Nephrology

Diagnostic Tests & Monitoring Your Labs

At a Glance

FHHNC is diagnosed by combining blood and urine findings, kidney ultrasound, and genetic testing for two disease-causing CLDN16 or CLDN19 variants. Ongoing monitoring tracks magnesium, calcium, PTH, eGFR, urine minerals, and kidney imaging.

Diagnosing FHHNC requires putting together several pieces of a puzzle: blood work, urine tests, and specialized imaging. Because the condition is rare and symptoms can overlap with other kidney issues, a specialist evaluation is required ^[1]^[2].

The Core Clinical Findings

Doctors typically suspect FHHNC when three specific findings occur together. However, this classic triad may be incomplete, especially early in the disease:

Hypomagnesemia: Low magnesium in the blood. Note that in some children, magnesium levels might only be slightly low or even in the “low-normal” range, so doctors must also check the urine (urinary magnesium or fractional magnesium excretion) for evidence that the kidney is “wasting” magnesium ^[3]^[4].
Hypercalciuria: Excessive calcium in the urine. Because normal calcium levels change as children grow, doctors use age-specific reference limits, often requiring a 24-hour urine collection to determine if the amount is too high ^[5]^[6].
Bilateral Nephrocalcinosis: Evidence of calcium deposits in both kidneys during an ultrasound. Note that nephrocalcinosis can be absent in early or milder presentations ^[1]^[7].

While these findings strongly point to FHHNC, the definitive diagnosis requires genetic testing ^[8]. This confirms the presence of biallelic (two) pathogenic mutations in either the CLDN16 or CLDN19 genes, which is essential for understanding the long-term outlook and checking other family members ^[9]^[10]. A single variant or a “variant of uncertain significance” does not automatically confirm the disease.

Nephrocalcinosis vs. Kidney Stones

It is common to hear the terms “nephrocalcinosis” and “kidney stones” (nephrolithiasis) used together, but they are different processes:

Nephrocalcinosis: This is a hallmark of FHHNC. It occurs when calcium deposits form inside the actual tissue of the kidney (the medulla) ^[11]. This can cause the kidney to become “bright” on an ultrasound and may lead to scarring over time ^[12]^[1].
Nephrolithiasis: These are discrete, solid stones that form in the open spaces of the kidney or urinary tract ^[13]. While nephrocalcinosis is the primary issue in FHHNC, about 25% of patients also develop these “traditional” stones, which can cause intense pain (renal colic) or blockages ^[14]^[15].

Interpreting PTH (Parathyroid Hormone)

Parathyroid Hormone (PTH) is a hormone that helps regulate calcium and magnesium. In FHHNC, PTH levels are often high—a condition called secondary hyperparathyroidism ^[16].

Research has shown that patients who have higher PTH levels at the time of diagnosis tend to experience a faster decline in kidney function (measured by eGFR) over the following years ^[17]. However, PTH is not a standalone predictor, nor should treatment decisions be based on it alone. PTH is affected by kidney disease stage, vitamin D, phosphate, and calcium levels. Your nephrologist will use the trend of your PTH alongside eGFR, calcium, and phosphate to assess overall risk and guide management ^[17]^[16].

A Common Starting Set for Monitoring

When reviewing lab results with your care team, ensure the following markers are tracked. Your nephrologist will select specific tests based on age, genotype, and kidney stage. Not every patient needs follow-up on a fixed schedule.

Category	Specific Lab Test	Why it is Monitored
Blood Minerals	Serum Magnesium (Mg)	To ensure levels are safe and assess if supplements are working ^[18].
	Serum Calcium & Potassium	Calcium fluctuates; potassium can be lost due to medications or the disease ^[4]^[16].
Kidney Health	Creatinine / eGFR	The primary way to measure how well the kidneys filter waste ^[17].
Hormone Balance	PTH & Vitamin D	Tracked together to assess mineral and bone health risks ^[17].
Urine Markers	Urine Ca, Mg, & Citrate	24-hour collections or ratios help measure ongoing mineral loss ^[5].
Imaging	Renal Ultrasound	Monitored periodically to check for progressive nephrocalcinosis or stones ^[7].

Once familial variants are confirmed, a baseline kidney and eye evaluation is established. Regular follow-up allows your team to review trends and catch changes early ^[18]^[1].

Common questions in this guide

How is FHHNC diagnosed?

Doctors look for a pattern of low or low-normal blood magnesium, excess calcium in the urine, and calcium deposits in both kidneys seen on ultrasound. Early or mild disease may not show all three findings, so urine magnesium testing and age-based urine calcium measurements are important. Genetic testing confirms the diagnosis when it finds disease-causing variants in both copies of CLDN16 or CLDN19.

Can FHHNC be present if blood magnesium is only slightly low?

Yes. Some children have low-normal or only slightly low blood magnesium while their kidneys still waste magnesium. A urine magnesium measurement or fractional magnesium excretion can show this loss, so a normal-looking blood result does not rule out FHHNC.

How are nephrocalcinosis and kidney stones different?

Nephrocalcinosis is calcium deposited within kidney tissue, often seen as increased brightness on an ultrasound. Kidney stones are discrete solid pieces in the kidney’s collecting spaces or urinary tract and can cause colicky pain or blockage. A person with FHHNC can have nephrocalcinosis, stones, or both.

Why are PTH and eGFR measured together in FHHNC?

PTH is often high in FHHNC, and higher PTH at diagnosis has been associated with a faster decline in kidney filtering function. However, PTH is not a stand-alone predictor. Nephrologists interpret its trend with eGFR, calcium, phosphate, vitamin D, and kidney disease stage.

What tests are usually included in FHHNC follow-up?

Follow-up may include blood magnesium, calcium, potassium, creatinine and eGFR, PTH, and vitamin D; urine calcium, magnesium, and citrate; and renal ultrasound. The exact tests and timing depend on age, genetic findings, and kidney function, so the schedule is individualized.

What does genetic testing mean if only one CLDN16 or CLDN19 variant is found?

Finding one variant or a variant of uncertain significance does not by itself confirm FHHNC. The diagnosis is confirmed by finding pathogenic variants in both copies of CLDN16 or CLDN19 along with matching clinical findings. A genetics professional or nephrologist can explain whether additional testing is needed.

Get notified when new evidence is published on Primary hypomagnesemia with hypercalciuria and nephrocalcinosis.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

References (18)

1
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PMID: 33595712
2
Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis: clinical and molecular characteristics.
Claverie-Martin F
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3
A novel mutation in CLDN16 results in rare familial hypomagnesaemia with hypercalciuria and nephrocalcinosis in a Chinese family.
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4
Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis Due to CLDN16 Gene Mutations: Novel Findings in Two Cases with Diverse Clinical Features.
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5
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6
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7
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8
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Rahmani N, Talebi S, Hooman N, Karamzade A
Journal of pediatric genetics 2021; (10(3)):230-235 doi:10.1055/s-0041-1733852.
PMID: 34504727
9
Identification of the first large deletion in the CLDN16 gene in a patient with FHHNC and late-onset of chronic kidney disease: case report.
Yamaguti PM, dos Santos PA, Leal BS, et al.
BMC nephrology 2015; (16()):92 doi:10.1186/s12882-015-0079-4.
PMID: 26136118
10
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García-Castaño A, Perdomo-Ramirez A, Vall-Palomar M, et al.
Molecular genetics & genomic medicine 2020; (8(11)):e1475 doi:10.1002/mgg3.1475.
PMID: 32869508
11
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12
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by CLDN16/CLDN19 mutations in four Chinese families.
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13
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14
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15
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16
Assessment of bone status and bone turnover in pediatric patients with familiar hypomagnesemia with hypercalciuria and nephrocalcinosis.
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18
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This page explains FHHNC diagnostic tests and lab monitoring for informational purposes only and does not constitute medical advice. Your nephrologist should interpret your results, genetic testing, and ultrasound in the context of your age and kidney function.

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