Hypophosphataemia, hyperphosphataemia and CKD mineral and

• Phosphate is essential for ATP, nucleic acids, bone and acid–base balance; it is controlled by intestinal absorption, renal excretion and the hormones parathyroid hormone (PTH), active vitamin D (calcitriol) and fibroblast growth factor 23 (FGF23).
• Hypophosphataemia (low serum phosphate) usually comes from poor intake, gastrointestinal or renal loss, intracellular shift, or drugs; it can present acutely with weakness, respiratory or cardiac dysfunction, or chronically with bone pain and osteomalacia.
• Hyperphosphataemia (high serum phosphate) is most often due to chronic kidney disease (CKD); in CKD the combination of phosphate retention, low calcitriol and hypocalcaemia drives secondary hyperparathyroidism and is called CKD–mineral and bone disorder (CKD-MBD).
• In CKD-MBD, phosphorus control comes first: limit dietary phosphate, use phosphate binders with meals and increase phosphate removal on dialysis; then correct PTH using vitamin D analogues or calcimimetics according to serum calcium.
• The newest guideline opened for this topic is KDIGO 2017 for CKD-MBD, supplemented by a 2025 umbrella review of hypophosphataemia and a 2026 review of secondary hyperparathyroidism pharmacotherapy.

By the end of this page you should be able to:

1. Explain how phosphate is normally absorbed, distributed, excreted and regulated by PTH, calcitriol and FGF23.
2. List the causes of hypophosphataemia and of hyperphosphataemia, separating acute from chronic and renal from non-renal mechanisms.
3. Recognise the clinical consequences of low and high phosphate, including osteomalacia, rhabdomyolysis, vascular calcification and renal osteodystrophy.
4. Interpret serum phosphate, calcium, PTH and alkaline phosphatase results in CKD, and state the KDIGO monitoring intervals.
5. Plan treatment of hypophosphataemia by severity and cause, including oral and intravenous phosphate replacement.
6. Manage hyperphosphataemia in CKD with diet, phosphate binders, dialysis and the vitamin D/PTH axis, including safety limits on calcium-based binders.

Phosphate is not just "bone mineral": every cell uses it to store energy in ATP, build DNA and RNA, and buffer acid. About 85% of body phosphate is in bone and teeth and 15% in soft tissues and extracellular fluid, so changes in serum phosphate are more a signal of whole-body mineral handling than of bone content alone (serum phosphate is only a fraction of the total). Because phosphate is central to energy metabolism, very low levels can weaken muscle, impair respiratory and cardiac muscle and confuse the brain, while persistently high levels in CKD push calcium–phosphate deposition into vessels and heart valves. This topic covers phosphate disorders on three levels: isolated low phosphate, isolated high phosphate, and the whole mineral–bone syndrome of CKD. Phosphate should always be interpreted with calcium, PTH, alkaline phosphatase and vitamin D rather than on its own.

In adults the plasma phosphate concentration is held in a narrow range, quoted in different sources as roughly 0.9–1.5 mmol/L (about 2.8–4.7 mg/dL) or, in other ranges, 0.81–1.45 mmol/L (2.5–4.5 mg/dL); laboratories use their own reference intervals, so the clinician should read the number against the local range rather than memorise one cut-off. Serum phosphate varies with age, sex and time of day, is higher in children, and changes after meals. About 70% of the filtered phosphate load is reabsorbed in the proximal convoluted tubule and about 10% in the proximal straight tubule and downstream segments. Reabsorption is regulated mainly by three hormones: PTH (which lowers phosphate by increasing urinary loss), 1,25-dihydroxyvitamin D (calcitriol, which increases intestinal phosphate absorption and renal insights through FGF23), and FGF23 itself (which reduces renal phosphate reabsorption and calcitriol synthesis). ^[4]

FGF23 is produced by osteocytes and osteoblasts. It decreases expression of the sodium–phosphate co-transporters NaPiIIa and NaPiIIc in the proximal tubule, increases urinary phosphate loss, suppresses 1α-hydroxylase and stimulates 24-hydroxylase so that calcitriol falls. Its release is stimulated by high dietary phosphate, high serum phosphate, calcitriol, calcium, erythropoietin, iron deficiency, metabolic acidosis and inflammatory cytokines. FGF23 acts through receptors FGFR1/3/4 with Klotho as an obligatory co-receptor in kidney and parathyroid gland; it also inhibits PTH through MAPK signalling. In health, FGF23 rises early when phosphate is available, keeps phosphate in range and suppresses calcitriol to avoid overdose.

Hypophosphataemia is a serum phosphate below the lower reference limit. The reviewed sources use two closely related definitions: in adults less than 0.80 mmol/L (less than 2.5 mg/dL), and in practice below 0.8 mmol/L (about 2.5 mg/dL). It is usually graded as mild 0.65–0.79 mmol/L (2.0–2.4 mg/dL), moderate 0.32–0.64 mmol/L (1.0–1.9 mg/dL) and severe less than 0.32 mmol/L (less than 1.0 mg/dL). Chronic hypophosphataemia has been defined as phosphate below the reference range on at least three consecutive morning fasting samples taken 3 months apart, because phosphate fluctuates with meals and diurnal rhythm. Children need age- and sex-adjusted reference intervals because normal concentrations are higher during growth. ^[2][4]

The causes fall into four mechanisms: inadequate intake, impaired intestinal absorption, renal phosphate wasting, and shift of phosphate from extracellular fluid into cells. Renal wasting may be FGF23-dependent, as in X-linked hypophosphataemia and tumour-induced osteomalacia, or FGF23-independent, as in acquired Fanconi syndrome, hyperparathyroidism, post-transplantation states and certain inherited rickets forms. Medications can cause renal wasting or malabsorption (ferric carboxymaltose, tenofovir, mammalian target of rapamycin inhibitors).

Hyperphosphataemia is a serum phosphate above the upper reference limit: more than 1.45 mmol/L (more than 4.5 mg/dL) in adults and 1.8–2.1 mmol/L (5.5–6.5 mg/dL) in children, depending on age. Chronic kidney disease is the most common cause of chronic hyperphosphataemia. Acute causes include mass cell breakdown (tumour lysis syndrome, rhabdomyolysis), acute kidney injury, reduced renal excretion, excess intake or vitamin D toxicity, and redistribution from hypoparathyroidism. ^[4]

CKD-MBD is the systemic syndrome of mineral, vitamin D, PTH, bone and vascular abnormalities that develops as kidney function falls. It is not merely "low vitamin D": phosphate retention, FGF23 excess and low calcitriol all begin early, often before serum phosphate rises, and they interact to produce secondary hyperparathyroidism, renal osteodystrophy and vascular calcification. The old term "renal osteodystrophy" now refers specifically to the bone lesions, whereas CKD-MBD describes the whole disorder.

CKD affects more than 10% of adults worldwide, and phosphate disorders are common along that pathway. Hypophosphataemia of some degree is reported in 5% to 30% of adults depending on the population and clinical setting, and is frequent after kidney transplantation and intensive dialysis. CKD-MBD develops as filtration falls; in one common formulation the rise in phosphate and FGF23 becomes overt when GFR drops below 30 mL/min. Among people on maintenance dialysis, secondary hyperparathyroidism persists in a large minority and both very low and very high PTH are associated with higher mortality in observational studies. Cardiovascular disease accounts for roughly 40% to 50% of all-cause mortality in dialysis patients, and disordered mineral metabolism is one of its drivers. Fractures in dialysis patients carry a markedly increased mortality risk (reported as a 3.7-fold increase). Gulf and Middle Eastern dialysis populations have high rates of vitamin D deficiency and diabetic nephropathy, so published targets may need adapting locally. ^[2][3]

Four mechanisms organise the causes. Inadequate intake or total-body depletion occurs in starvation, eating disorders and severe malnutrition. Reduced absorption occurs in chronic diarrhoea, inflammatory bowel disease, bariatric or small-bowel surgery, coeliac disease and vitamin D deficiency. Renal wasting occurs in primary and secondary hyperparathyroidism, genetic and acquired tubular disorders (including Fanconi syndrome), tumour-induced osteomalacia and drug-induced tubulopathy. Intracellular shift occurs with insulin treatment of diabetic ketoacidosis or refeeding, respiratory or metabolic alkalosis, catecholamines and rapid cell proliferation. Clinical risk groups that need phosphate testing include patients with malnutrition or refeeding risk, alcoholic ketoacidosis, hyperglycaemic hyperosmolar state, COPD or asthma exacerbations that do not improve, repeated iron infusions and tenofovir therapy, especially with worsening renal function.

FGF23-dependent hypophosphataemia includes X-linked hypophosphataemia (PHEX mutations, incidence about 1 in 20,000, causing a lack of mineralisation, bone deformity in children and musculoskeletal pain and muscle weakness in adults) and tumour-induced osteomalacia (usually a small FGF23-secreting mesenchymal tumour, producing bone pain, weakness, fatigue, reduced mobility and fractures). Tumour removal is the definitive treatment; a new targeted therapy for some FGF23-mediated disease is the monoclonal antibody burosumab, which improves phosphate reabsorption and bone mineralisation but is limited by indication, availability and cost. ^[4]

Non-renal causes of chronic hyperphosphataemia include hypoparathyroidism (PTH absence increases renal phosphate reabsorption), acromegaly and tissue damage; acute causes include tumour lysis syndrome and rhabdomyolysis, where intracellular phosphate floods the circulation and can precipitate in renal tubules and soft tissues causing hypocalcaemia, arrhythmias, tetany and metastatic calcification. Excess vitamin D increases intestinal phosphate absorption. High dietary phosphate alone rarely causes acute hyperphosphataemia in people with normal kidneys, but observational studies link chronic high intake to vascular stiffness and bone disease.

Within CKD, the chain is mechanistic: phosphate retention raises FGF23, low calcitriol and hypocalcaemia then raise PTH, and PTH becomes autonomous with time. After transplantation, renal phosphate wasting is common in the first three months, so hypophosphataemia (not hyperphosphataemia) is the early problem. Drug-induced hypophosphataemia from ferric carboxymaltose, tenofovir and mTOR inhibitors can superimpose on any CKD stage and needs monitoring.

The central axis is phosphate–FGF23–vitamin D–PTH. As GFR declines, renal phosphate excretion falls. FGF23 rises early and keeps phosphate in range by wasting phosphate and suppressing calcitriol, but eventually fails; calcitriol then falls because the kidney cannot 1α-hydroxylate 25-hydroxyvitamin D, and low calcitriol plus hypocalcaemia drives PTH secretion. Hyperphosphataemia also stimulates PTH gene transcription directly, independent of calcium, even at phosphate levels inside the normal range. Over years the parathyroid glands enlarge from diffuse hyperplasia to nodular, often autonomous, tissue that resists medical therapy. FGF23 itself has endocrine actions beyond phosphate: it is associated with left ventricular hypertrophy, inflammation (IL-6 and CRP), endothelial effects and bone mineralisation changes.

High phosphate is not passive. Vascular smooth muscle cells transdifferentiate toward an osteochondrogenic phenotype, nucleating calcium–phosphate deposition in the medial arterial wall and heart valves. This makes hyperphosphataemia a modifiable driver of cardiovascular disease rather than an incidental laboratory finding. At bone, chronically raised PTH produces high-turnover renal osteodystrophy (osteitis fibrosa), bone pain and fractures, while oversuppressed PTH produces adynamic, low-turnover bone that also fractures easily. The clinical target is therefore avoidance of both extremes.

Acute, severe hypophosphataemia produces symptoms from energy failure: worsening weakness, malaise, anorexia, paraesthesiae, confusion, seizures, arrhythmias and, when respiratory or cardiac muscle is involved, ventilatory failure or pump impairment. Moderate hypophosphataemia may be asymptomatic or produce fatigue and muscular aches. Chronic hypophosphataemia produces bone pain, muscle weakness, pseudofractures, fractures, short stature and gait disturbance in children, and after long-standing disease osteomalacia in adults. Bone symptoms and insufficiency fractures are the clues that should trigger phosphate testing. Drug-induced forms (for example after ferric carboxymaltose) may present with fatigue, bone pain and muscle weakness weeks after infusion. Renal wasting forms present with bone disease and an inappropriately low or normal 24-hour urinary phosphate relative to serum; FGF23-mediated forms show a renal phosphate leak, normal calcium, raised FGF23 and low calcitriol.

Mild hyperphosphataemia is usually asymptomatic. With rising levels comes a fall in ionised calcium, and patients may develop tetany, perioral numbness, carpopedal spasm, muscle cramps, prolonged QT or arrhythmias, particularly after acute loads such as tumour lysis syndrome. Chronic CKD-MBD presents with bone pain, proximal muscle weakness, fractures, pruritus, extraskeletal (vascular and valvular) calcification, and evidence of secondary hyperparathyroidism. Many patients remain asymptomatic until advanced. On examination one may find bone deformity, short stature, pathological fractures and vascular calcification; after parathyroidectomy the "hungry bone" picture is possible.

Two separate questions arise: what causes the phosphate change, and what else explains the presentation. For chronic hypophosphataemia, tumour-induced osteomalacia, X-linked hypophosphataemia and other rickets forms are rare but treatable; malabsorption and the drug-induced causes are more common. For a patient presenting with bone pain and weakness, exclude osteoporosis, vitamin D deficiency, multiple myeloma, metastatic disease, inflammatory myopathy and polymyalgia. For hyperphosphataemia, pseudohyperphosphataemia (haemolysis in the sample, extreme hyperlipidaemia or hyperbilirubinaemia in some methods) and spurious elevations should be considered before embarking on management. In CKD-MBD, distinguish adynamic bone disease (low PTH) from high-turnover renal osteodystrophy (high PTH), because treatments differ.

The basic set is serum phosphate, calcium (total, with albumin correction or ionised), PTH (assay type must be known), alkaline phosphatase or bone-specific alkaline phosphatase, 25-hydroxyvitamin D and creatinine/estimated GFR. KDIGO recommends monitoring calcium, phosphate, PTH and alkaline phosphatase from CKD stage G3a (level 1C), and in children from stage G2 (level 2D). A single abnormal value should not drive treatment; decisions are based on trends and the full clinical picture (level 1C). 25(OH)D is measured with repeat testing guided by baseline values and therapy (level 2C), and deficiency is corrected as in the general population (level 2C). PTH assays vary, and reporting must state the method and any change, so compare using the same assay ideally (level 1B). For chronic hypophosphataemia, fasting morning phosphate is preferred because diet and diurnal variation alter levels. ^[1]

KDIGO suggests interval by stage: CKD G3a–G3b calcium and phosphate every 6–12 months, PTH guided by baseline; CKD G4 calcium and phosphate every 3–6 months and PTH every 6–12 months; CKD G5 including G5D calcium and phosphate every 1–3 months and PTH every 3–6 months; alkaline phosphatase every 12 months or more often if PTH is raised. After kidney transplantation, measure calcium and phosphate at least weekly in the immediate post-transplant period until stable, then by stage-adjusted intervals. Intervals should be shortened if biochemical abnormalities are present or treatments are being changed. ^[1]

In CKD-MBD, a lateral abdominal radiograph or echocardiogram can detect vascular or valvular calcification as a proxy for highest cardiovascular risk (level 2C). Bone mineral density testing is suggested when evidence of CKD-MBD or osteoporosis risk factors exist and the result would change management (level 2B). Bone biopsy is reasonable when the type of renal osteodystrophy would alter treatment (not graded). Measurement of bone-specific alkaline phosphatase can evaluate bone turnover because markedly high or low values predict underlying turnover (level 2B); routine collagen turnover markers are not suggested (level 2C).

CKD itself is defined as kidney structure or function abnormality present for more than 3 months, staged by cause, GFR category (G1–G5) and albuminuria. There is no single phosphate-based diagnostic score. Biochemical patterns help subtype renal osteodystrophy: high PTH and high ALP point toward high-turnover disease; low PTH toward adynamic bone disease; both occur on a background of abnormal calcium, phosphate and vitamin D. Hypophosphataemia severity grades (mild/moderate/severe) guide urgency and route of replacement. In severe hyperparathyroidism unresponsive to medical therapy, parathyroidectomy is considered (level 2B). When evaluating hypophosphataemia, chronic forms are defined by repeat fasting samples and rare genetic forms by age of onset, family history, renal phosphate leak and imaging of possible tumours.

The first management principle is to treat the underlying cause: stop offending drugs when possible, replace hormones appropriately, resect tumours, manage refeeding. Supplementation is added when phosphate is very low or symptomatic.

Chronic hypophosphataemia is treated mainly with oral phosphate. Evidence-reviewed oral dose ranges in clinical practice include 20–60 mg (about 0.65–1.93 mmol) per kg per day in divided doses until clinical improvement for osteomalacia, or generally 0.75–2 g per day in 2–4 divided doses (lower end for simple replacement, up to about 2 g in pregnancy or menopause in some schemes), with gradual upward titration. Doses up to about 750–1600 mg per day in divided doses are used in X-linked hypophosphataemia, and 155–300 mg per day titrated in fibrous dysplasia/McCune–Albright syndrome. Therapy is usually 2–6 divided doses because phosphate is rapidly absorbed and excreted, and slow titration reduces diarrhoea and dyspepsia. Monitoring is commonly every 3–6 months, or sooner after initiation and after surgery. Side effects of replacement include gastrointestinal symptoms, secondary or tertiary hyperparathyroidism and renal calcification/nephrocalcinosis, so the principle is the lowest effective dose with regular phosphate, calcium and PTH checks. X-linked hypophosphatemia therapy should be stopped if PTH becomes markedly raised. ^[2]

X-linked hypophosphataemia in particular progresses from diffuse to nodular parathyroid change and benefits from surveillance; burosumab is used where approved. Tumour-induced osteomalacia is treated surgically, with phosphate supplementation as a bridge, continued if cure is impossible.

Post-transplant hypophosphataemia is common in the first three months because of renal phosphate wasting. Supplementation is often started when phosphate falls below 0.65 mmol/L (2.0 mg/dL), or below 0.5 mmol/L (1.55 mg/dL) or below 1.0 mmol/L (3.1 mg/dL) with muscle weakness depending on the review. Oral replacement continues until phosphate is 0.65 mmol/L (2 mg/dL). ^[2]

Drug-associated hypophosphataemia (for example ferric carboxymaltose or tenofovir) is managed by monitoring severity and cause. Replacement is oral for moderate asymptomatic cases and intravenous for severe or symptomatic cases. For ferric carboxymaltose, consideration of supplementation applies to moderate (under 0.65 mmol/L, about 2 mg/dL) or severe (under 0.35 mmol/L, about 1 mg/dL) hypophosphataemia; mTOR inhibitor–associated forms are supplemented when phosphate is below 0.81 mmol/L (2.5 mg/dL). Testing and rechecking after infusions vary between guides and should be risk-based. ^[2]

Acute hypophosphataemia is often transient, caused by intracellular shift such as insulin treatment of ketoacidosis or refeeding; such shifts frequently correct without replacement, though severe or symptomatic cases are treated. Testing is recommended during refeeding, ketoacidotic states, hyperglycaemic hyperosmolar crises, COPD or asthma exacerbations that fail to improve, and intensive haemodialysis. Supplementation thresholds used in reviews include phosphate below 0.8 mmol/L (2.5 mg/dL) when initiating nutrition in at-risk refeeding patients; in other causes below 0.32 mmol/L (1 mg/dL), or up to 0.65 mmol/L (2 mg/dL) if symptoms such as altered mental status, hypotension, arrhythmia, respiratory distress or rhabdomyolysis are present. Intravenous replacement rates quoted for severe acute cases are 0.3–0.6 mmol (9–18 mg) per kilogram per day over 4–12 hours, or weight-based schemes such as 0.08–0.24 mmol/kg over 6 hours when phosphate is above 0.4 mmol/L and 0.25–0.5 mmol/kg over 8–12 hours when it is below 0.4 mmol/L, with a maximum of 30 mmol (above 0.4) or 80 mmol (below 0.4) and switching to oral therapy once phosphate reaches 0.48 mmol/L. Acute intravenous replacement should be given over several hours at rates not exceeding about 7.5 mmol per hour, with calcium monitoring, to avoid hypocalcaemia, arrhythmia and ectopic calcification. In refeeding syndrome, some guidelines recommend assessing risk (BMI below 16 kg/m2, major weight loss, prolonged poor intake) before starting nutrition and giving phosphate prophylactically in very high-risk patients, then monitoring next-day in mild cases and after 8–12 hours in moderate cases. ^[1][2][4]

The KDIGO 2017 approach is to look at calcium, phosphate and PTH together as trends, treat phosphate first, then treat PTH with agents chosen by calcium level.

Phosphate binders reduce intestinal absorption: the tablet is taken with every meal and snack. KDIGO recommends first-line phosphate binders for elevated phosphate in dialysis patients, with dietary restriction as an essential adjunct, and suggests limiting dietary phosphate in all stages of CKD (level 2D), considering phosphate source (animal, vegetable, additives) (not graded). In adults receiving phosphate-lowering treatment, the dose of calcium-based binders should be restricted (level 2B); in children the choice should be guided by serum calcium (not graded). Long-term aluminium-containing binders and dialysate aluminium contamination must be avoided to prevent aluminium intoxication (level 1C). Where phosphate remains high on dialysis, increase dialytic removal (level 2C). In the immediate post-transplant period measure phosphate (and calcium) at least weekly until stable (level 1B). ^[1][3]

Practical burden: dialysis patients often take 6 to 12 binder tablets daily plus their other drugs, and reported non-adherence is 22% to 74% across dialysis populations; gastrointestinal intolerance (nausea, constipation, diarrhoea, bloating) is common across classes. Non-adherence maintains the phosphate stimulus for PTH secretion and can undercut calcimimetics and vitamin D. Combining classes with different mechanisms allows lower doses and fewer side effects. ^[3]

Vitamin D enters the system as 25(OH)D (calcidiol), which rises in summer and with supplementation, and is activated in the kidney to 1,25(OH)2D (calcitriol). Calcitriol suppresses PTH gene transcription and enhances intestinal calcium absorption, indirectly suppressing PTH through the calcium-sensing receptor (CaSR). PTH also inhibits renal phosphate reabsorption and stimulates calcitriol. FGF23, as above, suppresses both 1α-hydroxylase and PTH. In CKD the 1α-hydroxylation step fails, so calcitriol falls even when calcidiol is replete; measuring calcidiol and correcting deficiency (as in the general population) is appropriate, but active vitamin D analogues should not be used routinely in adults with CKD G3–5 not on dialysis (level 2C); reserve them for severe, progressive hyperparathyroidism in G4–5 (not graded). In children, calcitriol/vitamin D analogues may be considered to maintain age-appropriate serum calcium.

In dialysis (G5D), maintain iPTH at roughly 2 to 9 times the upper limit of normal for the assay (level 2C), watching both directions because both very low and very high PTH associate with mortality. PTH-lowering therapy options are calcimimetics, calcitriol/vitamin D analogues, or combinations (level 2B).

Calcimimetics increase CaSR sensitivity in parathyroid chief cells and lower PTH without raising calcium or phosphate, so they suit patients with hypercalcaemia or hyperphosphataemia and those who have not responded to vitamin D. Cinacalcet reduced median PTH by about 43% in a trial of 741 haemodialysis patients, with 43% reaching PTH 250 pg/mL or less versus 5% on placebo; it also lowered phosphate and the calcium–phosphate product. Hypocalcaemia and gastrointestinal symptoms (nausea, vomiting, diarrhoea) can limit use. The EVOLVE trial of cinacalcet in over 3800 haemodialysis patients did not show a statistically significant reduction in the primary cardiovascular composite end point (hazard ratio 0.93) despite clear PTH lowering; an adjusted analysis suggested a possible 12% relative risk reduction (hazard ratio 0.88), but discontinuation was high at 58%. Etelcalcetide is given intravenously three times weekly through the dialysis circuit, so adherence is supervised; it achieves superior PTH suppression (a higher proportion with more than 30% reduction) and fewer gastrointestinal events than cinacalcet but a higher rate of hypocalcaemia. Evocalcet is an oral calcimimetic with non-inferior PTH reduction and fewer gastrointestinal effects than cinacalcet in trials, and is approved only in some regions. ^[3]

Vitamin D analogues bind vitamin D receptors in parathyroid nuclei to inhibit PTH gene transcription and raise intestinal calcium absorption (dual suppression). Calcitriol is the native active form; selective receptor activators such as paricalcitol and doxercalciferol aim for less calcemic and phosphataemic effect. In a randomised trial in haemodialysis both paricalcitol and calcitriol significantly lowered PTH, with fewer episodes of hypercalcaemia on paricalcitol; an observational cohort reported paricalcitol associated with an approximate 16% relative reduction in all-cause mortality versus calcitriol (not causal). Vitamin D therapy has a narrow window; in hypercalcaemia or severe hyperphosphataemia it may need dose reduction or withholding. Combination therapy is common and logical: binders address the phosphate stimulus, vitamin D suppresses PTH transcription, calcimimetics raise CaSR sensitivity. Address phosphate control first, then choose vitamin D analogue (if calcium low/normal) or calcimimetic (if calcium high) for PTH, individualising by response, tolerability and cost (level 2B). Severe refractory hyperparathyroidism despite medical therapy warrants parathyroidectomy (level 2B). ^[3]

Children require growing-bone adjusted ranges and closer attention to growth. KDIGO 2017 recommends annual linear growth assessment in children with CKD G2–G5D; infants should have length measured at least quarterly (level 1B). In children, calcitriol/vitamin D analogues may be used to maintain age-appropriate serum calcium (not graded), and phosphate-lowering choices should be guided by serum calcium (not graded). Growth hormone is recommended when height deficit persists after addressing malnutrition and CKD-MBD abnormalities (level 1A). For kidney transplant recipients in the first 12 months with eGFR above about 30 mL/min/1.73 m2 and low bone mineral density, vitamin D, calcitriol/alfacalcidol and/or antiresorptives are considered (level 2D), guided by calcium, phosphate, PTH, alkaline phosphatase and 25(OH)D. Pregnant patients with renal phosphate wasting need specialist multidisciplinary care and individualised supplementation. ^[1]

Acute, severe hypophosphataemia deserves urgent IV replacement with cardiac monitoring. Tumour lysis syndrome is prevented and managed with fluids, rasburicase/monitoring and control of hyperphosphataemia to prevent calcium–phosphate precipitation. Rhabdomyolysis needs fluids, cause control and monitoring. In CKD, acute deterioration of filtration can suddenly worsen phosphate and potassium homeostasis and should prompt closer monitoring even if previous values were stable.

• Suspected tumour-induced osteomalacia (unexplained chronic hypophosphataemia, bone pain, low or inappropriately FGF23 level) to endocrinology/rheumatology and for imaging to find the tumour.
• Severe or symptomatic hypophosphataemia, or hypophosphataemia with arrhythmia or respiratory failure: acute/emergency care.
• CKD with progressive hyperphosphataemia or uncontrolled PTH despite diet and binders: nephrology/pharmacy review.
• Severe or refractory secondary hyperparathyroidism: parathyroidectomy assessment.
• Any CKD-MBD plus low bone mineral density plus fragility fractures: bone and nephrology teams.
• Post-transplant patients with unstable calcium/phosphate or bone loss.
• Children with suspected rickets or growth failure: paediatric nephrology/endocrinology.

• Hypophosphataemia: weakness, fatigue, myopathy, rhabdomyolysis, respiratory and cardiac muscle dysfunction, arrhythmias, confusion/seizures, haemolysis and cellular energy failure when severe; osteomalacia, pseudofractures, fragility fractures and chronic musculoskeletal pain when chronic. IV replacement can itself cause hypocalcaemia, thrombophlebitis and arrhythmias, and oral replacement can cause gastrointestinal symptoms and long-term hyperparathyroidism/renal calcification.
• Hyperphosphataemia: hypocalcaemia, tetany, metastatic calcification, vascular and valvular calcification, secondary hyperparathyroidism, renal osteodystrophy and increased cardiovascular risk.
• CKD-MBD: fractures (3.7-fold increase in mortality risk reported in dialysis patients), osteitis fibrosa (high turnover), adynamic bone disease (low turnover), extraskeletal calcification, left ventricular hypertrophy, pruritus and hospitalisation. Both very low and very high PTH associate with higher mortality in dialysis populations.

Prognosis is determined more by the degree and duration of dysregulation than by a single phosphate value. Early CKD-MBD is reversible if recognised: suppressors of PTH (phosphate control, vitamin D replacement where appropriate, calcimimetics) and withdrawal of calcium-heavy treatments can prevent gland autonomy. Once parathyroid tissue becomes nodular, medication controls but rarely cures, and surgery is needed. In dialysis populations, keeping iPTH within 2–9 times the upper limit of normal is associated with better survival in observational data. Hypophosphataemia without an established cause can lead to delayed diagnosis of osteomalacia or tumours; chronic muscle weakness and multiple fractures substantially impair quality of life.

Testing phosphate when indicated is the main preventive step: persistent musculoskeletal symptoms, osteoporosis or unexplained fractures, evaluation of primary hyperparathyroidism or hypocalcaemia, high-risk refeeding situations, acute ketoacidotic and hyperosmolar crises, COPD/asthma not responding, post-transplant follow-up, repeat ferric carboxymaltose infusions, and tenofovir use (especially with renal dysfunction). In CKD, start mineral monitoring at stage G3a in adults and G2 in children. Use fasting samples for chronic hypophosphataemia. In the general population, avoid routine correction of normal phosphate. Public-health prevention focuses on CKD detection and slowing of progression, diabetes and hypertension control, and avoiding unnecessary long-term aluminium-containing binders. Dietary education matters: inorganic phosphate additives in ultra-processed foods are absorbed 90–100% (versus 40–60% for naturally bound organic phosphate and under 30% from many plant sources, because of phytates), so high intake is common. ^[4]

Children. Normal phosphate ranges are higher and change with pubertal growth; use age- and sex-specific intervals. Growth and bone mineralisation depend on phosphate and vitamin D; rickets forms present with delayed gait, bowing and growth failure. Managed by paediatric nephrology/endocrinology, with calcitriol/vitamin D analogues allowed to keep calcium in the age-appropriate normal range.

Pregnancy. Phosphate needs increase with fetal skeletal mineralisation; rare inherited or drug-induced hypophosphataemia requires specialist, often higher-dose, divided supplementation until delivery and the end of breastfeeding (commonly up to about 2 g per day in some inherited forms). Targeted therapy in X-linked hypophosphataemia is pregnancy-supervised.

Older adults. Renal function falls with age and phosphate handling changes; sex differences in phosphate become more marked after age 45. Frailty, malnutrition and refeeding risk are higher. Avoid over-treating mild abnormalities, but recognise that hyperphosphataemia may worsen vascular calcification in high-risk elderly patients.

Dialysis populations. Calcimimetic use, binder choice and vitamin D use vary by availability and cost; Gulf/Middle Eastern populations have lower calcimimetic uptake and near-universal vitamin D deficiency, so trial generalisability is uncertain.

Where advanced testing is limited, the following still applies: measure phosphate and calcium together with creatinine; use fasting morning samples; adjust treatments by trends; use calcium-based binders responsibly where non-calcium agents are unaffordable, but respect the caution on calcium load and calcification, monitor calcium and PTH when possible; encourage dietary phosphate awareness; use enteral/IV phosphate as available; increase dialytic phosphate removal where dialysis exists; and refer for severe/refractory cases. Calcimimetics and tenapanor may be unavailable or unaffordable, which is a real limit on how far western protocols can be generalised.

• Phosphate is essential for energy, nucleic acids and bone; it is regulated by PTH, calcitriol and FGF23, mainly in the kidney.
• Hypophosphataemia is usually under 0.80 mmol/L; severity grades guide treatment. Chronic forms need 3 fasting morning levels.
• Hypophosphataemia causes include poor intake, malabsorption, renal wasting and cellular shifts, plus drugs (ferric carboxymaltose, tenofovir, mTOR inhibitors); effects include weakness, respiratory/cardiac dysfunction, confusion and osteomalacia.
• Hyperphosphataemia exceeds 1.45 mmol/L in adults; CKD is the commonest cause, with GFR below 30 mL/min often unmasking it.
• In CKD-MBD, rising FGF23 precedes overt phosphate abnormalities; the chain runs phosphate retention, low calcitriol, hypocalcaemia, secondary hyperparathyroidism and vascular/bone disease.
• Treat phosphate first: limit intake, use binders with meals (restrict calcium-based doses; avoid aluminium long-term), and increase dialytic removal.
• Non-calcium binders reduce calcium load and calcification but impose heavy pill burden and cost; adherence is commonly low (22% to 74%).
• In dialysis maintain iPTH at about 2–9 times the upper limit; choose vitamin D analogue (if calcium low/normal) or calcimimetic (if calcium high) for PTH control.
• Calcitriol/vitamin D analogues are not routine in non-dialysis adults with CKD; reserve them for severe progressive hyperparathyroidism.
• Hypophosphataemia treatment: oral divided doses for chronic/asymptomatic; IV for severe or symptomatic acute cases, with rate limits and calcium monitoring.
• Test phosphate in the listed high-risk situations rather than universally.
• Hyperphosphataemia is partly reversible if phosphate control and PTH management are started early, before gland autonomy.

• Chronic kidney disease (T number pending): assessment, staging and management
• Renal osteodystrophy and bone mineral density in CKD
• Calcium disorders: hypercalcaemia and hypocalcaemia
• Vitamin D deficiency and rickets/osteomalacia
• Phosphate and calcium homeostasis: the FGF23–Klotho axis
• Tumour-induced osteomalacia and X-linked hypophosphataemia
• Secondary and tertiary hyperparathyroidism
• Phosphate binders and their adverse effects
• Refeeding syndrome and nutrition in malnourished patients
• Acute kidney injury and electrolyte management
• Kidney transplantation: immunosuppression and long-term follow-up
• Vascular calcification and cardiovascular risk in CKD