Nephrocalcinosis, once known as Albright's calcinosis after Fuller Albright, is a term originally used to describe the deposition of poorly soluble

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

salts in the

renal parenchyma upright=1.6, Lung parenchyma showing damage due to large subpleural bullae. Parenchyma () is the bulk of functional substance in an animal organ such as the brain or lungs, or a structure such as a tumour. In zoology, it is the tissue that ...

due to

hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands ( primary hyperparathyroidism) or as response to external stimuli ( secondary hyperparathyroi ...

. The term nephrocalcinosis is used to describe the deposition of both

calcium oxalate Calcium oxalate (in archaic terminology, oxalate of lime) is a calcium salt of oxalic acid with the chemical formula or . It forms hydrates , where ''n'' varies from 1 to 3. Anhydrous and all hydrated forms are colorless or white. The monohydr ...

and

calcium phosphate The term calcium phosphate refers to a family of materials and minerals containing calcium ions (Ca2+) together with inorganic phosphate anions. Some so-called calcium phosphates contain oxide and hydroxide as well. Calcium phosphates are white ...

. It may cause acute kidney injury. It is now more commonly used to describe diffuse, fine, renal

parenchyma upright=1.6, Lung parenchyma showing damage due to large subpleural bullae. Parenchyma () is the bulk of functional substance in an animal organ such as the brain or lungs, or a structure such as a tumour. In zoology, it is the tissue that ...

calcification Calcification is the accumulation of calcium salts in a body tissue. It normally occurs in the formation of bone, but calcium can be deposited abnormally in soft tissue,Miller, J. D. Cardiovascular calcification: Orbicular origins. ''Nature M ...

radiology Radiology ( ) is the medical specialty that uses medical imaging to diagnose diseases and guide treatment within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiation), but tod ...

. It is caused by multiple different conditions and is determined by progressive kidney dysfunction. These outlines eventually come together to form a dense mass. During its early stages, nephrocalcinosis is visible on

x-ray An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...

, and appears as a fine granular mottling over the renal outlines. It is most commonly seen as an incidental finding with

medullary sponge kidney Medullary sponge kidney is a congenital disorder of the kidneys characterized by cystic dilatation of the collecting tubules in one or both kidneys. Individuals with medullary sponge kidney are at increased risk for kidney stones and urinary tra ...

on an abdominal x-ray. It may be severe enough to cause (as well as be caused by)

renal tubular acidosis Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. In renal physiology, when blood is filtered by the kidney, the filtrate ...

or even end stage kidney disease, due to disruption of the kidney tissue by the deposited calcium salts.

Signs and symptoms

Though this condition is usually

asymptomatic Asymptomatic (or clinically silent) is an adjective categorising the medical conditions (i.e., injuries or diseases) that patients carry but without experiencing their symptoms, despite an explicit diagnosis (e.g., a positive medical test). P ...

, if symptoms are present they are usually related to the causative process, (e.g.

hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L def ...

). Some of the symptoms that can happen are

blood in the urine Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. "Gross hematuria" occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable with ...

, fever and chills, nausea and vomiting, severe pain in the belly area, flanks of the back, groin, or testicles. These include

renal colic Renal colic (literally, kidney pain), also known as ureteric colic (literally, pain in the ureters), is characterized by severe abdominal pain that is spasmodic in nature. This pain is primarily caused by an obstruction of one or both ureters fr ...

polyuria Polyuria () is excessive or an abnormally large production or Frequent urination, passage of urine (greater than 2.5 L or 3 L over 24 hours in adults). Increased production and passage of urine may also be termed as diuresis. Polyuria often appe ...

and

polydipsia Polydipsia is excessive thirst or excess drinking.Porth, C. M. (1990). ''Pathophysiology: Concepts of altered health states''. Philadelphia: J.B. Lippincott Company. The word derives , which is derived . Polydipsia is a nonspecific symptom in v ...

: * Renal colic is usually caused by pre-existing

nephrolithiasis Kidney stone disease (known as nephrolithiasis, renal calculus disease, or urolithiasis) is a crystallopathy and occurs when there are too many minerals in the urine and not enough liquid or hydration. This imbalance causes tiny pieces of cr ...

, as may occur in patients with chronic

hypercalciuria Hypercalciuria is the condition of elevated calcium in the urine. Chronic hypercalciuria may lead to impairment of renal function, nephrocalcinosis, and chronic kidney disease. Patients with hypercalciuria have kidneys that excrete higher levels ...

. Less commonly, it can result from calcified bodies moving into the calyceal system. *

Nocturia Nocturia is defined by the International Continence Society (ICS) as "the complaint that the individual has to wake at night one or more times for voiding (''i.e., to urinate'')". The term is derived from Latin ''nox'' – "night", and Greek '' ...

, and

from reduced urinary concentrating capacity (i.e. nephrogenic diabetes insipidus) as can be seen in

, medullary nephrocalcinosis of any cause, or in children with Bartter syndrome in whom essential tubular salt reabsorption is compromised. There are several causes of nephrocalcinosis that are typically acute and present only with

kidney failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...

. These include

tumor lysis syndrome Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off ( lysed) from the treatment, releasing their contents into the blood ...

, acute phosphate nephropathy, and occasional cases of enteric

hyperoxaluria Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones. It is sometimes called Bird's disease, after Golding Bird, who first described the condition. Presentation Caus ...

Cause

Nephrocalcinosis is connected with conditions that cause

hypercalcaemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defin ...

hyperphosphatemia Hyperphosphatemia is an electrolyte disorder in which there is an elevated level of phosphate in the blood. Most people have no symptoms while others develop calcium deposits in the soft tissue. The disorder is often accompanied by low calci ...

, and the increased excretion of calcium, phosphate, and/or oxalate in the urine. A high urine pH can lead to nephrocalcinosis but only if it is accompanied by

and hypocitraturia, since having a normal urinary

citrate Citric acid is an organic compound with the formula . It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relati ...

usually inhibits the

crystallization Crystallization is a process that leads to solids with highly organized Atom, atoms or Molecule, molecules, i.e. a crystal. The ordered nature of a crystalline solid can be contrasted with amorphous solids in which atoms or molecules lack regu ...

of calcium. In conjunction with nephrocalcinosis, hypercalcaemia and hypercalciuria the following can occur: * Primary hyperparathyroidism: Nephrocalcinosis is one of the most common symptoms of primary

. *

Sarcoidosis Sarcoidosis (; also known as Besnier–Boeck–Schaumann disease) is a disease involving abnormal collections of White blood cell, inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph n ...

: Nephrocalcinosis is one of the most common symptoms. *

Vitamin D Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...

: This can cause nephrocalcinosis because of vitamin D therapy because it increases the absorption of ingested calcium and

bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nuclea ...

, resulting in

and

Medullary nephrocalcinosis

Medullary sponge kidney Medullary sponge kidney is a congenital disorder of the kidneys characterized by cystic dilatation of the collecting tubules in one or both kidneys. Individuals with medullary sponge kidney are at increased risk for kidney stones and urinary tra ...

* Distal

Hyperoxaluria Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones. It is sometimes called Bird's disease, after Golding Bird, who first described the condition. Presentation Caus ...

Renal papillary necrosis Renal papillary necrosis is a form of nephropathy involving the necrosis of the renal papilla. Lesions that characterize renal papillary necrosis come from an impairment of the blood supply and from subsequent ischemic necrosis that is diffuse. Sig ...

And other causes of

(and thus

) * Immobilization (leading to hypercalcaemia and hypercalciuria) *

Milk-alkali syndrome Milk-alkali syndrome (MAS), also referred to as calcium-alkali syndrome, is the third most common cause of elevated blood calcium levels ( hypercalcemia). Milk-alkali syndrome is characterized by hypercalcemia, metabolic alkalosis, and acute ki ...

Hypervitaminosis D Vitamin D toxicity, or hypervitaminosis D, is the toxic state of an excess of vitamin D. The normal range for blood concentration of 25-hydroxyvitamin D in adults is 20 to 50 nanograms per milliliter (ng/mL). Blood levels necessary to cause a ...

Multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

Hypercalciuria without hypercalcaemia

These conditions can cause nephrocalcinosis in association with hypercalciuria without hypercalcaemia: * Distal renal tubular acidosis *

* Neonatal nephrocalcinosis and loop diuretics * Inherited tubulopathies * Chronic hypokalemia *

Beta thalassemia Beta-thalassemia (β-thalassemia) is an genetic disorder, inherited hemoglobinopathy, blood disorder, a form of thalassemia resulting in variable outcomes ranging from clinically asymptomatic to severe anemia individuals. It is caused by reduce ...

* Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC)

Mechanism

Nephrocalcinosis is caused by an increase in the urinary excretion of

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

, and/or

oxalate Oxalate (systematic IUPAC name: ethanedioate) is an anion with the chemical formula . This dianion is colorless. It occurs naturally, including in some foods. It forms a variety of salts, for example sodium oxalate (), and several esters such as ...

. Nephrocalcinosis is closely associated with

, and patients frequently present with both conditions, however there have been cases where one occurs without the other.

Calcium oxalate Calcium oxalate (in archaic terminology, oxalate of lime) is a calcium salt of oxalic acid with the chemical formula or . It forms hydrates , where ''n'' varies from 1 to 3. Anhydrous and all hydrated forms are colorless or white. The monohydr ...

and

crystal A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macros ...

s form when the

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

of the

reactants In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...

exceeds the limit of solubility of these compounds under the physiological conditions prevailing locally in the organism. The deposits are collected in the inner medullary interstitium in the basement membranes of the thin limbs of the

loop of Henle In the kidney, the loop of Henle () (or Henle's loop, Henle loop, nephron loop or its Latin counterpart ''ansa nephroni'') is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after it ...

. The calcium phosphate plaques can enlarge into the surrounding interstitial tissue, or even rupture into the tubule lumen and can promote calcium oxalate stone formation.

Diagnosis

Nephrocalcinosis is diagnosed for the most part by imaging techniques. The imagings used are

ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...

(US), abdominal plain film and CT imaging. Of the 3 techniques CT and US are the preferred modalities. In some cases a renal

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...

is done instead if imaging is not enough to confirm nephrocalcinosis. Once the diagnosis is confirmed additional testing is needed to find the underlying cause because the underlying condition may require treatment for reasons independent of nephrocalcinosis. These additional tests will measure serum,

electrolyte An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble Salt (chemistry), salts, acids, and Base (chemistry), bases, dissolved in a polar solven ...

, and

, and the urine pH. If no underlying cause can be found then urine collection should be done for 24 hours and measurements of the excretion of calcium, phosphate,

, and

creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an impor ...

are looked at.

Stages of nephrocalcinosis

* Chemical or Molecular nephrocalcinosis: Defined as a measurable increase in intracellular

concentrations, however, it is not visible through

X-ray An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...

or microscopically. * Microscopic nephrocalcinosis: Occurs when depositis are visible by light

microscope A microscope () is a laboratory equipment, laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic ...

by obtaining a tissue sample from a biopsy. However, this cannot be seen in an X-ray. * Macroscopic nephrocalcinosis: Occurs when calcification can be seen through X-ray imaging.

Treatment

Increasing fluid intake to yield a urine output of greater than 2 liters a day can be advantageous for all patients with nephrocalcinosis. Patients with hypercalciuria can reduce calcium excretion by restricting animal protein, limiting

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

intake to less than 100 meq a day and being lax of potassium intake. If changing one's diet alone does not result in a suitable reduction of hypercalciuria, a thiazide diuretic can be administered in patients who do not have hypercalcemia.

Citrate Citric acid is an organic compound with the formula . It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relati ...

can increase the solubility of calcium in urine and limit the development of nephrocalcinosis. Citrate is not given to patients who have urine pH equal to or greater than 7.

Prognosis

The prognosis of nephrocalcinosis is determined by the underlying cause. Most cases of nephrocalcinosis do not progress to end stage

renal disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can b ...

, however if not treated it can lead to renal dysfunction this includes primary

, hypomagnesemic hypercalciuric nephrocalcinosis and

Dent's disease Dent's disease (or Dent disease) is a rare X-linked recessive inherited condition that affects the proximal renal tubules of the kidney. It is one cause of Fanconi syndrome, and is characterized by tubular proteinuria, hypercalciuria, excess calciu ...

. Once nephrocalcinosis is found, it is unlikely to be reversed, however, partial reversal has been reported in patients who have had successful treatment of hypercalciuria and hyperoxaluria following corrective intestinal surgery.

Recent research

In recent findings they have found that there is a genetic predisposition to nephrocalciosis, however the specific genetic and epigenetic factors are not clear. There seems to be multiple genetic factors that regulate the excretion of the different urinary risk factors. There has been some correlation seen that shows

gene polymorphism A gene is said to be polymorphic if more than one allele occupies that gene's Locus (genetics), locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of ...

s related to stone formation for

calcium-sensing receptor The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ions. It is primarily expressed in the parathyroid gland, the renal tubules of the kidney, pancreatic islets and the br ...

and vitamin D receptors. Repeated calcium stones associated with

may be related to an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

mutation of a still unknown gene, however the genes is ''

GDNF Glial cell line-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the ''GDNF'' gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particul ...

'' seems to be a gene involved in renal morphogenesis. In conjunction with the gene research is another theory of how the disease manifests. This is called the free particle theory. This theory says that the increasing concentration of lithogenic solutes along the segments of the nephron leads to the formation, growth, and collection of crystals that might get trapped in the tubular lumen and begin the process of stone formation. Some of the backing behind this theory is the speed of growth of the crystals, the diameter of the segments of the

nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structu ...

, and the transit time in the nephron. All of these combined show more and more support for this theory.

References

External links

{{Authority control Kidney diseases