Nephrology Topic

Fix the electrolyte, find the cause.

Hypokalemia, hypernatremia, calcium, magnesium and phosphate: urine and PTH-based workup, correction limits, ES 2023 hypercalcemia treatment, IV calcium, refeeding, and label doses with kidney limits.

Reviewed October 2026 · verify against current guidelines

Scope — adult hypokalemia, hypernatremia, calcium, magnesium and phosphate disorders. High potassium and low sodium have their own pages: hyperkalemia and hyponatremia. For numbers at the bedside, open the electrolyte calculator: K⁺, Mg²⁺ and phosphate repletion, a hypernatremia free-water plan, corrected calcium with treatment steps, and unit conversion.
Electrolytes · 1 of 6

Hypokalemia: find the leak, fix the magnesium.

Read it

SymptomsUsually none until K⁺ is below 3.0 mEq/L, unless the fall is fast or the patient takes digoxin. Then cramps, weakness, ascending paralysis, ileus, respiratory failure and rhabdomyolysis (Kardalas 2018).
ECGST depression, flattened T waves and prominent U waves, often in V4–V6. Arrhythmias run from ectopy and AV block to VT and VF. Get an ECG in every patient (Kardalas 2018).
ShiftInsulin, sympathetic surge or beta-agonists, thyrotoxicosis, periodic paralysis, and feeding that drives insulin release (Kardalas 2018).
LossGI: diarrhea, laxatives. Renal: diuretics, vomiting with bicarbonaturia, mineralocorticoid excess, Bartter and Gitelman syndromes, magnesium depletion (Kardalas 2018; Kamel 2021).

Ask the urine where it went

Spot K⁺/creatinineBelow about 2 mmol K⁺ per mmol creatinine (18 per gram) with no acid–base disorder points to a shift into cells; extrarenal losses can also run low (Kamel 2021). Above 13 mEq/g (1.5 mEq/mmol) usually means renal wasting (Kardalas 2018). Between 1.5 and 2.0 mmol/mmol the two cutoffs disagree — treat it as a grey zone and lean on the acid–base pattern. Low muscle mass distorts any creatinine ratio.
24-hour urineMore than 15 mEq of K⁺ per day despite hypokalemia is inappropriate renal loss (Kardalas 2018).
Then acid–baseMetabolic acidosis: diarrhea or renal tubular acidosis. Metabolic alkalosis: vomiting, diuretics or mineralocorticoid excess — sort by volume status and blood pressure (Kamel 2021). Work it through on the acid–base page.
Drop the TTKG — its originators no longer use the transtubular K⁺ gradient. It assumes no osmoles are reabsorbed beyond the cortical collecting duct, but a large amount of urea is reabsorbed in the inner medullary collecting duct, so the assumption fails (Kamel and Halperin 2011; 2021). Use the spot urine K⁺/creatinine ratio instead.

Replete

  • Magnesium first. More than half of clinically significant hypokalemia comes with magnesium deficiency, and that hypokalemia is often refractory to K⁺ until magnesium is replaced (Kardalas 2018).
  • Size the hole. Each 1 mEq/L fall in serum K⁺ reflects roughly 200–400 mEq of total deficit — a rough estimate that can miss either way (Kardalas 2018).
  • Route. Oral for 2.5–3.5 mEq/L when the gut works, 40 mEq or less per dose. IV with continuous ECG monitoring below 2.5, or with paralysis, arrhythmia, vomiting or no enteral route (Kardalas 2018; Bulloch 2024).
  • Rate. No faster than 10 mEq/h peripherally and 20 mEq/h centrally (Bulloch 2024). KCl label: with K⁺ above 2.5, usually 10 mEq/h and 200 mEq per day; up to 40 mEq/h only for K⁺ less than 2.0 with ECG changes or paralysis, on continuous ECG. Use 0.9% saline, not dextrose, as the diluent: glucose shifts K⁺ into cells (Kardalas 2018; KCl label).
  • Recheck after every 40–60 mEq (Bulloch 2024). With kidney impairment, give smaller doses and check more often.
  • Targets. After CABG, supplementing only below 3.6 mEq/L was noninferior to holding K⁺ at 4.5 or more for atrial fibrillation: 27.8% vs 26.2% (TIGHT K, JAMA 2024).
  • Dose bands, rate caps and recheck times: electrolyte calculator, K · Mg · Phosphate tab.
Electrolytes · 2 of 6

Hypernatremia: replace water, watch the clock.

Recognize

DefinitionSodium above 145 mmol/L (AAFP 2023). Outcome studies define severe as 155 or more (Feigin 2023) or above 155 (Chauhan 2019).
SymptomsThirst and signs of dehydration first. Neurologic signs — lethargy progressing to coma — are worst when sodium rises fast or exceeds 160 (StatPearls 2023).
CausesWater loss without access to water (impaired thirst, altered mental status, the very young and very old), diabetes insipidus, hypotonic GI or renal losses, and sodium gain, which is usually iatrogenic (StatPearls 2023).
Urine osmolalityLower than serum osmolality: diabetes insipidus. Higher: the kidney is conserving water, so look for extrarenal losses (StatPearls 2023).

Calculate

Total body waterWeight × 0.6 for men 65 or younger, 0.5 for women 65 or younger and men over 65, 0.45 for women over 65 (AAFP 2015).
Water deficitTBW × (Na ÷ 140 − 1). An 80-year-old man of 70 kg with Na 165: 35 × (165 ÷ 140 − 1) = 6.25 L (AAFP 2015 formula).
Per litreChange in Na = (infusate Na − serum Na) ÷ (TBW + 1). Same patient: each litre of D5W lowers Na by about 4.6 mmol/L, so a 10 mmol/L fall needs about 2.2 L, plus ongoing losses: about 133 mL/h over 24 hours with 1 L of losses, 153 mL/h with 1.5 L (Adrogué–Madias worked example, Medscape).

Correct

RateChronic or unknown onset: no faster than 0.5 mmol/L per hour and about 10 per day (expert opinion, summarized by Feigin 2023; AAFP 2015 gives 8–10, AAFP 2023 accepts up to 12). Hypernatremia known to have developed over hours: up to 1 mmol/L per hour (AAFP 2015), and no more than 12 per 24 hours (expert opinion: AAFP 2023, SORT B; Medscape). Aim for 145 (AAFP 2015).
FluidShock or severe volume depletion: isotonic fluid first (StatPearls 2023). Then free water — enteral water when the gut works; IV D5W (Na 0), D5 with 0.2% saline (34) or 0.45% saline (77) (AAFP 2015).
MonitorSodium at least every 4 hours while symptomatic and at least twice daily otherwise (Bulloch 2024). Count urine, GI and insensible losses, and re-set the rate from measured sodium — individual responses to the formula vary widely.
OvershootSlow or stop free water. Do not deliberately raise sodium again (AAFP 2023).
The 0.5 rule is soft — no randomized trial supports it in adults. In 4,265 patients with sodium of 155 or more, correction faster than 0.5 mmol/L per hour went with lower 30-day mortality (31.8% vs 50.7%) and no attributed neurologic harm (Feigin 2023). A 2025 meta-analysis found no significant overall difference (OR 0.68, 95% CI 0.38–1.24), with lower mortality after fast correction in subgroups: hypernatremia present on admission (OR 0.48, 0.35–0.68), correction within the first 24 hours (OR 0.48, 0.31–0.73) and severe hypernatremia (OR 0.55, 0.33–0.92) (Kitisin 2025), while a 2025 cohort of 37,913 adults linked slow correction to lower in-hospital mortality (Chacon-Palma 2025). Correct promptly within the conventional limit; plan it in the calculator, Hypernatremia tab.
Electrolytes · 3 of 6

Calcium: measure the right one, then ask PTH.

Corrected calcium (mg/dL) = measured calcium + 0.8 × (4 − albumin in g/dL), the formula printed in the zoledronic acid and pamidronate labels. Multiply mg/dL by 0.25 for mmol/L (Labcorp). The correction is a convenience, not a measurement.

Where the albumin correction fails

Critical illnessIn a 2026 prospective ICU study of 250 patients, albumin-corrected calcium caught 15.2% of those with low ionized calcium; uncorrected total calcium caught 62.8%. No simple correction beat total calcium (Özdemir 2026).
CKD 3–5In 691 patients, neither corrected nor uncorrected total calcium predicted ionized calcium well; low total CO₂ biased both toward underestimating it (Gauci 2008).
Measure ionizedIn critical illness, CKD, acid–base disorders and after large transfusions, and whenever a borderline value would change treatment. It needs anaerobic handling and prompt analysis (Özdemir 2026).

PTH splits the workup

High Ca, PTH high or normalPTH-mediated: primary hyperparathyroidism, with raised or inappropriately normal PTH. A urinary calcium/creatinine clearance ratio below 0.01 points to familial hypocalciuric hypercalcemia, which surgery does not help (English 2024). Outside primary hyperparathyroidism, PTH-mediated hypercalcemia is rare: parathyroid carcinoma or ectopic PTH (Sheehan 2021).
High Ca, PTH suppressedMeasure PTHrP — humoral hypercalcemia is the most common mechanism in cancer — then 1,25-dihydroxyvitamin D (lymphoma, granulomatous disease). Both low: osteolytic metastases or myeloma (Almuradova 2023; ES 2023).
Low Ca, PTH low or normalHypoparathyroidism — total thyroidectomy is the most common cause in hospital — or magnesium deficiency, which blunts PTH release and action (SfE 2016; Hansen 2018).
Low Ca, PTH highSecondary hyperparathyroidism from vitamin D deficiency or CKD; also pancreatitis, rhabdomyolysis, large transfusions and cytotoxic drugs (SfE 2016; KDIGO 2017).

Symptoms and ECG

High calciumAnorexia, constipation and nausea; polyuria from nephrogenic diabetes insipidus, with volume depletion and a rising creatinine; fatigue, confusion, coma. ECG: short QT (Almuradova 2023).
Low calciumPerioral and digital paresthesia, Chvostek and Trousseau signs, tetany, laryngospasm, seizures. ECG: long QT and arrhythmia. Symptoms usually start below about 1.9 mmol/L (7.6 mg/dL) adjusted, sooner when the fall is fast (SfE 2016). Check the QTc.
Electrolytes · 4 of 6

Hypercalcemia: hydrate, then stop the bone.

Severity, albumin-adjusted (ES 2023)

MildAbove the lab’s upper limit and below 12 mg/dL (3 mmol/L). Reference limits run 10.2–10.5 mg/dL (Sheehan 2021).
Moderate12–14 mg/dL (3–3.5 mmol/L).
SevereAbove 14 mg/dL (3.5 mmol/L).

Treat — hypercalcemia of malignancy, Endocrine Society 2023

  • Malignancy first. These drug steps and the label doses below are for hypercalcemia of malignancy. With a high PTH or no cancer, hydrate and get endocrinology input; the zoledronic acid label does not establish use for other causes.
  • Fluids first. Isotonic saline 1–2 L, then 200–500 mL/h to a urine output of 100–150 mL/h, tailored to cardiac function. Loop diuretics are not routine; use them only after volume repletion, to prevent overload.
  • Antiresorptive for everyone with HCM: denosumab or an IV bisphosphonate (R1, strong). Denosumab is suggested over a bisphosphonate (R2, conditional, very low certainty) and for HCM that is refractory or recurrent on a bisphosphonate.
  • Severe HCM: add calcitonin to the antiresorptive at the start (conditional). It works within hours, but tachyphylaxis sets in after 48–72 hours — stop by then.
  • Calcitriol-mediated (lymphoma): glucocorticoids, then add an antiresorptive if hypercalcemia stays severe or symptomatic. In granulomatous disease, exclude infection such as histoplasmosis before starting steroids (Gurram 2020).
  • Parathyroid carcinoma: a calcimimetic or an antiresorptive, adding the other if control is inadequate.
  • Severe, with advanced kidney disease: evaluate for hemodialysis with a low-calcium dialysate (Almuradova 2023).
  • Mild and asymptomatic: treat the cause and hydrate; the zoledronic acid label reserves its dose for corrected calcium of 12 mg/dL or more.

Doses and kidney limits

Zoledronic acid4 mg IV over at least 15 minutes for corrected Ca of 12 mg/dL or more; no change if creatinine is below 4.5 mg/dL — above that, patients were excluded from the trials. The 3.0–3.5 mg CrCl-based doses are for myeloma and bone metastases, not HCM. Hydrate first, check creatinine before every dose, retreat after at least 7 days (label). ES 2023 Table 1 differs from the label: dose adjustment if GFR is below 60, infusion over 30–60 minutes, and kidney damage risk especially below 30–35 mL/min. Severe renal impairment: label says use only after weighing risks and benefits.
Pamidronate60–90 mg for corrected Ca of about 12–13.5, 90 mg above 13.5, IV over 2–24 hours; single dose no more than 90 mg; creatinine above 3.0 mg/dL not studied (label). Kidney damage risk especially with GFR below 30–35 mL/min (ES 2023).
Denosumab120 mg SC on days 1, 8 and 15, then every 4 weeks; labeled for HCM refractory to bisphosphonates. Not cleared by the kidney, but CrCl below 30 or dialysis carries a high risk of severe hypocalcemia, and ES 2023 says to consider a lower dose. Correct hypocalcemia first and give calcium and vitamin D as needed (label).
Calcitonin4 units/kg SC or IM every 12 hours; 8 units/kg every 12 hours after 1–2 days if needed; maximum 8 units/kg every 6 hours (label).
GlucocorticoidsHydrocortisone 200–400 mg IV daily for 3–5 days, or prednisone 60 mg daily for 10 days (ES 2023 Table 1).
Electrolytes · 5 of 6

Hypocalcemia: calcium now, magnesium always.

IV calcium for symptoms or adjusted Ca below 1.9 mmol/L

Gluconate 10%9.3 mg elemental calcium per mL. Bolus 1–2 g (10–20 mL), diluted, no faster than 200 mg/min, with ECG monitoring; repeat every 6 hours as needed. Infusion 5.4–21.5 mg/kg/h, titrated to calcium checked every 1–4 hours. Kidney impairment: start at the lowest dose and check calcium every 4 hours (label).
SfE regimen10–20 mL of 10% gluconate in 50–100 mL over 10 minutes, repeated until symptoms settle; then 100 mL of 10% in 1 L at 50–100 mL/h, titrated to normocalcemia. Not in end-stage kidney disease or dialysis: SfE 2016 advises against large-volume calcium infusions there — use small boluses and plan with nephrology.
Chloride 10%27 mg elemental calcium per mL — about three times gluconate. 200–1,000 mg via a central or deep vein, no faster than 1 mL/min; start at 200 mg with kidney impairment (label). Never swap the two millilitre for millilitre.
NeverMix with bicarbonate or phosphate, or run with ceftriaxone in the same line. With digoxin, give slowly, in small amounts, on ECG monitoring (labels).

Then

  • Magnesium. Check it and replace it; calcium will not hold while magnesium is low. SfE 2016 gives IV magnesium 24 mmol over 24 hours for hypomagnesemia-related hypocalcemia.
  • Mild and asymptomatic (adjusted Ca above 1.9 mmol/L): oral calcium, vitamin D if deficient, and treat the cause (SfE 2016).
  • After total thyroidectomy, PTH above 10 pg/mL at 12–24 hours virtually excludes long-term hypoparathyroidism (Second International Workshop 2022).
  • Corrected calcium with caveats, severity band and label doses: calculator, Calcium tab.
Electrolytes · 6 of 6

Magnesium and phosphate: the quiet ones.

Magnesium

Low: causesLoop and osmotic diuretics, PPIs, GI losses (diarrhea, short bowel, pancreatitis), alcohol, aminoglycosides, amphotericin B, calcineurin inhibitors, DKA (Hansen 2018; Australian Prescriber).
Renal or GI?Fractional excretion of magnesium above 2% during hypomagnesemia means renal wasting; below 2% is the appropriate renal response (Australian Prescriber).
Low: symptoms, ECGNeuromuscular excitability — Chvostek and Trousseau signs, tetany, cramps — and seizures; impaired PTH secretion with hypocalcemia; hypokalemia. ECG: long QT, atrial and ventricular arrhythmias, torsades (Hansen 2018).
ReplaceOral for mild, asymptomatic deficiency; IV below 0.5 mmol/L or with significant symptoms (Hansen 2018). Bulloch 2024: 1–2 g over an hour, then 4–8 g slowly over 12–24 hours, and recheck 2 hours later. Severe kidney failure: label maximum 20 g per 48 hours, with frequent levels.
TorsadesSustained polymorphic VT: immediate unsynchronized shock (2025 AHA, Class 1). For recurrences with a long QT, magnesium may be considered (class 2b; no dose given); Bulloch 2024 uses 1–2 g IV over 15 minutes.
HighMagnesium leaves only through the kidneys. Reflexes fade above 4 mEq/L and disappear near 10 mEq/L, where respiratory paralysis can occur; heart block can appear at that level or lower. Stop magnesium, give IV calcium to antagonize it, and support ventilation (magnesium sulfate label).

Phosphate

Low: causesShift into cells (refeeding, insulin and glucose, respiratory alkalosis, hungry bone), renal wasting from FGF-23 excess — including after ferric carboxymaltose — alcohol use and critical illness (Portales-Castillo 2023).
Low: effectsAcute severe deficiency causes rhabdomyolysis, respiratory dysfunction and hemolysis (Portales-Castillo 2023).
Low: IV dosePhosphorus 0.16–0.31 mmol/kg (1.8 mg/dL to the lower limit), 0.32–0.43 (1.0–1.7), 0.44–0.64 (below 1.0); maximum 45 mmol per dose. Potassium phosphate only if K⁺ is below 4 and eGFR is 30 or more; about 6.8 mmol/h peripherally. Single doses of 50 mmol or more, or infusions over 1–3 hours, have caused death and arrhythmia (potassium phosphates label).
High: causesCKD — phosphate usually stays normal until GFR falls below about 20 mL/min — tumor lysis, rhabdomyolysis, phosphate-containing laxatives, hypoparathyroidism (Portales-Castillo 2023).
High: treatCKD G3a–G5D: lower elevated phosphate toward the normal range (KDIGO 2017, recommendation 4.1.2, 2C) and limit calcium-based binders (KDIGO 2017, 4.1.6, 2B). Acute loads with poor kidney function: involve nephrology early. See AKI.
Refeeding, US — ASPEN 2020: check potassium, magnesium and phosphorus before feeding and every 12 hours for the first 3 days in high-risk patients; start with 100–150 g of dextrose or 10–20 kcal/kg for the first 24 hours and advance by a third of goal every 1–2 days; thiamin 100 mg before feeding or before dextrose-containing IV fluids. It grades refeeding by the fall in phosphorus, potassium or magnesium within 5 days: 10–20% mild, 20–30% moderate, more than 30% or organ dysfunction severe. Australasian — AuSPEN 2025: start at 50% or more of requirements and reach goal within 24–72 hours when monitoring is close; thiamin before feeding and for the first 7–10 days. See ICU nutrition and malnutrition.
TTKG transtubular potassium gradientTBW total body waterHCM hypercalcemia of malignancyPTHrP PTH-related peptideES Endocrine SocietySfE Society for EndocrinologyAAFP American Academy of Family PhysiciansASPEN American Society for Parenteral and Enteral NutritionAuSPEN Australasian Society of Parenteral and Enteral NutritionKDIGO Kidney Disease: Improving Global OutcomesFGF-23 fibroblast growth factor 23CrCl creatinine clearance

Educational reference only — not medical advice. Verify against local protocol.

Sources

Verify against current guidelines and local protocol before acting.

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