The word “nephrocalcinosis,” first used in 1934 by Fuller Albright, describes an increase in the amount of calcium in the kidneys. This calcium might take the form of calcium phosphate and calcium oxalate. There have been proposals, nonetheless, that the term “nephrocalcinosis” should exclusively refer to the accumulation of calcium phosphate and that the term “calcium oxalosis” should be used for the accumulation of calcium oxalate.
The renal parenchyma & tubules exhibit typical calcium accumulation due to the disease. It may show up on a radiograph inadvertently from a person with normal renal function, or it may be present with chronic or acute kidney damage. This entity can be caused by a variety of diseases, and the underlying causal issue will determine the overall renal outcome.
Epidemiology
Primary Hyperparathyroidism
The most frequent renal symptoms of primary hyperparathyroidism are nephrocalcinosis & nephrolithiasis. According to reports, nephrocalcinosis can occur in up to 22% of people with primary hyperparathyroidism. Even while the parathyroid hormone increases calcium absorption in the distal tubules, the benefit is overwhelmed by a rise in filtered calcium, which raises urine calcium excretion.
Sarcoidosis
Hypercalcemia & hypercalciuria are linked to sarcoidosis. In up to 50% of instances where the kidneys are involved, nephrocalcinosis is present.
Distal Renal Tubular Acidosis
Hypercalciuria without hypercalcemia is the most significant complication of nephrocalcinosis. Hypocitraturia, which encourages calcium precipitation in the proximal tubule, is associated with it. Moreover, it leads to metabolic acidosis, which increases the amount of acid that bone buffers can buffer, leading to the release of phosphate and calcium. In research by Brenner et al., which assessed the radiological incidence of nephrocalcinosis in different renal tubular acidoses, nephrocalcinosis was detected in up to 29% of the 92 cases investigated, with the majority of cases occurring in those with distal kidney tubular acidosis.
Medullary Sponge Kidney
Stones are frequent in this illness, which has distorted papillary collection ducts. It causes nephrocalcinosis because it is linked to hypercalciuria & hypocitraturia. Nephrocalcinosis was noted in up to 50% of patients of the medullary sponge kidney in research by Yendt et al.
Nephrocalcinosis-Related Hereditary Disorders
X-linked hypophosphatemic rickets, X-linked hypercalciuric nephrolithiasis, Bartter syndrome, and hypomagnesemia-hypercalciuria syndrome are a few of them. The condition known as Dent disease, which is associated with some abnormalities affecting the CLCN5 allele on the X chromosome that result in the deactivation of CLC-5 voltage-gated chloride channels, is X-linked hypercalciuric nephrolithiasis. This leads to a clinical condition that typically affects young boys & involves rickets, low molecular weight proteinuria, glycosuria, nephrocalcinosis, hypercalciuria, hematuria, and aminoaciduria.
Nephrocalcinosis caused by Usage Of Loop Diuretics
Those who take large doses of loop diuretics over an extended period of time run the risk of developing nephrocalcinosis. 18 consecutive adult people who regularly took furosemide for gaining weight & edema were assessed in a study by Kim et al. The research discovered nephrocalcinosis in 15 patients who received a mean daily dose of 538 mg. The authors concluded that the dose of furosemide taken correlates with the probability of nephrocalcinosis.
Anatomy
Pathophysiology
Nephrocalcinosis is divided into the following categories:
Chemical or molecular: a rise in intracellular calcium concentration that can be measured but is not visible by imaging.
Microscopic: Light microscopic analysis of renal biopsy samples revealed deposits that were not radiologically evident.
The renal medulla is typically involved, whereas the cortex is considerably less frequent.
The following conditions are linked to cortical nephrocalcinosis:
Oxalosis
Tuberculosis
Trauma
Chronic glomerulonephritis
Transplant rejection
The cortical necrosis that develops during pregnancy
One disease that can result in both medullary & cortical nephrocalcinosis is oxalosis.
Hypercalciuria, either with or without hypercalcemia, is the most frequent cause of nephrocalcinosis. Nephrolithiasis is frequently linked to the metabolic abnormalities of hyperphosphaturia, hyperoxaluria, and hypercalciuria & patients frequently have both disorders at the same time. When the solute concentration in the tubular fluid exceeds the saturation limit, calcium oxalate & calcium phosphate crystals form.
Randall’s plaques were identified in a study by Evan AP et al. as being a component of the basement membranes of the narrow limb of the loop of Henle, which is where the tubule fluid is saturated. Once formed, calcium phosphate plaques can grow into the surrounding interstitial tissue or burst into the tubular lumen, producing a nidus for luminal Ca oxalate stones.
Basophilic calcifications can be seen with light microscopy in nephrocalcinosis in tubular, interstitial, and intracellular settings. Interstitial fibrosis and lymphocyte-predominant interstitial infiltration accompany calcium phosphate accumulation.
Etiology
The term “nephrocalcinosis” refers to a broad buildup of calcium in the kidneys, not to the focal calcium accumulation linked to a specific focal renal damage. Diseases that result in hypercalcemia, hypercalciuria, hyperphosphatemia, hyperoxaluria, and hyperphosphaturia are the root cause of this condition.
Alkaline urinary pH leads to the production of calcium phosphate particles. It has connections to numerous diseases that are caused by underlying mechanisms.
Hyperphosphaturia in the absence of hyperphosphatemia
Having hyperphosphatemia and hyperphosphaturia
Hypercalciuria in the absence of hypercalcemia
Combined hypercalcemia and hypercalciuria
1. Diseases that both cause hypercalcemia & hypercalciuria
Inherited tubulopathies like Lowe syndrome & Dent illness
Genetics
Prognostic Factors
If they are not adequately treated, specific forms of nephrocalcinosis such as primary hyperoxaluria, Dent illness, & hypomagnesemia hypercalciuric nephrocalcinosis will proceed to chronic kidney failure or end-stage kidney disease. Rarely is nephrocalcinosis reversible once radiologically discovered.
Clinical History
Clinical history
Nephrocalcinosis’s presentation is mostly determined by its underlying etiology, even though it frequently manifests without any symptoms and is only seen as a radiologic anomaly. The non-specific physical signs reflect the underlying diseases that cause nephrocalcinosis. The three kinds of nephrocalcinosis’ potential clinical characteristics are mentioned below.
Hypercalcemic nephropathy / chemical nephrocalcinosis
In addition to impaired renal concentrating ability and increased free water diuresis (nephrogenic diabetic insipidus), which manifest as polyuria and polydipsia, hypercalcemic nephropathy is frequently characterized by relative vasopressin resistance. There have also been a few reports of renal glycosuria, lower glucose tubular maximum, aminoaciduria, & non-glomerular proteinuria. Around 50% of individuals get reversible hypertension as a result of enhanced peripheral vasoconstriction.
By direct renal vasoconstriction and volume depletion brought on by severe diuresis, hypercalcemia is also a well-established cause of kidney failure. Normal renal function will recover as soon as the hypercalcemia is treated with volume replacement, making this procedure typically reversible. However, persistent hypercalcemia can lead to permanent failure, which is always accompanied by Ca+ crystal formation.
Microscopic nephrocalcinosis
A single nephron’s transit time in a distal tubule is prolonged, blood urea nitrogen (BUN) levels are elevated, and less concentration capacity is seen, despite the fact that there are no comprehensive studies of glomerular filtration or renal tubular function in these models. Acute pyelonephritis or calculous ureteral blockage with kidney failure can occasionally occur in rats with the pelvic variety of nephrocalcinosis.
Macroscopic nephrocalcinosis
Medullary nephrocalcinosis can lead to a wide spectrum of problems. Calcium nodules have the potential to break through the papillary epithelium into the calyceal system & form urinary stones, which can cause renal colic, hematuria, urinary stone passage, or bladder infection as clinical manifestations. Nephrocalcinosis typically denotes a more severe metabolic disturbance, therefore, macroscopic nephrocalcinosis shouldn’t be mistaken for a kidney stone.
It’s worth noting the following:
Because of the excess of free water diuresis and the decreased renal concentrating ability, polyuria & polydipsia may be apparent.
The relative rarity of hypertension is likely due to a diminished capacity to store salt.
Although it is often less than 500 mg per day and in the non-nephrotic range, proteinuria may be seen.
Loss of low-molecular-weight proteins may surpass 2 g/day in Dent disease, and other presenting symptoms include nephrolithiasis, hypercalciuria, & nephrocalcinosis.
It is typical to have microscopic pyuria, which is a persistent inflammatory reaction to medullary calcification.
With the exception of tubular proteinuria and the aminoaciduria associated with Dent disease, proximal tubular impairment is uncommon.
Any etiology of medullary nephrocalcinosis may result in subsequent distal tubular acidosis due to distal tubular calcium accumulation & chronic medullary inflammation.
Individuals may show signs of their underlying disease or renal failure when they first arrive.
Physical Examination
Physical examination
Nephrocalcinosis is a diagnostic imaging finding, although, in rare instances, physical examination findings may hint at an underlining genetic problem. Nephrocalcinosis and dental symptoms such as enamel abnormalities, gingival hyperplasia, & eruption problems are characteristics of enamel-renal syndrome. A group of disorders with tooth enamel abnormalities is represented by the term “amelogenesis imperfect.”
It is now understood that some patients with claudin-16 mutation-induced familial hypercalciuria, hypomagnesemia, & nephrocalcinosis would have indications of AI during the examination. Without enough phosphorus supplements, severe bone deformities associated with rickets can be seen in individuals with X-linked hypophosphatemia, while the role of phosphate supplementation is debatable. Decompressive laminectomy and joint replacement are frequently needed in those over 40.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Differential diagnosis
Instead of the precipitation of excessive urinary components, dystrophic calcification, which follows the death of parenchymal tissue, often leads to cortical nephrocalcinosis. Infarction, cancer, and infection are some of the contributing factors.
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Nephrocalcinosis is treated by addressing its underlying reason. There are methods for lowering the amount of phosphate, oxalate, or calcium in the urine. Increased fluid ingestion results in at least 1 – 2 liters of urine produced per day.
Restricting animal protein intake, lowering sodium intake to fewer than 100 milliequivalents per day, increasing potassium intake, and using a thiazide diuretic to lower urine calcium excretion are all ways to lower urinary calcium excretion in people with hypercalciuria. Nevertheless, thiazide diuretics shouldn’t be used by people with hypercalcemia.
Patients with hypocitraturia with a pH lower than 7 are treated with potassium citrate for nephrocalcinosis brought on by distal renal tubular acidosis. In addition to replacing the lost potassium, this leads to a normal urine citrate level and raises calcium solubility.
The word “nephrocalcinosis,” first used in 1934 by Fuller Albright, describes an increase in the amount of calcium in the kidneys. This calcium might take the form of calcium phosphate and calcium oxalate. There have been proposals, nonetheless, that the term “nephrocalcinosis” should exclusively refer to the accumulation of calcium phosphate and that the term “calcium oxalosis” should be used for the accumulation of calcium oxalate.
The renal parenchyma & tubules exhibit typical calcium accumulation due to the disease. It may show up on a radiograph inadvertently from a person with normal renal function, or it may be present with chronic or acute kidney damage. This entity can be caused by a variety of diseases, and the underlying causal issue will determine the overall renal outcome.
Primary Hyperparathyroidism
The most frequent renal symptoms of primary hyperparathyroidism are nephrocalcinosis & nephrolithiasis. According to reports, nephrocalcinosis can occur in up to 22% of people with primary hyperparathyroidism. Even while the parathyroid hormone increases calcium absorption in the distal tubules, the benefit is overwhelmed by a rise in filtered calcium, which raises urine calcium excretion.
Sarcoidosis
Hypercalcemia & hypercalciuria are linked to sarcoidosis. In up to 50% of instances where the kidneys are involved, nephrocalcinosis is present.
Distal Renal Tubular Acidosis
Hypercalciuria without hypercalcemia is the most significant complication of nephrocalcinosis. Hypocitraturia, which encourages calcium precipitation in the proximal tubule, is associated with it. Moreover, it leads to metabolic acidosis, which increases the amount of acid that bone buffers can buffer, leading to the release of phosphate and calcium. In research by Brenner et al., which assessed the radiological incidence of nephrocalcinosis in different renal tubular acidoses, nephrocalcinosis was detected in up to 29% of the 92 cases investigated, with the majority of cases occurring in those with distal kidney tubular acidosis.
Medullary Sponge Kidney
Stones are frequent in this illness, which has distorted papillary collection ducts. It causes nephrocalcinosis because it is linked to hypercalciuria & hypocitraturia. Nephrocalcinosis was noted in up to 50% of patients of the medullary sponge kidney in research by Yendt et al.
Nephrocalcinosis-Related Hereditary Disorders
X-linked hypophosphatemic rickets, X-linked hypercalciuric nephrolithiasis, Bartter syndrome, and hypomagnesemia-hypercalciuria syndrome are a few of them. The condition known as Dent disease, which is associated with some abnormalities affecting the CLCN5 allele on the X chromosome that result in the deactivation of CLC-5 voltage-gated chloride channels, is X-linked hypercalciuric nephrolithiasis. This leads to a clinical condition that typically affects young boys & involves rickets, low molecular weight proteinuria, glycosuria, nephrocalcinosis, hypercalciuria, hematuria, and aminoaciduria.
Nephrocalcinosis caused by Usage Of Loop Diuretics
Those who take large doses of loop diuretics over an extended period of time run the risk of developing nephrocalcinosis. 18 consecutive adult people who regularly took furosemide for gaining weight & edema were assessed in a study by Kim et al. The research discovered nephrocalcinosis in 15 patients who received a mean daily dose of 538 mg. The authors concluded that the dose of furosemide taken correlates with the probability of nephrocalcinosis.
Nephrocalcinosis is divided into the following categories:
Chemical or molecular: a rise in intracellular calcium concentration that can be measured but is not visible by imaging.
Microscopic: Light microscopic analysis of renal biopsy samples revealed deposits that were not radiologically evident.
The renal medulla is typically involved, whereas the cortex is considerably less frequent.
The following conditions are linked to cortical nephrocalcinosis:
Oxalosis
Tuberculosis
Trauma
Chronic glomerulonephritis
Transplant rejection
The cortical necrosis that develops during pregnancy
One disease that can result in both medullary & cortical nephrocalcinosis is oxalosis.
Hypercalciuria, either with or without hypercalcemia, is the most frequent cause of nephrocalcinosis. Nephrolithiasis is frequently linked to the metabolic abnormalities of hyperphosphaturia, hyperoxaluria, and hypercalciuria & patients frequently have both disorders at the same time. When the solute concentration in the tubular fluid exceeds the saturation limit, calcium oxalate & calcium phosphate crystals form.
Randall’s plaques were identified in a study by Evan AP et al. as being a component of the basement membranes of the narrow limb of the loop of Henle, which is where the tubule fluid is saturated. Once formed, calcium phosphate plaques can grow into the surrounding interstitial tissue or burst into the tubular lumen, producing a nidus for luminal Ca oxalate stones.
Basophilic calcifications can be seen with light microscopy in nephrocalcinosis in tubular, interstitial, and intracellular settings. Interstitial fibrosis and lymphocyte-predominant interstitial infiltration accompany calcium phosphate accumulation.
The term “nephrocalcinosis” refers to a broad buildup of calcium in the kidneys, not to the focal calcium accumulation linked to a specific focal renal damage. Diseases that result in hypercalcemia, hypercalciuria, hyperphosphatemia, hyperoxaluria, and hyperphosphaturia are the root cause of this condition.
Alkaline urinary pH leads to the production of calcium phosphate particles. It has connections to numerous diseases that are caused by underlying mechanisms.
Hyperphosphaturia in the absence of hyperphosphatemia
Having hyperphosphatemia and hyperphosphaturia
Hypercalciuria in the absence of hypercalcemia
Combined hypercalcemia and hypercalciuria
1. Diseases that both cause hypercalcemia & hypercalciuria
Inherited tubulopathies like Lowe syndrome & Dent illness
If they are not adequately treated, specific forms of nephrocalcinosis such as primary hyperoxaluria, Dent illness, & hypomagnesemia hypercalciuric nephrocalcinosis will proceed to chronic kidney failure or end-stage kidney disease. Rarely is nephrocalcinosis reversible once radiologically discovered.
Clinical history
Nephrocalcinosis’s presentation is mostly determined by its underlying etiology, even though it frequently manifests without any symptoms and is only seen as a radiologic anomaly. The non-specific physical signs reflect the underlying diseases that cause nephrocalcinosis. The three kinds of nephrocalcinosis’ potential clinical characteristics are mentioned below.
Hypercalcemic nephropathy / chemical nephrocalcinosis
In addition to impaired renal concentrating ability and increased free water diuresis (nephrogenic diabetic insipidus), which manifest as polyuria and polydipsia, hypercalcemic nephropathy is frequently characterized by relative vasopressin resistance. There have also been a few reports of renal glycosuria, lower glucose tubular maximum, aminoaciduria, & non-glomerular proteinuria. Around 50% of individuals get reversible hypertension as a result of enhanced peripheral vasoconstriction.
By direct renal vasoconstriction and volume depletion brought on by severe diuresis, hypercalcemia is also a well-established cause of kidney failure. Normal renal function will recover as soon as the hypercalcemia is treated with volume replacement, making this procedure typically reversible. However, persistent hypercalcemia can lead to permanent failure, which is always accompanied by Ca+ crystal formation.
Microscopic nephrocalcinosis
A single nephron’s transit time in a distal tubule is prolonged, blood urea nitrogen (BUN) levels are elevated, and less concentration capacity is seen, despite the fact that there are no comprehensive studies of glomerular filtration or renal tubular function in these models. Acute pyelonephritis or calculous ureteral blockage with kidney failure can occasionally occur in rats with the pelvic variety of nephrocalcinosis.
Macroscopic nephrocalcinosis
Medullary nephrocalcinosis can lead to a wide spectrum of problems. Calcium nodules have the potential to break through the papillary epithelium into the calyceal system & form urinary stones, which can cause renal colic, hematuria, urinary stone passage, or bladder infection as clinical manifestations. Nephrocalcinosis typically denotes a more severe metabolic disturbance, therefore, macroscopic nephrocalcinosis shouldn’t be mistaken for a kidney stone.
It’s worth noting the following:
Because of the excess of free water diuresis and the decreased renal concentrating ability, polyuria & polydipsia may be apparent.
The relative rarity of hypertension is likely due to a diminished capacity to store salt.
Although it is often less than 500 mg per day and in the non-nephrotic range, proteinuria may be seen.
Loss of low-molecular-weight proteins may surpass 2 g/day in Dent disease, and other presenting symptoms include nephrolithiasis, hypercalciuria, & nephrocalcinosis.
It is typical to have microscopic pyuria, which is a persistent inflammatory reaction to medullary calcification.
With the exception of tubular proteinuria and the aminoaciduria associated with Dent disease, proximal tubular impairment is uncommon.
Any etiology of medullary nephrocalcinosis may result in subsequent distal tubular acidosis due to distal tubular calcium accumulation & chronic medullary inflammation.
Individuals may show signs of their underlying disease or renal failure when they first arrive.
Physical examination
Nephrocalcinosis is a diagnostic imaging finding, although, in rare instances, physical examination findings may hint at an underlining genetic problem. Nephrocalcinosis and dental symptoms such as enamel abnormalities, gingival hyperplasia, & eruption problems are characteristics of enamel-renal syndrome. A group of disorders with tooth enamel abnormalities is represented by the term “amelogenesis imperfect.”
It is now understood that some patients with claudin-16 mutation-induced familial hypercalciuria, hypomagnesemia, & nephrocalcinosis would have indications of AI during the examination. Without enough phosphorus supplements, severe bone deformities associated with rickets can be seen in individuals with X-linked hypophosphatemia, while the role of phosphate supplementation is debatable. Decompressive laminectomy and joint replacement are frequently needed in those over 40.
Differential diagnosis
Instead of the precipitation of excessive urinary components, dystrophic calcification, which follows the death of parenchymal tissue, often leads to cortical nephrocalcinosis. Infarction, cancer, and infection are some of the contributing factors.
Nephrocalcinosis is treated by addressing its underlying reason. There are methods for lowering the amount of phosphate, oxalate, or calcium in the urine. Increased fluid ingestion results in at least 1 – 2 liters of urine produced per day.
Restricting animal protein intake, lowering sodium intake to fewer than 100 milliequivalents per day, increasing potassium intake, and using a thiazide diuretic to lower urine calcium excretion are all ways to lower urinary calcium excretion in people with hypercalciuria. Nevertheless, thiazide diuretics shouldn’t be used by people with hypercalcemia.
Patients with hypocitraturia with a pH lower than 7 are treated with potassium citrate for nephrocalcinosis brought on by distal renal tubular acidosis. In addition to replacing the lost potassium, this leads to a normal urine citrate level and raises calcium solubility.
The word “nephrocalcinosis,” first used in 1934 by Fuller Albright, describes an increase in the amount of calcium in the kidneys. This calcium might take the form of calcium phosphate and calcium oxalate. There have been proposals, nonetheless, that the term “nephrocalcinosis” should exclusively refer to the accumulation of calcium phosphate and that the term “calcium oxalosis” should be used for the accumulation of calcium oxalate.
The renal parenchyma & tubules exhibit typical calcium accumulation due to the disease. It may show up on a radiograph inadvertently from a person with normal renal function, or it may be present with chronic or acute kidney damage. This entity can be caused by a variety of diseases, and the underlying causal issue will determine the overall renal outcome.
Primary Hyperparathyroidism
The most frequent renal symptoms of primary hyperparathyroidism are nephrocalcinosis & nephrolithiasis. According to reports, nephrocalcinosis can occur in up to 22% of people with primary hyperparathyroidism. Even while the parathyroid hormone increases calcium absorption in the distal tubules, the benefit is overwhelmed by a rise in filtered calcium, which raises urine calcium excretion.
Sarcoidosis
Hypercalcemia & hypercalciuria are linked to sarcoidosis. In up to 50% of instances where the kidneys are involved, nephrocalcinosis is present.
Distal Renal Tubular Acidosis
Hypercalciuria without hypercalcemia is the most significant complication of nephrocalcinosis. Hypocitraturia, which encourages calcium precipitation in the proximal tubule, is associated with it. Moreover, it leads to metabolic acidosis, which increases the amount of acid that bone buffers can buffer, leading to the release of phosphate and calcium. In research by Brenner et al., which assessed the radiological incidence of nephrocalcinosis in different renal tubular acidoses, nephrocalcinosis was detected in up to 29% of the 92 cases investigated, with the majority of cases occurring in those with distal kidney tubular acidosis.
Medullary Sponge Kidney
Stones are frequent in this illness, which has distorted papillary collection ducts. It causes nephrocalcinosis because it is linked to hypercalciuria & hypocitraturia. Nephrocalcinosis was noted in up to 50% of patients of the medullary sponge kidney in research by Yendt et al.
Nephrocalcinosis-Related Hereditary Disorders
X-linked hypophosphatemic rickets, X-linked hypercalciuric nephrolithiasis, Bartter syndrome, and hypomagnesemia-hypercalciuria syndrome are a few of them. The condition known as Dent disease, which is associated with some abnormalities affecting the CLCN5 allele on the X chromosome that result in the deactivation of CLC-5 voltage-gated chloride channels, is X-linked hypercalciuric nephrolithiasis. This leads to a clinical condition that typically affects young boys & involves rickets, low molecular weight proteinuria, glycosuria, nephrocalcinosis, hypercalciuria, hematuria, and aminoaciduria.
Nephrocalcinosis caused by Usage Of Loop Diuretics
Those who take large doses of loop diuretics over an extended period of time run the risk of developing nephrocalcinosis. 18 consecutive adult people who regularly took furosemide for gaining weight & edema were assessed in a study by Kim et al. The research discovered nephrocalcinosis in 15 patients who received a mean daily dose of 538 mg. The authors concluded that the dose of furosemide taken correlates with the probability of nephrocalcinosis.
Nephrocalcinosis is divided into the following categories:
Chemical or molecular: a rise in intracellular calcium concentration that can be measured but is not visible by imaging.
Microscopic: Light microscopic analysis of renal biopsy samples revealed deposits that were not radiologically evident.
The renal medulla is typically involved, whereas the cortex is considerably less frequent.
The following conditions are linked to cortical nephrocalcinosis:
Oxalosis
Tuberculosis
Trauma
Chronic glomerulonephritis
Transplant rejection
The cortical necrosis that develops during pregnancy
One disease that can result in both medullary & cortical nephrocalcinosis is oxalosis.
Hypercalciuria, either with or without hypercalcemia, is the most frequent cause of nephrocalcinosis. Nephrolithiasis is frequently linked to the metabolic abnormalities of hyperphosphaturia, hyperoxaluria, and hypercalciuria & patients frequently have both disorders at the same time. When the solute concentration in the tubular fluid exceeds the saturation limit, calcium oxalate & calcium phosphate crystals form.
Randall’s plaques were identified in a study by Evan AP et al. as being a component of the basement membranes of the narrow limb of the loop of Henle, which is where the tubule fluid is saturated. Once formed, calcium phosphate plaques can grow into the surrounding interstitial tissue or burst into the tubular lumen, producing a nidus for luminal Ca oxalate stones.
Basophilic calcifications can be seen with light microscopy in nephrocalcinosis in tubular, interstitial, and intracellular settings. Interstitial fibrosis and lymphocyte-predominant interstitial infiltration accompany calcium phosphate accumulation.
The term “nephrocalcinosis” refers to a broad buildup of calcium in the kidneys, not to the focal calcium accumulation linked to a specific focal renal damage. Diseases that result in hypercalcemia, hypercalciuria, hyperphosphatemia, hyperoxaluria, and hyperphosphaturia are the root cause of this condition.
Alkaline urinary pH leads to the production of calcium phosphate particles. It has connections to numerous diseases that are caused by underlying mechanisms.
Hyperphosphaturia in the absence of hyperphosphatemia
Having hyperphosphatemia and hyperphosphaturia
Hypercalciuria in the absence of hypercalcemia
Combined hypercalcemia and hypercalciuria
1. Diseases that both cause hypercalcemia & hypercalciuria
Inherited tubulopathies like Lowe syndrome & Dent illness
If they are not adequately treated, specific forms of nephrocalcinosis such as primary hyperoxaluria, Dent illness, & hypomagnesemia hypercalciuric nephrocalcinosis will proceed to chronic kidney failure or end-stage kidney disease. Rarely is nephrocalcinosis reversible once radiologically discovered.
Clinical history
Nephrocalcinosis’s presentation is mostly determined by its underlying etiology, even though it frequently manifests without any symptoms and is only seen as a radiologic anomaly. The non-specific physical signs reflect the underlying diseases that cause nephrocalcinosis. The three kinds of nephrocalcinosis’ potential clinical characteristics are mentioned below.
Hypercalcemic nephropathy / chemical nephrocalcinosis
In addition to impaired renal concentrating ability and increased free water diuresis (nephrogenic diabetic insipidus), which manifest as polyuria and polydipsia, hypercalcemic nephropathy is frequently characterized by relative vasopressin resistance. There have also been a few reports of renal glycosuria, lower glucose tubular maximum, aminoaciduria, & non-glomerular proteinuria. Around 50% of individuals get reversible hypertension as a result of enhanced peripheral vasoconstriction.
By direct renal vasoconstriction and volume depletion brought on by severe diuresis, hypercalcemia is also a well-established cause of kidney failure. Normal renal function will recover as soon as the hypercalcemia is treated with volume replacement, making this procedure typically reversible. However, persistent hypercalcemia can lead to permanent failure, which is always accompanied by Ca+ crystal formation.
Microscopic nephrocalcinosis
A single nephron’s transit time in a distal tubule is prolonged, blood urea nitrogen (BUN) levels are elevated, and less concentration capacity is seen, despite the fact that there are no comprehensive studies of glomerular filtration or renal tubular function in these models. Acute pyelonephritis or calculous ureteral blockage with kidney failure can occasionally occur in rats with the pelvic variety of nephrocalcinosis.
Macroscopic nephrocalcinosis
Medullary nephrocalcinosis can lead to a wide spectrum of problems. Calcium nodules have the potential to break through the papillary epithelium into the calyceal system & form urinary stones, which can cause renal colic, hematuria, urinary stone passage, or bladder infection as clinical manifestations. Nephrocalcinosis typically denotes a more severe metabolic disturbance, therefore, macroscopic nephrocalcinosis shouldn’t be mistaken for a kidney stone.
It’s worth noting the following:
Because of the excess of free water diuresis and the decreased renal concentrating ability, polyuria & polydipsia may be apparent.
The relative rarity of hypertension is likely due to a diminished capacity to store salt.
Although it is often less than 500 mg per day and in the non-nephrotic range, proteinuria may be seen.
Loss of low-molecular-weight proteins may surpass 2 g/day in Dent disease, and other presenting symptoms include nephrolithiasis, hypercalciuria, & nephrocalcinosis.
It is typical to have microscopic pyuria, which is a persistent inflammatory reaction to medullary calcification.
With the exception of tubular proteinuria and the aminoaciduria associated with Dent disease, proximal tubular impairment is uncommon.
Any etiology of medullary nephrocalcinosis may result in subsequent distal tubular acidosis due to distal tubular calcium accumulation & chronic medullary inflammation.
Individuals may show signs of their underlying disease or renal failure when they first arrive.
Physical examination
Nephrocalcinosis is a diagnostic imaging finding, although, in rare instances, physical examination findings may hint at an underlining genetic problem. Nephrocalcinosis and dental symptoms such as enamel abnormalities, gingival hyperplasia, & eruption problems are characteristics of enamel-renal syndrome. A group of disorders with tooth enamel abnormalities is represented by the term “amelogenesis imperfect.”
It is now understood that some patients with claudin-16 mutation-induced familial hypercalciuria, hypomagnesemia, & nephrocalcinosis would have indications of AI during the examination. Without enough phosphorus supplements, severe bone deformities associated with rickets can be seen in individuals with X-linked hypophosphatemia, while the role of phosphate supplementation is debatable. Decompressive laminectomy and joint replacement are frequently needed in those over 40.
Differential diagnosis
Instead of the precipitation of excessive urinary components, dystrophic calcification, which follows the death of parenchymal tissue, often leads to cortical nephrocalcinosis. Infarction, cancer, and infection are some of the contributing factors.
Nephrocalcinosis is treated by addressing its underlying reason. There are methods for lowering the amount of phosphate, oxalate, or calcium in the urine. Increased fluid ingestion results in at least 1 – 2 liters of urine produced per day.
Restricting animal protein intake, lowering sodium intake to fewer than 100 milliequivalents per day, increasing potassium intake, and using a thiazide diuretic to lower urine calcium excretion are all ways to lower urinary calcium excretion in people with hypercalciuria. Nevertheless, thiazide diuretics shouldn’t be used by people with hypercalcemia.
Patients with hypocitraturia with a pH lower than 7 are treated with potassium citrate for nephrocalcinosis brought on by distal renal tubular acidosis. In addition to replacing the lost potassium, this leads to a normal urine citrate level and raises calcium solubility.
Both our subscription plans include Free CME/CPD AMA PRA Category 1 credits.
Digital Certificate PDF
On course completion, you will receive a full-sized presentation quality digital certificate.
medtigo Simulation
A dynamic medical simulation platform designed to train healthcare professionals and students to effectively run code situations through an immersive hands-on experience in a live, interactive 3D environment.
medtigo Points
medtigo points is our unique point redemption system created to award users for interacting on our site. These points can be redeemed for special discounts on the medtigo marketplace as well as towards the membership cost itself.
Community Forum post/reply = 5 points
*Redemption of points can occur only through the medtigo marketplace, courses, or simulation system. Money will not be credited to your bank account. 10 points = $1.
All Your Certificates in One Place
When you have your licenses, certificates and CMEs in one place, it's easier to track your career growth. You can easily share these with hospitals as well, using your medtigo app.
