Nephrocalcinosis, once known as Albright's calcinosis after

Fuller Albright Fuller Albright (January 12, 1900 – December 8, 1969) was an American endocrinologist who made numerous contributions to his field, especially to the area of calcium metabolism. Albright made great strides and contributions to the understanding ...

, is a term originally used to describe deposition of

calcium Calcium is a chemical element with the 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 t ...

salts in the

renal parenchyma Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms. Etymology The term ''parenchyma'' is New Latin from the word π ...

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 hyperparathyroidism). ...

. The term nephrocalcinosis is used to describe the deposition of both calcium oxalate and calcium phosphate. It may cause acute kidney injury. It is now more commonly used to describe diffuse, fine, renal parenchymal calcification in radiology. It is caused by multiple different conditions and is determined 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, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...

, 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 trac ...

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

end stage kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

, due to disruption of the kidney tissue by the deposited calcium.

Signs and symptoms

Though this condition is usually asymptomatic, if symptoms are present they are usually related to the causative process, (e.g. hypercalcemia). Some of the symptoms that can happen are blood in the urine, 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 is a type of abdominal pain commonly caused by obstruction of ureter from dislodged kidney stones. The most frequent site of obstruction is the vesico-ureteric junction (VUJ), the narrowest point of the upper urinary tract. Acute ob ...

polyuria Polyuria () is excessive or an abnormally large production or 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 diuresis. Polyuria often appears in conjunction wit ...

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 from the Greek () "very thirsty", which is derived from (, "mu ...

: * Renal colic is usually caused by pre-existing

nephrolithiasis Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...

, 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 put out higher levels ...

. Less commonly, it can result from calcified bodies moving into the calyceal system. * Nocturia, polyuria, and polydipsia from reduced urinary concentrating capacity (i.e.

nephrogenic diabetes insipidus Nephrogenic diabetes insipidus, also known as renal diabetes insipidus, is a form of diabetes insipidus primarily due to pathology of the kidney. This is in contrast to central or neurogenic diabetes insipidus, which is caused by insufficient le ...

) as can be seen in hypercalcemia, medullary nephrocalcinosis of any cause, or in children with

Bartter syndrome Bartter syndrome (BS) is a rare inherited disease characterised by a defect in the thick ascending limb of the loop of Henle, which results in low potassium levels (hypokalemia), increased blood pH (alkalosis), and normal to low blood pressure. T ...

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 end-stage kidney disease, 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 failure is classified as eit ...

. 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. Causes Hyperoxalur ...

Cause

Nephrocalcinosis is connected with conditions that cause hypercalcemia, hyperphosphatemia, 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 usually inhibits the crystallization of calcium. In conjunction with Nephrocalcinosis, hypercalcemia 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 inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly a ...

: Nephrocalcinosis is one of the most common symptoms. *

Vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...

: This can cause nephrocalcinosis because of Vitamin D therapy because it increases the absorption of ingested calcium and bone resorption, resulting in hypercalcemia 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 trac ...

* Distal renal tubular acidosis *

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. Causes Hyperoxalur ...

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. ...

And other causes of hypercalcemia (and thus

) * Immobilization (leading to hypercalcemia and hypercalciuria) *

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

Hypervitaminosis D Vitamin D toxicity, or hypervitaminosis D is the toxic state of an excess of vitamin D. The normal range for blood concentration is 20 to 50 nanograms per milliliter (ng/mL). However, the toxic state is known to be a value of 100 ng/ml or more in ...

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 antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, an ...

Hypercalciuria without hypercalcemia

These conditions can cause nephrocalcinosis in association with hypercalciuria without hypercalcemia: *

Distal renal tubular acidosis Distal renal tubular acidosis (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the distal tubule and cortical collecting duct of the di ...

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

Beta thalassemia Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to cl ...

Mechanism

Nephrocalcinosis is caused by an increase in the urinary excretion of calcium, phosphate, and/or oxalate. 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 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 whi ...

crystals form when the concentration of the reactants exceeds the limit. 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 its ...

. 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 waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...

(US), abdominal plain film and CT imaging. Of the 3 techniques CT and US are the more preferred. Nephrocalcinosis is considered present if at least two

radiologists Radiology ( ) is the medical discipline that uses medical imaging to diagnose diseases and guide their treatment, within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiat ...

make the diagnosis on US and/or CT. In some cases a renal

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...

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, electrolytes, calcium, and

phosphate 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 orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

, 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, oxalate, citrate, and creatinine 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, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...

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

microscope A microscope () is a 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 means being invisibl ...

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 with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...

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 Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...

can be administered in patients who do not have hypercalcemia.

Citrate Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the ...

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, excess calcium in the urin ...

. 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 polymorphisms 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 and the brain. In the parathyroi ...

and vitamin D receptors. Repeated calcium stones associated with medullary sponge kidney 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 effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

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, particula ...

'' 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 Free may refer to: Concept * Freedom, having the ability to do something, without having to obey anyone/anything * Freethought, a position that beliefs should be formed only on the basis of logic, reason, and empiricism * Emancipate, to proc ...

. 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, 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