 300-600 orally three times daily) should be considered.
should be given to achieve this goal. 16.5 Treatment of disturbances in
bone and mineral metabolism is deter-
16. Bone Disease in the Kidney mined by the level of kidney function
Transplant Recipient in the transplant recipient.
16.1 Serum levels of calcium, phosphorus, Table 7. Frequency of measurement of calcium,
total CO2 and plasma intact PTH should phosphorus, PTH and total CO2 after
be monitored following kidney kidney transplantation
transplant-tation. Parameter First 3 Months 3months to 1
16.1a The frequency of these measure- year
ments should be based on the time Calcium Every 2 weeks Monthly
following transplantation. Phosphorus Every 2 weeks Monthly
PTH Monthly Every 3 months
Total CO2 Every 2 weeks Monthly
S20 Guidelines for management of bone and mineral metabolism in CKD
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These Guidelines are based upon the best information available at the time of
publication. They are designed to provide information and assist decision-making.
They are not intended to define a standard of care, and should not be construed as
one. Neither should they be interpreted as prescribing an exclusive course of
Variations in practice will inevitably and appropriately occur when clinicians take
into account the needs of individual patients, available resources, and limitations
unique to an institution or type of practice. Every health-care professional making
use of these Guidelines is responsible for evaluating the appropriateness of applying
them in the setting of any particular clinical situation.
patients. Am J Kidney Dis 1998;
99. Mitwalli AH, Alam AA. Intermittent
Oral Versus Intravenous Alfacalcidol in