History

Note that hypercalciuria has no significant physical examination findings and is purely a laboratory diagnosis. Important aspects of the patient’s history may include the following:

Skeletal diseases (eg, osteoporosis, Paget disease) may produce hypercalciuria.
Immobilization for various reasons (eg, postoperative, orthopedic injury, burns, intensive care, spinal cord injury, bone marrow transplants) can cause rapid bone remodeling and, hence, elevated calcium excretion; fortunately, this has become less common owing to the use of early mobilization strategies and physical therapy
Nephrolithiasis is commonly associated with hypercalciuria
Malignancy is a common cause of hypercalcemia and hypercalciuria in hospitalized patients; it usually results from bone destruction, bone reabsorption, or humoral factors such as PTH-related protein.
Human immunodeficiency virus (HIV) infection or its treatment may be associated with a higher risk of hypercalciuria in children

Medications

Certain medications, such as vitamin-D supplements and furosemide, may contribute to hypercalciuria. All loop diuretics decrease the tubular reabsorption of calcium.^[30]

Dietary and fluid intake

Many dietary factors can alter urinary calcium excretion, including the following:

Sodium chloride
Protein
Glucose
Sucrose
Magnesium
Phosphate

An inverse relationship between phosphate intake and urinary calcium excretion is observed; thus, phosphate-restricted diets result in an increase in urinary calcium excretion. With all of the other dietary items mentioned above, a direct relationship between dietary intake and urinary calcium excretion is observed.

Family history

Idiopathic hypercalciuria can run in families, as can diseases that are associated with secondary hypercalciuria. Approximately 50% of persons with kidney stones and hypercalciuria have a first-degree relative who also has hypercalciuria.

Signs and symptoms in children

In children, hypercalciuria is often associated with some degree of hematuria and back or abdominal pain, and is also sometimes associated with voiding symptoms. The standard treatment for pediatric hypercalciuria is limited to dietary or short-term medical therapy, because the patients become asymptomatic when the hypercalciuria is corrected and are often lost to follow-up.

A study involving 124 children with idiopathic hypercalciuria found that 50% of these patients had a family history of kidney stone disease. Fifty-two children developed clinical symptoms of flank or abdominal pain during the study period, but only 6 of these children had actual renal calculi. Twenty-seven children had hematuria, and 10 had incontinence. The children were treated with increased fluid intake and a reduction in dietary oxalate and sodium. Some required treatment with thiazides. All but 5 of the patients responded to therapy. Resolution of the hypercalciuria eliminated the recurrent pain in this patient population.^[31]

Another study, looking at the long-term effects of hypercalciuria in children and several possible therapies over a 4- to 11-year period, concluded that, regardless of treatment, most children with hypercalciuria eventually become asymptomatic while remaining hypercalciuric.^[32]Because limiting calcium intake in children is unwise, the recommended dietary therapy for hypercalciuria is to use a low-sodium/high-potassium diet, which normalizes the hypercalciuria in most pediatric patients.

In children with hypercalciuria, microcrystallization of calcium with urinary anions has been suggested to lead to injury of the uroepithelium. Consequently, when taking the history of the illness, attempt to identify symptoms relating to the urinary tract. Pay particular attention to the following signs and symptoms:

Dysuria
Abdominal pain
Irritability (infants)
Urinary frequency
Urinary urgency
Change of urinary appearance
Colic
Daytime incontinence
Isolated or recurrent urinary tract infections^[2]
Vesicourethral reflux^[3]

Some clinical manifestations are age dependent. For instance, irritability may be the only manifestation in infants, but a teenager may experience renal colic and hematuria.

Differential Diagnoses

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Calcium-rich foods.

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Table 1. Definitions of Hypercalciuria

Diet	Definition
Regular diet (unrestricted)	Women: Urinary excretion >250 mg calcium (6.2 mmol/24 h) Men: Urinary excretion >275-300 mg calcium (7.5 mmol/24 h)
Regular diet (unrestricted)	Urinary excretion >4 mg calcium (0.1 mmol) per kilogram of body weight per day Urinary concentration >200 mg calcium per liter
Restricted diet (400 mg calcium, 100 mEq sodium)	Urinary excretion >200 mg calcium per day
Restricted diet (400 mg calcium, 100 mEq sodium)	Urinary excretion >3 mg calcium per kilogram of body weight per day

Table 2. Hypercalciuria Simplified Test Guideline

Hypercalciuria Diagnosis	Urinary Calcium on 400-mg Calcium Diet (Normal = < 200 mg/24 h)	Fasting Calcium/Creatinine (mg/dL) Ratio (Normal = < 0.11)	Post–Calcium Load Calcium/Creatinine Ratio (Normal = < 0.20)
Normal	Normal	Normal	Normal
Absorptive type I	High	Normal	High
Absorptive type II	Normal	Normal	High
Absorptive type III (renal phosphate leak)	High	High	High
Renal leak	High	High	High
Resorptive (hyperparathyroidism)	High	High	High

Table 3. Calcium-Loading Test Interpretation Guide

Criteria	Absorptive Type I Vitamin D–Dependent (Classic Form)	Absorptive Type I Vitamin D–Dependent (Variant Form)	Absorptive Type II Dietary Calcium Responsive	Absorptive Type III (Renal Phosphate Leak)	Renal Calcium Leak	Resorptive
Urinary calcium on regular diet^*	High	High	High	High	High	High
Urinary calcium on low-calcium diet^†	High	High	NL	High	High	High
Urinary calcium fasting^‡	NL	High	NL	High	High	High
Urinary calcium after 1-g calcium load^§	High	High	NL	High	High	High
Serum PO₄ (fasting)	NL	NL	NL	Low	NL or high	Low
Serum calcium (fasting)	NL	NL or high	NL	NL or high	NL or low	High
Serum PTH	NL or low	NL or low	NL	Low	High	High
Serum PTH after 1-g calcium load	NL or low	NL or low	NL	Low	High	High
Serum vitamin D3 (calcitriol)	NL	High	NL	High	High	High
Fasting normocalciuria while on ketoconazole	No	Yes	No	Yes	No	No
Bone calcium density	NL	NL or low	NL	NL or low	Low	Low
NL = normal; PO₄ = phosphate; PTH = parathyroid hormone. ^* Regular diet is unrestricted calcium and sodium intake. Normal upper limit calciuria is < 4 mg/kg body weight per day. ^† Low-calcium diet is 400 mg calcium and 100 mEq of sodium per day. Normal upper limit calciuria is < 200 mg/day. ^‡ Fasting is a 12-hour fast. Normal upper limit is < 0.11 mg calcium/mg creatinine. ^§ After 1-g calcium load, normal upper limit is < 0.20 mg calcium/mg creatinine.

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Author

Stephen W Leslie, MD, FACS Founder and Medical Director, Lorain Kidney Stone Research Center; Associate Professor of Surgery, Creighton University School of Medicine, Chief of Urology, Creighton University Medical Center

Stephen W Leslie, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, National Kidney Foundation, Ohio State Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Sahar Fathallah-Shaykh, MD Associate Professor of Pediatric Nephrology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Division of Pediatric Nephrology, Medical Director of Pediatric Dialysis Unit, Children's of Alabama

Sahar Fathallah-Shaykh, MD is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Interim Chair, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Acknowledgements

Sahar Fathallah-Shaykh, MD Assistant Professor in Pediatric Nephrology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Division of Pediatric Nephrology, Medical Director of Pediatric Dialysis Unit, Children's of Alabama

Sahar Fathallah-Shaykh, MD is a member of the following medical societies: American Society of Nephrology and American Society of Pediatric Nephrology

Disclosure: Medscape Reference Honoraria Other

Frederick J Kaskel, MD, PhD Director of the Division and Training Program in Pediatric Nephrology, Vice Chair, Department of Pediatrics, Montefiore Medical Center and Albert Einstein School of Medicine

Frederick J Kaskel, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Physiological Society, American Society of Nephrology, American Society of Pediatric Nephrology, American Society of Transplantation, Eastern Society for Pediatric Research, Federation of American Societies for Experimental Biology, International Society of Nephrology, NationalKidneyFoundation, New York Academy of Sciences, Renal Physicians Association, Sigma Xi, and Society for Pediatric Research