Medullary Nephrocalcinosis - Causes, Symptoms, and Treatment

What Is Medullary Nephrocalcinosis?

Renal medullary nephrocalcinosis is the most common type of nephrocalcinosis and is the deposition of calcium salts in the renal medulla. The concentrating effects of the loops of Henle, and the biochemical impact of the medulla, compared to the cortex, are twenty times more common than cortical nephrocalcinosis. The exact reasons may also direct to renal calculi (kidney stones). Nephrocalcinosis is calcium phosphate deposition only and deposition of calcium oxalate is called oxalosis. It can be accidentally detected in a radiographic examination in a patient with normal kidney function or patients with an acute or chronic kidney injury. Many disorders cause this entity, and the all-around renal prognosis depends on the underlying causative condition causing it.

What Causes Medullary Nephrocalcinosis?

Nephrocalcinosis is generalized calcium deposition in the renal tissues and does not include focal calcium deposition related to focal renal injury. It is induced by diseases that cause hyperphosphatemia, hypercalcemia, hypercalciuria, hyperphosphaturia, and hyperoxaluria. Calcium phosphate crystal formation arises in alkaline urine pH. It is related to many diseases which utilize the underlying mechanisms.

• Hypercalciuria without hypercalcemia.

• Hypercalciuria with hypercalcemia.

• Hyper-phosphaturia with hyperphosphatemia.

• Hyper-phosphaturia without hyperphosphatemia.

1. Disorders causing hypercalciuria without hyperglycemia include -

• Medullary sponge kidney.

• Distal renal tubular acidosis.

• Inherited tubulopathies.

• Beta thalassemia.

• Neonatal nephrocalcinosis and loop diuretics.

• Chronic hypokalemia.

2. Disorders causing both hypercalcemia and hypercalciuria include -

• Vitamin D therapy.

• Primary hyperparathyroidism.

• Sarcoidosis.

• Congenital hypothyroidism.

• Milk-alkali syndrome.

3. Disorders causing hyper-phosphaturia and hyperphosphatemia include -

• Oral sodium phosphate bowel preparations.

• Tumor lysis syndrome.

4. Disorders causing hyper-phosphaturia without hyperphosphatemia include -

• Inherited tubulopathies such as Lowe syndrome and Dent disease.

• Autosomal recessive, X-linked, and autosomal dominant hypophosphatemic rickets.

What Are the Diseases Causing Medullary Nephrocalcinosis?

Primary Hyperparathyroidism:

Nephrocalcinosis and nephrolithiasis are very common renal manifestations of primary hyperparathyroidism. Nephrocalcinosis is reported in up to 22 % of cases of primary hyperparathyroidism. Even if parathyroid hormone facilitates the distal tubular reabsorption of calcium, the effect is surpassed by the increase in filtered calcium thereby, rising the urinary calcium excretion.

Hypervitaminosis D:

Vitamin D functions by increasing the intestinal absorption of calcium and also bone resorption, which results in hypercalcemia and hypercalciuria. Nephrocalcinosis can occur most commonly when activated vitamin D such as calcitriol in conjunction with phosphate supplements. This procedure is common in X-linked hypophosphatemic rickets. Children with nephropathic cystinosis excrete considerable amounts of calcium and phosphate due to renal tubular Fanconi syndrome and also get significant supplements of phosphate and alkalinizing agents.

Sarcoidosis:

Sarcoidosis is related to hypercalcemia and hypercalciuria. Nephrocalcinosis is noticed in up to 50 % of cases with renal involvement.

Distal Renal Tubular Acidosis:

It is the most expected reason for nephrocalcinosis due to hypercalciuria without hypercalcemia. It is associated with hypocitraturia, which stimulates calcium precipitation in renal tubules. It also leads to metabolic acidosis which results in increased buffering of acid by bone buffers with the successive releases of calcium and phosphate.

Nephrocalcinosis Due to Loop Diuretics:

There is a risk of growth of nephrocalcinosis in patients taking high doses of loop diuretics for a prolonged period. Adult patients who habitually take Furosemide for weight gain and edema were evaluated and found to have nephrocalcinosis risk that correlates with the dose of Furosemide taken.

Medullary Sponge Kidney:

This condition is a disease with dilated papillary collecting ducts, and stones are common. It is related to hypercalciuria and hypocitraturia, resulting in nephrocalcinosis. In a study, nephrocalcinosis was observed in up to 50 % of cases of the medullary sponge kidney.

Hereditary Disorders Associated with Nephrocalcinosis:

These include X-linked hypophosphatemic rickets, X-linked hypercalciuric nephrolithiasis, hypomagnesemia-hypercalciuria syndrome, and Bartter syndrome. X-linked hypercalciuric nephrolithiasis is also called Dent disease and is related to mutations affecting the CLCN5 gene on the X chromosome that leads to the inactivation of CLC-5 voltage-gated chloride channels. This develops in a clinical syndrome affecting young boys and usually encloses nephrocalcinosis, hypercalciuria, nephrolithiasis, low molecular weight proteinuria, hematuria, glycosuria, aminoaciduria, renal failure, hypophosphatemia, and rickets.

What Are the Symptoms of Medullary Nephrocalcinosis?

Patients with kidney stones can also have-

• Fever and chills.

• Severe pain in the sides of the back (flank), belly area, groin, or testicles.

• Nausea and vomiting.

• Hematuria.

• Delayed symptoms related to nephrocalcinosis can be related to chronic kidney failure.

How to Diagnose Medullary Nephrocalcinosis?

• Kidney Ultrasound - Radiologic determination of nephrocalcinosis investigation needs to be followed for diagnosis.

• Blood Analysis - Serum electrolytes such as calcium and phosphate should be measured.

• Urine Analysis - Measurement of urine pH can help determine the presence of distal renal tubular acidosis. Besides, the recommendation is to obtain two 24-hour urine collections for measuring the excretion of calcium, oxalate, phosphate, citrate, and creatinine.

How to Treat Medullary Nephrocalcinosis?

Treatment is subjected to treating the underlying cause of nephrocalcinosis. Techniques to reduce the urinary concentration of calcium, phosphate, or oxalate are employed. Fluid intake is increased to create at least two liters of urine a day. Among patients with hypercalciuria, urinary calcium excretion can be decreased by limiting the amount of animal protein, reducing the sodium intake to less than 100 milliequivalents per day, increasing the potassium intake, and using a thiazide diuretic to decrease the urinary calcium excretion. Regardless, patients with hypercalcemia must not use a thiazide diuretic. In nephrocalcinosis because of the distal renal tubular acidosis, potassium citrate is used in patients with hypocitraturia and pH less than 7. This not only restocks the potassium loss but also attains a normal urinary citrate level, thereby increasing the solubility of calcium.

Treatment should involve strategies to reduce abnormal levels of calcium, phosphate, and oxalate in the blood and urine. Treatment should include making changes in the diet and taking medicines and supplements. If the ongoing medicine causes calcium loss then it needs to be stopped immediately. One should never stop taking any medicine before talking to a physician. Other symptoms like kidney stones, should be treated appropriately.

Conclusion

Nephrocalcinosis largely presents as an asymptomatic, chronic disease process found on radiographic imaging of the abdomen. Nevertheless, requesting radiographs might be possible due to the evaluation of pain caused by existing nephrolithiasis. Nephrolithiasis can arise due to chronic hypercalcemia and hypercalciuria. It can induce renal colic. Polyuria and polydipsia can arise with chronic hypercalcemia, medullary nephrocalcinosis, and Bartter syndrome. It can also appear acutely with renal failure in instances such as tumor lysis syndrome and acute phosphate nephropathy.