Last updated: Peritoneal Dialysis (PD)
on 31 Oct 2012



CKD-MBD (previously known as Renal Osteodystrophy, or Renal Bone Disease; RBD) is a collective term describing the mixture of pathophysio­logical conditions that affect the skeletal system of patients with chronic kidney disease (CKD). It has been classified by KDIGO in August 2009

It is most evident in patients on renal replacement therapy (RRT). However, hyperparathyroidoism usually starts early in the course of CKD. The spectrum of skeletal abnormalities seen in CKD-MBD is classified according to the state of bone turnover. High turnover bone disease (or osteitis fibrosa cystica) is a manifestation of hyperparathyroidism, characterised by increased osteoblast and osteoclast activity and peri-trabecular fibrosis

Low turnover bone disease includes; (1) Osteomalacia, with defective minerali­sation of newly formed osteoid, most often caused by aluminum deposition; and, (2) Aynamic bone disease, which is characterised by an abnormally low bone turnover including osteopenia or osteoporosis

  High Turnover Low Turnover
PTH Inc Dec
Alk Phos Inc Normal
Bone Alk Phos Inc Normal or Dec
Osteocalcin Inc Normal
Calcium Variable Can be inc
Phosphate Inc Normal or Inc
Xrays Resporption, sclerosis Normal
Symptoms Usually asymptomatic Asymptomatic (Adymamic)
Symptomatic (Aluminium OM)

 Combinations of these abnormalities are called mixed CKD-MBD

Secondary Hyperparathyroidism


Key Point: Secondary hyperparathyroidism occurs as a result of hyperphosphataemia, hypocalcaemia and impaired synthesis of renal vitamin D with reduction in serum calcitriol levels


Hypocalcaemia stimulates release of para­thyroid hormone (PTH) directly by inactivation of the calcium sensing receptors (CaR) on para­thyroid cells. The plasma PTH concentration increases within minutes of fall in serum calcium levels. Reduction of extracellular calcium levels for weeks or months promotes the development of parathyroid gland hyper­plasia, which is the characteristic of hyperparathyroidism (Goodman, 2003)


Metastatic calcification has been attributed to hyperphosphataemia since the early 1960s (Parfitt, 1969). However, the clinical impact and toxicity of hyperphosphataemia was not widely emphasised until the groundbreaking studies carried out of Bricker et al (Bricker, 1969). Using animal models, they delineated the pathophysiological cascade triggered by hyperphosphatemia, leading to hypocalcaemia, secondary hyperparathyroidism, reduced 1,25 vitamin D3, and progressive metabolic bone disease

Hyperphosphataemia does not become evident until the glomerular filtration rate (GFR) has decreased to between 25 and 40% of normal (CKD4)

Until that stage, in the course of CKD, compensatory hyperparathyroidism results in increased phosphate excretion and main­tains serum phosphate levels within the normal range (Alfrey, 2004). Due to declining GFR, phosphate retention leads to a decrease in serum free calcium levels, which in turn stimulates PTH secretion (Drueke, 1995).This is the 'trade-off' hypothesis (Bricker, 1972). It also leads to decreased production of calcitriol by the kidney, which in turn decreases intestinal calcium absorption leading to hypocalcaemia and consequently, stimulation of PTH secretion (Tallon, 1996)

Hyperphosphataemia is associated with resistance to the actions of calcitriol on the parathyroid glands, which also leads to increased PTH secretion - and causes resistance to the action of PTH on bone (Llach, 1995). Also high phosphate levels have a direct stimulatory effect on PTH secretion, independent of changes in calcium and 1,25 vitamin D3 levels (Almaden, 1998)

Vitamin D Deficiency

The kidney is a major site for calcitriol production. WIth CKD, calcitriol production falls. Calcitriol has several direct and indirect effects on parathyroid glands. In CKD, vitamin D receptors (VDR) in parathyroid glands are down regulated by low levels of calcitriol. This direct mechanism leads to stimulation of PTH gene expression and increases PTH secretion

Administration of calcitriol increases vitamin D receptors in the parathyroid glands and suppresses PTH secretion. Also, low circulating calcitriol levels may facilitate parathyroid cell proliferation (Drueke, 2000). Thus, calcitriol deficiency indirectly leads to secondary hyperpara­thyroidism (Friedman, 2005) in addition to causing skeletal resistance to the calcaemic actions of PTH in CKD

Metabolic Acidosis

This increases the dissolution of calcium from bone and possibly alters deposition, exacerbating CKD-MBD

Alterations in Parathyroid glands in Uraemia

Parathyroid glands develop develop nodular hyperplasia due to monoclonal expansion, in which VDR and CaR expression are significantly decreased. This contributes to the reduced capacity of the parathyroid glands to respond to therapy such as vitamin D, as well as changes in serum calcium levels (Locatelli, 2002). Hyperparathyroidism starts early in the course of CKD:

Clinical Features of Secondary Hyperparathyroidism

Early bone disease in patients with CKD is usually asymptomatic. Symptoms, if any, appear late in the course of CKD-MBD (Llach, 2003). Patients with secondary hyperparathyroidism have a range of symptoms, including:

Musculoskeletal symptoms
Bone pain, which occurs in the low back, hips and legs and is aggravated by weigh bearing. Bone deformities are common in patients with severe hyperparathyroidism. This is due to fractures, which can lead to kypho-scoliosis or chest wall deformity

Pruritus occurs in advanced CKD, especially in patients on dialysis. The cause is uncertain. It may relate to deposition of calcium and phosphate in the skin

Cardiovascular calcification
Coronary artery calcification is commoner and more severe in patients on haemodialysis than in persons without renal failure (Braun, 1996) and is probably due to excessive use of calcium-containing phosphate binders and vitamin D analogues

Coronary artery calcification is found in the majority of patients on RRT and can be detected by non-invasive electron-beam computed tomography (EBCT). In addition to coronary artery calcification, calcium deposits on the heart valves (especially mitral and aortic valves), and in the myocardium - causing arrhythmias, left ventricular dysfunction, aortic and mitral stenosis, ischaemia, congestive heart failure, and death

A relation between left ventricular hyper­trophy (LVH) and PTH has been described in patients with CKD and secondary hyper­parathyroidism. PTH induces hypertrophic growth of cardiomyocytes and smooth muscle cells through the activation of the cardiomyocyte protein kinase (De Fransisco, 2004)

Another serious complication of secondary hyperparathyroidism is soft tissue calcification. This is called calcific uraemic arteriolopathy (CUA), also known as calci­phylaxis. It is a syndrome of calcification of small arterioles and venules with severe intimal hyperplasia. It is often complicated by thrombosis and recanalisation, which results in painful skin necrosis. It carries a high mortality rate due to secondary infection, sepsis and ischaemia

Calciphylaxis is caused by high PTH levels, hyperphosphatemia and hypercalcaemia; induced by high calcium dialysate and use of calcium-containing phosphate binders. Obesity, hypo-albuminaemia and diabetes increase the risk of calciphy­laxis (Llach, 2003); as does warfarin usage and hyper­coagulable states (protein C and protein S deficiency) (Willmer, 2002). The management of CUA includes: stopping oral calcium; using non-calcium containing binders; and parathyroidectomy if PTH levels are high and cannot be controlled

Diagnosis of CKD-MBD

Bone biopsy remains the gold standard for the definitive diagnosis of CKD-MBD but bio­chemical parameters may be helpful in establishing the diagnosis

PTH levels greater than 50 pcmol/L are highly indicative of osteitis fibrosa, whereas an adynamic lesion is suspected when levels are below 10 pcmol/L. The serum alkaline phosphatase level may be elevated in hyperparathyroidism indicating increased osteoblastic activity (Gonzalez, 2001)

Pathology of Secondary Hyperparathyroidism

                                 This biopsy shows zones of decalcification and increased numbers of osteoclasts

Radiology of Secondary Hyperparathyroidism

Resorption of distal clavicles; usually bilateral and symmetrical 

Subperiosteal resorption along the radial surface of the proximal and middle phalanges of the second and/or third digits

Principles of Treatment

Key Point: The aim of treatment is is to reduce: (1) the occurrence and/or severity of uraemic bone disease; and, (2) cardiovascular morbidity and mortality caused by elevated serum levels of PTH and 'calcium x phosphate' product

Ket Point: Treatment includes control of phosphate retention, maintaining serum calcium concentration within the normal range and prevention of excess PTH secretion

Key Points: Renal Association Treatment Guidelines 

  1. The UK Renal Association recommends measuring serum calcium, phosphate and PTH levels when GFR is < 60ml/min/1.73m 2 (CKD stage 3 and above). It also recommends, in dialysis patients:
  2. Serum calcium, should be maintained within the normal range and be between 2.2 and 2.5 mmol/L, with avoidance of hypercalcaemic episodes
  3. Serum phosphate should be maintained between 1.1 and 1.7 mmol/L
  4. The target range for parathyroid hormone (measured using an intact PTH assay) should be 2-9 times the upper limit of normal for the assay used



Adynamic and Other Bone Diseases

Adynamic bone disease (ABD) is a common skeletal lesion in adult patients with CKD. It is characterised histopatho­logically by marked decrease in osteoblasts and osteoclasts with increase in osteoid formation (Salusky, 2001). Adynamic bone disease is also caused by over-suppression of PTH levels by aggressive use of high-calcium dialysate, calcium-containing phosphate binders and vitamin D analogues. It is also frequently seen in patients on peritoneal dialysis and those with diabetes

Adynamic Bone Disease


Osteomalacia is characterised by a reduction in the number of osteoblasts and osteoclasts, with an increase in the amount of osteoid. It is related to aluminum accumulation due to use of aluminum-containing phosphate binders. Long standing severe metabolic acidosis may also cause osteomalacia

DIalysis (β2-Microglobulin) Amyloidosis

ESRF patients typically have serum concentrations of β2-microglobulin (β2M) 30-50 fold higher than normal, and are risk of developing dialysis amyloidosis (Aβ2M) affecting the skeletal system. Risk factors include: older patients; duration on dialysis; and, loss of residual renal function

Dialysis amyloidosis can affect any joint, but especially affects the shoulder joint. So the disease often presents as shoulder pain in a dialysis patient, who has had many years on dialysis. Other clinical manifestations include carpal tunnel syndrome, tendon rupture/contracture, spondyloarthropathy, osseous involvement, subcutaneous masses and renal calculi

MRI is the best radiological test. Histological evidence is required to make a definite diagnosis. Although of unproven benefit, it is reasonable to consider using biocompatible HD membranes, haemofiltration or haemodiafiltration at high flow rates, with ultrapure dialysate. Successful transplantation will restore β2M levels to the normal range. But it is unclear whether this causes the lesions to regress






Phosphate Binders

This diagram illustrates the mechanism of action of phosphate binders and other treatments:

Dietary Phosphate Restriction

Restricting phosphate intake can be achieved by reducing intake of dairy products, certain vegetables, and colas. Many physicians recommend phosphate restriction (to 800-1000 mg daily) when the serum phosphate level is > 1.8 mmol/L in patients with CKD5

Other treatments include calcium influx and phosphate removal through dialysis; phosphate binders; and, vitamin D. These will now be described

Aluminium-Containing Phosphate Binders

Aluminium hydroxide was first used as a phosphate binder by Freeman and Freeman in 1941. Aluminium-containing phosphate binders were, for many years, the phosphate binders of choice, forming insoluble and non­absorbable aluminium phosphate precipitates in the intestinal lumen. They are still the most effective phosphate binders but due to their renal elimination, patients with impaired renal function have a gradual tissue accumulation of absorbed aluminium with resultant toxicity (Ritz, 2004). The major manifestations of aluminium toxicity are in skeletal muscle, CNS and bone; leading to low-bone turnover osteomalacia, adynamic bone disease. Clinically, refractory micro­cytic anaemia, bone and muscle pain, and dementia develop (Salusky, 1991)

However, many physicians still prescribe low doses of aluminium hydroxide. The K/DOQI guidelines recommend the use of aluminium-containing phosphate binders only in patients with serum phosphorus levels >7.0 mg/dL (2.26 mmol/L). If used, one course of short-term therapy (4 weeks) is recommended; then replaced by another phosphate binder

Calcium-Containing Phosphate Binders 

Problems with aluminium-containing phosphate binders led to the development of calcium salts to bind intestinal phosphate. In addition to lowering plasma phosphate concentration, absorption of some calcium can raise plasma calcium concentration, providing an additional mecha­nism by which PTH secretion can be reduced

Calcium carbonate has been the most widely used calcium salt. Calcium acetate is a more efficient phosphate binder than calcium car­bonate, as it dissolves in both acid and alkaline environments; whilst calcium carbonate dissolves only in acid pH and many patients with advanced renal failure have achlorhydria or, are taking H2-blockers or proton pump inhibitors (Emmett, 2004)

The required dose of calcium carbonate to control phosphate level ranges from 6 gm up to 15 gm/day (40 % of which is elemental calcium). Calcium salts are most effective if taken with meals, because they bind dietary phosphate - and therefore, leave less free calcium available for absorption

Calcium salts in patients with ESRF can lead to hypercalceamia and metastatic calcification; including coronary artery calcification, which are in turn is asso­ciated with cardiovascular mortality. To avoid metastatic calcification, K/DOQI guidelines suggest that the total dose of elemental calcium (including dietary sources) should not exceed 2000 mg/day

Non-Calcium, Non-Aluminium Phosphate Binders 

Because of hypercalcaemia asscoiated with calcium salts, leading to metastatic and vascular calcification, there arose the need for non-calcium, non-aluminium phosphate binders

Sevelamer hydrochloride
This was the first synthetic non-calcium, non-aluminum phosphate binder to become widely available in the USA and Europe for the treatment of hyperphosphataemia in patients with CKD (Hutchinson, 2004). This cross linked poly allylamine hydrochloride exchange resin binds phosphate and releases chloride

While the potency of sevelamer is low when compared with aluminium, beneficial effects of this drug include attenuation of the progression of coronary and aortic calcification, seen with calcium­-containing phosphate binders. Also, significant improvement in lipid profile, with reduction in total and low-density lipoprotein (LDL) cholesterol, has been noted with sevelamer (Sturtevant, 2004)

Sevelamer hydrochloride causes metabolic acidosis, which can exacerbate secondary hyperparathyroidism and renal osteodystrophy. Each 800 mg tablet of sevelamer hydrochloride could theoretically lead to an acid load equivalent to 4 mEq hydrochloric acid (Brezina, 2004). More recently, Sevelamar Carbonate has been introduced to avoid this problem with metabolic acidosis

Sevelamer hydrochloride is considered a moderate phosphate binder because its optimal phosphate binding capacity occurs at a pH of 7; whereas the pH of the stomach and first part of the duodenum is much lower than this level. Also, high doses of this drug may reduce the absorption of vitamin D from the gut. Additionally, sevelamer hydrochloride is not selective for phosphate ions only; as it can bind other negatively charged ions such as chloride and bicarbonate. The dose range of 2.4 to 4.8g daily provides effective phosphate control without hypercalcaemia

Lanthanum carbonate
This is a more recent non-­calcium, non-aluminium phosphate binder.  It is a salt of a rare earth metal, and is a highly effective phosphate binder (Hutchison, 2004). It is minimally absorbed from the gastrointestinal tract and is not excreted by the kidneys (D'Haese, 2003). Lanthanum carbonate has been shown to be as effective as aluminium in binding phosphate but without the asso­ciated toxic effects

It has minimal tissue accumulation when compared to aluminium, but long-term toxicity with bone accumulation cannot be ruled out. A dose between 1350 and 2250mg daily is effective in reducing and maintaining phosphate levels in most patients. And the effect is seen within three weeks of treatment. Also, the incidence of hypocalcaemia is lower, and the calcium x phosphorus product reduced, when compared to calcium carbonate (De Broe, 2004)

Both calcium-based phosphate binders and other non-calcium, non-aluminium containing phosphate-binding agents are effective in lowering serum phosphate levels and may be used as the primary therapy

Other Phosphate Binders

Magnesium salts may be used as an alter­native to calcium-containing phosphate binders in patients who develop hypercalcemia. Magnesium carbonate reduces PTH and phosphorus levels when used with magnesium-­free dialysate (O'Donovan, 1986)

Summary of Phosphate Binders

Calcium or Aluminium Containing Non-Calcium, Non-Aluminium Containing
Aluminium Hydroxide Lanthanum Carbonate
Calcium Acetate Magnesium Carbonate
Calcium Carbonate Sevelamar Hydrochloride and Carbonate




Other Treatments

Correction of Metabolic Acidosis

Correction of metabolic acidosis may be useful because studies of alkali therapy in patients who are not in renal failure suggest an improvement in bone parameters (Domrongkitchaiporn, 2002)

Vitamin D

Calcitriol is the most active metabolite of vitamin D that has direct effects on the para­thyroid gland by suppressing the synthesis and secretion of PTH and limiting parathyroid cell growth. It was first shown to be effective by Berl in 1978

It can be administered orally and intravenously for the treatment of secondary hyperparathyroidism. It may cause hyperphos­phataemia and hypercalcaemia by increasing absorption of both calcium and phosphate. Intravenous 'pulse' therapy has a greater effect in reducing bone turnover by diminishing the number of active ostoblasts rather than the reduction in PTH levels. There is indirect evidence that pulse therapy with calcitriol, combined with use of calcium-containing phosphate binding agents, increases the prevalence of adynamic bone disease (Coburn, 2003)

Due to the potential of calcitriol to cause hyperphosphataemia, hypercalcaemia and an increase in calcium x phosphate product, new vitamin D analogues have been developed. These analogues are relatively selective for the parathyroid gland with lesser effect on intestinal absorption of calcium and phosphate. 22-oxacalcitriol has a decreased affinity for vitamin D binding protein and a short plasma half-life - resulting in rapid clearance from the circulation. This may be the mechanism for its lesser effect on calcium and phosphate levels. It also decreases PTH secretion without affecting bone turnover (Tsukamoto, 2000)

The effects of calcitriol and 22-oxacalcitriol on serum calcium, phosphate levels and calciim x phosphate product are similar, and the suppressive effects of these drugs on PTH secretion are not significantly different (Hayashi, 2004)

Paricalcitol adequately controls PTH secretion with minimal hypercalcaemia and hyperphosphataemia com­pared to calcitriol (Llach, 2001). Also, doxercalciferol has the same suppressive effect on PTH with minimal changes in serum calcium and phosphate levels (Salusky, 2005). 22-oxacalcitriol and doxercalciferol are not yet available in the UK

The American Food and Drug Administration (FDA) has indicated that there is no difference in the ability of intravenous paricalcitol and calcitriol to suppress PTH, and control calcium and phosphate levels, in paediatric haemodialysis patients (Cunningham, 2004). Of interest, other studies have suggested that none of the newer vitamin D analogues is superior to calcitriol or alfacalcidol in suppressing PTH; or controlling calcium, phosphate, or calcium x phosphate product

According to K/DOQI guidelines, both haemodialysis and peritoneal dialysis patients with serum PTH levels > 300 pg/ml (31.9 pmol/L) should receive an active vitamin D sterol such as calcitriol, alfacalcidol, pari­calcitol, or doxercalciferol to reduce the serum levels of PTH to the target range 


Therapy with calcimimetics is another, more recent, approach for the treatment of secondary hyperpara­thyroidism. These agents act at the level of the CaR, which is found in the parathyroid and C thyroid glands as well as renal tubular cells (Urena, 2003). Activation of this receptor by calci­mimetics increases intracellular calcium concentration, which causes rapid reduction in PTH secretion, serum phosphate, and the calcium x phosphate product, which remain suppressed for up to three years (Block, 2003)

Cinacalcet is a CaR sensitiser which is usually used in dialysis patients when parathyroid hormone exceeds 85 pmol/L, or at lower levels with hypercalcaemia, despite conventional treatment. Doses are titrated from 30 mg to 180 mg daily. Cinacalcet has the advantage of lowering levels of parathyroid hormone, and serum calcium and phosphate ; whereas vitamin D tends to increase serum calcium. It should be taken at the same hour every day to avoid overdose and adverse effects

The patient should be started with a low dose, which is increased progressively every two weeks until target PTH levels are achieved. The serum PTH, phosphate and calcium levels should be checked regularly. Transient hypocalcaemia may occur which can be corrected by increasing the dialysate calcium levels, or dose of calcium-containing phosphate binders and vitamin D (Block, 2004)

Transient episodes of nausea, vomiting have occurred in patients who were treated with cinacalcet. Also, upper respiratory tract infe­ctions, hypotension, diarrhoea and headache have been observed (Lindberg, 2005)


This is divided into surgical parathyroidectomy (PTx) and percutaneous direct injection therapy into parathyroid glands. The need for para­thyroidectomy in patients with secondary hyperparathyroidism has decreased signi­ficantly in recent years. This is due to increased efficacy of medical measures that can suppress parathyroid hormone (PTH) secretion, especially vitamin D (Kestenbaum, 2004)

Parathyroid sestamibi scan (with technetium Tc 99m-MIBI) demonstrating uptake in all 4 glands consistent with 4-gland hyperplasia

The main indications for PTx include: therapy-resistant hypercalcaemia and/or hyper­phosphatemia in the presence of a high PTH level; pruritus that does not respond to medical or dialysis therapy; progressive extra-skeletal calcification or calciphylaxis; un­explained symptomatic myopathy; and in renal transplant recipients with persistent hyper­parathyroidism and hyper­calcaemia

Indications for Parathyroidectomy = High PTH levels +

  • Uncontrollable hyercalcaemia
  • Uncontrollable hyperphosphataemia
  • Unresponsive to phosphate binders and Vitamin D
  • Metastatic calcification
  • Calciphylaxis
  • Potential renal transplant recipient

There are two main types of parathyroidectomy: subtotal PTx; or total PTx with or without re-implantation of parathyroid tissue in the forearm. The latter is considered the procedure of choice in patients with metastatic calcification. Subtotal or total PTx with re-implantation is performed to avoid hypoparathyroidism, particularly after renal transplantataion

Percutaneous ethanol injection is an alternative procedure to surgical parathyroidectomy but may cause recurrent laryngeal nerve injury

Thus, it has recently been replaced by using calcitriol for percutaneous injection into the parathyroid glands (Akizawa, 2003). Also, percutaneous calcitriol analogues (eg 22-oxacalcitriol) have been shown to have a suppressive effect on PTH levels, as well as reduction in the size of enlarged glands







Top Tip: Consider a phosphate binder and vitamin D analogue in all ESRF patients

  1. Secondary hyperparathyroidism occurs as a result of hyperphosphataemia, hypocalcaemia and impaired synthesis of renal vitamin D with reduction in serum calcitriol levels
  2. Patients with secondary hyperparathyroidism have a range of symptoms
  3. The UK Renal Association recommends measuring serum calcium, phosphate and PTH levels when GFR is < 60ml/min/1.73m 2 (CKD stage 3 and above). It also recommends, in dialysis patients:
  4. Serum calcium, should be maintained within the normal range and be between 2.2 and 2.5 mmol/L, with avoidance of hypercalcaemic episodes
  5. Serum phosphate should be maintained between 1.1 and 1.7 mmol/L
  6. The target range for parathyroid hormone (measured using an intact PTH assay) should be 2-9 times the upper limit of normal for the assay used
  7. The aim of treatment is is to reduce: (1) the occurrence and/or severity of uraemic bone disease; and, (2) cardiovascular morbidity and mortality caused by elevated serum levels of PTH and 'calcium x phosphate' product
  8. Treatment includes control of phosphate retention, maintaining serum calcium concentration within the normal range and prevention of excess PTH secretion




Akizawa T, Shiizaki K, Hatamura I, et al. New strategies for the treatment of secondary hyperparathyroidism. Am J Kidney Dis 2003; 41(3 Suppl 1): S100-3

Alfrey AC. The role of abnormal phosphorus metabolism in the progression of chronic kidney disease and metastatic calcification. Kidney Int Suppl 2004; (90): S13-7

Almaden Y, Hernandez A, Torregrosa V, et al. High phosphate level directly stimulates parathyroid hormone secretion and synthesis by human parathyroid tissue in vitro. J Am Soc Nephrol 1998; 9(10):1845-52

Berl T et al. 1,25 dihydroxycholecalciferol effects in chronic dialysis. A double-blind controlled study. Ann Intern Med 1978; 88(6): 774-80

Block GA. The impact of calcimimetics on mineral metabolism and secondary hyper­parathyroidism in end-stage renal disease. Kidney Int Suppl 2003; (87): S131-6 

Block GA, Martin KJ, de Francisco AL, et al. Cinacalcet for secondary hyperpara­thyroidism in patients receiving hemodialysis. N Engl J Med 2004; 350(15): 1516-25

Braun J, Oldendorf M, Moshage W, et al. Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis 1996; 27(3): 394-401

Brezina B, Qunibi WY, Nolan CR. Acid loading during treatment with sevelamer hydrochloride: mechanisms and clinical impli­cations. Kidney Int Suppl 2004; (90): S39-45

Bricker NS et al. Calcium, phosphorous, and bone in renal disease and transplantation. Arch Intern Med 1969; 123: 543-553

Bricker NS. On the pathogenesis of the uremic state. An exposition of the "trade-off hypothesis." N Engl J Med 1972; 286: 1093-1099

Coburn JW. An update on vitamin D as related to nephrology practice: 2003. Kidney Int Suppl 2003; (87): S125-30

Cunningham J. New Vitamin D analogues for osteodystrophy in chronic kidney disease. Pediatr Nephrol 2004; 19(7): 705-8

D'Haese PC, Spasovski GB, Sikole A, et al. A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. Kidney Int Suppl 2003; (85): S73-8 

De Broe ME, D'Haese PC. Improving outcomes in hyperphosphataemia. Nephrol Dial Transplant 2004; 19 Suppl 1: i14-8

De Francisco AL. Secondary hyperpara­thyroidism: review of the disease and its treatment. Clin Ther 2004; 26(12):1976-93

Domrongkitchaiporn S, Pongskul C, Sirikulchayanonta V, Stitchantrakul W, Leeprasert V, Ongphiphadhanakul B, et al. Bone histology and bone mineral density after correction of acidosis in distal renal tubular acidosis. Kidney Int 2002; 62: 2160-6

Drueke TB. The pathogenesis of parathyroid gland hyperplasia in chronic renal failure. Kidney Int 1995; 48(1): 259-72

Drueke TB. Cell biology of parathyroid gland hyperplasia in chronic renal failure. J Am Soc Nephrol 2000; 11(6): 1141-52

Emmett M. A comparison of clinically useful phosphorus binders for patients with chronic kidney failure. Kidney Int Suppl 2004; 90: S25-32
This is a very good summary of phosphate binding agents, and worth reading

Freeman S, Freeman WMC. Phosphorus retention in children with chronic renal insufficiency. The effect of diet and of the ingestion of aluminum hydroxide. Am J Dis Child 1941; 61: 981-1002

Friedman EA. Consequences and manage­ment of hyperphosphatemia in patients with renal insufficiency. Kidney Int Suppl 2005; (95): S1-7

Gonzalez EA, Martin KJ. Renal osteodystrophy. Rev Endocr Metab Disord 2001; 2(2):187-93

Goodman WG. Medical management of secondary hyperparathyroidism in chronic renal failure. Nephrol Dial Transplant 2003;18 Suppl 3:iii2-8

Hayashi M, Tsuchiya Y, Itaya Y, et al. Comparison of the effects of calcitriol and maxacalcitol on secondary hyperparathyroidism in patients on chronic haemodialysis: a randomized prospective multicentre trial. Nephrol Dial Transplant 2004; 19(8): 2067-73

Hutchison AJ. Improving phosphate-binder therapy as a way forward. Nephrol Dial Transplant 2004; 19 Suppl 1: i19-24

Hutchison AJ, Speake M, Al-Baaj F. Reducing high phosphate levels in patients with chronic renal failure undergoing dialysis: a 4-week, dose-finding, open-label study with lanthanum carbonate. Nephrol Dial Transplant 2004; 19(7): 1902-6

Kestenbaum B, Seliger SL, Gillen DL, et al. Parathyroidectomy rates among United States dialysis patients: 1990-1999. Kidney Int 2004; 65(1): 282-8

Lindberg JS, Culleton B, Wong G, et al. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperpara­thyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multi­center study. J Am Soc Nephrol 2005; 16(3): 800-7

Llach F. Secondary hyperparathyroidism in renal failure: the trade-off hypothesis re­visited. Am J Kidney Dis 1995;25(5): 663-79

Llach F, Yudd M. Paricalcitol in dialysis patients with calcitriol-resistant secondary hyperparathyroidism. Am J Kidney Dis 2001; 38(5 Suppl 5): S45-50

Llach F. The evolving clinical features of calciphylaxis. Kidney Int Suppl 2003; (85): S122-4

Llach F, Fernandez E. Overview of renal bone disease: causes of treatment failure, clinical observations, the changing pattern of bone lesions, and future therapeutic approach. Kidney Int Suppl 2003; (87): S113-9

Locatelli F, Cannata-Andia JB, Drueke TB, et al. Management of disturbances of calcium and phosphate metabolism in chronic renal insufficiency, with emphasis on the control of hyperphosphataemia. Nephrol Dial Transplant 2002; 17(5): 723-31

Martin KJ, Olgaard K, Coburn JW, et al. Diagnosis, assessment, and treatment of bone turnover abnormalities in renal osteodys­trophy. Am J Kidney Dis 2004; 43(3): 558-65

Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006; 69: 1945-53

Navaneethan SD et al. Benefits and Harms of Phosphate Binders in CKD: A Systematic Review of Randomized Controlled Trials. Am J Kid Dis 2009; 54 (4): 619-637

O'Donovan R, Baldwin D, Hammer M, et al. Substitution of aluminium salts by magnesium salts in control of dialysis hyper­phosphataemia. Lancet 1986; 1(8486): 880-2

Parfitt AM. Soft-tissue calcification in uremia. Arch Intern Med 1969; 124: 544-556

Ritz E. Managing mineral balance in end­stage renal disease. Nephrol Dial Transplant 2004;19 Suppl 1: i1-3

Roberts DM, Singer RF. Management of renal bone disease. Aust Prescr 2010; 33: 34-7
Good practical guide to prescribing in CKD-MBD

Salusky IB, Foley J, Nelson P, Goodman WG. Aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease. N Engl J Med 1991; 324(8): 527-31

Salusky IB, Goodman WG. Adynamic renal osteodystrophy: is there a problem? J Am Soc Nephrol 2001;12(9):1978-85

Salusky IB. Are new vitamin D analogues in renal bone disease superior to calcitriol? Pediatr Nephrol 2005; 20(3): 393-8

Sturtevant JM, Hawley CM, Reiger K, et al. Efficacy and side- effect profile of sevelamer hydrochloride used in combination with conventional phosphate binders. Nephrology (Carlton) 2004; 9(6): 406-13

Tallon S, Berdud I, Hernandez A, et al. Relative effects of PTH and dietary phosphorus on calcitriol production in normal and azotemic rats. Kidney Int 1996; 49(5):1441-6

Tsukamoto Y, Hanaoka M, Matsuo T, et al. Effect of 22-oxacalcitriol on bone histology of hemodialyzed patients with severe secondary hyperparathyroidism. Am J Kidney Dis 2000; 35(3): 458-64

Urena P. Use of calcimimetics in uremic patients with secondary hyperparathyroidism: review. Artif Organs 2003; 27(9): 759-64

Wilmer WA, Magro CM. Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment. Semin Dial 2002;15(3): 172-86


Moorthi RN, Moe SM. CKD–Mineral and Bone Disorder: Core Curriculum 2011.  American Journal of Kidney Diseases 2011; 58 (6): 1022-1036


Australasian/CARI (April 2006). Haematological and Biochemical Targets

Australasian/CARI (April 2006). Vitamin D, Calcimimetics and Phosphate Binders

Canada/Canadian Society of Nephrology (May 2010). Canadian Society of Nephrology Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD–Mineral and Bone Disorder (CKD-MBD)

Europe/European Best Practice Guideline (September 2010). Endorsement of the Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guidelines: a European Renal Best Practice (ERBP) commentary statement

Global/KDIGO (August 2009). KDIGO Guideline for Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

US/KDOQI (May 2010). KDOQI US Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD–Mineral and Bone Disorder (CKD-MBD)

UK/Renal Association (December 2010). CKD-MBD guideline. Steddon S, Sharples E