Hypercalcaemia

Also known as: Hypercalcemia, High calcium

Hypercalcaemia is a raised corrected serum calcium, graded broadly as mild (up to about 3.0 mmol/L), moderate (3.0–3.4 mmol/L) and severe (≥3.4 mmol/L, or any level with significant symptoms).

Because roughly 40% of calcium is albumin-bound, the corrected value must be used, or hypercalcaemia will be missed in hypoalbuminaemic patients and over-diagnosed in others.

Primary hyperparathyroidism and malignancy together account for around 90% of cases, and the distinction is usually straightforward: primary hyperparathyroidism tends to be chronic, mild and asymptomatic in an outpatient, while malignancy-associated hypercalcaemia is usually higher, symptomatic and of shorter history.

Other causes include granulomatous disease (sarcoidosis, tuberculosis), vitamin D toxicity, thiazides, lithium, thyrotoxicosis, immobilisation, milk-alkali syndrome and familial hypocalciuric hypercalcaemia.

The classic summary of "bones, stones, abdominal groans and psychic moans" remains a useful memory aid.

Renal: polyuria and polydipsia (nephrogenic diabetes insipidus), nephrolithiasis, nephrocalcinosis, and acute kidney injury from volume depletion
Gastrointestinal: anorexia, nausea, vomiting, constipation, abdominal pain, peptic ulceration and pancreatitis
Neuropsychiatric: fatigue, poor concentration, depression, confusion, and in severe hypercalcaemia drowsiness, stupor and coma
Musculoskeletal: bone pain, proximal muscle weakness, and in longstanding hyperparathyroidism osteitis fibrosa cystica
Cardiac: shortened QT interval, bradycardia, and arrhythmia in severe cases, with increased digoxin sensitivity

Volume depletion is central to the pathophysiology and drives a vicious cycle: hypercalcaemia causes polyuria and vomiting, which cause dehydration, which reduces renal calcium excretion, which raises calcium further. Breaking that cycle with fluid is the first therapeutic priority.

Corrected calcium, repeated to confirm, alongside albumin. Ionised calcium is preferable where available and where the correction is unreliable, as in critical illness or acid-base disturbance
PTH is the single most useful discriminating test: an inappropriately normal or raised PTH indicates primary (or tertiary) hyperparathyroidism, while a suppressed PTH points to a non-parathyroid cause, principally malignancy
If PTH is suppressed: PTHrP (humoral hypercalcaemia of malignancy), vitamin D metabolites (raised 1,25-dihydroxyvitamin D suggests granulomatous disease or lymphoma), myeloma screen, and imaging directed by the clinical picture
Renal function, phosphate, magnesium, alkaline phosphatase
ECG for QT shortening
24-hour urinary calcium and the calcium-creatinine clearance ratio to identify familial hypocalciuric hypercalcaemia, an important benign mimic in which parathyroidectomy is inappropriate and which is otherwise easily mistaken for mild primary hyperparathyroidism
Review medications, particularly thiazides, lithium, calcium and vitamin D supplements

Differentials: as above, with the practical task usually being to separate parathyroid-driven from non-parathyroid causes and then to identify the specific underlying disease.

Severe or symptomatic hypercalcaemia:

Intravenous isotonic saline is the first and most important step, typically several litres over the first 24 hours, correcting volume depletion and promoting calciuresis. This alone often produces a substantial fall
Loop diuretics are no longer recommended routinely and should be used only once the patient is genuinely volume replete and where fluid overload is a concern; giving furosemide to a dehydrated hypercalcaemic patient worsens the problem
Intravenous bisphosphonate (zoledronic acid or pamidronate) for malignancy-associated hypercalcaemia, with the important caveat that the effect takes 2–4 days, so it does not substitute for fluid in the acute phase. Dose adjustment is needed in renal impairment
Calcitonin works within hours and is useful as a bridge while awaiting bisphosphonate effect, though tachyphylaxis limits it to a few days
Denosumab is an option in bisphosphonate-refractory hypercalcaemia or significant renal impairment
Corticosteroids are effective specifically in granulomatous disease, lymphoma and vitamin D toxicity, where the mechanism is excess 1,25-dihydroxyvitamin D
Haemodialysis for severe hypercalcaemia with renal failure or where the patient is unable to tolerate fluid loading
Stop contributing drugs and mobilise the patient where possible

Underlying cause:

Primary hyperparathyroidism: parathyroidectomy where criteria are met; cinacalcet where surgery is not appropriate
Malignancy: treat the underlying disease, recognising that hypercalcaemia of malignancy carries a poor prognosis and that discussion of goals of care is often appropriate alongside treatment

Referral: endocrinology for parathyroid disease; oncology or palliative care for malignancy-associated hypercalcaemia; nephrology for dialysis or severe renal impairment.

Clinical toolsCalculators

BMI GCS EDD Parkland Formula

Corrected Sodium Corrected Calcium Anion Gap Creatinine Clearance Insulin Calculations qSOFA Wells PE Wells DVT CHA₂DS₂-VASc HAS-BLED CURB-65 Centor/McIsaac

Chronic Kidney Disease

Also known as: CKD, Chronic renal failure

Chronic kidney disease is abnormal kidney structure or function present for more than three months, with implications for health.

It is classified by cause, GFR category (G1–G5) and albuminuria category (A1–A3) — the "CGA" system — because albuminuria independently predicts progression and cardiovascular risk, and staging on GFR alone substantially underestimates risk in a patient with heavy proteinuria.

G1: GFR ≥90 with evidence of kidney damage; G2: 60–89; G3a: 45–59; G3b: 30–44; G4: 15–29; G5: below 15 (kidney failure)
A1: ACR below 3 mg/mmol; A2: 3–30; A3: above 30

The commonest causes are diabetes and hypertension, followed by glomerulonephritis, polycystic kidney disease, obstructive uropathy and recurrent pyelonephritis. Most patients with chronic kidney disease die of cardiovascular disease rather than reaching dialysis, which is why cardiovascular risk management is not a secondary consideration but a central part of treatment.

eGFR and urine albumin-to-creatinine ratio, both required for staging, and both confirmed on repeat over at least three months to establish chronicity and to distinguish from acute kidney injury
Urinalysis for haematuria and proteinuria; the combination of haematuria and proteinuria suggests glomerular disease and warrants nephrology referral
Renal ultrasound to assess size, symmetry and obstruction; small echogenic kidneys support chronicity, while asymmetry suggests renovascular disease and normal-sized kidneys in advanced disease suggest diabetes, amyloid or polycystic disease
Cause-directed investigations: HbA1c, blood pressure, autoimmune screen, myeloma screen in older patients with unexplained disease, hepatitis and HIV serology where relevant
Complication screening, which should be systematic: FBC for anaemia, calcium, phosphate, PTH and vitamin D for mineral and bone disorder, bicarbonate for metabolic acidosis, potassium, and lipids
Track the rate of decline rather than single values; a rapid fall (more than 5 mL/min/1.73m² per year) changes management and prompts referral
Medication review at every visit, since nephrotoxins and inappropriately dosed drugs are a major modifiable cause of progression

Slowing progression, which is the central goal:

Blood pressure control, generally targeting below 130/80 mmHg where tolerated, and lower in significant proteinuria
ACE inhibitor or ARB for proteinuric chronic kidney disease and for diabetic kidney disease, titrated to the maximum tolerated dose. Expect a creatinine rise of up to 25–30% after initiation, which is acceptable and reflects the intended haemodynamic effect; a larger rise warrants investigation for renovascular disease
SGLT2 inhibitors are now a cornerstone of treatment, with clear benefit in slowing progression in both diabetic and non-diabetic chronic kidney disease, and additional cardiovascular and heart failure benefit
Glycaemic control in diabetes, with agent selection accounting for renal clearance
Finerenone for diabetic kidney disease with albuminuria, as an additional option
Dietary sodium restriction, smoking cessation, weight management and exercise
Avoid nephrotoxins: NSAIDs, unnecessary contrast, aminoglycosides; adjust drug doses for renal function and provide sick-day guidance for holding ACE inhibitors, ARBs, diuretics, metformin and SGLT2 inhibitors during acute illness

Managing complications:

Anaemia: iron studies first and iron replacement before considering erythropoiesis-stimulating agents, targeting a haemoglobin around 100–120 g/L rather than normalising it, since higher targets increase cardiovascular events
Mineral and bone disorder: dietary phosphate restriction and phosphate binders taken with meals, activated vitamin D and calcimimetics for secondary hyperparathyroidism
Metabolic acidosis: oral sodium bicarbonate where bicarbonate is persistently below about 22 mmol/L, which slows progression and reduces muscle wasting
Hyperkalaemia: dietary advice, potassium binders where needed to allow continuation of prognostically important ACE inhibitors and ARBs rather than stopping them
Cardiovascular risk: statin therapy for essentially all patients, and active management of all modifiable risk factors

Advanced disease:

Timely nephrology referral — generally for G4 and above, rapid progression, heavy proteinuria, unexplained disease, refractory hypertension, or persistent haematuria — allowing planning rather than crisis management
Preparation for renal replacement therapy well before it is needed, including modality choice, dialysis access creation, and pre-emptive transplant assessment, which offers the best outcomes
Conservative kidney management is an appropriate and actively chosen pathway for frail or comorbid patients, focusing on symptom control and quality of life, and should be discussed rather than presented as the absence of treatment

Referral: nephrology per the criteria above; dietitian for phosphate, potassium and protein management; cardiology where cardiovascular disease coexists.

Hypercalcaemia

Overview

Clinical Features

Diagnosis

Management

Overview

Diagnosis

Management