# Situation: A 62-year-old woman with breast cancer that has spread to her bones is admitted with confusion, constipation, thirst, and passing large amounts of urine. Her mucous membranes are dry. Her serum calcium is 13.6 mg/dL (3.39 mmol/L) (8.6–10.2 mg/dL; 2.15–2.55 mmol/L), and her albumin is 3.8 g/dL (38 g/L). Her daughter asks why her mother passes so much urine even though she is dehydrated. Which explanation by the nurse is correct?

> source: MyMerci (mymerci.kr)  
> url: https://mymerci.kr/pages/nclex_q.php?qn_id=629904  
> language: ko  
> subject: Nursing Practice III — Care of Clients with Problems in Surgery, Oxygenation, Fluid and Electrolytes, Infectious, Inflammatory and Immunologic Response, Cellular Aberrations

## 문제

Situation: A 62-year-old woman with breast cancer that has spread to her bones is admitted with confusion, constipation, thirst, and passing large amounts of urine. Her mucous membranes are dry. Her serum calcium is 13.6 mg/dL (3.39 mmol/L) (8.6–10.2 mg/dL; 2.15–2.55 mmol/L), and her albumin is 3.8 g/dL (38 g/L).

Her daughter asks why her mother passes so much urine even though she is dehydrated. Which explanation by the nurse is correct?

## 보기

1. Her confusion has led her to drink far more water than she needs
2. High calcium raises her blood pressure, which increases filtration
3. Her cancer is releasing extra antidiuretic hormone into her blood
4. High calcium keeps her kidneys from concentrating the urine **✔ 정답**

**정답: 4**

## 해설

High calcium makes the kidney tubules resistant to antidiuretic hormone, so they cannot concentrate the urine and a large volume of dilute urine is lost (a form of arginine vasopressin resistance, or nephrogenic diabetes insipidus). The polyuria causes dehydration, which in turn reduces calcium excretion and worsens the hypercalcemia.

## 심화 해설

Core mechanism

The correct explanation is that hypercalcemia interferes with the kidney’s ability to concentrate urine. In the collecting duct, antidiuretic hormone (ADH, also called arginine vasopressin or AVP) normally binds to the vasopressin V2 receptor on the basolateral membrane of principal cells. That binding triggers translocation of aquaporin-2 (AQP2) water channels to the apical membrane, allowing water to move back into the body along an osmotic gradient [2]. When serum calcium is markedly elevated, as in this patient’s 13.6 mg/dL (normal 8.6–10.2 mg/dL), the collecting duct becomes resistant to ADH. The kidney tubules cannot respond normally to ADH, so water reabsorption fails and a large volume of dilute urine is lost. This acquired form of ADH resistance is called nephrogenic diabetes insipidus (NDI) [1][3].

Why the polyuria worsens dehydration

The patient’s confusion, dry mucous membranes, thirst, and constipation all point to dehydration. The polyuria is not caused by drinking too much water; rather, it is the primary driver of volume loss. The inability to concentrate urine produces hypotonic, high-volume urine, which depletes extracellular fluid and reduces renal calcium excretion. Because calcium clearance falls when the intravascular volume contracts, the hypercalcemia becomes self-perpetuating: high calcium causes polyuria, polyuria causes dehydration, and dehydration further raises serum calcium [1][3].

Pathophysiology at the cellular level

In acquired NDI, the common downstream defect is loss of AQP2 from the apical membrane of collecting duct principal cells [4]. Even though circulating ADH may be normal or even elevated, the collecting duct cannot insert enough AQP2 to become water-permeable. Hypercalcemia is one of the principal acquired causes of this AQP2 loss, along with hypokalemia, lithium use, and chronic kidney disease [1][4]. This explains why the patient’s urine remains dilute despite clinical dehydration and why simply giving more ADH would not correct the problem.

Why the other options are incorrect

| Option | Why it is wrong |
| --- | --- |
| 1. Confusion led to excessive water intake | Primary polydipsia would produce polyuria, but this patient has objective hypercalcemia and signs of dehydration. The polyuria is the cause of thirst, not the result of overdrinking. |
| 2. High calcium raises blood pressure and filtration | Hypercalcemia does not raise glomerular filtration through hypertension. Even if filtration increased slightly, it would not explain the profound inability to concentrate urine seen in NDI. |
| 3. Cancer releases extra ADH | Excess ADH would cause water retention and concentrated urine, the opposite of this patient’s presentation. The defect is renal resistance to ADH, not increased ADH secretion. |

Key point! Hypercalcemia-induced NDI is a form of arginine vasopressin resistance, not ADH deficiency. The urine is dilute because the collecting duct cannot respond to ADH, even when ADH levels are normal or high.

Watch out! The combination of hypercalcemia, polyuria, and dehydration is a dangerous cycle. Dehydration reduces calcium excretion, which worsens hypercalcemia, which worsens polyuria. Early recognition and correction of volume status are essential to interrupt this loop.References (research sources)

- [1][Nephrogenic diabetes insipidus].Research articleBichet DG (2006) · DOI: 10.1016/j.nephro.2006.07.010

- [2][Nephrogenic diabetes insipidus].Research articleVelásquez-Jones L, Medeiros-Domingo M (2014) · DOI: 10.1016/j.bmhimx.2015.01.004

- [3]Miliary tuberculosis with hypercalcaemia-induced nephrogenic diabetes insipidus in an infant.Research articleTousifullah M, Rastogi A. (2025) · DOI: 10.1136/bcr-2025-269609

- [4]'Aquaporin-omics': mechanisms of aquaporin-2 loss in polyuric disorders.Research articleMak A, Sung CC, Pisitkun T, Khositseth S, Knepper MA (2024) · DOI: 10.1113/JP284634

## 임상 시나리오

Hypercalcemia-Induced PolyuriaWhy dehydration and dilute urine coexist
In marked hypercalcemia, the collecting duct becomes resistant to ADH, producing nephrogenic diabetes insipidus. The result is high-volume, dilute urine despite dehydration.

The polyuria depletes intravascular volume, which lowers renal calcium clearance and further raises serum calcium. This creates a self-perpetuating cycle: high calcium causes polyuria, polyuria causes dehydration, and dehydration worsens hypercalcemia.

CautionDo not attribute polyuria to excessive water intake. The primary problem is impaired urinary concentration, so volume replacement and calcium lowering are the priorities.

## 핵심 개념

- **Nephrogenic diabetes insipidus** — Kidney tubule resistance to ADH, causing inability to concentrate urine and dilute polyuria
- **Aquaporin-2** — ADH-regulated water channel in collecting duct principal cells that is impaired in hypercalcemia-induced NDI
- **Hypercalcemia** — Elevated serum calcium that interferes with ADH action and reduces renal calcium excretion when dehydration occurs
- **Polyuria** — Excessive dilute urine output that drives dehydration and worsens hypercalcemia

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